Latin American Dialysis and Renal Transplant Registry: 2008 report (data 2006). Between 1991 and 2006, the Latin American Dialysis and Renal Transplantation Registry collected data from 20 countries (Argentina, Brazil, Bolivia, Chile, Colombia, Costa Rica, Cuba, Ecuador, El Salvador, Guatemala, Honduras, Mexico, Nicaragua, Panama, Paraguay, Peru, Puerto Rico, Dominican Republic, Venezuela and Uruguay). Access to RRT was universal in Argentina, Brazil, Chile, Cuba, Puerto Rico, Venezuela and Uruguay, all countries belonging to the medium-high or high income group. Data about patients on renal replacement therapy (RRT) were supplied by national affiliates or the Registry's Coordination Committee. Transplant data were gathered and shared with the Latin American and Caribbean Society of Transplantation. RRT prevalence increased from 162 patients per million population (pmp) in 1991 to 478 pmp in 2005 and 473 pmp in 2006 (59.2% hemodialysis, 20.4% peritoneal dialysis and 20.4% with a functioning kidney allograft). Countries with the highest prevalence were Puerto Rico (1,148.9 pmp), Uruguay (924.5 pmp) and Chile (907.6 pmp). Latin America's (LA) incidence increased from 27.8 pmp in 1992 to 188 pmp in 2006. The LA Kidney transplant rate increased from 3.7 pmp in 1987 to 15,4 pmp in 2006, and 166 combined transplants - kidney and another organ, mainly pancreas - were performed. In the medium-high income group 2006, (Argentina, Brazil, Chile, Costa Rica, Cuba, Mexico, Panama, Uruguay, Venezuela) the prevalence rate was 534.8 pmp vs. 289.5 pmp in the middle-low income group. The transplant rate was 18.4 pmp in the medium-high income group vs. 7 pmp in the middle-low group (p < 0.01). RRT incidence and prevalence continue to grow steadily. Access to RRT is universal only in some countries included in the medium-high or high income group. It is imperative to accomplish the goal of making RRT available to all who need it.


Burden of end-stage renal disease in sub-Saharan Africa. To review prevalence, causes and management of end-stage renal disease (ESRD) in sub-Saharan Africa (SSA). Review of literature and data. Approximately 70% of the least developed countries of the world are in SSA. Rapid urbanization is occurring in many parts of the continent, contributing to overcrowding and poverty. While infections and parasitic diseases are still the leading cause of death in Africa, non-communicable diseases are coming to the forefront. There is a continuing "brain drain" of healthcare workers (physicians and nurses) from Africa to more affluent regions. There are large rural areas of Africa that have no health professionals to serve these populations. There are no nephrologists in many parts of SSA; the numbers vary from 0.5 per million population (pmp) in Kenya to 0.6 pmp in Nigeria, 0.7 pmp in Sudan and 1.1 pmp in South Africa. Chronic kidney disease affects mainly young adults aged 20 - 50 years in SSA and is primarily due to hypertension and glomerular diseases. HIV- related glomerular disease often presents late, with patients requiring dialysis. Diabetes mellitus affects 9.4 million people in Africa. The prevalence of diabetic nephropathy is estimated to be 6 - 16% in SSA. The current dialysis treatment rate is < 20 pmp (and nil in many countries of SSA), with in-center hemodialysis the modality of RRT for the majority. Transplantation is carried out in a few SSA countries: South Africa, Nigeria, Mauritius and Ghana, with most of the transplants being living donor transplants, except in South Africa where the majority are from deceased donors. Chronic kidney disease care is especially challenging in SSA, with large numbers of ESRD patients, inadequate facilities, funding and support.


Renal replacement therapies for end-stage renal disease in North Africa. Despite population, social and cultural similarities between the countries in the region, large differences in the management of end-stage renal disease (ESRD) are found. This reflects the varying policies and health priorities of different countries, leading to differences in terms of renal replacement therapies (RRT) facilities. Hemodialysis remains the most frequent modality. Demographic and epidemiological transition has lead to an increased incidence of diabetes mellitus and arterial hypertension, but glomerulonephritis and interstitial nephropathies remain important causes of ESRD in the region.


Current burden and probable increasing incidence of ESRD in China. To illustrate the incidence and prevalence of ESRD in mainland China, and estimate future trends. The Chinese Society of Blood Purification (CSBP) produced a survey form. The form was designed for use at the facility level, rather than at the patient level. The data were those prevailing at the end of 2008, i.e., the total number of patients at the end of 2007 and the number of new patients during the year 2008; numbers of males and females and each of the age groups; numbers of diabetes, hypertension, polycystic kidney disease, chronic interstitial nephritis, etc. as primary cause of ESRD; and numbers of cardiovascular disease, stroke, infection, etc. as primary cause of death. The forms were distributed to each dialysis facility, and returned to CSBP for analysis. The point prevalence of ESRD patients on maintenance hemodialysis (MHD) at the end of 2007 and 2008, and the annual incidence in 2008 were calculated. The primary cause of ESRD and primary cause of death were also reported. Among 31 provinces and/or regions, 27 responded. At the end of 2007, there were totally 65,074 ESRD patients on MHD or PD; the point prevalence was estimated to be 51.7 per million population (pmp) around mainland China. The number increased to 102,863 at the end of 2008; point prevalence increased to 79.1 pmp. The annual increasing rate of prevalence was 52.9%. The number of new ESRD patients was 45,423; the annual incidence was 36.1 pmp in the year 2008. The main causes of ESRD were glomerulonephritis (45%), diabetes (19%), hypertension (13%), polycystic kidney disease (2%) and others or unknown (20%). The main cause of death was cardiovascular (31.0%), stroke (20.3%), infection (19.9%) and others (28.8%). Although the prevalence was relatively low compared with other Asian regions, the incidence of MHD was high. Mainland China is anticipating an increasing burden of ESRD in the near future.


Burden of disease - prevalence and incidence of ESRD in selected European regions and populations. Rates of renal replacement therapy (RRT) vary markedly between Eastern and Western European countries. This review aims to establish the characteristics of healthcare systems and renal services that are independently associated with rates of initiation of RRT in these countries. The incidence of RRT varied from 12 to 455 per million populations (pmp); the only general population indicator independently associated with RRT incidence was aged 65+. Economic and financial conditions could also play an important role. Gross Domestic Product (GDP) per capita and the proportion of GDP spent on healthcare independently predicted RRT incidence. Each increase in hemodialysis (HD) facilities and competition between providers is associated with higher RRT incidence. In this context, macroeconomic and potentially modifiable renal service organizational factors appear more important determinants of provision of RRT than measurable medical factors. The economic, financial or medical conditions could also play an important role in treatment strategy. The proportion of patients receiving HD, peritoneal dialysis (PD) or transplantation shows marked variation in Europe. The East Europeans use more HD and less RTx as compared to West Europeans; the use of PD is similar. Treatment of anemia and mineral metabolism disorders also varies from one region to another. The mean baseline hemoglobin level and the prevalence of patients reaching this value are higher in West Europeans. Regarding mineral metabolism, the percent of patients achieving all four parameters (Ca, P, CaxP and PTH) was also higher in Western Europe. The adherence to EBPG (European Best Practice Guidelines) was also higher in these countries.


Incidence and treatment of ESRD among indigenous peoples of Australasia. Indigenous people in Australia and New Zealand experience rates of ESKD several times higher than non-indigenous people. This relative rate is highest among people aged 45 - 54 for Aboriginal Australians, and 65 - 74 years for Maori. The majority of this is driven by diabetic nephropathy. Both groups have lesser utilization of transplantation as a renal replacement therapy than non-indigenous comparators, and lesser utilization of home dialysis modalities.


Hypertension and kidney disease.

Hypertension and kidney disease. The relationship between chronic kidney disease and hypertension remains enigmatic and a matter of considerable clinical and academic interest, with evidence suggesting that hypertension is both a cause and a consequence of kidney disease. The kidney has a pivotal role in setting the blood pressure in any individual, and this is likely to be related to that individual's sensitivity to salt. The relationship between low birth weight and subsequent hypertension and kidney disease may be predicated on changes in post glomerular phenomena, including sodium transport, although there are differences observed between white and black populations, there being no such clear relationship demonstrable in the latter. Differences in vascular structure may account for some of this variation. There is , by way of example a considerable difference in the risk of death from cardiovascular disease between blacks and Caucasoid populations with renal disease, the former being at greater risk. International moves are now afoot to reduce dietary salt intake. Successful efforts to reduce blood pressure by these or by pharmacological means are likely to reduce death rates, although precise blood pressure targets remain an elusive concept. The possible role of non muscular heavy chain type II isoform A protein which is associated with non diabetic chronic kidney disease in subjects of African ancestry remains to be determined.


The impact of disadvantage on the development and progression of diabetic kidney disease. Disadvantaged people include those experiencing economic, social or educational deprivation and, in some cases, those undergoing rapid transition from subsistence to industrial economies. Disadvantaged people worldwide are affected disproportionately by the global epidemic of diabetes. They are also at increased risk of kidney disease attributable to diabetes, and for many, the cost of managing their kidney disease far exceeds their available resources. We review factors associated with disadvantage that may increase the risk of diabetic kidney disease, and the barriers to care that hinder attempts to provide an adequate therapeutic response. A rapidly rising prevalence and magnitude of obesity among children and adults, increasing frequency of intrauterine exposure to diabetes, and inadequate access to healthcare are responsible, in part, for a surge in the frequency of diabetes and, in turn, diabetic kidney disease among disadvantaged people. These factors may also predispose to an earlier onset of diabetes and kidney disease, thereby perpetuating the disadvantage by reducing the earning potential of those affected through illness and disability.


