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At least 19 recordsLinked to original sources
PubMed2005

Simulating the collaborative cross: power of quantitative trait loci detection and mapping resolution in large sets of recombinant inbred strains of mice.

It has been suggested that the collaborative cross, a large set of recombinant inbred strains derived from eight inbred mouse strains, would be a powerful resource for the dissection of complex phenotypes. Here we use simulation to investigate the power of the collaborative cross to detect and map small genetic effects. We show that for a fixed population of 1000 individuals, 500 RI lines bred using a modified version of the collaborative cross design are adequate to map a single additive locus that accounts for 5% of the phenotypic variation to within 0.96 cM. In the presence of strong epistasis more strains can improve detection, but 500 lines still provide sufficient resolution to meet most goals of the collaborative cross. However, even with a very large panel of RILs, mapping resolution may not be sufficient to identify single genes unambiguously. Our results are generally applicable to the design of RILs in other species.

Animals↗
PubMed2026

Genetic diversity of Collaborative Cross mice implicates FFAR3 as a target for ILC2 anti-inflammatory reprogramming.

Pulmonary group 2 innate lymphoid cells (ILC2s) are key drivers of Type 2 inflammation in diseases like asthma, yet the molecular mechanisms regulating their function are incompletely understood. Using the genetically diverse Collaborative Cross (CC) mouse panel, we mapped a quantitative trait locus (QTL) that governs ILC2 prevalence in the lung after aeroallergen exposure. This QTL induces a large population of ILC2s in the lung that are resistant to activation and have diminished Type 2 effector function. We identified free-fatty acid receptor 3 (Ffar3) as a gene responsible for this effect and demonstrated that FFAR3 signaling reprograms ILC2s to an anti-inflammatory state by promoting their survival, reducing Type 2 cytokine production, and enhancing IL-10 expression. This anti-inflammatory state is dependent on IL-2 signaling, is characterized by decreased ST2 expression, and is distinct from previously described IL-10-producing ILC2 phenotypes. FFAR3-dependent reprogramming is mediated by epidermal growth factor receptor (EGFR) upregulation, and FFAR3's anti-inflammatory effect is partially conserved in human ILC2s.

Animals↗
PubMed2004

The Collaborative Cross, a community resource for the genetic analysis of complex traits.

The goal of the Complex Trait Consortium is to promote the development of resources that can be used to understand, treat and ultimately prevent pervasive human diseases. Existing and proposed mouse resources that are optimized to study the actions of isolated genetic loci on a fixed background are less effective for studying intact polygenic networks and interactions among genes, environments, pathogens and other factors. The Collaborative Cross will provide a common reference panel specifically designed for the integrative analysis of complex systems and will change the way we approach human health and disease.

Animals↗
PubMed1983

Hepatitis B and the dental profession: response to hepatitis B vaccine in Canadian dental personnel. A study by the Canadian Red Cross Collaborative Group.

Reports from North America and Western Europe based on the prevalence of hepatitis B virus markers and frequency of hepatitis B in dentists indicate that this professional group is at increased risk of HBV infection. We gave hepatitis B vaccine (Merck Sharp and Dohme) to 251 dental students and faculty/staff members at faculties of dentistry in three Canadian universities. Participants received three 20 micrograms doses of vaccine, at 0, 1 and 5.5 months. Anti-HBs was detected in 42.9 per cent of persons after the first dose of vaccine, in 96.8 per cent after the second dose and in 99.6 per cent after the third dose. A follow-up of 150 persons 22 months after the first dose of vaccine indicated that high or medium levels of anti-HBs were maintained in nearly 87 per cent of the participants and only six per cent had no detectable antibody. Female vaccinees in each age group developed anti-HBs more promptly, and more of them were in the high antibody-response range in comparison to male participants. There were no unacceptable reactions to the vaccine. Our favourable experience with this vaccine would support recommendations for its routine use among dental professionals in Canada and other countries where this group is at increased risk of HBV infection.

Adult↗
PubMed2005

Therapeutic efficacy of antimalarial drugs along the eastern Indo-Nepal border: a cross-border collaborative study.

This collaborative cross-border study was performed to determine the therapeutic efficacy of antimalarial drugs used by the National Programmes for falciparum malaria along the eastern Indo-Nepal border where there is unregulated population movement across the border. The study was conducted at sites in Jhapa District, Nepal and Darjeeling District, India. The study was conducted from August 2003 to February 2004, following the WHO 28 day treatment protocol. The efficacy of chloroquine was tested in India among 91 subjects and of sulfadoxine-pyrimethamine in Nepal among 107 subjects with laboratory-confirmed Plasmodium falciparum malaria. Of the 102 subjects who completed the study in Nepal, there were 21 (20.6%) treatment failures comprising 7 (6.9%) early treatment failures (ETF) and 14 (14.7%) late treatment failures (LTF) (5 late clinical failures [LCF] and 9 late parasitological failures [LPF]). Of the 89 subjects who completed the study in India, there were 46 (51.7%) treatment failures comprising 7 (7.9%) ETFs and 39 (43.8%) LTFs (13 LCFs and 26 LPFs). Based on WHO guidelines both countries need to review their drug policy urgently and make appropriate changes, taking into account aspects of cross-border collaboration in the control of drug-resistant malaria.

