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PubMed2025

Relative quantification of proteins and post-translational modifications in proteomic experiments with shared peptides: a weight-based approach.

MOTIVATION: Bottom-up mass spectrometry-based proteomics studies changes in protein abundance and structure across conditions. Since the currency of these experiments are peptides, i.e. subsets of protein sequences that carry the quantitative information, conclusions at a different level must be computationally inferred. The inference is particularly challenging in situations where the peptides are shared by multiple proteins or post-translational modifications. While many approaches infer the underlying abundances from unique peptides, there is a need to distinguish the quantitative patterns when peptides are shared. RESULTS: We propose a statistical approach for estimating protein abundances, as well as site occupancies of post-translational modifications, based on quantitative information from shared peptides. The approach treats the quantitative patterns of shared peptides as convex combinations of abundances of individual proteins or modification sites, and estimates the abundance of each source in a sample together with the weights of the combination. In simulation-based evaluations, the proposed approach improved the precision of estimated fold changes between conditions. We further demonstrated the practical utility of the approach in experiments with diverse biological objectives, ranging from protein degradation and thermal proteome stability, to changes in protein post-translational modifications. AVAILABILITY AND IMPLEMENTATION: The approach is implemented in an open-source R package MSstatsWeightedSummary. The package is currently available at https://github.com/Vitek-Lab/MSstatsWeightedSummary (doi: 10.5281/zenodo.14662989). Code required to reproduce the results presented in this article can be found in a repository https://github.com/mstaniak/MWS_reproduction (doi: 10.5281/zenodo.14656053).

Protein Processing, Post-Translational↗

PubMed2026

Common genetic mechanisms between obesity and COVID-19 severity: unravelling pleiotropic loci and biological pathways.

COVID-19 and obesity are complex conditions marked by immune and metabolic dysfunction, with the former still ranking among the leading causes of death from infectious diseases worldwide and the latter reaching pandemic proportions. Clinical evidence consistently shows that obesity increases the risk of severe COVID-19, yet the biological mechanisms underlying this association remain unclear. Given their physiological and clinical overlap, they may share genetic pathways. We investigated genetic variants jointly associated with body mass index (BMI) and COVID-19 using publicly available genome-wide data. A conjunctional false discovery rate (conjFDR) approach identified shared variants between BMI and three COVID-19 phenotypes: infection, hospitalization and very severe respiratory illness. Functional annotation and pathway enrichment analyses were performed to explore the biological context of these variants, followed by a phenome-wide association study (PheWAS) to characterize pleiotropy. Shared variants were enriched in immune, metabolic and hormonal signaling pathways, including metal ion transport and glycosylation. The overlap with BMI was strongest for hospitalized and severe cases, suggesting common mechanisms underlying disease progression rather than infection. These findings suggest a biologically meaningful genetic overlap between obesity and COVID-19 severity, highlighting pleiotropy as a key feature in complex disease interactions and potential shared therapeutic targets.

BMI↗

PubMed1999

Socially shared cognition, affect, and behavior: a review and integration.

In this article, we review 4 classes of models of socially shared cognition and behavior: supraindividual models, information-processing models, communication models, and social interaction models. Our review draws on research and theory in social psychology, sociology, and organization behavior. We conclude that these innovative perspectives on socially shared behavior represent a new approach to the study of groups and are distinct from traditional models of the group mind and crowd behavior. The key processes implicated in these models focus on the potency of immediate interaction, reciprocal influence processes between individuals and groups, goal-directed behavior, negotiated processing of information and ideas, and the maintenance and enhancement of social identity. This approach to socially shared understanding is not antagonistic toward the analysis of individual-level processes but rather maintains that individual-level processes are necessary but not sufficient to build a social psychology of shared understanding.

Journal Article↗

PubMed2001

Using financial incentives to promote shared mental health care.

OBJECTIVES: To consider the most common primary care reimbursement structures, to identify incentives inherent in each, and to discuss how each could be used to encourage a shared-care approach to treating mental disorders at the primary care level. METHOD: Three major financial reimbursement models--fee-for-service, capitation, and blended payment mechanisms--are examined. Each is considered in terms of its risk-sharing elements and the consequent incentives. We offer several scenarios to illustrate how the shared-care practice model might be encouraged under each financing mechanism. RESULTS: The current fee-for-service system does not encourage shared care. For wide adoption of the shared-care practice model, there must be a change in the reimbursement system's incentives. While none of the financing mechanisms offers a perfect solution, each has potential. Each, however, must be carefully tailored to its environment. CONCLUSIONS: Financial considerations are just one aspect to achieving shared care. Nevertheless, in designing a system to encourage collaborative, coordinated care for those suffering from mental illness, decision makers should be wary of creating or maintaining obstacles (financial or otherwise) to provision of accessible, high-quality care.