Glomerulonephritis in disadvantaged populations. Glomerulonephritis (GN) still enjoys a high rank as a cause of chronic kidney disease (CKD) worldwide. Its burden is particularly manifest in disadvantaged populations, with a proportional contribution up to 6-folds compared to that in the USA. There are several overlapping risk factors that render a particular population "disadvantaged" in this respect. It is envisaged that these may be categorized into a triad of genetic, climatic and socioeconomic factors. An attempt is made to dissect the impact of each of these factors, which combine in different proportions in different populations thereby explaining regional disparity in the epidemiology, clinical manifestations and outcomes of CKD. The genetic impact is manifest in racial variations in the incidence of GN as a whole, the predominance of FSGS mainly in blacks and IgA nephropathy in Asians, the increased susceptibility to SLE and decreased incidence of IgAN and vasculitis in blacks, with similar trends in other "subraces" as Indians, Afro-Caribbean's, Martinique and other indigenous populations. The climatic impact is mainly displayed in the tropics, where the "rich bioecological environment" increases the incidence of infection-associated GN, usually proliferative with a few exceptions. The socioeconomic impact, reflecting low national economy in the developing world, modifies the two other arms of the triad according to the level of primary care, efficiency of the referral system and adequate management of primary infections as well as associated glomerular injury.


Risk factors for the development of chronic kidney disease with HIV/AIDS. A review of the prevalence and risk factors for chronic kidney disease (CKD) in HIV infection. A review of published literature. High risk for development of chronic kidney disease with HIV infection are black race, CD4 count < 200 cells/mm3, HIV RNA levels > 4,000 copies/ml, family history of CKD and presence of diabetes mellitus, hypertension or hepatitis C co-infection. In 2004, the risk of developing ESRD was reported as 50 times higher in HIV-infected African-Americans than in HIV-infected whites and in 2007, African Americans accounted for nearly 90% of ESRD attributed to HIVAN. Once CKD was established, African-Americans were 18 times more likely to progress to ESRD than whites and their decline in GFR was six times more rapid than white subjects. The prevalence of CKD with HIV infection was 3.5 - 4.7% in 31 European countries, Israel and Argentina, and 1.1 - 5.6% Brazil; 18% Switzerland; 27% India and 12.3% Iran. Reported prevalence of CKD in HIV-infected patients in sub-Saharan Africa ranges from 6 - 48.5%. Few renal biopsy studies have been performed. In South Africa, HIVAN was present in variable numbers in three studies, ranging from 5 - 83% and immune complex disease in 21 - 40%. A variation in the MYH9 locus of chromosome 22 has been associated with increased risk for idiopathic FSGS, hypertensive nephrosclerosis and HIVAN and may explain much of the increased risks of ESRD and FSGS among African-Americans. A strong correlation with serum creatinine levels and progression to ESRD in HIV patients has been linked to an index of chronic damage on renal histology. The role of genetics and variations in MYH9 gene loci in renal disease has to be established in other HIV-infected populations. The histological classification for HIV-associated chronic kidney disease requires review, as well as the utility of chronicity scores to evaluate prognosis and response to therapy of HIV-associated kidney disease.


Chronic kidney disease among Aboriginal people living in Canada. Chronic kidney disease (CKD) poses a significant health burden on Aboriginal communities around the world. High rates of diabetes among Aboriginal Canadians are an important contributing factor to the rising rates of CKD in this population, and diabetes has been the leading cause of kidney failure among Aboriginal patients initiating dialysis in Canada for the last decade. This paper will describe access to, quality of, and outcomes associated with the renal care of Aboriginal people living in Canada. Research shows that rates of CKD are higher among Aboriginal people residing in Canada, and that despite remote residence location, use of peritoneal dialysis is substantially lower than in white patients. Similarly, although mortality rates among Canadian hemodialysis patients are similar for Aboriginals and for whites, Aboriginal patients have substantially reduced access to kidney transplantation. A concerted effort to lower rates of CKD in this population is needed. Changes in healthcare policy that successfully translate into healthcare provider and patient level improvements in access to and the quality of care will be needed to significantly reduce the risk of CKD and progression to kidney failure.


Kidney disease in Maori and Pacific people in New Zealand. To highlight the population demographics and socio-economic status of Maori and Pacific people in New Zealand, and relate this to their relative incidence and prevalence of kidney disease, relative access to renal replacement therapies and provide a comparison of their outcomes relative to non-Maori/non-Pacific people with kidney disease in New Zealand. A review was carried out of relevant New Zealand Statistics and Health data, literature on kidney disease in New Zealand including reports of the Australian and New Zealand Dialysis and Transplant Registry and further analysis of the New Zealand Diabetic Cohort Study. There are large differences in the incidence of microalbuminuria, glomerulonephritis and hypertension amongst Maori and Pacific people in comparison to others. There is a 3.5 fold higher relative incidence of Maori and Pacific patients commencing renal replacement therapy. Identified associations with CKD include an increased incidence of obesity, smoking and poverty relative to other members of the population. Maori and Pacific people are less likely to be transplanted and have a reduced graft survival. Maori and Pacific people have a higher incidence of chronic kidney disease and end-stage renal failure in comparison to the rest of the population with poorer outcomes. The causes are likely to be multi-factorial with poverty an important contributor.


Disparities in end-stage renal disease care in South America. South America is one of the most heterogeneous regions in the world regarding ethnical composition and socioeconomic development level. Our aim was to analyze the status of end-stage renal disease (ESRD) management in the Portuguese-speaking and Spanish-speaking countries of South America. Data were collected using a survey sent to the Society of Nephrology of each country, and complemented with data available in the Latin American Dialysis and Transplant Registry or personal communication with collaborators within the nephrology societies. Most of South America countries have a hybrid of public and private healthcare system. Universal access to renal replacement therapy (RRT) is provided in Argentina, Brazil, Chile, Uruguay and Venezuela which comprise nearly 73% of South America population. The expenditure on health per capita varies from nearly US$ 200 per year in Bolivia to more than US$ 1,600 per year in Argentina. The prevalence of patients on RRT varies from 95 pmp. in Paraguay and 924 pmp in Chile. There is an important association between the prevalence of diabetes and the number of patients on RRT. Older people also are at a higher risk of developing ESRD. The rapid aging of the population and a higher prevalence of diabetes will probably translate into a burden of ESRD in the future. It is to be hoped that political and economical stability in the region can ease the adoption of universal access to ESRD treatment in all South American countries.


Racial differences in chronic kidney disease (CKD) and end-stage renal disease (ESRD) in the United States: a social and economic dilemma. Chronic kidney disease (CKD), defined as an eGFR < 60 ml/min/1.73 m², affects up to 25% of the United States population. In addition, it is estimated that approximately 6% of the population have early evidence of CKD and will likely progress to end stage renal disease (ESRD) in the near future. Further, ESRD is more common in many ethnic minorities, with African-Americans having the highest rates of treated ESRD, closely followed by Hispanic Americans, when compared to non- Hispanic White persons. Although African-Americans with CKD are more likely to die than non-Hispanic White persons with CKD, these trends reverse once progression to ESRD is established. The reasons for the disparities in the prevalence and incidence of CKD, ESRD, and mortality are unclear, but likely involve a complex interaction of socioeconomic, environmental and genetic factors. This review highlights current data pertaining to the social and economic impact of ethnic differences in the prevalence and incidence of CKD and ESRD in the United Stated. It is hoped that highlighting the current trend of kidney related health disparities will not only lead to an improved understanding of these issues, but also more informed research agendas, that are ultimately aimed at alleviating ethnic differences in kidney health outcomes.


Racial minority groups on dialysis in Europe: a literature review. To provide an overview of the existing data on non-Caucasian dialysis patients within Europe, and to explore whether these data confirm differences between non-Caucasian and Caucasian dialysis patients that were found in other parts of the world. A query consisting of the combination "dialysis", "ethnicity", and "Europe" was applied in PubMed, EMBASE, Web of Science, CINAHL, and the Cochrane Library. Ten papers were included in this study. Studies from the United Kingdom (UK) and the Netherlands confirm the higher incidence of end-stage renal disease (ESRD) in non-Caucasians. In other European countries these findings were not confirmed. In studies from the UK, the Netherlands, and Spain a younger age at initiation of dialysis treatment for non-Caucasians compared to Caucasians was reported, this is also found in non-European studies. Regarding comorbid conditions at the start of renal replacement therapy (RRT), vascular disease was less common, while diabetes was more common among non-Caucasians compared to Caucasians. Large non-European studies also demonstrated less vascular disease among non-Caucasians initiating RRT than among Caucasians. The survival advantage for non-Caucasian compared to Caucasian RRT patients is confirmed in one large study from the UK and in a Dutch study. Reasons for the better survival of non-Caucasians are not understood completely. Only a few studies are available on non-Caucasian dialysis patients in Europe. The available data confirm findings of other studies throughout the world on racial differences on dialysis. More research is needed to understand the higher incidence and better survival in non-Caucasian patients, and also in countries where there are currently no relevant data.


Kidney health in the Middle East.

Kidney health in the Middle East. Chronic kidney disease (CKD) is a common and costly health problem in the Middle East. The incidence of CKD is still unknown, and the incidence of end-stage renal disease (ESRD) is estimated at 100 - 140 incident cases per million population in the Middle East countries. Most of the available statistics about prevalence are of treated ESRD. Published population-based studies for incidence and prevalence of CKD and ESRD are still lacking in most of the Middle East countries. This negatively affects the health planning and effectiveness of preventive and therapeutic measures in the region. The prevalence of renal replacement therapy varies among the different countries in the Middle East. The infrastructure for these services is also variable among these countries and affects the outcome, which as yet cannot be measured accurately. The low gross national income of the Middle East countries is a major factor in negating the implementation of research, planning, and improvement of the services for CKD patients. To overcome the obstacles for the renal services in the Middle East countries, the constraints on health expenditure need to be surmounted, which is not an easy task, and related appropriately to the gross national income. Awareness within the medical community and the public at large about the advances of therapeutic and preventive measures is also an important factor for progress toward better kidney health in the Middle East.


