Building a population-based diabetes register: an Italian experience.

PubMed

Ballotari, Paola; Chiatamone Ranieri, Sofia; Vicentini, Massimo; Caroli, Stefania; Gardini, Andrea; Rodolfi, Rossella; Crucco, Roberto; Greci, Marina; Manicardi, Valeria; Giorgi Rossi, Paolo

2014-01-01

To describe the methodology used to set up the Reggio Emilia (northern Italy) Diabetes Register. The prevalence estimates on December 31st, 2009 are also provided. The Diabetes Register covers all residents in the Reggio Emilia province. The register was created by deterministic linkage of six routinely collected data sources through a definite algorithm able to ascertain cases and to distinguish type of diabetes and model of care: Hospital Discharge, Drug Dispensation, Biochemistry Laboratory, Disease-specific Exemption, Diabetes Outpatient Clinics, and Mortality databases. Using these data, we estimated crude prevalence on December 31st, 2009 by sex, age groups, and type of diabetes. There were 25,425 ascertained prevalent cases on December 31st, 2009. Drug Dispensation and Exemption databases made the greatest contribution to prevalence. Analyzing overlapping sources, more than 80% of cases were reported by at least two sources. Crude prevalence was 4.8% and 5.9% for the whole population and for people aged 18 years and over, respectively. Males accounted for 53.6%. Type 1 diabetes accounted for 3.8% of cases, while people with Type 2 diabetes were the overriding majority (91.2%), and Diabetes Outpatient Clinics treated 75.4% of people with Type 2 diabetes. The Register is able to quantify the burden of disease, the first step in planning, implementing, and monitoring appropriate interventions. All data sources contributed to completeness and/or accuracy of the Register. Although all cases are identified by deterministic record linkage, manual revision and General Practitioner involvement are still necessary when information is insufficient or conflicting. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Abbreviated HIV counselling and testing and enhanced referral to care in Uganda: a factorial randomised controlled trial.

PubMed

Wanyenze, Rhoda K; Kamya, Moses R; Fatch, Robin; Mayanja-Kizza, Harriet; Baveewo, Steven; Szekeres, Gregory; Bangsberg, David R; Coates, Thomas; Hahn, Judith A

2013-09-01

HIV counselling and testing and linkage to care are crucial for successful HIV prevention and treatment. Abbreviated counselling could save time; however, its effect on HIV risk is uncertain and methods to improve linkage to care have not been studied. We did this factorial randomised controlled study at Mulago Hospital, Uganda. Participants were randomly assigned to abbreviated or traditional HIV counselling and testing; HIV-infected patients were randomly assigned to enhanced linkage to care or standard linkage to care. All study personnel except counsellors and the data officer were masked to study group assignment. Participants had structured interviews, given once every 3 months. We compared sexual risk behaviour by counselling strategy with a 6·5% non-inferiority margin. We used Cox proportional hazards analyses to compare HIV outcomes by linkage to care over 1 year and tested for interaction by sex. This trial is registered with ClinicalTrials.gov (NCT00648232). We enrolled 3415 participants; 1707 assigned to abbreviated counselling versus 1708 assigned to traditional. Unprotected sex with an HIV discordant or status unknown partner was similar in each group (232/823 [27·9%] vs 251/890 [28·2%], difference -0·3%, one-sided 95% CI 3·2). Loss to follow-up was lower for traditional counselling than for abbreviated counselling (adjusted hazard ratio [HR] 0·61, 95% CI 0·44-0·83). 1003 HIV-positive participants were assigned to enhanced linkage (n=504) or standard linkage to care (n=499). Linkage to care did not have a significant effect on mortality or receipt of co-trimoxazole. Time to treatment in men with CD4 cell counts of 250 cells per μL or fewer was lower for enhanced linkage versus standard linkage (adjusted HR 0·60, 95% CI 0·41-0·87) and time to HIV care was decreased among women (0·80, 0·66-0·96). Abbreviated HIV counselling and testing did not adversely affect risk behaviour. Linkage to care interventions might decrease time to enrolment in HIV care and antiretroviral treatment and thus might affect secondary HIV transmission and improve treatment outcomes. US National Institute of Mental Health. Copyright © 2013 Wanyenze et al. Open Access article distributed under the terms of CC BY. Published by .. All rights reserved.

