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PubMed2004

Building the centromere: from foundation proteins to 3D organization.

At each mitosis, accurate segregation of every chromosome is ensured by the assembly of a kinetochore at each centromeric locus. Six foundation kinetochore proteins that assemble hierarchically and co-dependently have been identified in vertebrates. CENP-A, Mis12, CENP-C, CENP-H and CENP-I localize to a core domain of centromeric chromatin. The sixth protein, CENP-B, although not essential in higher eukaryotes, has homologues in fission yeast that bind pericentric DNA and are essential for heterochromatin formation. Foundation kinetochore proteins have various roles and mutual interactions, and their associations with centromeric DNA and heterochromatin create structural domains that support the different functions of the centromere. Advances in molecular and microscopic techniques, coupled with rare centromere variants, have enabled us to gain fresh insights into the linear and 3D organization of centromeric chromatin.

Animals↗
PubMed2005

Dimensions of the epilepsy foundation concerns index.

We performed principal component analysis (PCA) of the Epilepsy Foundation Concerns Index scale in 189 patients undergoing evaluation for epilepsy surgery. We identified a five-factor solution in which there were no varimax-rotated factors consisting of fewer than two questions. Factor 1 reflects affective impact on enjoyment of life, Factor 2 reflects general autonomy concerns, Factor 3 reflects fear of seizure recurrence, Factor 4 reflects concern of being a burden to one's family, and Factor 5 reflects a perceived lack of understanding by others. Multiple regression using the Quality of Life in Epilepsy--89 question version; Minnesota Multiphasic Personality Inventory--2; Wechsler Adult Intelligence Scale--third edition; and verbal and visual memory tests as predictors demonstrated a different pattern of association with the factor and summary scores. We conclude that the Epilepsy Foundation Concerns Index is multidimensional, and using a global score based on all items may mask specific concerns that may be relevant when applied to individual patients.

Adult↗
PubMed2003

Experimental evaluation of an elastic foundation model to predict contact pressures in knee replacements.

Computational wear prediction is an attractive concept for evaluating new total knee replacement designs prior to physical testing and implementation. An important hurdle to such technology is the lack of in vivo contact pressure predictions. To address this issue, this study evaluates a computationally efficient simulation approach that combines the advantages of rigid and deformable body modeling. The hybrid method uses rigid body dynamics to predict body positions and orientations and elastic foundation theory to predict contact pressures between general three-dimensional surfaces. To evaluate the method, we performed static pressure experiments with a commercial knee implant in neutral alignment using flexion angles of 0, 30, 60, and 90 degrees and loads of 750, 1500, 2250, and 3000N. Using manufacturer CAD geometry for the same implant, an elastic foundation model with linear or nonlinear polyethylene material properties was implemented within a commercial multibody dynamics software program. The model's ability to predict experimental peak and average contact pressures simultaneously was evaluated by performing dynamic simulations to find the static configuration. Both the linear and nonlinear material models predicted the average contact pressure data well, while only the linear material model could simultaneously predict the trends in the peak contact pressure data. This novel modeling approach is sufficiently fast and accurate to be used in design sensitivity and optimization studies of knee implant mechanics and ultimately wear.

Compressive Strength↗
PubMed1998

Evaluation of the use of a skills acquisition manual within the common foundation programme for pre-registration nursing.

A skills acquisition manual had been developed for use in the common foundation programme. This article describes an evaluative study of the use of this manual by two cohorts within the pre-registration programme. Information was gained by analysis of the skills acquisition manual and interviewing a sample of participants from both the student cohorts, clinical staff and lecturers involved with the programme. Findings identify a number of issues of interest and demonstrate that the range of clinical opportunities within the common foundation programme enable students to achieve a wide range of transferable skills within a programme that reflects all aspects of nursing.

Clinical Competence↗
PubMed2000

The modern National Kidney Foundation: broad scope, clear vision, better lives.