Acute kidney injury as a risk factor for chronic kidney diseases in disadvantaged populations. Acute kidney injury (AKI) is considered to be a potential cause for developing chronic kidney disease (CKD); on the other hand, CKD predisposes to AKI. The lack of adequate epidemiological data makes it difficult to determine if AKI induces CKD in less developed countries. The etiology of AKI in rich populations, in whom sophisticated surgery, interventional radiology and oncology treatments are usually the cause of AKI, is very different from that of disadvantaged populations, where the origin of AKI is associated with endemic infections, obstetric problems, poisons, toxins and natural disasters. Any conclusions extrapolated from these two settings should be treated with caution. Moreover, people living in disadvantaged conditions are usually much younger than those in rich areas and this age factor could facilitate total recovery of renal function after AKI if treatment based on an adequate supply of water, rehydration and anti-infectious measures were provided. In the small segment of the population of less developed countries having an income per capita similar to that observed in the developed countries, the long-term outcome of AKI should also be expected to be similar. New data coming from two single centers analyzing only the long-term outcome of acute tubular necrosis (ATN) patients, with a normal or near normal renal function prior to the AKI episode, coincide in reporting a requirement for chronic dialysis among the surviving patients of 2%. If these data are confirmed, the importance of AKI as cause of CKD should be reconsidered, both in developed and less developed countries.


Hypovitaminosis D, neighborhood poverty, and progression of chronic kidney disease in disadvantaged populations. In the United States, there are significant racial disparities in the incidence and prevalence of end-stage renal disease. The disparities are greatest for the Blacks and the magnitude of disparity is significantly greater than is evident from the incidence and prevalence data of end-stage renal disease - early stage chronic kidney disease is less common in Blacks and during that stage, mortality rate is significantly higher for that racial group. Recent studies have identified a genetic predisposition for non-diabetic renal disease among Blacks. However, genetic factors explain only part of the higher risk and the racial disparities are a result of a complex interplay of biology and sociology. Herein we focus on two factors and their role in explaining the higher risk for progression of chronic kidney disease among Blacks - one biologic (vitamin D deficiency) and one sociologic (neighborhood poverty). A greater Understanding of these factors is important in order to reduce the racial disparities in the United States.


Management of chronic kidney disease: primary health-care setting, self-care and multidisciplinary approach. End-stage renal disease (ESRD) is a growing problem, particularly in developing countries. Factors closely related with lifestyle and dietary habits that negatively affect kidney function are rarely modified by isolated medical intervention. Therefore, the present study was designed to determine the effect of an educational program with a multidisciplinary health-care approach supported by self-help groups on the lifestyle and dietary habits of patients at high risk of developing chronic kidney disease (CKD). 51 patients with overweight/obesity, 45 with hypertension and 88 with Type 2 diabetes mellitus (DM2) from a Family Medicine Unit, who had failed to meet clinical practice recommendations, were studied over 6 months. Patients received educational intervention guided by a multidisciplinary health team for 4 weeks (including topics such as emotional management, nutritional patterns, exercise and health-related problems). Reinforcement of goals and group dynamics were performed every 3 months. Additionally, self-help groups were constituted during the first month, and functioned with free activities, selected by patients and supported by the health team, for the duration of the study. A lifestyle questionnaire was administered at baseline and the end of the study; clinical and biochemical evaluations were performed every 3 months. Baseline lifestyle and dietary habits were unhealthy in all groups, particularly with regard to diet and exercise, and clinical and biochemical variables were concordant with inadequate achievement of clinical practice recommendations. After 6 months experience within this program, many of the negative lifestyle characteristics significantly improved. All groups reported a notable improvement in nutritional and exercise habits, as well as in management of the emotions. Only diabetic and hypertensive patients significantly improved the knowledge of their disease and adherence to treatment. None of the groups managed to reduce smoking or to cut their alcohol intake habits; however, relatively few participants had displayed these behaviors at the start of the study. Compared to baseline, all the groups significantly reduced body mass index and waist circumference. Additionally, diabetics and overweight/ obese patients significantly reduced blood glucose and increased GFR, and hypertensive patients significantly decreased systolic blood pressure and tended, although not significantly, to increase GFR. Remarkably, all these changes were independent of drug treatment, because none of the therapeutic interventions that had been formerly prescribed by family physicians had been significantly changed by the end of the follow-up in any of the groups. The implementation of educational strategies comprising multiple interventions for patients, guided by health professionals (multidisciplinary teams including primary doctors, dietitians, nurses, social workers), and probably supported by self-help groups, may be very helpful in modifying negative lifestyle and dietary habits. Educational interventions by both doctors and patients should be adopted concurrently and may help to control the enormous and growing problem of ESRD.


Distribution of volumes of individual glomeruli in kidneys at autopsy: association with age, nephron number, birth weight and body mass index. Glomerular hypertrophy occurs in a number of normal and pathological states. Glomerular volume in kidneys at autopsy is usually indirectly derived from estimates of total glomerular mass and nephron number, and provides only a single value per kidney, with no indication of the range of volumes of glomeruli within the kidney of any given subject. We review findings of the distribution of volumes of different glomeruli within subjects without kidney disease, and their correlations with age, nephron number, birth weight and body mass index (BMI). The study describes findings from autopsy kidneys of selected adult white males from the Southeast USA who had unexpected deaths, and who did not have renal scarring or renal disease. Total glomerular (nephron) number and total glomerular volume were estimated using the disector/fractionator combination, and mean glomerular volume (Vglom) was derived. The volumes of 30 individual glomeruli (IGV) in each subject were determined using the disector/Cavalieri method. IGV values were compared by categories of age, nephron number, birth weight and BMI. There was substantial variation in IGV within subjects. Older age, lower nephron number, lower birth weight and gross obesity were associated with higher mean IGV and with greater IGV heterogeneity. High Vglom and high IGVs were associated with more glomerulosclerosis. However, amongst the generally modest numbers of sclerosed glomeruli, the pattern was uniformly of ischemic collapse of the glomerular tuft. There was no detectable focal segmental glomerular tuft injury. In this series of people without overt renal disease, greater age, nephron deficit, lower birth weight and obesity were marked by glomerular enlargement and greater glomerular volume heterogeneity within individuals.


Is there a need for early detection programs for chronic kidney disease? The aims of this paper are to examine whether early detection programs are needed to assist in detecting and managing chronic kidney disease (CKD). It draws on existing material which indicates that CKD and its precursor risk factors or illnesses such as hypertension, diabetes mellitus and HIV infection are very clearly major challenges faced by health systems worldwide. This paper evaluates whether CKD meets the epidemiological criteria to justify early screening. More compelling evidence is becoming available which indicates that the prevalence of CKD is significant in both developing and developed countries and that CKD can be easily detected and treated with only small changes to existing practice and this may be improved through screening programs. A brief evaluation of the challenges of establishing early detection programs is provided, as well as an examination of the capacity which exists for establishing such programs. It concludes that, despite the lack of randomized studies, these programs appear to provide an opportunity to integrate CKD management with common chronic illnesses and, through this approach, provide clinical and cost-effective management of both CKD and cardiovascular disease.


Prevention of CKD in Guatemala.

Prevention of CKD in Guatemala. The rapidly growing burden of chronic kidney diseases (CKD) is a major public health problem that will stretch the healthcare system of all countries, especially those not yet industrialized. Guatemala has a population of approximately 14 million, of which 60% are younger than 20 years. It is estimated that only 35% of Guatemalan patients with CKD Stage 5 (ESRD) are diagnosed and treated. Therefore, the cost of death and disability due to CKD in this young population is particularly profound. CKD programs have to compete with many demands (often viewed in the short term as more urgent or widespread) for finite healthcare resources. FUNDANIER (Foundation for Children with Kidney Diseases) has been the instrument that facilitated changes in the Guatemalan health system, in order to establish a comprehensive Pediatric Nephrology program. FUNDANIER is the first local initiative to provide comprehensive prevention and management of kidney disease in children and adolescents in Guatemala. Through an agreement with the National Health Authorities, FUNDANIER is involved in the primary, secondary and tertiary prevention of CKD in the pediatric population. This might be a model applicable in other developing countries.


Social experience among vulnerable populations: conflicts and negotiations between chronic patients and their doctors seen as a challenge to medical practice. This article attempts to explore the impact of a chronic illness, end-stage renal disease, on the management of every day life between the actors involved: lay people, the affected children and their families and the medical personnel. The focus is on the nature and the process of interaction between these parties which are confronted from the onset of the illness with fundamental uncertainty concerning length of survival and the reliability of sophisticated technology such as dialysis techniques and transplantation. Within the framework of the organization of this serious illness, such interaction is concretized in the form of certain tasks to be accomplished. These constitute medical work which combines to shape the social relationships between lay people and professionals into confrontation. First, information was gathered from direct observation and fieldwork in two Units of Pediatric Nephrology located in two different hospitals in Paris. Fieldwork was followed by surveys using semi-structured interviews carried out among patients in a private clinic and the unit's personnel, medical and non medical, the families in their homes, and some adolescents in the units. Then questions were raised about strategies and negotiations, in order to reach an agreement as to when a conflict arises. The medical work is carried out in a context of changing situations, constantly called into question by the illness, and thus discovering a social order in which lay people become actors in these new situations.


Shortage of healthcare workers in sub-Saharan Africa: a nephrological perspective. The paper assesses the lack of healthcare workers, the consequences, and possible solutions. Review of existing literature and global health reports. The 47 countries of sub-Saharan Africa have a critical shortage of healthcare workers, the deficit amounting to 2.4 million doctors and nurses. There are 2 doctors and 11 nursing/midwifery personnel per 10,000 population, compared with 19 doctors and 49 nursing/midwifery personnel per 10,000 for the Americas, and 32 doctors and 78 nursing/midwifery personnel per 10,000 for Europe. And, whereas there are 28 doctors and 87 nurses/midwifery personnel per 10,000 in high income regions of the world, there are only 5 doctors and 11 nurses/ midwifery personnel per 10,000 in low income regions. The shortage of nephrologists in Africa, and especially sub-Saharan Africa, remains a critical issue, with many countries having < 1 nephrologist per million population; some have no nephrologists at all. The USA, UK, Canada and Australia have benefitted considerably from the migration of nurses and doctors over the past half century. Opportunities for training as well as employment have attracted doctors from many countries to these developed countries. Since 2006, new legislation in the UK has limited the inflow of health workers. Developing countries are also beginning to take steps to mitigate the problem of health worker loss and are developing strategies to both train increasing numbers of different cadres of healthcare worker and also to retain those already working in these countries. The forces of globalization are tending to increase the worldwide movement of all types of professionals, including those working in health care. It is this lack of health workers in developing countries that has been such a major constraint in limiting progress on initiatives such as the HIV "3 by 5" and Millennium Development Goals. More specifically, lack of resources, both human and financial, in developing countries has hampered nephrology programs both in the detection and prevention of chronic kidney disease and in the ability of doctors, nurses and other nephrological personnel to provide acute/chronic dialysis and transplantation.