[Linkage of large secondary and registry data sources with data of cohort studies : usage of a dual potential].

PubMed

Jacobs, Svenja; Stallmann, Christoph; Pigeot, Iris

2015-08-01

Cohort studies provide the best evidence of all epidemiological observational studies for the identification of causal relationships between risk factors and diseases. However, this design may lead to drawbacks that may affect the validity and reliability of the results. This follows in particular from systematic errors, such as selection bias or recall bias. One possibility to avoid or counteract some of these drawbacks is to link primary data from cohort studies with secondary and register data. The linkage of these data may also be used for mutual validations. Data that were previously linked with primary data within the context of cohort studies in Germany were obtained from statutory health insurances and pensions as well as data from the Federal Employment Agency and cancer registries. All these data have two features in common: First, they all cover detailed information about a large population and over a long period of time. Second, all sources are in principle able to provide data on an individual level such that an individual data linkage, e.g. with primary data, is possible. However, use and linkage of each of these data sources are restricted by several limitations. These have to be accounted for as well as numerous legal restrictions that exist in Germany to especially prevent the misuse of social data.

The Norwegian immunisation register--SYSVAK.

PubMed

Trogstad, L; Ung, G; Hagerup-Jenssen, M; Cappelen, I; Haugen, I L; Feiring, B

2012-04-19

The Norwegian immunisation register, SYSVAK, is a national electronic immunisation register. It became nationwide in 1995. The major aim was to register all vaccinations in the Childhood Immunisation Programme to ensure that all children are offered adequate vaccination according to schedule in the programme, and to secure high vaccination coverage. Notification to SYSVAK is mandatory, based on personal identification numbers. This allows follow up of individual vaccination schedules and linkage of SYSVAK data to other national health registers for information on outcome diagnoses, such as the surveillance system for communicable diseases. Information from SYSVAK is used to determine vaccine coverage in a timely manner. Coverage can be broken down to regional/local levels and used for active surveillance of vaccination coverage and decisions about interventions. During the 2009 influenza A(H1N1)pdm09 pandemic, an adaptation of SYSVAK enabled daily surveillance of vaccination coverage on national and regional levels. Currently, data from SYSVAK are used, among others, in studies on adverse events related to pandemic vaccination. Future challenges include maximising usage of collected data in surveillance and research, and continued improvement of data quality. Immunisation registers are rich sources for high quality surveillance of vaccination coverage, effectiveness, vaccine failure and adverse events, and gold mines for research.

Social Media Interventions to Promote HIV Testing, Linkage, Adherence, and Retention: Systematic Review and Meta-Analysis

PubMed Central

Gupta, Somya; Wang, Jiangtao; Hightow-Weidman, Lisa B; Muessig, Kathryn E; Tang, Weiming; Pan, Stephen; Pendse, Razia; Tucker, Joseph D

