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PubMed2003

An overview of recent findings of the Stanley Foundation Bipolar Network (Part I).

AIM AND METHODS: Selected recent findings of the Stanley Foundation Bipolar Network are briefly reviewed and their clinical implications discussed. RESULTS: Daily prospective ratings on the NIMH-LCM indicate a high degree of residual depressive morbidity (three times that of hypomania or mania) despite active psychopharmacological treatment with a variety of modalities including mood stabilizers, antidepressants, and benzodiazepines, as well as antipsychotics as necessary. The rates of switching into brief to full hypomania or mania during the use of antidepressants is described, and new data suggesting the potential utility of continuing antidepressants in the small group of patients showing an initial acute and persistent response is noted. Bipolar patients with a history of major environmental adversities in childhood have a more severe course of illness and an increased incidence of suicide attempts compared with those without. Preliminary open data suggest useful antidepressant effects of the atypical antipsychotic quetiapine, while a double-blind randomized controlled study failed to show efficacy of omega-3 fatty acids (6 g of eicosapentaenoic acid compared with placebo for 4 months) in the treatment of either acute depression or rapid cycling. The high prevalence of overweight and increased incidence of antithyroid antibodies in patients with bipolar illness is highlighted. CONCLUSIONS: Together, these findings suggest a very high degree of comorbidity and treatment resistance in outpatients with bipolar illness treated in academic settings and the need to develop not only new treatment approaches, but also much earlier illness recognition, diagnosis, and intervention in an attempt to reverse or prevent this illness burden.

Antidepressive Agents↗
PubMed2002

The Rockefeller Foundation and the rise of molecular biology.

The Rockefeller Foundation began to support a systematic transfer of physico-chemical technology to experimental biology in the early 1930s. A close look at three key projects in the United Kingdom shows the impact and limits of private philanthropy on scientific innovation.

Academies and Institutes↗
PubMed2000

Methods used to evaluate the quality of evidence underlying the National Kidney Foundation-Dialysis Outcomes Quality Initiative Clinical Practice Guidelines: description, findings, and implications.

This report describes the approach the National Kidney Foundation-Dialysis Outcomes Quality Initiative (NKF-DOQI) used to assess the strength of published evidence pertinent to individual NKF-DOQI Clinical Practice Guidelines, as well as the relationship between that approach and methods used by the US Preventive Services Task Force, the Cochrane Collaboration, and the Agency for Health Care Policy and Research to rate the quality and/or strength of evidence. We also present the results of an analysis of the strength of evidence underlying the NKF-DOQI Guidelines showing that one cannot infer the quality of evidence reported in a study (rated either on a 0-to-1 scale or categorically as excellent, very good, good, fair, or poor) simply by knowing the type of study design used (randomized trial, nonrandomized trial, natural experiment, cohort study, cross-sectional study, case-control study, case report). Issues related to assessment of the strength of evidence underlying a practice guideline opposed to that reported in an individual study are highlighted.

Evidence-Based Medicine↗
PubMed2001

The National Kidney Foundation K/DOQI clinical practice guidelines for dietary protein intake for chronic dialysis patients.

This paper discusses two of the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (K/DOQI) clinical practice guidelines for nutrition in chronic renal failure. These are the guidelines that recommend a dietary protein intake of 1.2 g protein/kg body weight/day for clinically stable maintenance hemodialysis (MHD) patients (Guideline 15) and 1.2 to 1.3 g protein/kg/day for clinically stable chronic peritoneal dialysis (CPD) patients (Guideline 16). These recommended protein intakes are greater than the usually ingested protein intakes of MHD and CPD patients and are also greater than the recommended protein intakes for healthy, nonpregnant, nonlactating adults. The possible mechanisms that engender these increased protein needs include (1) the substantial quantity of amino acids, peptides, and proteins removed by the dialysis procedure and (2) the protein catabolic or antianabolic state caused by the uremic milieu, the inflammatory state, the oxidative and carbonyl stress, and the bioincompatible dialysis materials to which MHD and CPD patients are exposed. There are a number of nitrogen balance studies that have been performed to identify the dietary protein needs of MHD and CPD patents. The results of this research as well as some of the methodological limitations of these studies are reviewed. The concepts of the average dietary protein intake required to maintain protein balance in MHD or CPD patients and the safe protein intake that will maintain protein balance in virtually all MHD and CPD patients are discussed.

Adult↗
PubMed2000

Patients' perspective of factors affecting modality selection: a National Kidney Foundation patient survey.