A comprehensive cooperative project for children with renal diseases in Nicaragua. In low-income countries renal diseases generally and chronic kidney disease (CKD) in particular represent a wide-spread and often underdiagnosed clinical problem. The aim of the cooperative project between the pediatric nephrology units of Milan, Italy, and Managua, Nicaragua was to improve the diagnosis and treatment of renal diseases and CKD in Nicaraguan children. When the project started, in 2000, there were many constraints in human and material resources in the Children's Hospital in Managua. Since 2001, a specialized Unit of Pediatric Nephrology and Urology has developed, offering free of charge basic clinical assistance to hospitalized children, and training abroad of the whole staff. Shared protocols, renovation of infrastructure and an information technology (IT) program were implemented. In 2003, renal replacement therapy (RRT) for selected children was initiated, along with a network of six department hospitals in 2005 and, in 2007, a CKD prevention program in the most peripheral Health Units, so that 61% of the Nicaraguan pediatric population is now covered by the project. To ensure implementation of the project, applications for funds to Italian private and public institutions were made and a Nicaraguan charity foundation was activated. The Nicaraguan Ministry of Health and the hospital directors were always involved in the plans of the development of the project and accepted the progressive transfer of the costs to the government, throughout the 9-year duration of the project. The IT program, inclusive of a database of children with kidney and other urinary tract (UT) diseases and a web connection between Milan and Managua, was crucial in monitoring the activities and providing epidemiological data, in order to better allocate resources. The clinical activities and the number of children managed in Managua in 2008 are similar to those of pediatric nephrology units worldwide and depict the level of clinical autonomy achieved. The sister-center model of cooperation and the top-down strategy we applied, along with the careful consideration of all the economic, logistic and political issues, were and are the key factors which explain the favorable results of this cooperative project.


Access to new drugs for dialysis patients: challenges for indigenous and non-indigenous populations. Most dialysis patients are on 5 - 10 medications. The costs of these medications vary widely, ranging from pennies per day for water soluble multivitamins, to several thousand dollars per year for erythropoietin-stimulating agents. In Canada, public funding for drug therapies is undertaken by each province, with wide variability in coverage and on restriction criteria for expensive new drugs. For native Canadians and Inuit, access to drugs is superior to that of other Canadians through a federal program. The Canadian system for drug evaluation, where strict evidence-based medicine (EBM) and comparative effectiveness research (CER) is applied, is instructive and may provide clues to the future from an international perspective. Given the unique challenges in nephrology, it is predicted that access to new drugs and other therapies will be restricted by these evaluation methods. Indeed, it seems desirable for nephrology organizations to respond to this new threat in a pragmatic and balanced way. Part of that response might be a call for exceptional status for dialysis, with adjusted criteria of EBM and CER that would be more suitable, and stimulate innovation and research in nephrology.


Population differentiation and selective constraints in Pelargonium line pattern virus. The genomic structure of Pelargonium line pattern virus (PLPV), a tentative member of a proposed new genus within the family Tombusviridae, has been recently determined. However, little is known about the genetic variability and population structure of this pathogen. Here, we have investigated the heterogeneity of PLPV isolates from different origins by sequence analysis of a 1817nt fragment encompassing the movement (p7 and p9.7) and coat protein genes as well as flanking segments including the complete 3' untranslated region. We have evaluated the selective pressures operating on both viral proteins and RNA genome in order to assess the relative functional and/or structural relevance of different amino acid or nucleotide sites. The results of the study have revealed that distinct protein domains are under different selective constraints and that maintenance of certain primary and/or secondary structures in RNA regulatory sequences might be an important factor limiting viral heterogeneity. We have also performed covariation analyses to uncover potential dependencies among amino acid sites of the same protein or of different proteins. The detection of linked amino acid substitutions has permitted to draw a putative network of intra- and interprotein interactions that are likely required to accomplish the different steps of the infection cycle. Finally, we have obtained phylogenetic trees that support geographical segregation of PLPV sequences.


Infectious salmon anemia virus--genetics and pathogenesis. The infectious salmon anemia virus (ISAV) is the causative agent of the ISA syndrome that affects mainly Atlantic salmon (Salmo salar) and has caused high mortality epidemics in Norway, Scotland, Canada, the United States and Chile. It is classified as an Orthomyxoviridae, its genome is composed of 8 single-strand RNA segments with negative polarity that code for 11 polypeptides. Through functional studies of the coded proteins it has been established that RNA segments 5 and 6 code for a fusion protein and hemagglutinin, respectively, while two polypeptides coded by segments 7 and 8 inhibit interferon induction. The functions of the rest of the possible proteins coded by the viral genome have been assigned by comparison with the corresponding ones of the influenza virus genome. As to its pathogenicity, some growth parameters such as incubation period, resistance to chemical and physical factors, establishment of the infection in other marine species, and dissemination ability among the different organs have been evaluated in several salmonids. Genomic analysis has shown (i) the existence of a high polymorphism region (HPR) in segment 6, and (ii) sequence insertion in segment 5. More than 20 HPR variants have been determined, all originating from HPR0, which is associated with low pathogenicity, while 4 different sequence insertions in segment 5 have not been related with some characteristic of the virus infection. Much progress has been made in the characterization of the virus in 20 years of study, but more detailed knowledge of the specific function of the proteins coded by all the viral genes is still missing, including the pathogenicity mechanism at the molecular level.


Living related renal transplants with lifelong follow-up. A model for the developing world. To describe the dynamic of a model of public government partnership for dialysis and transplantation in developing countries. A model was established on the philosophy of public-government partnership to provide an integrated dialysis and transplant service "Free with dignity" with lifelong follow-up care and medications. The government provided 50% of funds and the public was motivated to donate the rest. This included affluent individuals, corporations, business houses and the general public. This model has been sustained for the last two decades. In 2008, 655,000 patients were treated at SIUT. Over 600 patients are dialyzed each day with a total of 165,411 dialysis sessions/year. Thus far 2,249 transplants have been performed, 431 in 2008. One- and 5-year graft survival rates were 92% and 85%, respectively. The laboratory performed 4.1 million tests and radiological investigations numbered 164,217. Over $ 6 million were spent on medications. Free services offered by the model have motivated the government to increase its funding from $ 2.1 million in 1998 to $ 10 million in 2008 and the public has matched these figures with total donations exceeding $ 20 million. For transplantation to be successful in developing countries, it has to be made available to the common people who constitute 90% of the population. Our model of public-government partnership has made dialysis and transplantation available to the disenfranchised with lifelong follow-up and medications. Transplantation has become relevant to them, resulting in societal acceptance of transplantation as a preferred mode of therapy. This has motivated society to support both living related and deceased donor programs.


The latest developments in synthetic peptides with immunoregulatory activities. In the past few years, many researches have provided us with much data demonstrating the abilities of synthetic peptides to impact immune response in vitro and in vivo. These peptides were designed according to the structure of some important protein molecules which play a key role in immune response, so they act with specific targets. The class I and II MHC-derived peptides inhibit the TCR recognition of antigen peptide-MHC complex. Rationally designed CD80 and CD154-binding peptides block the interaction between cell surface costimulatory molecules on antigen-presenting cells (APCs) and T cells. Some peptides were designed to inhibit the activities of cell signal proteins, including JNK, NF-κB and NFAT. Some peptide antagonists competitively bind to important cytokines and inhibit their activities, such as TNF-α, TGF-β and IL-1β inhibitory peptides. Adhesion molecule ICAM-1 derived peptides block the T cell adhesion and activation. These immunoregulatory peptides showed therapeutic effect in several animal models, including collagen-induced arthritis (CIA), autoimmune cystitis model, murine skin transplant model and cardiac allograft model. These results give us important implications for the development of a novel therapy for immune mediated diseases.


Formation of pyrophosphate-like adducts from nerve agents sarin, soman and cyclosarin in phosphate buffer: implications for analytical and toxicological investigations. Phosphate buffer is frequently used in biological, biochemical and biomedical applications especially when pH is to be controlled around the physiological value of 7.4. One of the prerequisites of a buffer compound among good buffering capacity and pH stability over time is its non-reactivity with other constituents of the solution. This is especially important for quantitative analytical or toxicological assays. Previous work has identified a number of amino alcohol buffers like TRIS to react with G-type nerve agents sarin, soman and cyclosarin to form stable phosphonic diesters. In case of phosphate buffer we were able to confirm not only the rapid hydrolysis of these agents to the respective alkyl methylphosphonates but also the formation of substantial amounts of pyrophosphate-like adducts (phosphorylated methylphosphonates), which very slowly hydrolyzed following zero-order kinetics. This led to a complex mixture of phosphorus containing species with changing concentrations over time. We identified the molecular structure of these buffer adducts using 1D ¹H-³¹P HSQC NMR and LC-ESI-MS/MS techniques. Reaction rates of adduct formation are fast enough to compete with hydrolysis in aqueous solution and to yield substantial amounts of buffer adduct over the course of just a couple of minutes. Possible reaction mechanisms are discussed with respect to the formation and subsequent hydrolysis of the pyrophosphate-like compounds as well as the increased rate of hydrolysis of the nerve agent to the corresponding alkyl methylphosphonates. In summary, the use of phosphate buffer for the development of new assays with sarin, soman and cyclosarin is discouraged. Already existing protocols should be carefully reexamined on an individual basis.