Canada↗

PubMed1996

Managing care, incentives, and information: an exploratory look inside the "black box" of hospital efficiency.

OBJECTIVE: We sought to estimate the impact of individual dimensions of hospitals' managed care strategies on the cost per hospital discharge. STUDY SETTING/DATA SOURCES: Thirty-seven member hospitals of seven health systems in the Pacific, Rocky Mountain, and Southwest regions of the United States were studied. STUDY DESIGN: Separate cross-sectional regression analyses of 21,135 inpatient discharges were performed in 1991 and 23,262 discharges in 1992. The multivariate model was estimated with hospital cost per discharge as the dependent variable. Model robustness was checked by comparing regression results at the individual discharge level with those at the level of the hospital/clinical condition pair. DATA COLLECTION/EXTRACTION METHODS: Information on hospitals' managed care strategies was provided by mail and phone survey of key informants in 1991 and 1992. Other hospital characteristics were collected from AHA Annual Survey data, and discharge data from hospital abstracting systems. PRINCIPAL FINDINGS: The pooled discharge analysis indicated three dimensions of hospital managed care strategy that consistently related to lower costs per hospital discharge: the proportion of hospital revenues derived from per case or capitation payment, the hospital's mechanisms for sharing information on resource consumption with clinicians, and the use of formalized, systematic care coordination mechanisms. CONCLUSIONS: Three strategies appear to hold promise for enhancing the efficiency of inpatient resource use: (1) "fixed price" hospital payment incentives, (2) hospital approaches to sharing resource use information with clinicians, and (3) the application of formal care management mechanisms for specific clinical conditions.

Aged↗

PubMedDate not supplied

Efficacy and concentration-response of murine anti-VEGF monoclonal antibody in tumor-bearing mice and extrapolation to humans.

The development of a neovascular supply (angiogenesis) is a major aspect of tumorigenesis. Recent work has indicated that vascular endothelial growth factor (VEGF) is a major regulator of angiogenesis. In vitro and in vivo studies have demonstrated that an anti-VEGF antibody is capable of suppressing the growth of human tumor cell lines. The following study was conducted in tumor-bearing nude mice to evaluate the concentration-response relationship of murine anti-VEGF monoclonal antibody (muMAb VEGF) so that an efficacious plasma concentration of the recombinant humanized form (rhuMAb VEGF) in cancer patients could be estimated. (This study was included in our Investigational New Drug application to support the clinical dosing regimen and projected human safety factors for the toxicology program.) Additionally, the growth dynamics of the tumors were evaluated as a function of dose to explore whether a mechanismic interpretation of tumor growth inhibition by muMAb VEGF is possible. On day 1, A673 human rhabdomyosarcoma cells (2 x 10(6) cells/mouse) were injected subcutaneously in 188 beige nude mice (16-24 g). Treatment with muMAb VEGF (0.05-5.0 mg/kg; n = 24/group), phosphate-buffered saline (n = 10), or anti-gp120 isotype-matched control antibody (5.0 mg/kg; n = 10) began 24 hr later. Each animal received intraperitoneal injections of test material twice weekly for 4 wk. Immediately prior to each dose, 2 mice from each muMAb VEGF group were selected randomly, and plasma was collected for pharmacokinetic evaluation; at the end of the study, samples were collected from all animals for pharmacokinetic evaluation. Tumor dimensions were recorded weekly, and at the end of the study, tumor weight and dimensions were recorded. Satisfactory tumor suppression in nude mice was achieved at muMAb VEGF doses of > or =2.5 mg/kg, where the average trough muMAb VEGF plasma concentration was 30 microg/ml (concentrations in individual animals >10 microg/ml). Assuming the pharmacokinetics of rhuMAb VEGF in patients will resemble the pharmacokinetics of a similar humanized anticancer monoclonal antibodies, a clinical dosing regimen was designed to maintain the rhuMAb VEGF plasma concentration in this efficacious range. This study shows an approach that can be used to estimate a human dosing regimen from preclinical pharmacokinetic/pharmacodynamic data. Because we have just initiated clinical trials with rhuMAb VEGF we cannot judge clinical outcome in relation to these preclinical predictions; nonetheless, it is hoped that by sharing our approach and thought processes with other investigators we can assist the discovery and development of anticancer therapeutics.