2017-01-01

Background Social media is increasingly used to deliver HIV interventions for key populations worldwide. However, little is known about the specific uses and effects of social media on human immunodeficiency virus (HIV) interventions. Objective This systematic review examines the effectiveness of social media interventions to promote HIV testing, linkage, adherence, and retention among key populations. Methods We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist and Cochrane guidelines for this review and registered it on the International Prospective Register of Systematic Reviews, PROSPERO. We systematically searched six databases and three conference websites using search terms related to HIV, social media, and key populations. We included studies where (1) the intervention was created or implemented on social media platforms, (2) study population included men who have sex with men (MSM), transgender individuals, people who inject drugs (PWID), and/or sex workers, and (3) outcomes included promoting HIV testing, linkage, adherence, and/or retention. Meta-analyses were conducted by Review Manager, version 5.3. Pooled relative risk (RR) and 95% confidence intervals were calculated by random-effects models. Results Among 981 manuscripts identified, 26 studies met the inclusion criteria. We found 18 studies from high-income countries, 8 in middle-income countries, and 0 in low-income countries. Eight were randomized controlled trials, and 18 were observational studies. All studies (n=26) included MSM; five studies also included transgender individuals. The focus of 21 studies was HIV testing, four on HIV testing and linkage to care, and one on antiretroviral therapy adherence. Social media interventions were used to do the following: build online interactive communities to encourage HIV testing/adherence (10 studies), provide HIV testing services (9 studies), disseminate HIV information (9 studies), and develop intervention materials (1 study). Of the studies providing HIV self-testing, 16% of participants requested HIV testing kits from social media platforms. Existing social media platforms such as Facebook (n=15) and the gay dating app Grindr (n=10) were used most frequently. Data from four studies show that HIV testing uptake increased after social media interventions (n=1283, RR 1.50, 95% CI 1.28-1.76). In the studies where social media interventions were participatory, HIV testing uptake was higher in the intervention arm than the comparison arm (n=1023, RR 1.64, 95% CI 1.19-2.26). Conclusions Social media interventions are effective in promoting HIV testing among MSM in many settings. Social media interventions to improve HIV services beyond HIV testing in low- and middle-income countries and among other key populations need to be considered. Trial Registration International Prospective Register of Systematic Reviews (PROSPERO): CRD42016048073; http://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42016048073 (Archived by WebCite at http://www. webcitation.org/6usLCJK3v) PMID:29175811

Cohort profile: the QSkin Sun and Health Study.

PubMed

Olsen, Catherine M; Green, Adèle C; Neale, Rachel E; Webb, Penelope M; Cicero, Rebekah A; Jackman, Lea M; O'Brien, Suzanne M; Perry, Susan L; Ranieri, Barbara A; Whiteman, David C

2012-08-01

The QSkin Sun and Health Study comprises a cohort of 43 794 men and women aged 40-69 years randomly sampled from the population of Queensland, Australia in 2011. The cohort was established to study the development of skin cancer and melanoma in the population with the highest reported incidence of these diseases in the world. At baseline, besides demographic items and general medical history, information about standard pigmentary characteristics (including hair and eye colour, freckling tendency, tanning ability and propensity to sunburn), past and recent history of sun exposure and sunburns, sun protection behaviours, use of tanning beds and history of skin cancer was collected by self-completed questionnaire. Participants have given their consent for data linkage to the universal national health insurance scheme and for linkage to cancer registries and pathology databases, thus ensuring complete ascertainment of all future skin cancer and melanoma occurrences and medical treatments and other cancer events. Linkage to these registers will occur at predetermined intervals. Approval to access QSkin data can be obtained on application to the study investigators and submission of a formal research plan that has previous approval from the human research ethics committee of the applicant's institution.

How did the recent increase in the supply of coronary operations in Finland affect socioeconomic and gender equity in their use?

PubMed Central

Hetemaa, T; Keskimaki, I; Manderbacka, K; Leyland, A; Koskinen, S

2003-01-01

Design: Register based linkage study; information on coronary procedures from the Finnish Hospital Discharge Register in 1988 and 1996 was individually linked to national population censuses in 1970–1995 to obtain patients' socioeconomic data. Data on both hospitalisations and mortality attributable to coronary heart disease obtained from similar linkage schemes were used to approximate the relative need of procedures in socioeconomic groups. Setting: Finland, 2 094 846 inhabitants in 1988 and 2 401 027 in 1996 aged 40 years and older, and Discharge Register data from all Finnish hospitals offering coronary procedures in 1988 and 1996. Main results: The overall rate of coronary revascularisations in Finland increased by about 140% for men and 250% for women from 1988 to 1996. Over the same period, socioeconomic and gender disparities in operation rates diminished, as did the influence of regional supply of procedures on the extent of these differences. However, men, and better off groups in terms of occupation, education, and family income, continued to receive more operations than women and the worse off with the same level of need. Conclusions: Although revascularisations in Finland increased 2.5-fold overall, some socioeconomic and gender inequities persisted in the use of cardiac operations relative to need. To improve equity, a further increase of resources may be needed, and practices taking socioeconomic and gender equity into account should be developed for the referral of coronary heart disease patients to hospital investigations. PMID:12594194

Copenhagen Airport Cohort: air pollution, manual baggage handling and health.