Structure-based in silico model profiles the binding constant of poorly soluble drugs with β-cyclodextrin. Cyclodextrin inclusion complexation technique is the key method to enhance the solubility and absorption of poorly soluble drugs in the early development stage, and thus it is essential to predict the binding constant between drug molecules and cyclodextrin. Structure-based in silico model was constructed for a data set of 86 poorly soluble drugs and used to profile the binding constant of drug-β-cyclodextrin inclusion complex. The stepwise regression was employed to select the optimum subset of the independent variables. The in silico model was built by the multiple linear regression method and validated by the residual analysis, the normal Probability-Probability plot and Williams plot. For the entire data set, the R(2) and Q(2) of the model were 0.78 and 0.67, respectively. The results indicated that the fitted model is robust, stable and satisfies all the prerequisites of the regression models. The chemical space position and important contributors were compared between selected drug molecules and organic compounds available in the literature. It was suggested that the binding behavior of drug molecules with β-CD should differ from that of the common organic compounds. Focusing on structurally diverse drugs, the in silico model can be used as an efficient tool to rapidly screen the drug-β-cyclodextrin inclusion complex stability and to rationally design the new drug delivery system of poorly soluble drugs.


Distinguishing non-spatial from spatial biases in visual selection: neuropsychological evidence. Recently, it has been shown that patients with visual extinction can show enhanced awareness of contralesional stimuli that match the contents of working memory [Soto, D., & Humphreys, G.W. (2006). Proceedings of the National Academy of Sciences, USA, 103, 4789-4792]. Here we investigate whether these effects extend to cases where the working memory cue is verbal rather than visual (Study 1), and we show that non-spatial cues can overcome problems in spatial disengagement in patients, and this can affect the first eye movement made in search (Study 2). We discuss the implications of the data for understanding the relations between the cueing of attention from visual and conceptual information held in working memory and the cueing of spatial attention, and for understanding the relations between non-spatial and spatial biases in selection.


Why were Turks unwilling to accept the A/H1N1 influenza-pandemic vaccination? People's beliefs and perceptions about the swine flu outbreak and vaccine in the later stage of the epidemic. This study investigated the acceptability of the A/H1N1 influenza vaccination and related factors among 1137 adults in the later stage of the A/H1N1 outbreak in Turkey. Having already been vaccinated or intending to get vaccinated were related to trust in the vaccine effectiveness, perceived risk of the side effects, and benefits of getting vaccinated. Perceived long term consequences of the A/H1N1 infection, perceptions of the A/H1N1 information in media, and barriers for getting vaccinated were related to intention whereas anticipated epidemic situation in Turkey, being chronically ill, and being not married were related to having already been vaccinated.


Evaluation of Psn, HmuR and a modified LcrV protein delivered to mice by live attenuated Salmonella as a vaccine against bubonic and pneumonic Yersinia pestis challenge. We evaluated the ability of Yersinia pestis antigens HmuR, Psn and modified forms of LcrV delivered by live attenuated Salmonella strains to stimulate a protective immune response against subcutaneous or intranasal challenge with Y. pestis CO92. LcrV196 is a previously described truncated protein that includes aa 131-326 of LcrV and LcrV5214 has been modified to replace five key amino acids required for interaction with the TLR2 receptor. Psn is the outer membrane receptor for the siderophore, yersiniabactin, and the bacteriocin, pesticin. Mice immunized with Salmonella synthesizing Psn, LcrV196 or LcrV5214 developed serum IgG responses to the respective Yersinia antigen and were protected against pneumonic challenge with Y. pestis. Immunization with Salmonella synthesizing Psn or LcrV196 was sufficient to afford nearly full protection against bubonic challenge, while immunization with the strain synthesizing LcrV5214 was not protective. Immunization with Salmonella synthesizing HmuR, an outer membrane protein involved in heme acquisition in Y. pestis, was poorly immunogenic and did not elicit a protective response against either challenge route. These findings indicate that both Psn and LcrV196 delivered by Salmonella provide protection against both bubonic and pneumonic plague.


The role of tumor necrosis factor-α for interleukin-10 production by murine dendritic cells. In the present study, we examined the role of tumor necrosis factor (TNF) in interleukin (IL)-10 production by dendritic cells (DCs) using bone-marrow derived DCs from wild type (WT) and TNF-α knockout (TNF-α(-/-)) mice. Toll-like receptor (TLR) stimulation induced substantial level of IL-10 production by WT DCs, but significantly low level of IL-10 production by TNF-α(-/-) DCs. In contrast, no significant difference was detected in IL-12 p40 production between WT and TNF-α(-/-) DCs. Addition of TNF-α during TLR stimulation recovered the impaired ability of TNF-α(-/-) DCs for IL-10 production. This recovery appeared to be associated with an activation of extracellular signal-regulated kinase, p38 mitogen-activated protein kinase, and phosphatidylinositol 3-kinase/Akt following the TNF-α addition. Blocking these kinases significantly inhibited IL-10 production by TNF-α(-/-) DCs stimulated with TLR ligands plus TNF-α. Thus, TNF-α may be a key molecule to regulate the balance between anti-inflammatory versus inflammatory cytokine production in DCs.


Correlation of biological properties with glucan-binding protein B expression profile in Streptococcus mutans clinical isolates. Streptococcus mutans is known to be a primary causative agent of dental caries and its surface proteins have been investigated to specify their association with its virulence. Amongst those, 4 glucan-binding proteins (Gbps) are considered to be important factors due to their glucan-binding properties, of which GbpB has been shown to participate in cell-wall construction and cell separation. We examined clinical isolates of S. mutans collected from the oral cavities of Japanese and Finnish subjects, and focused on the association of their GbpB expression profiles and biological properties related to virulence. Western blot analysis of GbpB expression by the isolates revealed a variety of patterns. Strains that showed single and multiple bands were used to designate S and M type strains, respectively, whilst those with no GbpB expression were classified as N type. The distribution of GbpB expression patterns was shown to be quite different between the Japanese and Finnish isolates. Furthermore, the chain length and doubling time of the N type in both populations were significantly longer than those of the other types. Our results suggest variations in S. mutans GbpB expression patterns, which may have relationships with the virulence of S. mutans.


Perceptual load influences auditory space perception in the ventriloquist aftereffect. A period of exposure to trains of simultaneous but spatially offset auditory and visual stimuli can induce a temporary shift in the perception of sound location. This phenomenon, known as the 'ventriloquist aftereffect', reflects a realignment of auditory and visual spatial representations such that they approach perceptual alignment despite their physical spatial discordance. Such dynamic changes to sensory representations are likely to underlie the brain's ability to accommodate inter-sensory discordance produced by sensory errors (particularly in sound localization) and variability in sensory transduction. It is currently unknown, however, whether these plastic changes induced by adaptation to spatially disparate inputs occurs automatically or whether they are dependent on selectively attending to the visual or auditory stimuli. Here, we demonstrate that robust auditory spatial aftereffects can be induced even in the presence of a competing visual stimulus. Importantly, we found that when attention is directed to the competing stimuli, the pattern of aftereffects is altered. These results indicate that attention can modulate the ventriloquist aftereffect.


Proteomic analysis of endometrium in fertile women during the prereceptive and receptive phases after luteinizing hormone surge. In fertile women the patterns of proteome during the prereceptive (day 2 after LH surge) and receptive (day 7 after LH surge) phases were analyzed by two-dimensional fluorescence difference gel electrophoresis and mass spectrometry. A total of 31 differentially expressed proteins (17 up-regulated and 14 down-regulated) were identified between the two phases, which is helpful in understanding the biological mechanisms underlying human endometrial receptivity.


A novel method of luteal supplementation with recombinant luteinizing hormone when a gonadotropin-releasing hormone agonist is used instead of human chorionic gonadotropin for ovulation triggering: a randomized prospective proof of concept study. This pilot study investigates the role of luteal supplementation with recombinant LH in an attempt to reverse the poor reproductive outcome previously noticed after GnRH-agonist triggering of final oocyte maturation for IVF. Similar implantation rates were achieved with the novel recombinant LH luteal supplementation scheme compared with the standard luteal P protocol (25.0% vs. 26.7%, respectively). No cases of ovarian hyperstimulation syndrome (OHSS) were noticed in either group.


Polycystic ovary syndrome: an ancient disorder? Polycystic ovary syndrome (PCOS) appears to be an ancient disorder, which has persisted in human evolution despite reduced fecundity because of the benefits to affected women such as greater sturdiness and improved energy utilization, a rearing advantage for their children and kin, and a reduction in the risk of perinatal mortality. This raises the possibility that gene variants that are eventually found to be associated with PCOS will be similar across ethnic groups and races.


Craniofacial morphometric variation and the biological history of the peopling of Sardinia. The aim of this work is to explore the pattern of craniofacial morphometric variation and the relationships among five prehistoric Sardinian groups dated from Late Neolithic to the Nuragic Period (Middle and Late Bronze Age), in order to formulate hypotheses on the peopling history of Sardinia. Biological relationships with coeval populations of central peninsular Italy were also analysed to detect influences from and towards extra-Sardinian sources. Furthermore, comparison with samples of contemporary populations from Sardinia and from continental Italy provided an indication of the trend leading to the final part of the peopling history. Finally, Upper Palaeolithic and Mesolithic samples were included in the analyses to compare the prehistoric Sardinians with some of their potential continental ancestors. The analysis is based on multivariate techniques including Mahalanobis D(2) distance, non-parametric multidimensional scaling (MDS) and principal component analysis (PCA). The results showed the tendency to progressive differentiation between Sardinian groups and peninsular Italian groups, with the possible exception of a discontinuity showed by the Bonnànaro (Early Bronze Age) Sardinian sample. Several aspects of the morphological results were found to agree with the current genetic evidence available for the present-day Sardinian population and a Nuragic sample: (1) biological divergence between the Sardinian and peninsular Italian populations; (2) similarity/continuity among Neolithic, Bronze Age and recent Sardinians; (3) biological separation between the Nuragic and Etruscan populations; (4) contribution of a Palaeo-Mesolithic gene pool to the genetic structure of current Sardinians.


Fractional order ultra low-speed position servo: improved performance via describing function analysis. In a reference of the previous work, a new systematic design method for fractional order proportional and derivative (FOPD) controller is proposed for a class of typical second-order plants. Simulation and experimental results in the reference show that, the dynamic performance and robustness with the designed FOPD controller outperforms that with the optimized traditional integer order proportional integral (IOPI) controller at normal speed. Furthermore, it is found that, for the ultra low-speed position tracking with a significant friction effect, the tracking performance using the designed FOPD controller is much better than that using the optimized IOPI controller. However, the reason of this advantage is unclear. In this paper, using the describing function method and Bode plots analysis, the observed advantage of the designed FOPD controller over the optimized IOPI controller, for the nonlinear low-speed position tracking system with friction effect, is explained with the theoretical analysis. This explanation for the priority of the designed FOPD controller is consistently demonstrated by the extended experimental results in this paper.