The mission of the National Kidney Foundation is very broad, going well beyond what its name implies. The Foundation works for, cares about, and represents millions of Americans, from the child who wets the bed to the diabetic with hypertension to the grandfather on dialysis. It is dedicated to making lives better through a variety of educational programs for patients and their families as well as physicians, social workers, nurses, dietitians, technicians, administrators, and clinical and transplant coordinators. It supports research, promotes organ and tissue donation, provides direct services to patients, and advocates for patients through public policy and legislative initiatives. Its programs aid people at risk of kidney and urinary tract disease, individuals affected by these diseases, living organ donors and families of donors, and recipients of all types of lifesaving organ and tissue transplants.

Adult↗
PubMed2000

Restructuring the National Kidney Foundation.

The National Kidney Foundation reorganized its governance structure for the first time in its 50-year history. Following a 2-year review, which involved all constituents of the Foundation and took advantage of the advice of professional consultants, the NKF delegated governance responsibilities to the Board of Directors and created a General Assembly of affiliate leaders and professional staff. NKF national and affiliate leaders agreed on this course of action so that power would be more appropriately shared between the national organization and the affiliates and the overall organization would be better positioned to succeed in the NKF's first national fund raising campaign.

Administrative Personnel↗
PubMed2000

The scientific and professional challenges for the National Kidney Foundation in the 21st century.

The coming century will witness many changes in the science and practice of nephrology and in cultural attitudes and behavior that should have profound effects on the National Kidney Foundation (NKF). There will be marked advances in our understanding and treatment of kidney disease. Concomitantly, there should be continued advances in the technology of communication and more widespread utilization of this technology by the NKF. There should be substantial growth in the numbers of individuals with end-stage renal disease and a growing recognition of and respect for the psychosocial and material needs of these individuals. Rising prosperity will lead to many improvements in the delivery of health care to patients with renal disease and renal failure. It is anticipated that the financial resources of the NKF will continue to increase and that this factor will enhance the ability of the NKF to carry out its many programs. These changes will present new opportunities and new challenges to the NKF. It is anticipated that these changes will be manifest in at least the following five areas of NKF activity: (1) There will be increased advocacy for funding for renal research from federal agencies, especially from the National Institutes of Health; the NKF research fellowship and grants program will also grow. (2) There will be a continued NKF commitment to facilitate the translation of new scientific and medical advances into routine health care delivered to the average renal patient. (3) There will be improved techniques for professional education. (4) There will be greater international cooperation among kidney-focused organizations, particularly among different kidney foundations. (5) There will be an increase in the scope of activities that promote patient empowerment and rehabilitation.

Financing, Government↗
PubMed2000

Foundational readings concerning pollen for allergists and aerobiologists.

BACKGROUND: In a medical culture being revolutionized by MEDLINE, MD-Consult, and full-text electronic journals, books are frequently dismissed as antiquated and hopelessly out of date. For those involved in the study of atmospheric pollen, however, books--many several decades old--still represent foundational reading. OBJECTIVES: This paper will present and briefly review 17 books dealing with the ecology of plants that cause pollinosis, pollen morphology, pollen movement in the atmosphere, and air sampling techniques. CONCLUSIONS: This small collection of books provides a foundation with which to approach the study of atmospheric pollen. Allergists and aerobiologists are encouraged to become familiar with these titles, particularly if they intend to publish pollen data in medical journals.

Air Pollution↗
PubMedDate not supplied

Building a foundation for the human proteome: the role of the Human Proteome Organization.

Proteomics holds both substantial promise and substantial challenges. For proteomics to bear fruit on a large scale from a disease investigation point of view, it is essential to build a solid foundation for the field. Given the magnitude of the challenges, it is necessary to build a foundation by bringing together the private and public sectors. The Human Proteome organization is promoting the field of proteomics by engaging in such an effort and is developing several major initiatives.

Antibodies↗
PubMed2004

Validation of the Restless Legs Syndrome Quality of Life Instrument (RLS-QLI): findings of a consortium of national experts and the RLS Foundation.