PubMed

Møller, Karina Lauenborg; Brauer, Charlotte; Mikkelsen, Sigurd; Loft, Steffen; Simonsen, Erik B; Koblauch, Henrik; Bern, Stine Hvid; Alkjær, Tine; Hertel, Ole; Becker, Thomas; Larsen, Karin Helweg; Bonde, Jens Peter; Thygesen, Lau Caspar

2017-05-06

Copenhagen Airport Cohort 1990-2012 presents a unique data source for studies of health effects of occupational exposure to air pollution (ultrafine particles) and manual baggage handling among airport employees. We describe the extent of information in the cohort and in the follow-up based on data linkage to the comprehensive Danish nationwide health registers. In the cohort, all information is linked to the personal identification number that also is used in Denmark Statistics demographic and socioeconomic databases and in the nationwide health registers. The cohort covers 69 175 men in unskilled positions. The exposed cohort includes men in unskilled jobs employed at Copenhagen Airport in the period 1990-2012 either as baggage handlers or in other outdoor work. The reference cohort includes men in unskilled jobs working in the greater Copenhagen area. The cohort includes environmental Global Positioning System (GPS) measurements in Copenhagen Airport, information on job function/task for each calendar year of employment between 1990 and 2012, exposure to air pollution at residence, average weight of baggage lifted per day and lifestyle. By linkage to registers, we retrieved socioeconomic and demographic data and data on healthcare contacts, drug subscriptions, incident cancer and mortality. The size of the cohort and the completeness of the register-based follow-up allow a more accurate assessment of the possible health risks of occupational exposure to ultrafine particles and manual baggage handling at airports than in previous studies. We plan to follow the cohort for the incidence of ischaemic heart diseases, cerebrovascular disease, lung and bladder cancer, asthma and chronic obstructive pulmonary disease, and further for associations between heavy manual baggage handling and musculoskeletal disorders. number 2012-41-0199. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Social Media Interventions to Promote HIV Testing, Linkage, Adherence, and Retention: Systematic Review and Meta-Analysis.

PubMed

Cao, Bolin; Gupta, Somya; Wang, Jiangtao; Hightow-Weidman, Lisa B; Muessig, Kathryn E; Tang, Weiming; Pan, Stephen; Pendse, Razia; Tucker, Joseph D

2017-11-24

Social media is increasingly used to deliver HIV interventions for key populations worldwide. However, little is known about the specific uses and effects of social media on human immunodeficiency virus (HIV) interventions. This systematic review examines the effectiveness of social media interventions to promote HIV testing, linkage, adherence, and retention among key populations. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist and Cochrane guidelines for this review and registered it on the International Prospective Register of Systematic Reviews, PROSPERO. We systematically searched six databases and three conference websites using search terms related to HIV, social media, and key populations. We included studies where (1) the intervention was created or implemented on social media platforms, (2) study population included men who have sex with men (MSM), transgender individuals, people who inject drugs (PWID), and/or sex workers, and (3) outcomes included promoting HIV testing, linkage, adherence, and/or retention. Meta-analyses were conducted by Review Manager, version 5.3. Pooled relative risk (RR) and 95% confidence intervals were calculated by random-effects models. Among 981 manuscripts identified, 26 studies met the inclusion criteria. We found 18 studies from high-income countries, 8 in middle-income countries, and 0 in low-income countries. Eight were randomized controlled trials, and 18 were observational studies. All studies (n=26) included MSM; five studies also included transgender individuals. The focus of 21 studies was HIV testing, four on HIV testing and linkage to care, and one on antiretroviral therapy adherence. Social media interventions were used to do the following: build online interactive communities to encourage HIV testing/adherence (10 studies), provide HIV testing services (9 studies), disseminate HIV information (9 studies), and develop intervention materials (1 study). Of the studies providing HIV self-testing, 16% of participants requested HIV testing kits from social media platforms. Existing social media platforms such as Facebook (n=15) and the gay dating app Grindr (n=10) were used most frequently. Data from four studies show that HIV testing uptake increased after social media interventions (n=1283, RR 1.50, 95% CI 1.28-1.76). In the studies where social media interventions were participatory, HIV testing uptake was higher in the intervention arm than the comparison arm (n=1023, RR 1.64, 95% CI 1.19-2.26). Social media interventions are effective in promoting HIV testing among MSM in many settings. Social media interventions to improve HIV services beyond HIV testing in low- and middle-income countries and among other key populations need to be considered. International Prospective Register of Systematic Reviews (PROSPERO): CRD42016048073; http://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42016048073 (Archived by WebCite at http://www. webcitation.org/6usLCJK3v). ©Bolin Cao, Somya Gupta, Jiangtao Wang, Lisa B Hightow-Weidman, Kathryn E Muessig, Weiming Tang, Stephen Pan, Razia Pendse, Joseph D. Tucker. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 24.11.2017.