Evaluation of subclinical atherosclerosis by computed tomography coronary angiography and its association with risk factors in familial hypercholesterolemia. Increasing age and cholesterol levels, male gender, and family history of early coronary heart disease (CHD) are associated with early onset of CHD in familial hypercholesterolemia (FH). Assess subclinical atherosclerosis by computed tomography coronary angiography (CTCA) and its association with clinical and laboratorial parameters in asymptomatic FH subjects. 102 FH subjects (36% male, 45 ± 13 years, LDL-c 280 ± 54 mg/dL) and 35 controls (40% male, 46 ± 12 years, LDL-c 103 ± 18 mg/dL) were submitted to CTCA. Plaques were divided into calcified, mixed and non-calcified; luminal stenosis was characterized as >50% obstruction. FH had a greater atherosclerotic burden represented by higher number of patients with: plaques (48% vs. 14%, p=0.0005), stenosis (19% vs. 3%, p=0.015), segments with plaques (2.05 ± 2.85 vs.0.43 ± 1.33, p=0.0016) and calcium scores (55 ± 129 vs. 38 ± 140, p=0.0028). After multivariate analysis, determinants of plaque presence were increasing age (OR=2.06, for age change of 10 years, CI95%: 1.38-3.07, p<0.001) and total cholesterol (OR=1.86, for cholesterol change by 1 standard deviation, CI95%: 1.09-3.15, p=0.027). Coronary calcium score was associated with the presence of stenosis (OR=1.54; CI95%: 1.27-1.86, p<0.001, for doubling the calcium score). Male gender was directly associated with the presence of non-calcified plaques (OR: 15.45, CI95% 1.72-138.23, p=0.014) and inversely with calcified plaques (OR=0.21, CI95%: 0.05-0.84, p=0.027). Family history of early CHD was associated with the presence of mixed plaques (OR=4.90, CI95%: 1.32-18.21, p=0.018). Patients with FH had an increased burden of coronary atherosclerosis by CTCA. The burden of atherosclerosis and individual plaque subtypes differed with the presence of other associated risk factors, with age and cholesterol being most important. A coronary calcium score of zero ruled out obstructive disease in this higher risk population.


Lifestyle and cardiovascular risk factors in 2001 child-parent pairs: the PEP Family Heart Study. Genes and environment are the main determinants of cardiovascular disease (CVD) risk factor clustering in families. Since individual risk factor profiles are easily predicted within families, we examined whether CVD risk factors are affected by lifestyle factors in these families. Nutrition, physical activity, and smoking habits were assessed in 2001 biological child-parent pairs from 852 families participating in the Prevention Education Program (PEP). Height, weight, body mass index, waist circumference, blood pressure, and fasting lipid levels were measured. Within-family associations were calculated using generalized estimating equations (GEE). Fathers possessed the most adverse risk profile. Daily energy consumption above the recommended levels was higher in children (daughters +35.4%, sons +26.7%) than in parents (fathers +15.7%, mothers +10.6%). Higher energy consumption was significantly associated with hypertension in mothers (OR 2.5) and in fathers (OR 1.7). Hyper-caloric nutrition of the parents predicted the energy intake of the children in: mother-daughter (OR 7.5), mother-son (OR 3.0), and father-son (OR 2.8) pairs. Low mono-unsaturated fatty acid intake was significantly associated with a high LDL/HDL-C ratio (OR 3.4) and hypertriglyceridemia (OR 2.2) in fathers. Approximately 25% of parents and children reported at least two physical activities twice a week. The 23% of children who were passive smokers presented a far more adverse risk profile than children without exposure to second-hand smoke. Intergenerational lifestyle habits affect cardiovascular risk factors within biological families. As lifestyle habits are predictable, they may be used for implementation of family-based CVD prevention strategies.


Elevated circulating soluble form of CD40 ligand in patients with cardiac syndrome X. The presence of effort induced angina, positive exercise stress test responses and angiographically normal coronary arteries defines cardiac syndrome X (CSX). Its pathogenesis, although mostly attributed to endothelial dysfunction and coronary microcirculation abnormalities, is incompletely understood. The soluble CD40 ligand (sCD40L) has multiple autocrine, paracrine and endocrine actions that may lead to endothelial dysfunction and atherothrombosis. We sought to investigate the relationship among sCD40L levels and ischemic burden in patients with CSX and whether sCD40L levels are increased in patients with CSX compared to control subjects. We assessed 30 prospectively enrolled patients with CSX and 28 apparently healthy subjects matched for coronary risk factors. All CSX patients and control subjects underwent myocardial perfusion scintigraphy. The summed difference score is taken to be an index of ischemic burden. This was classified as mildly, moderately and severely abnormal. White blood cells, sCD40L and C-reactive protein (CRP) concentrations were measured at peak exercise. At peak exercise, sCD40L levels were significantly greater in CSX patients than in the control group (P=0.008). Similarly, white blood cell count and CRP levels were higher in patients with CSX than in normal controls (P=0.02). After multivariable adjustment, sCD40L (P=0.03) was the only independent predictor of severe ischemic burden in CSX patients. The present study showed for the first time that sCD40L is associated with ischemic burden in patients with CSX. The potential role of this inflammatory molecule in the pathogenesis of CSX deserves investigation in future studies.


A non-linear morphometric feature selection approach for breast tumor contour from ultrasonic images. Ultrasound breast images have been used to improve diagnostics and decrease the number of unneeded biopsies. Malignant breast tumors tend to present irregular and blurred contours while benign ones are usually round, smooth and well-defined. Accordingly, investigating the tumor contour may help in establishing diagnosis. Herein, Mutual Information and Linear Discriminant Analysis were implemented to rank morphometric features in discriminating breast tumors in ultrasound images. Seven features were extracted from Convex Polygon and the Normalized Radial Length techniques. By applying a Mutual Information based approach, it was possible to identity features with possibly non-linear contributions to the outcome.


Selective role of sterol regulatory element binding protein isoforms in aggregated LDL-induced vascular low density lipoprotein receptor-related protein-1 expression. Low density lipoprotein receptor-related protein (LRP1) is upregulated in vascular smooth muscle cells by intravascular aggregated LDL (agLDL) - LDL trapped in the arterial intima and systemic LDL. LRP1 upregulation in hypercholesterolemic aortas is concomitant with SREBP downregulation. However, the specific role of SREBP isoforms in LRP1 transcription and LDL-induced LRP1 upregulation in human vascular smooth muscle cells (VSMC) is unknown. In the present study we report that specific silencing of either SREBP-1 or SREBP-2 enhanced LRP1 whereas overexpression of the active SREBP isoforms decreased LRP1 expression. Gel mobility shift and ChIP assays demonstrated that SREBP-1a, SREBP-1c and SREBP-2 were able to bind to three putative SRE sequences; SRE-A (-1042 to -1028), SRE-B (-115 to -101) and SRE-C (+226 to +234). ChIP assays demonstrated that agLDL (100μg/mL, 24h) significantly and specifically decreased SREBP-2 binding to the LRP1 promoter. Luciferase assays demonstrated that agLDL increased the transcriptional activity of A/B or A/C double mutants but failed to increase that of the double B/C mutant. Our results show that both SREBP-1 and SREBP-2 negatively modulated LRP1 transcription. Furthermore, agLDL exerted an upregulatory effect on LRP1 expression by decreasing SREBP-2 binding to LRP1 promoter. Two SRE-like sequences control the response of LRP1 to agLDL.


Pole vault performance for anthropometric variability via a dynamical optimal control model. Optimal performance of a dynamical pole vault process was modeled as a constrained nonlinear optimization problem. That is, given a vaulter's anthropomorphic data and approach speed, the vaulter chose a specific take-off angle, pole stiffness and gripping height in order to yield the greatest jumping height compromised by feasible bar-crossing velocities. The optimization problem was solved by nesting a technique of searching an input-to-output mapping arising from the vaulting trajectory and a method of nonlinear sequential quadratic programming (SQP). It was suggested from the optimization results that the body's weight has an important influence on the vaulting performance beside the vaulter's height and approach speed; the less skilled vaulter should gradually adopt a longer pole to improve the performance.


Support vector machines for detecting age-related changes in running kinematics. Age-related changes in running kinematics have been reported in the literature using classical inferential statistics. However, this approach has been hampered by the increased number of biomechanical gait variables reported and subsequently the lack of differences presented in these studies. Data mining techniques have been applied in recent biomedical studies to solve this problem using a more general approach. In the present work, we re-analyzed lower extremity running kinematic data of 17 young and 17 elderly male runners using the Support Vector Machine (SVM) classification approach. In total, 31 kinematic variables were extracted to train the classification algorithm and test the generalized performance. The results revealed different accuracy rates across three different kernel methods adopted in the classifier, with the linear kernel performing the best. A subsequent forward feature selection algorithm demonstrated that with only six features, the linear kernel SVM achieved 100% classification performance rate, showing that these features provided powerful combined information to distinguish age groups. The results of the present work demonstrate potential in applying this approach to improve knowledge about the age-related differences in running gait biomechanics and encourages the use of the SVM in other clinical contexts.


Material properties of the cornea and sclera: a modelling approach to test experimental analysis. Material properties of cornea and sclera are important for maintaining the shape of the eye and the requisite surface curvatures for optics. They also need to withstand the forces of external and internal musculature and fluctuations in intraocular pressure (IOP). These properties are difficult to measure and variable results have been reported. A previously published experimental procedure, from which the material properties of the eyeball coats were obtained, has been modelled in this paper using Finite Element Analysis, in order to test the accuracy of the experiment. Material parameters were calculated from the model and the resulting relationships between stress and strain for the cornea and sclera compared to their experimentally obtained counterparts. The comparison between model and experiment was close for the sclera but more varied for the cornea. The pressure vessel model can be applied for measuring the material properties of the sclera but is less accurate for the cornea.