The National Kidney Foundation undertook a survey of individuals with chronic renal failure to assess factors that may have influenced their treatment selection. Areas examined included demographic data, patient education, movement between modalities, patient satisfaction with treatment, and sense of well-being. The results point to a need for additional patient education and assurance that every ESRD patient is informed about all treatment options that are not medically contraindicated. There is an additional need for enhanced treatment decision making that involves both the patient and the nephrologist. Respondents were highly satisfied with their current treatment modality although 17% had previously changed treatment owing to personal dissatisfaction. Center hemodialysis patients identified staff performance of treatment and dialyzing only 3 times weekly as the main advantages of that modality. Those on peritoneal dialysis identified its flexibility that allows control over one's personal schedule as important. Transplant recipients stressed the importance of living a more normal life than that afforded by dialysis. Most respondents expressed a positive sense of well-being. While transplant patients expressed a higher sense of well-being than individuals on dialysis, it is important to note that approximately 70% of those on dialysis reported a positive sense of well-being.

Data Collection↗
PubMed2001

Funding ESRD care through charity: the paradigm of the National Kidney Foundation of Singapore.

Given the prohibitive costs of end-stage renal disease (ESRD) care for certain countries and the increasing incidence of ESRD worldwide, alternative methods of funding dialysis care are increasingly necessary. We describe the paradigm of the National Kidney Foundation of Singapore (NKF-S), the provider of subsidized dialysis care and comprehensive rehabilitative services to approximately 60% of all ESRD patients in the country, whose activities are funded entirely by charitable public donations. Unique to the NKF-S model are the considerations of the donor as an "investor" in the health care of NKF-S dialysis patients, the personal responsibility of the dialysis patient as a recipient of this "investment" to play an active role in achieving good clinical and rehabilitative outcomes, and the fostering of community-based support systems to facilitate patient rehabilitation such as partnerships with employers willing to employ dialysis patients. The success of the system is shown by its clinical outcomes, which approximate those observed in the United States. We believe that several aspects of the NKF-S model for ESRD care may be implemented in other communities, particularly in countries that have yet to develop financially and clinically mature dialysis programs.

Charities↗
PubMed2006

ESRD in Guatemala and a model for preventive strategies: outlook of the Guatemalan Foundation for Children with Kidney Diseases.

The rapidly growing burden of chronic renal failure (CRF) is a major public health problem that will stretch the health care system of all countries, especially those that are not yet industrialized. It is estimated that only 35% of Guatemalan patients with end stage renal disease (ESRD) would be diagnosed and treated, and unlike many developed countries, the age of presentation in 60% of the patients is before the forth decade. Therefore, the cost of death and disability due to a CRF in this young population is particularly profound, resulting in reduced productivity and economic growth of the country. It is also estimated that 400 pediatric cases develop progressive kidney disorder (neurogenic bladder, reflux nephropathy, chronic glomerulonephritis) annually, which, if left untreated, could result in ESRD in adulthood. This reality justifies initiatives such as FUNDANIER (Foundation for Children with Kidney Diseases), whose mission is to offer comprehensive nephrological treatment to children and adolescents and enable health care providers to prevent ESRD by early identification, diagnosis, and timely referral of children with risk factors. Efforts should be taken to better involve pediatricians and pediatric nephrologists in the fight against the burden of CRF.

Biomedical Research↗
PubMed2006

Biomanufacturing: a US-China National Science Foundation-sponsored workshop.

A recent US-China National Science Foundation-sponsored workshop on biomanufacturing reviewed the state-of-the-art of an array of new technologies for producing scaffolds for tissue engineering, providing precision multi-scale control of material, architecture, and cells. One broad category of such techniques has been termed solid freeform fabrication. The techniques in this category include: stereolithography, selected laser sintering, single- and multiple-nozzle deposition and fused deposition modeling, and three-dimensional printing. The precise and repetitive placement of material and cells in a three-dimensional construct at the micrometer length scale demands computer control. These novel computer-controlled scaffold production techniques, when coupled with computer-based imaging and structural modeling methods for the production of the templates for the scaffolds, define an emerging field of computer-aided tissue engineering. In formulating the questions that remain to be answered and discussing the knowledge required to further advance the field, the Workshop provided a basis for recommendations for future work.

Biocompatible Materials↗
PubMed1995

Interrelationships of peak expiratory flow rate with physical and cognitive function in the elderly: MacArthur Foundation studies of aging.