Interventions to increase testing, linkage to care and treatment of hepatitis C virus (HCV) infection among people in prisons: A systematic review.

PubMed

Kronfli, Nadine; Linthwaite, Blake; Kouyoumdjian, Fiona; Klein, Marina B; Lebouché, Bertrand; Sebastiani, Giada; Cox, Joseph

2018-04-28

While the burden of chronic hepatitis C virus (HCV) infection is significantly higher among people in prisons compared to the general population, testing and treatment uptake remain suboptimal. The aim of this systematic review was to synthesize evidence on the effectiveness of interventions to increase HCV testing, linkage to care and treatment uptake among people in prisons. We searched Medline (Ovid 1996-present), Embase (Ovid 1996-present), and the Cochrane Central Register of Controlled Trials for English language articles published between January 2007 and November 2017. Studies evaluating interventions to enhance HCV testing, linkage to care and treatment uptake for people in prison were included. Two independent reviewers evaluated articles selected for full-text review. Disagreements were resolved by consensus. A total of 475 unique articles were identified, 29 were eligible for full text review, and six studies were included. All but one study was conducted in the pre-direct-acting antiviral (DAA) era; no studies were conducted in low- or middle-income countries. Of the six studies, all but one focused on testing. Only two were randomised controlled trials; the remaining were single arm studies. Interventions to enhance HCV testing in prison settings included combination risk-based and birth-cohort screening strategies, on-site nurse-led opt-in screening clinics with pre-test counselling and education, and systematic dried blood spot testing. All interventions increased HCV testing, but risk of study bias was high in all studies. Interventions to enhance linkage to care included facilitated referral for HCV assessment and scheduling of specialist appointments; however, risk of study bias was critical. There is a lack of recent data on interventions to improve the HCV care cascade in people in prisons. With the introduction of short-course, well-tolerated DAAs, rigorous controlled studies evaluating interventions to improve testing, linkage and treatment uptake for people in prison are necessary. Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.

Comparative analysis of premature mortality among urban immigrants in Bremen, Germany: a retrospective register-based linkage study.

PubMed

Makarova, Nataliya; Brand, Tilman; Brünings-Kuppe, Claudia; Pohlabeln, Hermann; Luttmann, Sabine

2016-03-21

The main objective of this study was to explore differences in mortality patterns among two large immigrant groups in Germany: one from Turkey and the other from the former Soviet Union (FSU). To this end, we investigated indicators of premature mortality. This study was conducted as a retrospective population-based study based on mortality register linkage. Using mortality data for the period 2004-2010, we calculated age-standardised death rates (SDR) and standardised mortality ratios (SMR) for premature deaths (

Comparative analysis of premature mortality among urban immigrants in Bremen, Germany: a retrospective register-based linkage study

PubMed Central

Makarova, Nataliya; Brand, Tilman; Brünings-Kuppe, Claudia; Pohlabeln, Hermann; Luttmann, Sabine

2016-01-01

Objectives The main objective of this study was to explore differences in mortality patterns among two large immigrant groups in Germany: one from Turkey and the other from the former Soviet Union (FSU). To this end, we investigated indicators of premature mortality. Design This study was conducted as a retrospective population-based study based on mortality register linkage. Using mortality data for the period 2004–2010, we calculated age-standardised death rates (SDR) and standardised mortality ratios (SMR) for premature deaths (

Odense Pharmacoepidemiological Database: A Review of Use and Content.