Adolescent↗
PubMedDate not supplied

An application of an effective interdisciplinary health-focused cross-cultural collaboration.

The phenomenon of cross-cultural collaboration is not new. What is lacking in the literature, however, is a discussion of how health professionals from various cultures, collaborating together, have addressed their patients' health care needs to improve their quality of life. Because of increased interest in global health issues, it seems logical that health professionals from various countries form collaborative partnerships to investigate and address these health issues. Although treatments to health problems are offered, it is not generally communicated in the literature how cross-cultural collaboration played a role in managing the process to solve the problem. By applying the concepts for global managers outlined by P. R. Harris and R. T. Moran (1996), this article describes how the investigators established a successful cross-cultural collaboration for conducting health research between teams in the United States and Russia.

Communication↗
PubMed1993

Proposed 'World Health Organization staging system for HIV infection and disease': preliminary testing by an international collaborative cross-sectional study. The WHO International Collaborating Group for the Study of the WHO Staging System.

OBJECTIVE: To evaluate a universally applicable staging system for HIV infection and disease proposed by the Global Programme on AIDS (GPA) of the World Health Organization (WHO). The system consists of both a 'clinical' and a 'laboratory' axis. The 'clinical axis' is represented by a sequential list of clinical conditions believed to have prognostic significance, which subdivides the course of HIV infection into four clinical stages. The 'laboratory axis' subdivides each clinical stage into three strata according to CD4+ cell or total lymphocyte count. DESIGN: International cross-sectional study. SETTING: Twenty-seven clinical centres in 20 countries. PATIENTS AND PARTICIPANTS: A total of 938 confirmed HIV-positive patients, aged at least 13 years. MAIN OUTCOME MEASURES: Presence of the clinical condition belonging to the highest stage and its correlation with recent laboratory data (CD4+ cell counts, total lymphocyte counts, beta 2-microglobulin levels, haemoglobin, haematocrit, erythrocyte sedimentation rate, p24 antigen, p24 antibody and delayed hypersensitivity skin test). RESULTS: There was general agreement between the proposed attribution of clinical conditions and the corresponding laboratory markers. Significant differences were observed between stages 3 and 4 for seven laboratory markers and between stages 2 and 3 for six, but not between stages 1 and 2, for any of the nine laboratory markers. CONCLUSIONS: Longitudinal studies are needed to assess whether the proposed system is useful in predicting survival time in patients with HIV disease.

Adolescent↗
PubMed1988

Overview of the Cross-National Collaborative Panic Study.

The Cross-National Collaborative Panic Study is a two-phase multinational, multicenter controlled trial for the evaluation of drug treatment of panic disorder and associated agoraphobia. The First Phase compared alprazolam with placebo in a large sample of more than 600 subjects at eight centers--five in the United States, two in Canada, and one in Australia. The Second Phase compared alprazolam, imipramine hydrochloride, placebo in more than 1100 patients in 14 countries. The scientific background, aims and purposes, governance, and policies regarding statistical analyses and scientific presentations and publications are reviewed as background for the series of individual articles reporting detailed findings from the First Phase.

Agoraphobia↗
PubMed2022

A Multitrait Locus Regulates Sarbecovirus Pathogenesis.

Infectious diseases have shaped the human population genetic structure, and genetic variation influences the susceptibility to many viral diseases. However, a variety of challenges have made the implementation of traditional human Genome-wide Association Studies (GWAS) approaches to study these infectious outcomes challenging. In contrast, mouse models of infectious diseases provide an experimental control and precision, which facilitates analyses and mechanistic studies of the role of genetic variation on infection. Here we use a genetic mapping cross between two distinct Collaborative Cross mouse strains with respect to severe acute respiratory syndrome coronavirus (SARS-CoV) disease outcomes. We find several loci control differential disease outcome for a variety of traits in the context of SARS-CoV infection. Importantly, we identify a locus on mouse chromosome 9 that shows conserved synteny with a human GWAS locus for SARS-CoV-2 severe disease. We follow-up and confirm a role for this locus, and identify two candidate genes, CCR9 and CXCR6, that both play a key role in regulating the severity of SARS-CoV, SARS-CoV-2, and a distantly related bat sarbecovirus disease outcomes. As such we provide a template for using experimental mouse crosses to identify and characterize multitrait loci that regulate pathogenic infectious outcomes across species. IMPORTANCE Host genetic variation is an important determinant that predicts disease outcomes following infection. In the setting of highly pathogenic coronavirus infections genetic determinants underlying host susceptibility and mortality remain unclear. To elucidate the role of host genetic variation on sarbecovirus pathogenesis and disease outcomes, we utilized the Collaborative Cross (CC) mouse genetic reference population as a model to identify susceptibility alleles to SARS-CoV and SARS-CoV-2 infections. Our findings reveal that a multitrait loci found in chromosome 9 is an important regulator of sarbecovirus pathogenesis in mice. Within this locus, we identified and validated CCR9 and CXCR6 as important regulators of host disease outcomes. Specifically, both CCR9 and CXCR6 are protective against severe SARS-CoV, SARS-CoV-2, and SARS-related HKU3 virus disease in mice. This chromosome 9 multitrait locus may be important to help identify genes that regulate coronavirus disease outcomes in humans.