UNLABELLED: This study was designed to assess the initial psychometric properties of a new disease-specific health-related quality of life (HRQL) measure, the Restless Legs Syndrome (RLS) Quality of Life Instrument (RLS-QLI). METHODS: Draft items were generated from a literature review, consultation with MD and PhD specialists in the fields of neurology and sleep medicine, and input from two patient focus groups. The initial item reduction was accomplished using a survey of 392 persons with self-reported RLS symptoms from the membership of the RLS Foundation. The final (independent) validation sample consisted of 574 of persons on the RLS Foundation's Interest Group List Serve who also reported having RLS. The mean age of participants was 54.5 (SD 12.3), with a sex ratio of 1M:2F, and the majority was on some form of medication for RLS (66%). RESULTS: Four factors were identified (Daily Function, Social Function, Sleep Quality, and Emotional Well-Being) consisting of 17 items that explained 73.3% of the total variance. Each scale had good internal consistency (Cronbach's alpha's between 0.85 and 0.91) and 2-week test retest stability (Pearson Correlations between 0.81 and 0.93). Convergent validity was demonstrated using related scales on the SF-36 (r = 0.47-0.60) and criterion-related validity was shown using the clinical IRLS Scale of Symptom Severity (r = -0.45 to -0.77). CONCLUSION: The RLS-QLI is a valid disease-specific HRQL instrument that will contribute to our understanding of how RLS impacts the lives of those affected with this CNS disorder.

Adult↗
PubMed1996

Personal ideology polarity: its emotional foundation and its manifestation in individual value systems, religiosity, political orientation, and assumptions concerning human nature.

Personal ideology is an individual's philosophy of how life should be and of what forces influence human living. In this study S.S. Tomkins's (1963b, 1965, 1978, 1987) polarity theory of ideology was used to examine the manifestation of personal ideology in 4 value-laden domains of personality. Tomkins's theoretical postulates concerning the emotional foundation of personal ideology also were tested. Analyses revealed that the 2 defining dimensions of polarity theory--humanism and normativism--are related in the predicted meaningful ways to value systems, assumptions concerning human nature, religiosity, and political orientation. Evidence also was found for Tomkins's contention that specific affect clusters serve as the foundation of personal ideology. Participants who scored high in humanism ideology related autobiographical memories containing the emotion cluster of joy, distress, fear, and shame, whereas the memories of participants with normative ideologies contained relatively more anger.

Adult↗
PubMed2025

Real-world deployment of a fine-tuned pathology foundation model for lung cancer biomarker detection.

Artificial intelligence models using digital histopathology slides stained with hematoxylin and eosin offer promising, tissue-preserving diagnostic tools for patients with cancer. Despite their advantages, their clinical utility in real-world settings remains unproven. Assessing EGFR mutations in lung adenocarcinoma demands rapid, accurate and cost-effective tests that preserve tissue for genomic sequencing. PCR-based assays provide rapid results but with reduced accuracy compared with next-generation sequencing and require additional tissue. Computational biomarkers leveraging modern foundation models can address these limitations. Here we assembled a large international clinical dataset of digital lung adenocarcinoma slides (N = 8,461) to develop a computational EGFR biomarker. Our model fine-tunes an open-source foundation model, improving task-specific performance with out-of-center generalization and clinical-grade accuracy on primary and metastatic specimens (mean area under the curve: internal 0.847, external 0.870). To evaluate real-world clinical translation, we conducted a prospective silent trial of the biomarker on primary samples, achieving an area under the curve of 0.890. The artificial-intelligence-assisted workflow reduced the number of rapid molecular tests needed by up to 43% while maintaining the current clinical standard performance. Our retrospective and prospective analyses demonstrate the real-world clinical utility of a computational pathology biomarker.

Humans↗
PubMed1996

Entry age, entry mode and academic performance on a Project 2000 common foundation programme.