PubMed

Hallas, Jesper; Hellfritzsch, Maja; Rix, Morten; Olesen, Morten; Reilev, Mette; Pottegård, Anton

2017-05-01

The Odense University Pharmacoepidemiological Database (OPED) is a prescription database established in 1990 by the University of Southern Denmark, covering reimbursed prescriptions from the county of Funen in Denmark and the region of Southern Denmark (1.2 million inhabitants). It is still active and thereby has more than 25 years of continuous coverage. In this MiniReview, we review its history, content, quality, coverage, governance and some of its uses. OPED's data include the Danish Civil Registration Number (CPR), which enables unambiguous linkage with virtually all other health-related registers in Denmark. Among its research uses, we review record linkage studies of drug effects, advanced drug utilization studies, some examples of method development and use of OPED as sampling frame to recruit patients for field studies or clinical trials. With the advent of other, more comprehensive sources of prescription data in Denmark, OPED may still play a role as in certain data-intensive regional studies. © 2017 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Trauma registry record linkage: methodological approach to benefit from complementary data using the example of the German Pelvic Injury Register and the TraumaRegister DGU®

PubMed Central

2013-01-01

Background In Germany, hospitals can deliver data from patients with pelvic fractures selectively or twofold to two different trauma registries, i.e. the German Pelvic Injury Register (PIR) and the TraumaRegister DGU® (TR). Both registers are anonymous and differ in composition and content. We describe the methodological approach of linking these registries and reidentifying twofold documented patients. The aim of the approach is to create an intersection set that benefit from complementary data of each registry, respectively. Furthermore, the concordance of data entry of some clinical variables entered in both registries was evaluated. Methods PIR (4,323 patients) and TR (34,134 patients) data from 2004-2009 were linked together by using a specific match code including code of the trauma department, dates of admission and discharge, patient’s age, and sex. Data entry concordance was evaluated using haemoglobin and blood pressure levels at emergency department arrival, Injury Severity Score (ISS), and mortality. Results Altogether, 420 patients were identified as documented in both data sets. Linkage rates for the intersection set were 15.7% for PIR and 44.4% for TR. Initial fluid management for different Tile/OTA types of pelvic ring fractures and the patient’s posttraumatic course, including intensive care unit data, were now available for the PIR population. TR is benefiting from clinical use of the Tile/OTA classification and from correlation with the distinct entity “complex pelvic injury.” Data entry verification showed high concordance for the ISS and mortality, whereas initial haemoglobin and blood pressure data showed significant differences, reflecting inconsistency at the data entry level. Conclusions Individually, the PIR and the TR reflect a valid source for documenting injured patients, although the data reflect the emphasis of the particular registry. Linking the two registries enabled new insights into care of multiple-trauma patients with pelvic fractures even when linkage rates were poor. Future considerations and development of the registries should be done in close bilateral consultation with the aim of benefiting from complementary data and improving data concordance. It is also conceivable to integrate individual modules, e.g. a pelvic fracture module, into the TR likewise a modular system in the future. PMID:23496832

Rest break organization in geriatric care and turnover: a multimethod cross-sectional study.

PubMed

Wendsche, Johannes; Hacker, Winfried; Wegge, Jürgen; Schrod, Nadine; Roitzsch, Katharina; Tomaschek, Anne; Kliegel, Matthias

2014-09-01

Various determinants of nurses' work motivation and turnover behavior have been examined in previous studies. In this research, we extend this work by investigating the impact of care setting (nursing homes vs. home care services) and the important role of rest break organization. We aimed to identify direct and indirect linkages between geriatric care setting, rest break organization, and registered nurses' turnover assessed over a period of one year. We designed a multimethod cross-sectional study. 80 nursing units (n=45 nursing homes, n=35 home care) in 51 German geriatric care services employing 597 registered nurses. We gathered documentary, interview, and observational data about the organization of rest breaks, registered nurses' turnover, and additional organizational characteristics (type of ownership, location, nursing staff, clients, and client-to-staff-ratio). The findings show that the rest break system in geriatric nursing home units is more regularly as well as collectively organized and causes less unauthorized rest breaks than in home care units. Moreover, the feasibility of collective rest breaks was, as predicted, negatively associated with registered nurses' turnover and affected indirectly the relation between care setting and registered nurses' turnover. Care setting, however, had no direct impact on turnover. Furthermore, registered nurses' turnover was higher in for-profit care units than in public or non-profit units. This study reveals significant differences in rest break organization as a function of geriatric care setting and highlights the role of collective rest breaks for nursing staff retention. Our study underlines the integration of organizational context variables and features of rest break organization for the analysis of nursing turnover. Copyright © 2014 Elsevier Ltd. All rights reserved.