Animals↗

PubMed1994

Continuity and change in infant shyness from 14 to 20 months.

Objective measures of shyness in the MacArthur Longitudinal Twin Study were obtained in two testing situations: the laboratory and the home. A longitudinal hierarchical model was fitted to the data, allowing estimation of the extent to which genetic, shared environmental, and unique environmental influences contributed to continuity and change of the shyness phenotype from 14 to 20 months of age. The sample consisted of 163 monozygotic and 138 same-sex dizygotic twin pairs. Models were fitted to raw data using a maximum-likelihood pedigree approach. Genetic, shared environmental, and unique environmental first-order factors, with specific variances, were modeled on each of four shyness ratings assessed in the laboratory and home at 14 and 20 months. Four second-order genetic, shared environmental, and unique environmental factors were also modeled. Results indicated that developmental change from 14 to 20 months and situational specificity between the laboratory and the home are mediated largely by shared and unique environmental influences. Genetic variation is largely responsible for both the stability in shyness from 14 to 20 months and the phenotypic correlations observed between the laboratory and the home settings.

Female↗

PubMed1999

Management forecast: optimizing the use of organizational and individual knowledge.

Knowledge management provides a means for sharing data, lessons learned, and accumulated knowledge throughout an organization or within an entire industry. Gone are the days of hoarding knowledge to ensure job security; today's workers and managers must work together to find new and innovative ways to use what they know and optimize how that knowledge is accessed. Knowledge management's new approach to shared intellectual resources has implications for workers and managers in all fields and promises to redraw the management landscape. But are healthcare organizations setting the stage for reengineering themselves all over again?

Administrative Personnel↗

PubMed2007

Participatory design in health sciences: Using cooperative experimental methods in developing health services and computer technology.

Participatory design (PD) is a research approach to the development of technological solutions to real-world problems, an approach that shares many concerns and some of its roots with action research. In this article, the authors discuss their experience in conducting a PD research project intended to develop a technological and a related organizational intervention to support the treatment of foot ulcers for people with diabetes at home. They provide a historical overview of the PD approach and a description of how they used it in their research study. They describe their experience in conducting the research, including the participants' responses, the outcomes of the research, and the challenges confronted in bridging the practical and disciplinary issues that arose. In the conclusion, they propose that PD holds potential as a research approach that might effectively merge computer technology and health-related interventional research.

Biomedical Research↗

PubMed2001

Sharing information with donor insemination offspring. A child-conception versus a family-building approach.

This paper suggests an innovative approach to the sharing of information between parents and their donor-conceived offspring. The 'family-building' approach is offered in the hope that it will stimulate discussion and development. Traditionally, the emphasis has been on telling the child about his/her donor conception. This has the potential to unintentionally separate the child from the parents. The family-building approach presents donor conception as an issue concerning all members of the family, thus encouraging the child to see him/herself as an integral part of this family's history. Within this approach, the semen provider is acknowledged for his contribution and for having an ongoing significance in the family. It is important, however, to clearly differentiate between him as the genitor and the child's father as the loving and nurturing male in the family. Implications for professionals include the need to acknowledge that donor insemination does not only enable a woman to become pregnant but that it creates a family with a past, present and future. Therefore it will be helpful to provide information about and explore attitudes towards this type of family-building before couples start treatment.

Disclosure↗

PubMed2006

The efficacy of family intervention in adolescent mental health.

The term 'family therapy' is used to encompass a range of approaches that share a common view about the importance of family involvement in psychiatric disorders. This paper reviews the effectiveness of family interventions in adolescent mental health with a special emphasis on single session therapy. Research evidence shows that the family intervention in psychiatric disorders such as schizophrenia, depression, attention deficit hyperactive disorder, anxiety and anorexia not only provides better outcomes, but also increases client satisfaction with services. Among the family therapy approaches, single session therapy (SST) seems to be a flexible and very effective model for adolescent mental disorders, which seem to offer an efficient means of providing rapid access to services whilst removing some of the difficulties associated with other forms of family therapy approaches. A new service development model is also discussed by drawing together a number of ideas encountered in practice settings.