Animals↗
PubMed1992

Drug treatment of panic disorder. Comparative efficacy of alprazolam, imipramine, and placebo. Cross-National Collaborative Panic Study, Second Phase Investigators.

The Cross-National Collaborative Panic Study, Phase Two, compared alprazolam with imipramine and with placebo in a sample of 1168 randomly assigned subjects. The study, conducted at 12 centres, assessed clinical change over eight weeks of double-blind drug treatment. Improvement occurred with alprazolam by week 1 and 2, and with imipramine by week 4. By the end of week 8, however, the effects of the two active drugs were similar to each other, and both were superior to placebo for most outcome measures.

Adult↗
PubMed1992

Center differences and cross-national invariance in help-seeking for panic disorder. A report from the cross-national collaborative panic study.

Help-seeking behaviour for treatment of panic disorder was investigated in the sample of the Cross-National Collaborative Panic Study Second Phase. A total of 1168 patients were entered into this trial in 14 countries. Although there were significant center differences in prior treatment and utilization of health services there were also similarities. Treatment had been provided mainly by general practitioners. Drug treatment consisted mostly of prescription of classical tranquilizers and had a longer duration than treatment by psychotherapy. Patients with agoraphobic avoidance, past major depression and longer duration of illness used medical and psychiatric treatment facilities more intensely. Older and more severely disabled subjects were more frequently treated by medical health care providers and were more likely to receive psychotropic drugs. The results indicate that general practitioners carry an important load in the treatment of panic disorders but may need more information about recent development in pharmacotherapy for this condition.

Adult↗
PubMed1991

Chronology of panic and avoidance, age of onset in panic disorder, and prediction of treatment response. A report from the Cross-National Collaborative Panic Study.

The relevance of the chronology between panic disorder and avoidance behavior and of an early, medium or late onset of panic disorder was tested. Groups from the sample of the cross-national collaborative panic study (CNCPS) were compared for differences in basic characteristics and for the ability to predict treatment response. Patients who developed avoidance behavior before the full syndrome of panic disorder had less often a full agoraphobia but were not different in their response to treatment. Patients with an early onset of panic disorder suffered more often from agoraphobia. The treatment response was similar in the groups with early, medium or late onset of panic disorder. Neither the chronology between panic disorder and avoidance behavior nor the age of onset of panic disorder predicted outcome in short-term treatment with alprazolam or imipramine.

Adult↗
PubMed1989

Avoidance behaviour and major depression in panic disorder: a report from the Cross-National Collaborative Panic Study.

Avoidance behaviour and secondary major depression are both frequent in clinical samples of patients with panic disorder. Their status is unclear: indicators of severity of panic disorder or indicators of separate psychiatric disorders. Among the data of the Cross-National Collaborative Panic Study (n = 1,168) we found that especially avoidance behaviour defines more severe states of panic disorder (earlier age at onset, higher frequency of panic attacks and higher level of psychopathology); co-occurrence of major depression is less clearly associated with more severe panic disorder. The results are compatible with the DSM-III-R concepts of comorbidity of panic disorder and major depression and of subtyping panic disorder by avoidance behaviour.

Adult↗
PubMed2026

IMPROVE kidney care: perspectives from marginalised people with CKD and risk factors for CKD on access to, and experience of, kidney care services: a cross-sector collaborative exploration, employing qualitative approaches.