Australian immunisation registers: established foundations and opportunities for improvement.

PubMed

Chin, L K; Crawford, N W; Rowles, G; Buttery, J P

2012-04-19

The National Immunisation Program Schedule in Australia is formulated and funded nationally under the population-wide Medicare system. The policy is implemented by the eight state and territory jurisdictions. The national immunisation registers consist of the Australian Childhood Immunisation Register (ACIR), and, more recently, the National Human Papillomavirus (HPV) Vaccination Program Register. Moreover, a variety of jurisdiction-based registers and primary care practice software systems exist, which interact with the national registers. General practitioners can obtain reports listing patients under seven years attending their practice and recorded as 'not fully immunised', and immunisation coverage rates for their practice linked to government incentives through Medicare. A 2011 report documents national coverage of 91.8% fully immunised at 12 months, and 92.6% at 24 months. The HPV register provides information on vaccination coverage with the potential to link with a register of cervical cancer screening results. Limitations of current national register include inability to easily access immunisation histories beyond seven years of age, and issues of underreporting and timeliness, which impact significantly the immunisation coverage estimates. The linkage of these registers with healthcare outcome data will further enhance public health outcomes by enabling rapid, population-level vaccine safety and effectiveness investigations in a nation with a track record as an 'early adopter' of new childhood vaccines.

Using probabilistic record linkage methods to identify Australian Indigenous women on the Queensland Pap Smear Register: the National Indigenous Cervical Screening Project

PubMed Central

Diaz, Abbey; Baade, Peter; Garvey, Gail; Cunningham, Joan; Brotherton, Julia M L; Canfell, Karen; Valery, Patricia C; O'Connell, Dianne L; Taylor, Catherine; Moore, Suzanne P; Condon, John R

2016-01-01

Objective To evaluate the feasibility and reliability of record linkage of existing population-based data sets to determine Indigenous status among women receiving Pap smears. This method may allow for the first ever population measure of Australian Indigenous women's cervical screening participation rates. Setting/participants A linked data set of women aged 20–69 in the Queensland Pap Smear Register (PSR; 1999–2011) and Queensland Cancer Registry (QCR; 1997–2010) formed the Initial Study Cohort. Two extracts (1995–2011) were taken from Queensland public hospitals data (Queensland Hospital Admitted Patient Data Collection, QHAPDC) for women, aged 20–69, who had ever been identified as Indigenous (extract 1) and had a diagnosis or procedure code relating to cervical cancer (extract 2). The Initial Study Cohort was linked to extract 1, and women with cervical cancer in the initial cohort were linked to extract 2. Outcome measures The proportion of women in the Initial Cohort who linked with the extracts (true -pairs) is reported, as well as the proportion of potential pairs that required clerical review. After assigning Indigenous status from QHAPDC to the PSR, the proportion of women identified as Indigenous was calculated using 4 algorithms, and compared. Results There were 28 872 women (2.1%) from the Initial Study Cohort who matched to an ever Indigenous record in extract 1 (n=76 831). Women with cervical cancer in the Initial Study Cohort linked to 1385 (71%) records in extract 2. The proportion of Indigenous women ranged from 2.00% to 2.08% when using different algorithms to define Indigenous status. The Final Study Cohort included 1 372 823 women (PSR n=1 374 401; QCR n=1955), and 5 062 118 records. Conclusions Indigenous status in Queensland cervical screening data was successfully ascertained through record linkage, allowing for the crucial assessment of the current cervical screening programme for Indigenous women. Our study highlights the need to include Indigenous status on Pap smear request and report forms in any renewed and redesigned cervical screening programme in Australia. PMID:26873047

[The effectiveness of compensation system for mesotheliomas due to occupational exposure to asbestos and determinants for requests and awards: an evaluation based on record-linkage between the Veneto Mesothelioma Register and the claims and compensations recorded by the National Insurance Institute (INAIL)].