Adolescent↗

PubMed1996

Interaction, language and the "narrative turn" in psychotherapy and psychiatry.

The traditional emphasis in psychiatry about "listening to patients" has recently been added to by the development of what we call the "narrative turn" in mental health care where clients' narratives are emphasised. We shall argue however that both approaches tend to embody similar assumptions about therapeutic transactions and roles, and that much work emphasising narratives reveals little about how therapists and researchers work to reconstruct the clients' accounts. It is therefore vital that the emphasis on narratives be supplemented by a more thoroughgoing approach to shared structures of knowledge which act to prefigure clients' distress, how professional records are a profoundly transformative medium, and how therapeutic encounters work to co-construct clients' narratives, rather than simply reflect or explore them. The radical implications of thinking about therapy in terms of narrative and language need to be more fully discussed in the therapy literature, so the narrative turn does not simply reproduce the common-sense assumptions of more conventional approaches.

Communication↗

PubMed2005

Impact of a collaborative shared antenatal care program for urban Indigenous women: a prospective cohort study.

OBJECTIVES: To evaluate the impact of a community-based, collaborative, shared antenatal care intervention (the Mums and Babies program) for Indigenous women in Townsville. DESIGN AND PARTICIPANTS: Prospective cohort study of women attending Townsville Aboriginal and Islander Health Service (TAIHS) for shared antenatal care with a singleton Indigenous birth between 1 January 2000 and 31 December 2003 (456 women; the MB group), compared with a historical control group of 84 women who attended TAIHS for antenatal care before the intervention between 1 January 1998 and 30 June1999, and a contemporary control group of 540 women who had a singleton birth at Townsville Hospital between 1 January 2000 and 30 June 2003, but did not attend TAIHS for antenatal care. INTERVENTION: Integration of previously autonomous service providers delivering shared antenatal care from TAIHS. MAIN OUTCOME MEASURES: Patterns of antenatal visits, proportion of women undertaking key antenatal screening, and perinatal outcomes. RESULTS: The number of Indigenous women who entered the MB program and gave birth at Townsville Hospital rose from 23.8% in 2000 to 61.2% in 2003. The number of antenatal care visits per pregnancy increased from three (interquartile [IQ] range, 2-6) in the historical control group to seven (IQ range, 4-10) in the MB group (P < 0.001). 88% of women in the MB group had at least one ultrasound. About 90% of all women attending for antenatal care were screened for sexually transmitted infections. In the MB group, there was a significant reduction in preterm births compared with the contemporary control group (8.7% v 14.3%, P < 0.01). There was no significant reduction in the prevalence of low birthweight births or perinatal mortality. CONCLUSION: A community-based collaborative approach to shared antenatal care services increased access to antenatal care and was associated with fewer preterm births among Indigenous women in Townsville. The model may be adaptable in other urban centres with multiple antenatal care providers and significant numbers of Indigenous people across Australia.

Adult↗

PubMed2004

Specialist drug misuse nurse's motivation, clinical decision-making and professional communication: an exploratory study.

UK guidelines advocate a multidisciplinary shared care approach to manage drug-related problems. While general practitioners (GPs), consultants and pharmacists have been researched, there has been little research into the role of nurses in this field. This study examined nurses specialized in the field of substance misuse. It specifically explored their motivation for entering this area, interaction with other health professionals and their role in clinical decision-making. Seventeen face-to-face interviews were undertaken with nurses from the study population of the 21 nursing staff currently employed in one service. Responses were tape-recorded, transcribed and analysed using qualitative methods. The majority of nurses entered this field because of a specific interest in its patients and their problems. Various professionals interacted with nurses: specialist medical staff, who served as an expert resource and pharmacists through the dispensing of substitute drugs. GP participation in services was inconsistent forcing some nurses to take undue responsibility for clinical decision-making. It is essential that nurses entering this field have an interest in this field and positive attitudes towards drug users, and greater emphasis should be placed on this attribute when selecting new employees. If a shared care model is to be successful, it is important that all GPs accept their responsibilities and relieve pressure currently placed on specialist services. Alternatively, it may be necessary to adopt a new model of care.

Decision Making↗

PubMed1997

Shared management of children with cancer.