BACKGROUND: Peak expiratory flow rate (PEFR) is correlated with several measures of health in the elderly, including physical and cognitive function. It is unclear, however, whether these relationships persist among the non-frail. METHODS: The Community-based Studies of the MacArthur Foundation Research Network on Successful Aging included measures of PEFR using a mini-Wright peak flow meter on a sample of 1,354 subjects selected from those aged 70-79 in three population samples. Subjects were chosen on the basis of simple measures of physical and cognitive function (high = 1192; medium = 80; low = 82), and were given a series of more detailed tests. RESULTS: Residual PEFR, adjusted for age, sex, height, weight, and smoking, was highly correlated (p < .001) with several physical performance measures, including number of steps in a tandem walk, number of seconds in a single leg stand, times to turn in a circle, write one's name, and walk 10 feet at a fast pace, foot-tapping (time per tap), and hand grip strength. The strongest association was evident for a combination of six physical function items. Residual PEFR was also correlated with cognitive performance, including tests of similarities, naming, spatial recognition, memory, and figure drawing. The strongest association was present for a combined measure. These associations persisted in analyses restricted to those in the "high" function group as well as with no history of previous myocardial infarction, stroke, or cancer. Residual PEFR also exhibited a strong independent association with urinary norepinephrine, as measured in 12-hour overnight urine specimens. This relation did not appear to be mediated by smoking or medication use.

Aged↗
PubMed2025

scPlantLLM: A Foundation Model for Exploring Single-cell Expression Atlases in Plants.

Single-cell RNA sequencing (scRNA-seq) provides unprecedented insights into plant cellular diversity by enabling high-resolution analyses of gene expression at the single-cell level. However, the complexity of scRNA-seq data, including challenges in batch integration, cell type annotation, and gene regulatory network (GRN) inference, demands advanced computational approaches. To address these challenges, we developed scPlantLLM, a Transformer model trained on millions of plant single-cell data points. Using a sequential pretraining strategy incorporating masked language modeling and cell type annotation tasks, scPlantLLM generates robust and interpretable single-cell data embeddings. When applied to Arabidopsis thaliana datasets, scPlantLLM excels in clustering, cell type annotation, and batch integration, achieving an accuracy of up to 0.91 in zero-shot learning scenarios. Furthermore, the model demonstrates an ability to identify biologically meaningful GRNs and subtle cellular subtypes, showcasing its potential to advance plant biology research. Compared to traditional methods, scPlantLLM outperforms in key metrics such as adjusted rand index (ARI), normalized mutual information (NMI), and silhouette score (SIL), highlighting its superior clustering accuracy and biological relevance. scPlantLLM represents a foundation model for exploring plant single-cell expression atlases, offering unprecedented capabilities to resolve cellular heterogeneity and regulatory dynamics across diverse plant systems. The code used in this study is available at https://github.com/compbioNJU/scPlantLLM.

Single-Cell Analysis↗
PubMed1997

National Kidney Foundation: Dialysis Outcome Quality Initiative--development of methodology for clinical practice guidelines.

BACKGROUND: The NKF-DOQI (National Kidney Foundation--Dialysis Outcomes Quality Initiative) began in March 1995 with the following objectives: To improve end-stage renal disease (ESRF) patient survival, to reduce patient morbidity, to increase efficiency of care, and to improve quality of life for ESRF patients. METHODS: The development of the NKF-DOQI Clinical Practice Guidelines focused on haemodialysis adequacy, peritoneal dialysis adequacy, vascular access, and anaemia. Principles guiding the methodology included scientific and methodological rigour, interdisciplinary approach, independence of the Work Groups, and an open review process. Unique features of this evidence-based guideline development process included the use of mock guidelines and rationales to guide the literature research, and an unprecedented three-stage review process. RESULTS: Work Groups reviewed more than 11,000 articles. A total of 114 clinical practice guidelines were developed by the Work Groups; these have been reviewed by more than 1200 professionals and patients. CONCLUSION: The NKF-DOQI Clinical Practice Guidelines has been a unifying effort for the entire renal community. The guidelines are an important step in the process of improving the quality of dialysis practice and improving ESRF patient outcomes. Priorities for implementation of the guidelines include education of ESRF professionals and patients, working with providers and insurers to encourage compliance, and follow-up evaluation of patient outcomes to quantify compliance results.

Foundations↗
PubMed1999

Integrating early clinical experience curricula at two medical schools: lessons learned from the Robert Wood Johnson Foundation's Generalist Physician Initiative.

The University of Texas Medical Branch and Eastern Virginia Medical School have created community-based generalist clinical experiences early in the first two years of medical school as part of The Robert Wood Johnson Foundation's Generalist Physician Initiative. This article describes these experiences and related curricula, outlining the common elements and differing approaches at the two institutions. It discusses the success of the new curriculum, presenting information from performance measures and surveys of students, clerkship directors, and faculty involved in the programs, and it describes further evaluative studies being planned. The authors discuss nine lessons learned and their conclusion that early clinical experience with generalist physicians is an important element of generalist curriculum reform. It improves student satisfaction with the first two years' experience and provides a structure for teaching patient-centered, integrated clinical medicine, which is important in the general professional education of all students. Whether or not the long-term goal of increasing students' interest in generalist careers is realized, incorporating early clinical experiences with generalists into a curriculum has positive effects on students, faculty, and the overall curriculum.