With the increasing academic expectations in the United Kingdom arising from the demands of the recently-introduced Diploma in Higher Education/Registration course (Project 2000) and with fairly substantial proportions of both unqualified (DC test) and mature entrants being admitted onto the course, a study was carried out into the relationship between entry age, entry qualifications and academic performance on the common foundation programme, which lasts for the first 18 months of the course. The entry data and common foundation programme results of each student from the first three intakes, 258 in total, were reviewed. A different subject design was used for the study in which students were placed into one of four groups, according to entry age and entry qualifications, which were: (a) 17-21 conventional entry requirements met; (b) 22 + conventional entry requirements met; (c) 17-21 unqualified (DC test entrant), and (d) 22 + unqualified (DC test entrant). Results indicated that the performance of most mature students, whether qualified or not, was above average, with the qualified group securing the best results of any of the four groups. Among the 17-21 age group, while the qualified performed as expected, the unqualified performed the worst of any of the four groups, registering both a high discontinuation rate and low overall mean scores for the programme. No improvement in the relative performance of the 17-21 unqualified group was noted over the three cohorts and there were indications that under-performance among the unqualified group extended beyond the 17-21 age range. In terms of recruitment, results could indicate a need for a change in policy, with evidence of proven academic ability being required from all younger applicants. If continued recruitment of unqualified younger students is planned, then a more vigorously targeted policy of academic support and guidance for these students will be required. Without this, it seems likely that poor performance and high wastage among this group will continue.

Achievement↗
PubMed1997

A conceptual foundation for human suffering in nursing care and research.

Suffering is a significant, yet elusive, phenomenon in nursing and health care. Despite the importance and prevalence of suffering, there is only a small body of substantive literature on this topic. Some of the difficulty in expanding this knowledge base undoubtedly is related to the lack of a solid conceptual foundation for exploration of this phenomenon. Although there have been attempts to provide needed conceptual clarity, these efforts typically have not been based on systematic inquiry. In this study, the method of concept analysis was used to inductively generate a definition of the concept of suffering and to clarify various contextual aspects of the concept. Suffering is defined as an individualized, subjective, and complex experience that involves the assignment of an intensely negative meaning to an event or a perceived threat. Implications of these findings and additional contextual aspects of the concept for nursing practice and inquiry are presented. These results help to provide the conceptual foundation needed to enhance recognition and understanding of the human experience of suffering.

Databases, Bibliographic↗
PubMed2002

Understanding people who smoke and how they change: a foundation for smoking cessation in primary care, part 2.

The purpose of this 2-part article is to develop an understanding of people who smoke and how they change as a foundation for the delivery of smoking cessation interventions in primary care. Central to our approach is the transtheoretical model of change (TMC). The TMC is an evidence-based model of behavior change that has been developed and tested during the past 2 decades by Prochaska and his colleagues in the context of smoking cessation. We use a review of the literature, in-depth interviews of people who successfully quit smoking, and our experience applying the TMC in the context of primary care and a smoking cessation clinic to explore the clinical work of smoking cessation. This is part 2 of the article "Understanding People Who Smoke and How They Change: A Foundation for Smoking Cessation in Primary Care." Part 1 describes the theoretical information known about smoking cessation: why smoking is a powerful behavior, the scientific background of the TMC, and the building-block constructs of the TMC. The first section of part 2 is a review of the Public Health Service clinical practice guideline, Treating Tobacco Use and Dependence, published in 2000. The second chapter of part 2 is a discussion of clinical assessments and strategies for working with smokers grounded in the Public Health Service practice guideline, our understanding of people who smoke, and the TMC. Woven throughout are transcripts of interviews with 4 people in which they describe their experiences smoking and their pathways to cessation.

Adult↗
PubMed2001

The moral foundation of medical leadership: the professional virtues of the physician as fiduciary of the patient.