OBJECTIVE: To determine the risks and benefits of university-based pediatric oncologists and community-based primary care physicians sharing the management of children with cancer. DESIGN: Physicians participating in shared management of children with cancer were surveyed, and the outcomes of the children were measured. SETTING AND PARTICIPANTS: One hundred thirty-seven community-based primary care physicians participated in the management of the 226 children with cancer in Iowa and western Illinois during the past 15 years. The survival of the 226 children was compared with that of 240 randomly selected children treated using the identical treatment protocols but treated only by pediatric oncologists. INTERVENTION: A 7-point Likert scale questionnaire was completed by 97 (71%) of the participating primary care physicians. RESULTS AND OUTCOME MEASURES: There were no differences in the survival of children using shared management compared with those treated only by pediatric oncologists. Primary care physicians believed that shared management is of economic and psychosocial benefit to patients, improves the treatment choices available to patients, does not require excessive time, and does not result in loss of practice income. The system strengthens the primary care physicians' relationships with oncologists and results in additional referrals to the university-based pediatric oncologists. It is of educational value, is personally satisfying, and provides relief from the stress associated with caring for these families. Primary care physicians would like to see this system expanded to include other children with special health care needs. CONCLUSION: The shared-management approach to care is a viable attractive option of health care provision for children.

Attitude of Health Personnel↗

PubMedDate not supplied

Scope and impact of financial conflicts of interest in biomedical research: a systematic review.

CONTEXT: Despite increasing awareness about the potential impact of financial conflicts of interest on biomedical research, no comprehensive synthesis of the body of evidence relating to financial conflicts of interest has been performed. OBJECTIVE: To review original, quantitative studies on the extent, impact, and management of financial conflicts of interest in biomedical research. DATA SOURCES: Studies were identified by searching MEDLINE (January 1980-October 2002), the Web of Science citation database, references of articles, letters, commentaries, editorials, and books and by contacting experts. STUDY SELECTION: All English-language studies containing original, quantitative data on financial relationships among industry, scientific investigators, and academic institutions were included. A total of 1664 citations were screened, 144 potentially eligible full articles were retrieved, and 37 studies met our inclusion criteria. DATA EXTRACTION: One investigator (J.E.B.) extracted data from each of the 37 studies. The main outcomes were the prevalence of specific types of industry relationships, the relation between industry sponsorship and study outcome or investigator behavior, and the process for disclosure, review, and management of financial conflicts of interest. DATA SYNTHESIS: Approximately one fourth of investigators have industry affiliations, and roughly two thirds of academic institutions hold equity in start-ups that sponsor research performed at the same institutions. Eight articles, which together evaluated 1140 original studies, assessed the relation between industry sponsorship and outcome in original research. Aggregating the results of these articles showed a statistically significant association between industry sponsorship and pro-industry conclusions (pooled Mantel-Haenszel odds ratio, 3.60; 95% confidence interval, 2.63-4.91). Industry sponsorship was also associated with restrictions on publication and data sharing. The approach to managing financial conflicts varied substantially across academic institutions and peer-reviewed journals. CONCLUSIONS: Financial relationships among industry, scientific investigators, and academic institutions are widespread. Conflicts of interest arising from these ties can influence biomedical research in important ways.

Academies and Institutes↗

PubMed2001

A mixed effects model for the analysis of ordinal longitudinal pain data subject to informative drop-out.

We extend the model of Pulkstenis et al. that models binary longitudinal data, subject to informative drop-out through remedication, to the ordinal response case. We present a selection model shared-parameter approach that specifies mixed models for both ordinal response and discrete survival time to remedication. In this fashion, the random parameter present in both models completely characterizes the relationship between response and time to remedication inducing their conditional independence. With a log-log link function for both response and study 'survival', as well as specification of a log-gamma distribution for the random effect, we obtain a closed-form expression for the marginal log-likelihood of response and time to remedication that does not require approximation or numerical integration techniques. A data analysis is performed and simulation results presented which support the consistency of parameter and standard error estimates.

Computer Simulation↗

PubMed1986

Advocacy skills and strategies for patient education managers.

In an era of increasing competition for patient education resources, patient education managers need to employ effective advocacy skills in order for their programs to continue to grow. In order to identify the advocacy skills and strategies currently being used, a series of four invitational seminars were convened around the country to allow patient education managers to share the approaches they have found to be useful. This paper summarizes those skills and strategies which fall into three categories: general advocacy, preparation, and implementation.

Education Department, Hospital↗