Hyperelastic properties of human meniscal attachments. Meniscal attachments are ligamentous tissues anchoring the menisci to the underlying subchondral bone. Currently little is known about the behavior of meniscal attachments, with only a few studies quantitatively documenting their properties. The objective of this study was to quantify and compare the tensile mechanical properties of human meniscal attachments in the transverse direction, curve fit experimental Cauchy stress-stretch data to evaluate the hyperelastic behavior, and couple these results with previously obtained longitudinal data to generate a more complete constitutive model. Meniscal attachment specimens were tested using a uniaxial tension test with the collagen fibers oriented perpendicular to the loading axis. Tests were run until failure and load-optical displacement data was recorded for each test. The medial posterior attachment was shown to have a significantly greater elastic modulus (6.42±0.78 MPa) and ultimate stress (1.73±0.32 MPa) when compared to the other three attachments. The Mooney-Rivlin material model was selected as the best fit for the transverse data and used in conjunction with the longitudinal data. A novel computational approach to determining the transition point between the toe and linear regions is presented for the hyperelastic stress-stretch curves. Results from piece-wise non-linear longitudinal curve fitting correlate well with previous linear elastic and SEM findings. These data can be used to advance the design of meniscal replacements and improve knee joint finite element models.


Prediction of applied forces in handrim wheelchair propulsion. Researchers of wheelchair propulsion have usually suggested that a wheelchair can be properly designed using anthropometrics to reduce high mechanical load and thus reduce pain and damage to joints. A model based on physiological features and biomechanical principles can be used to determine anthropometric relationships for wheelchair fitting. To improve the understanding of man-machine interaction and the mechanism through which propulsion performance been enhanced, this study develops and validates an energy model for wheelchair propulsion. Kinematic data obtained from ten able-bodied and ten wheelchair-dependent users during level propulsion at an average velocity of 1m/s were used as the input of a planar model with the criteria of increasing efficiency and reducing joint load. Results demonstrate that for both experienced and inexperienced users, predicted handrim contact forces agree with experimental data through an extensive range of the push. Significant deviations that were mostly observed in the early stage of the push phase might result from the lack of consideration of muscle dynamics and wrist joint biomechanics. The proposed model effectively verified the handrim contact force patterns during dynamic propulsion. Users do not aim to generate mechanically most effective forces to avoid high loadings on the joints.


Capillary zone electrophoresis of graphene oxide and chemically converted graphene. The preparation of processable graphene oxide colloids called chemically converted graphene (CCG) involves the following steps: oxidation of graphite to form graphite oxide; exfoliation of graphite oxide to form graphene oxide (GO); and reduction of GO to form CCG. In this work, the exfoliation and reduction steps were monitored by capillary zone electrophoresis (CZE). CZE was performed in fused silica capillaries with UV absorbance at 230 nm (GO) and 270 nm (CCG) using 250 μM tetrapropylammonium hydroxide (pH 10.4). The results indicate that almost complete exfoliation of graphite oxide (0.05 wt%) and higher recovery of CCG were obtained by sonication at 50% power for more than 15 h. CZE is considered a valuable tool for the fractionation and analysis of GO nanoparticles and, hence, for the control of different steps in preparation of CCG.


Determination of nicotine and nicotine metabolites in urine by hydrophilic interaction chromatography-tandem mass spectrometry: Potential use of smokeless tobacco products by ice hockey players. Consumption of nicotine in the form of smokeless tobacco (snus, snuff, chewing tobacco) or nicotine-containing medication (gum, patch) may benefit sport practice. Indeed, use of snus seems to be a growing trend and investigating nicotine consumption amongst professional athletes is of major interest to sport authorities. Thus, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the detection and quantification of nicotine and its principal metabolites cotinine, trans-3-hydroxycotinine, nicotine-N'-oxide and cotinine-N-oxide in urine was developed. Sample preparation was performed by liquid-liquid extraction followed by hydrophilic interaction chromatography-tandem mass spectrometry (HILIC-MS/MS) operated in electrospray positive ionization (ESI) mode with selective reaction monitoring (SRM) data acquisition. The method was validated and calibration curves were linear over the selected concentration ranges of 10-10,000 ng/mL for nicotine, cotinine, trans-3-hydroxycotinine and 10-5000 ng/mL for nicotine-N'-oxide and cotinine-N-oxide, with calculated coefficients of determination (R(2)) greater than 0.95. The total extraction efficiency (%) was concentration dependent and ranged between 70.4 and 100.4%. The lower limit of quantification (LLOQ) for all analytes was 10 ng/mL. Repeatability and intermediate precision were ≤9.4 and ≤9.9%, respectively. In order to measure the prevalence of nicotine exposure during the 2009 Ice Hockey World Championships, 72 samples were collected and analyzed after the minimum of 3 months storage period and complete removal of identification means as required by the 2009 International Standards for Laboratories (ISL). Nicotine and/or metabolites were detected in every urine sample, while concentration measurements indicated an exposure within the last 3 days for eight specimens out of ten. Concentrations of nicotine, cotinine, trans-3-hydroxycotinine, nicotine-N'-oxide and cotinine-N-oxide were found to range between 11 and 19,750, 13 and 10,475, 10 and 8217, 11 and 3396, and 13 and 1640 ng/mL, respectively. When proposing conservative concentration limits for nicotine consumption prior and/or during the games (50 ng/mL for nicotine, cotinine and trans-3-hydroxycotinine and 25 ng/mL for nicotine-N'-oxide and cotinine-N-oxide), about half of the hockey players were qualified as consumers. These findings significantly support the likelihood of extensive smokeless nicotine consumption. However, since such conclusions can only be hypothesized, the potential use of smokeless tobacco as a doping agent in ice hockey requires further investigation.


Towards porous polymer monoliths for the efficient, retention-independent performance in the isocratic separation of small molecules by means of nano-liquid chromatography. We have investigated the free-radical copolymerization dynamics of styrene and divinylbenzene in the presence of micro- and macro-porogenic diluents in 100 μm I.D. sized molds under conditions of slow thermal initiation leading to (macro)porous poly(styrene-co-divinylbenzene) monolithic scaffolds. These specifically designed experiments allowed the quantitative determination of monomer specific conversion against polymerization time to derive the porous polymer scaffold composition at each desirable copolymerization stage after phase separation. This was carried out over a time scale of 3h up to 48 h polymerization time, enabling the efficient and repeatable termination of the polymerization reactions. In parallel, the porous and hydrodynamic properties of the derived monolithic columns were thoroughly studied in isocratic nano-LC mode for the reversed-phase separation of a homologous series of small retained molecules. At the optimized initiator concentration, polymerization temperature and time, the macroporous poly(styrene-co-divinylbenzene) monoliths show a permanent mesoporous pore space, which was readily observable by electron microscopy and indicated by nitrogen adsorption experiments. Under these conditions, we consistently find a polymer scaffold composition which suggests a high degree of cross-linking and thus minimum amount of gel porosity. These columns reveal a retention-insensitive plate height in the separation of small retained molecules which only slightly decreases at increased linear mobile phase velocity. As the polymerization progresses, a build-up of less-densely cross-linked material occurs, which is directly reflected in the observed consistent increase in retention and plate heights. This leads to a significant deterioration in overall isocratic separation performance. The decrease in performance is ascribed in particular to the increased mass transfer resistance governing the monoliths' performance over the whole linear chromatographic flow velocity range at polymerization times significantly higher than that of phase separation. The performance of the optimized monoliths only becomes limited by fluid dispersion due to the poorly structured macroporous pore space.


Identification of amino-tadalafil and rimonabant in electronic cigarette products using high pressure liquid chromatography with diode array and tandem mass spectrometric detection. A high-pressure liquid chromatography-diode array detection and multi-mode ionization tandem mass spectrometry (HPLC-DAD-MMI-MS/MS) method was used to identify amino-tadalafil and rimonabant in electronic cigarette (e-cigarette) cartridges. Amino-tadalafil is a drug analogue of the commercially approved Cialis™ (i.e. tadalafil). Rimonabant is a drug that was, at one time, approved for weight loss in Europe (although approval has been retracted), but not in the United States. In addition, poor quality control over the e-cigarette products analyzed here is shown by the presence of nicotine in products labeled as containing no nicotine or by the presence of significant amounts of rimonabant oxidative degradant in e-cigarette products containing rimonabant. Identification was accomplished by comparing the retention time of relevant peaks in the sample with those of standard compounds, in addition to comparison of the UV spectra, mass spectra and/or product ion mass spectra.


In-tube solid-phase microextraction based on hybrid silica monolith coupled to liquid chromatography-mass spectrometry for automated analysis of ten antidepressants in human urine and plasma. A rapid, sensitive and automated in-tube solid-phase microextraction-liquid chromatography-mass spectrometry (in-tube SPME/LC-MS) method was developed for the analysis of ten antidepressants in urine and plasma. A hybrid organic-inorganic silica monolith with cyanoethyl functional groups was prepared and used as a sorbent for in-tube SPME. Integration of the sample extraction, LC separation and MS detection into a single system permitted direct injection of the diluted urine or plasma after filtration. Under the optimized conditions, good extraction efficiencies for the targets were obtained with no matrix interference in the subsequent LC-MS. Automation of the sampling, extraction and separation procedures was realized under the control of a program in this study. The total process time was 30 min and only 30 μL of urine or plasma was required in one analysis cycle. Good linearities were obtained for ten antidepressants with the correlation coefficients (R) above 0.9933. The limits of detection (S/N=3) for ten antidepressants were found to be 0.06-2.84 ng/mL in urine and 0.07-2.95 ng/mL in plasma. The recoveries of antidepressants spiked in urine and plasma were from 75.2% to 113.0%, with relative standard deviations less than 16.5%. The developed method was successfully used to analyze urine sample from ageing patients undergoing therapy with antidepressants.