BACKGROUND: Access to, and experience of, chronic kidney disease (CKD) care is inequitable-with barriers to accessing quality care for marginalised groups. We conducted an exploratory study employing qualitative approaches to understand the factors that influence access to, and experience of, healthcare services for marginalised people with CKD and at risk of CKD. METHODS: An exploratory study employing qualitative approaches was conducted as a cross-sector collaboration between kidney care services and an activist, antiracist community-based research and social justice organisation (Mabadiliko Community Interest Company (CIC)). Two groups were recruited: 1) those with risk factors for CKD or early-stage CKD, and 2) people who presented late to kidney care services. Semi-structured interviews were co-designed with people with lived experience and conducted by Mabadiliko CIC. Thematic analysis was undertaken, with themes refined by participants. RESULTS: Twenty interviews were undertaken with a diverse cohort of participants. Knowledge and awareness of CKD was limited, and compounded by a lack of delivery of accessible, culturally congruent information. Significant barriers to accessing kidney care exist for marginalised people, including people who are from global majority ethnic backgrounds, Disabled people, and/or people experiencing material hardship. These barriers are compounded by interpersonal discrimination and paternalistic power dynamics within healthcare interactions. CONCLUSION: This study captures the experiences of marginalised people at different stages of their journey with CKD, in accessing and engaging with kidney care services. Participants faced a complex array of challenges, highlighting opportunities for multi-level intervention. We outline recommendations to address these issues, co-developed with participants.

chronic kidney disease↗
PubMed1992

The changing rate of major depression. Cross-national comparisons. Cross-National Collaborative Group.

OBJECTIVE: To estimate temporal trends in the rates of major depression cross-nationally. DESIGN: Nine epidemiologic surveys and three family studies. SETTING AND PARTICIPANTS: Approximately 39,000 subjects in population-based samples from nine epidemiologic surveys, and 4000 relatives from three family studies that were conducted independently but using similar methodology in the 1980s in North America, Puerto Rico, Western Europe, the Middle East, Asia, and the Pacific Rim. OUTCOME MEASURES: Age at first onset of major depression by birth cohort and time period. RESULTS: There was an increase in the cumulative lifetime rates of major depression with each successively younger birth cohort at all sites with the exception of the Hispanic samples, in whom the rates in the older cohort (1915 through 1935) were approximately equal to those of the younger cohorts. However, results of fitting statistical models that separate period and cohort effects showed an overall increase in the rates of major depression over time over all countries, although the magnitude of the increase varied by country. The average relative risk of major depression between a particular cohort and the cohort born immediately before varied between 2.6 (95% confidence interval, 1.8 to 3.7) in Florence, Italy, and 1.3 (95% confidence interval, 1.2 to 1.4) in Christchurch, New Zealand. Short-term fluctuations in the rates of major depression during specific time periods and in specific cohorts also varied by country. CONCLUSIONS: Cross-nationally, the more recent birth cohorts are at increased risk for major depression. There are, however, variations in the long- and short-term trends for major depression by country, which suggests that the rates in these countries may have been affected by differing historical, social, economic, or biological environmental events. The linking of demographic, epidemiologic, economic, and social indices by country to these changes may clarify environmental conditions that influence the rates of major depression.

Adult↗
PubMed2004

Cross institutional collaboration in assessment: a case on progress testing.

The practice of assessment is governed by an interesting paradox. On the one hand good assessment requires substantial resources which may exceed the capacity of a single institution and we have reason to doubt the quality of our in-house examinations. On the other hand, our parsimonity with regard to our resources makes us reluctant to pool efforts and share our test material. This paper reports on an initiative to share test material across different medical schools. Three medical schools in The Netherlands have successfully set up a partnership for a specific testing method: progress testing. At present, these three schools collaboratively produce high-quality test items. The jointly produced progress tests are administered concurrently by these three schools and one other school, which buys the test. The steps taken in establishing this partnership are described and results are presented to illustrate the unique sort of information that is obtained by cross-institutional assessment. In addition, plans to improve test content and procedure and to expand the partnership are outlined. Eventually, the collaboration may even extend to other test formats. This article is intended to give evidence of the feasibility and exciting potential of between school collaboration in test development and test administration. Our experiences have demonstrated that such collaboration has excellent potential to combine economic benefit with educational advantages, which exceed what is achievable by individual schools.

Cooperative Behavior↗
PubMed1994

The cross national epidemiology of obsessive compulsive disorder. The Cross National Collaborative Group.

Data on the epidemiology of psychiatric disorders from different parts of the world using similar methods and diagnostic criteria have previously not been available. This article presents data on lifetime and annual prevalence rates, age at onset, symptom profiles, and comorbidity of obsessive compulsive disorder (OCD), using DSM-III criteria, from community surveys in seven countries: the United States, Canada, Puerto Rico, Germany, Taiwan, Korea, and New Zealand. The OCD annual prevalence rates are remarkably consistent among these countries, ranging from 1.1/100 in Korea and New Zealand to 1.8/100 in Puerto Rico. The only exception is Taiwan (0.4/100), which has the lowest prevalence rates for all psychiatric disorders. The data for age at onset and comorbidity with major depression and the other anxiety disorders are also consistent among countries, but the predominance of obsessions or compulsions varies. These findings suggest the robustness of OCD as a disorder in diverse parts of the world.

Adolescent↗