Curriculum↗
PubMed1995

Helping community health centers adapt to changing environments: one foundation's response.

The history of community health centers (CHCs) reflects attitudes toward health care delivery in general. Developed as part of the war on poverty, they later survived the more conservative attitudes of the early 1970s to flourish in the late 1970s. In the 1980s, we again witnessed a reduction in the funding available to CHCs. In response to this, The Robert Wood Johnson Foundation (RWJF) established The Program to Strengthen Primary Care Health Centers. The program was designed to help centers to adapt to this environment by becoming more businesslike in their operations and decreasing their dependence on public dollars.

Community Health Centers↗
PubMed1995

Reflections from The Robert Wood Johnson Foundation on The Program to Strengthen Primary Care Health Centers.

Given the modest amount of resources provided by the Foundation through The Program to Strengthen Primary Care Health Centers, the grantees undertook a high level of activity. Perhaps centers were aided by the momentum and focus of the Program in addition to financial resources. Such grants seem to move longer-range projects onto the daily agendas of managers. It might be worthwhile to convert some portion of federal community health center funding to support financial and managerial innovations. Generally, positive evaluation findings should encourage centers to explore some of the demonstrated initiatives. Evolution and innovation are considered key to the survival of primary care health centers.

Community Health Centers↗
PubMed1997

Saline-filled breast implants: a Plastic Surgery Educational Foundation multicenter outcomes study.

In 1993, the Plastic Surgery Educational Foundation commissioned the senior author (Cunningham) to design an 11-center retrospective cohort outcomes study to obtain physician- and patient-reported data on saline-filled breast implants. Data were obtained from 504 patients with 995 saline-filled breast implants placed between January 1, 1980 and December 31, 1989, with a mean follow-up of 6 years. Most (93.8 percent) saline-filled breast implants were placed for breast augmentation. Of the 504 patients, 104 (20.6 percent) required reoperation for open capsulotomy or for replacement or removal of a deflated implant. Complications occurred in 22 patients (4.4 percent), with hematoma being most common. Implant deflation occurred in 55 implants (5.5 percent) and affected 51 patients (10.1 percent) but was underreported by chart abstraction alone. Risk factors for implant deflation included underfilling the implant by more than 25 cc (odds ratio 3.3, p = 0.0400), the use of model 1800 saline-filled breast implants (odds ratio 3.1, p = 0.0010), intraluminal antibiotics (odds ratio 2.6, p = 0.0183), and intraluminal steroids (odds ratio 2.4, p = 0.0711). Based on 44 of 55 saline-filled breast implants with known deflation dates, actuarial survival is 95.7 to 98.0 percent at 5 years and 90.2 to 95.2 percent at 10 years (95 percent confidence interval). Significant periprosthetic capsular contracture affected 103 patients (20.4 percent) during follow-up. Risk factors for capsular contracture included omitting intraluminal antibiotics (odds ratio 16.7, p = 0.0001), omitting intraluminal steroids (odds ratio 12.5, p = 0.0001), submammary placement of the saline-filled breast implant (odds ratio 7.8, p = 0.0001), and use of antibiotics in the implant pocket (odds ratio 6.1, p = 0.0001). Overall patient satisfaction with saline-filled breast implants was rated as high by 94.2 percent, and 94.8 percent of patients would choose saline-filled breast implants again. Dissatisfaction with their saline-filled breast implants was more frequent in patients with significant breast firmness (odds ratio 22.9, p = 0.0001), those undergoing prophylactic mastectomy (odds ratio 8.2, p = 0.0005), and those desiring smaller implants (odds ratio 6.9, p = 0.0001). In conclusion, saline-filled breast implants are a safe alternative to silicone gel-filled breast implants and demonstrate a high rate of patient satisfaction. Underfilling of saline-filled breast implants should be avoided because it contributes to deflation. Although intraluminal antibiotics and steroids protect against capsular contracture, they also contribute to saline-filled breast implant deflation. The incidence of capsular contracture is decreased by placing the saline-filled breast implant in the subpectoral position. Finally, patients should be aware of the possible need for reoperations related to their implants.

Actuarial Analysis↗
PubMed1997

The high grade match kidney sharing algorithm of the South-Eastern Organ Procurement Foundation (SEOPF): altering recipient demographics through improved matching.