Flux decline during cross flow membrane filtration of electrolytic solution in presence of charged nano-colloids: a simple electrokinetic model. An electrokinetic transport based approach for quantification of reversible flux decline due to the concentration polarization of an electrolyte solution in presence of charged colloids is presented. The model envisions the electrolyte transport across a charged cake or gel layer as transport of ions through charged cylindrical capillaries. This model is coupled with the standard theory of concentration polarization during cross flow membrane filtration. The analysis is carried out entirely in terms of generalized, non-dimensional variables. A dimensionless group termed as the scaled gel layer resistance evolves from the analysis, which accounts for the electrical properties of the charged nano-colloids and the electrolyte solution. A parametric study is performed to elucidate the coupled influence of mass transfer, membrane resistance, gel resistance, and electrical properties of the gel-electrolyte polarized layer. The effects of these parameters are examined on the filtration performance through the model equations.


Solid state white light emitting systems based on CeF3: RE3+ nanoparticles and their composites with polymers. A series of doped CeF(3): RE(3+) (RE(3+): Tb(3+), Eu(3+) and Dy(3+)) nanoparticles were synthesized, with the aim of obtaining a white light emitting composition, by a simple polyol route at 160°C and characterized by X-ray diffraction (XRD), high resolution transmission electron microscopy (HR-TEM), Fourier transform infrared spectroscopy (FT-IR) and photoluminescence. Uniformly distributed and highly water-dispersible rectangular nanoparticles (length ~15-20 nm, breadth ~5-10 nm) were obtained. The steady state and time resolved luminescence studies confirmed efficient energy transfer from the host to activator ions. Lifetime studies revealed that optimum luminescence is observed for 2.5 mol% Dy(3+) and 7.5 mol% Tb(3+). The energy transfer efficiencies (Ce(3+) to activators) were found to be 89% for CeF(3): Tb(3+) (7.5 mol%) nanoparticles and 60% for CeF(3): Dy(3+) (2.5 mol%) nanoparticles. Different concentrations of Tb(3+), Eu(3+) and Dy(3+) were doped to achieve a white light emitting phosphor for UV-based LEDs (light emitting diodes). Finally CeF(3), triply doped with 2.0 mol%Tb(3+), 4.5 mol% Eu(3+) and 3.5 mol% Dy(3+), was found to have impressive chromaticity co-ordinates, close to broad day light. The colloidal solutions of doped CeF(3) nanoparticles emitted bright green (Tb(3+)), blue (Dy(3+)) and white (triply doped) luminescence upon host excitation. Composites of poly methyl methacrylate (PMMA) and poly vinyl alcohol (PVA) were made with CeF(3): 5.0 mol%Tb(3+), CeF(3): 5.0 mol% Dy(3+) and triply doped white light emitting composition. The CeF(3)/PMMA (PVA) nanocomposite films, so obtained, are highly transparent (in the visible spectral range) and exhibit strong photoluminescence upon UV excitation.


Adsorption of CO2 and CH4 on a magnesium-based metal organic framework. A magnesium-based metal organic framework (MOF), also known as Mg-MOF-74, was successfully synthesized, characterized, and evaluated for adsorption equilibria and kinetics of CO(2) and CH(4). The Mg-MOF-74 crystals were characterized with scanning electron microscopy for crystal structure, powder X-ray diffraction for phase structure, and nitrogen adsorption for pore textural properties. Adsorption equilibrium and kinetics of CO(2) and CH(4) on the Mg-MOF-74 adsorbent were measured in a volumetric adsorption unit at 278, 298, and 318 K and pressures up to 1 bar. It was found that the Mg-MOF-74 adsorbent prepared in this work has a median pore width of 10.2 Å, a BET specific surface area of 1174 m(2)/g, CO(2) and CH(4) adsorption capacities of 8.61 mmol g(-1) (37.8 wt.%) and 1.05 mmol g(-1) (1.7 wt.%), respectively, at 298 K and 1 bar. Both CO(2) and CH(4) adsorption capacities are significantly higher than those of zeolite 13X under similar conditions. The pressure-dependent equilibrium selectivity of CO(2) over CH(4) (q(CO2)/q(CH4)) in the Mg-MOF-74 adsorbent showed a trend similar to that of zeolite 13X and the intrinsic selectivity of Mg-MOF-74 at zero adsorption loading is 283 at 298 K. The initial heats of adsorption of CO(2) and CH(4) on the Mg-MOF-74 adsorbent were found to be 73.0 and 18.5 kJ mol(-1), respectively. The adsorption kinetic measurements suggest that the diffusivities of CO(2) and CH(4) on Mg-MOF-74 were comparable to those on zeolite 13X. CH(4) showed relatively faster adsorption kinetics than CO(2) in both adsorbents. The diffusion time constants of CO(2) and CH(4) in the Mg-MOF-74 adsorbent at 298 K were estimated to be 8.11 × 10(-3) and 4.05 × 10(-2) s(-1), respectively, showing a modest kinetic selectivity of about 5 for the separation CH(4) from CO(2).


Reversible organogels triggered by dynamic K+ binding and release. In this study, a new lipophilic guanosine derivative was synthesized as an organogelator. The self-aggregation behavior of this organogelator was investigated by NMR, XRD and AFM. In solution, the lipophilic guanosine derivative can form a stable ribbon-like structure through NH(1)-N(7) and NH(2)-O(6) hydrogen bonds. However, gelation would occur in some aprotic solvents after the concentration reached a definite value. More interesting, the ribbon-like structure was able to change to G-quartets in the presence of K(+), which led to the transformation from a gel to a sol. Upon the addition of the cryptand [2.2.2], which can efficiently complex with K(+), G-quartets reverted to the original ribbon-like structure and the gel recovered. Subsequently, upon the addition of acids, K(+) was released from the cryptate with the transformation of gel-to-sol simultaneously. Finally, upon the addition of bases which deprotonated [H(+) ⊂ 2.2.2], the liberated cryptand [2.2.2] recaptured K(+) and the gel was regenerated again. This process of interconversion between G-ribbon 1(n) and octamer 1(8)·K(+) was well monitored by circular dichroism spectra.


Copper hydroxide nano and microcrystal: facile synthesis, shape evolution and their catalytic properties. In this paper, the morphology of copper hydroxide nano/microcrystals is finely controlled by adjusting the concentration of surfactant and NH(4)Cl as well as the reaction temperature, to provide plates, belts, wires, rods and urchin-like spheres, among others. A tree-type multiple head surfactant, bis (amidoethyl-carbamoylethyl) octadecylamine (C18N3), was used to prepare the copper hydroxide nano/microcrystals and it acted as a face-selective additive in the reaction system. The morphology of the Cu(OH)(2) microcrystals could be transformed from elliptical plates into truncated square plates as the NH(4)Cl concentration was increased. The results showed that the Cu(OH)(2) crystals were better than the amorphous type of Cu(OH)(2) in catalyzing the oxidation of resorcinol with H(2)O(2). Additionally, an investigation of the formation process of the nano/microcrystals was performed, which we believe is valuable for a precise understanding of the formation and fabrication of other metal hydroxides and metal oxides.


Phonemes matter: the role of phoneme-level awareness in emergent Chinese readers. The importance of phonological awareness for learning to read may depend on the linguistic properties of a language. This study provides a careful examination of this language-specific theory by exploring the role of phoneme-level awareness in Mandarin Chinese, a language with an orthography that, at its surface, appears to require little phoneme-level insight. A sample of 71 monolingual Mandarin-speaking children completed a phonological elision task and a measure of single-character reading. In this sample, 4- and 5-year-old preschoolers were unable to complete phoneme-level deletions, whereas 6- to 8-year-old first graders were able to complete initial, final, and medial phoneme-level deletions. In this older group, performance on phoneme deletions was significantly related to reading ability even after controlling for syllable- and onset/rime-level awareness, vocabulary, and Pinyin knowledge. We believe that these results reopen the question of the role of phonological awareness in reading in Chinese and, more generally, the nature of the mechanisms underlying this relationship.


Preschoolers' total daily screen time at home and by type of child care. To assess preschoolers' cumulative daily screen time, measure the contributions of the home and the child care setting to this total, and characterize children that are most at risk for excessive screen time. We used data from the Early Childhood Longitudinal Study-Birth Cohort, to calculate daily screen time based on reports by preschooler's parents and care providers. The sample size of 8950 represented approximately 4 million children. By preschool age, >80% of children were in some child care. On average, children in this study were exposed to 4.1 hours of screen time daily, including 3.6 hours at home and 0.4 hours in child care. Children in centers had the lowest screen time (3.2 hours) compared with children in parental care only (4.4 hours), home-based care (5.5 hours), and Head Start (4.2 hours). Even when adjusted for relevant covariates, these differences remained significant (P < .001). Preschoolers' cumulative screen time exceeds recommendations and most previous estimates. Pediatric clinicians are uniquely positioned to encourage families to discuss screen time with their children's caregivers and to advocate for high quality child care. Efforts to decrease screen time in homes and home-based child care settings are needed.


Seasonal severity of depressive symptoms as a predictor of health service use in a community-based sample. To determine whether severity of seasonal depressive symptoms is an independent predictor of depression-specific health service use. Cross-sectional telephone survey evaluating mood-related symptom changes across seasons using a structured interview based on the World Mental Health Composite International Diagnostic Interview, in a community sample representative of the province of Ontario, Canada (N = 1605). This study focuses on the 625 individuals (out of a total of 1605 interviewed) who screened positive for lifetime depressive symptoms. Severity of seasonal symptoms of depression (or "seasonality") was measured using the Seasonal Depression Severity (SDS) score (range 0-36). The primary outcome was lifetime depression-specific use of health services from a physician (family physician or psychiatrist). Lifetime psychotropic medication use, use of health services from a non-physician therapist, and psychiatric hospitalization were secondary outcomes. Other important variables that are known to predict depression-specific health service use were considered in multivariable analysis. In our sample of individuals with depressive symptoms, those who had used physician health services had higher SDS scores than non-users (11.5 (SD 7.2) vs. 9.7 (SD 6.4), t(616) = 3.182, P = 0.001). In multivariable analysis, SDS score was independently associated with depression-specific health service use by a physician (OR = 1.04, 95% CI 1.01-1.07, p = 0.004). The relationship between seasonality and use of psychotropic medication use was similar (OR = 1.04, 95% CI 1.01-1.07, p = 0.007). Seasonality was independently associated with depression-specific health service use for individuals with depressive symptoms. The results imply that greater seasonality may independently reflect increased severity and need for treatment of depression.