Leadership in medicine, as in other settings, should be based on values that provide appropriate direction for the use of institutional power and authority. Leadership also requires managerial competence. Managerial knowledge and skills can be used for worthy and unworthy goals and therefore require a moral foundation. Using the methods of ethics, we argue that the concept of the physician as the moral fiduciary of the patient should be the moral foundation of management decisions by physician-leaders. We take this concept from the history of eighteenth century medical ethics and develop it in terms of four professional virtues--self-effacement, self-sacrifice, compassion, and integrity. We apply these four virtues to show how physician-leaders should create a moral culture of professionalism in health care organizations. We then identify four vices--unwarranted bias, primacy of self-interest, hard-heartedness, and corruption--that undermine this moral culture of professionalism. Because health care organizations now play a central role in patient care, their moral culture and therefore physician-leaders have become vital elements in physicians being able to maintain their professionalism. Physician-leaders bear major responsibility to shape organizational cultures that support the fiduciary professionalism of physicians.

Ethics, Medical↗
PubMed1998

Greetings: 50 years of Atomic Bomb Casualty Commission-Radiation Effects Research Foundation studies.

The Atomic Bomb Casualty Commission was established in Hiroshima in 1947 and in Nagasaki in 1948 under the auspices of the U.S. National Academy of Sciences to initiate a long-term and comprehensive epidemiological and genetic study of the atomic bomb survivors. It was replaced in 1975 by the Radiation Effects Research Foundation which is a nonprofit Japanese foundation binationally managed and supported with equal funding by the governments of Japan and the United States. Thanks to the cooperation of the survivors and the contributions of a multitude of scientists, these studies flourish to this day in what must be the most successful long-term research collaboration between the two countries. Although these studies are necessarily limited to the effects of acute, whole-body, mixed gamma-neutron radiation from the atom bombs, their comprehensiveness and duration make them the most definitive descriptions of the late effects of radiation in humans. For this reason, the entire world relies heavily on these data to set radiation standards. As vital as the study results are, they still represent primarily the effects of radiation on older survivors. Another decade or two should correct this deficiency and allow us to measure definitively the human risk of heritable mutation from radiation. We look to the worldwide radiation and risk community as well as to the survivors who have contributed so much to what has been done already to accomplish this goal.

Humans↗
PubMed2026

Bridging ancestry gaps in genomic risk prediction with tabular foundation models.

MOTIVATION: Models deployed for genomic prediction of diseases perform unevenly across populations, limiting clinical utility. Two factors drive this limitation: large imbalances in sample availability across ancestry groups and non-stationarity of genotype-phenotype effect sizes across the ancestry continuum. While tabular foundation models with in-context learning (ICL) have shown strong sample efficiency in other domains, their effectiveness for genotype-to-phenotype prediction and their robustness to ancestry-driven effect heterogeneity remain unclear. RESULTS: Using large, ancestrally diverse biobank data, we show that ICL-capable tabular foundation models reduce performance degradation in under-sampled ancestry groups compared to conventional supervised approaches. However, we find that prevailing models trained on existing synthetic tabular tasks fail when allele effect sizes vary across ancestry space. Treating genetic ancestry as a continuous variable, we introduce an instruction-tuning framework that exposes models to synthetic tasks with ancestry-dependent non-stationary effects. Instruction-tuned models achieve improved and more stable predictive performance across the genetic ancestry continuum, including for individuals distant from in-context exemplars in ancestry space. AVAILABILITY AND IMPLEMENTATION: All code for instruction-tuning models, synthetic task generation, data wrangling, and model evaluation, is publicly available at https://github.com/ai4pm/Bridging-Ancestry-Gaps-in-Genomic-Risk-Prediction-with-Tabular-Foundation-Models. The final instruction-tuned model (ICL-NS-G2P-proto) is also released in this repository. Detailed documentation is provided, including environment setup instructions and guidelines for running various parts. The instruction-tuning task datasets are available at https://zenodo.org/records/18309187.

Humans↗