BACKGROUND: Studies of kidneys shared through the South-Eastern Organ Procurement Foundation (SEOPF) have shown that regional organ procurement (ROP) trays can predict negative crossmatch in highly sensitized patients when the HLA match is of a high grade. In an attempt to offer more well-matched kidneys to highly sensitized patients, SEOPF organized the High Grade Match (HGM) Program. METHODS: This United Network for Organ Sharing (UNOS)-approved allocation variance requires mandatory sharing of all kidneys by participating centers after UNOS mandatory sharing requirements have been met. The HGM levels of sharing are: (1) 0 A,B mismatch (MM); panel-reactive antibody (PRA) > or = 40%; negative ROP crossmatch; (2) 0 B,DR MM with > or = 40% PRA; negative ROP crossmatch; (3) 0 B,DR MM with PRA < 40%. Non-HGM cadaveric transplants at the same participating centers--locally or distally procured--serve as the control group. RESULTS: During the first 18 months of this program, the 23 participating centers shared 124 kidneys of the 1592 that were available. Well-matched kidneys (two mismatches or less) accounted for 91.1% in the HGM group, but only 19% of the controls (P<0.0001). Highly sensitized patients (PRA > or = 40%) represented 13.8% of the HGM group, but only 3.3% of the non-HGM group (P<.0001). With HGM kidneys, there was a shift in recipient demographics. Patients with blood group O, female patients, older patients, and retransplanted patients all accounted for significantly larger percentages of the HGM group compared with the non-HGM control group. The racial composition of the recipients of high-grade matches was, however, no different than that of the control recipients at the same centers. CONCLUSION: The HGM Program resulted in longer ischemia times, but graft survival was not affected. The 1-year actuarial graft survival rate (Kaplan-Meier) for HGM kidneys was not different from the control cadaveric graft survival rate. By sharing kidneys based on improved HLA matches with consideration for high PRA, the HGM Program offered more transplant opportunities to women, blood group O recipients, retransplants, and older patients.

ABO Blood-Group System↗
PubMed2003

Longitudinal Study of the National Kidney Foundation's (NKF) Kidney Early Evaluation Program (KEEP).

In 2000, the National Kidney Foundation implemented the Kidney Early Evaluation Program (KEEP 2.0) to increase awareness of kidney disease among those at highest risk, and improve outcomes through early detection and referral for care. The KEEP 2.0 screening program identified significant numbers of persons with reduced kidney function, with previously undetected kidney disease risk factors, and with inadequate risk factor control. These data support the evolution to KEEP 3.0, which will continue to identify individuals at high risk for kidney disease, and will address the educational needs of health care providers and consumers, given that preventing and managing kidney disease requires their joint effort. Consumers need to embrace lifestyle behaviors that reduce risk, and adhere to medical recommendations in managing their existing conditions. At the same time, providers need to ensure that the latest evidence-based guidelines in diagnosis and treatment are being implemented in their clinical practice. KEEP 3.0 participants will be randomly assigned to one of several educational programs that vary on whether they provide individually tailored or nontailored information, with long-term follow-up for evaluation of clinical outcomes. Tailored programs may be more successful in supporting behavioral change as these consider the individuals' "readiness to change." In addition, participant-identified providers will be randomly assigned to one of several educational protocols designed to provide evidence-based recommendations for clinical and pharmaceutical management of kidney disease and risk factors; these programs vary on whether they require active or passive participation of providers. Analytic evaluations will examine changes from baseline in participant kidney disease and risk factor status during follow-up, and estimate the influence of the various educational protocols on both process of care measures and clinical outcomes.

Cohort Studies↗
PubMed2003

Current trends in brain-computer interface research at the Neil Squire Foundation.

The Neil Squire Foundation (NSF) is a Canadian nonprofit organization whose purpose is to create opportunities for independence for individuals who have significant physical disabilities. Over the last ten years, our team in partnership with researchers at the Electrical and Computer Engineering Department, the University of British Columbia, has been working to develop a direct brain-controlled switch for individuals with significant physical disabilities. The NSF Brain Interface Project primarily focuses on the development of brain-computer interface switch technologies for intermittent (or asynchronous) control in natural environments. That is, technologies that will work when the User intends control but also remains in a stable off state when there is no intent to control. A prototype of such a switch has successfully been developed. This switch has demonstrated classification accuracies greater than 94%. The initial results are promising, but further research is required to improve switch accuracies and reliability and to test these switch technologies over a larger population of users and operating conditions. This paper provides an overview of the NSF brain-switch technologies and details our approach to future work in this area.

Adult↗