PubMed

Merler, Enzo; Bressan, Vittoria; Bilato, Anna Maria; Marinaccio, Alessandro

2011-01-01

To determine the rate of requests for compensation and of compensations awarded for mesothelioma cases due to occupational exposure to asbestos; to identify factors that may influence the outcome; to provide an appreciation of the amount of compensation. Record-linkage study at individual level between the new cases of mesothelioma occurred among the residents of the Veneto Region (Northern Italy) between 1999- 2007 and the file of the Insurance Institute, with individual data on all claims and compensations. Adjusted logistic regression models were used to estimated the association between submitting claims and obtaining an award and socio-demographic and other characteristics. 349 on 499 mesotheliomas considered to be due to occupational exposure to asbestos submitted a claim (70% of those of occupational origin) and 72%of claims were accepted. The welfare system covers only 35%of mesothelioma occurred. The probability of submitting and obtaining a claim was associated with gender, cancer site, age at diagnosis, vital status, and residence or local office in charge of the evaluation. A strong discrimination against women is observed. If exposure to asbestos at work was due to a direct manipulation of asbestos, claims were more easily accepted.As a consequence,mesothelioma occurred among construction workers, the occupational activity at the origin of the largest number of occurring mesotheliomas, are more frequently rejected.When submitted by a relative, the lag between a request for compensation and the decision is on average of about two years. This is the first study in Italy using a record-linkage method and was made possible thanks to a population based mesothelioma Register and the availability of memorized information of the Insurance Institute.The welfare system shown clear limitations and there is the need for more appropriate strategies.

FT-IR spectrum of grape seed oil and quantum models of fatty acids triglycerides

NASA Astrophysics Data System (ADS)

Berezin, K. V.; Antonova, E. M.; Shagautdinova, I. T.; Chernavina, M. L.; Dvoretskiy, K. N.; Grechukhina, O. N.; Vasilyeva, L. M.; Rybakov, A. V.; Likhter, A. M.

2018-04-01

FT-IR spectra of grape seed oil and glycerol were registered in the 650-4000 cm-1 range. Molecular models of glycerol and some fatty acids that compose the oil under study - linoleic, oleic, palmitic and stearic acids - as well as their triglycerides were developed within B3LYP/6-31G(d) density functional model. A vibrating FT-IR spectrum of grape seed oil was modeled on the basis of calculated values of vibrating wave numbers and IR intensities of the fatty acids triglycerides and with regard to their percentage. Triglyceride spectral bands that were formed by glycerol linkage vibrations were revealed. It was identified that triglycerol linkage has a small impact on the structure of fatty acids and, consequently, on vibrating wave numbers. The conducted molecular modeling became a basis for theoretical interpretation on 10 experimentally observed absorption bands in FT-IR spectrum of grape seed oil.

Work environment as predictor of long-term sickness absence: linkage of self-reported DWECS data with the DREAM register.

PubMed

Burr, Hermann; Pedersen, Jacob; Hansen, Jørgen Vinsløv

2011-07-01

The present overview discusses ten papers dealing with four research topics using self-reported work environment in the Danish Work Environment Cohort Study (DWECS) linked with register data on long-term sickness absence (LTSA) in the Danish Register for Evaluation of Marginalisation (DREAM). Research relied on self-reported data among 3000-5000 employees linked with registered LTSA data. Analyses were performed with Cox regression models. Risk groups: Kindergarten teachers and daycare workers were at high risk for LTSA. Mainly physical exposures but also psychosocial factors were risk factors for LTSA. Attributable fractions: A quarter of LTSA spells could be attributed to the physical work environment. Most of the association between social class and LTSA was explained by physical work environment and smoking. Mechanisms: Depressive symptoms, severe pain in hands, and low back and pain intensity were risk factors for LTSA. Only in work sites with traditional leadership did health problems predict LTSA. The linking of DWECS with DREAM has made it possible to estimate the importance of work environment factors for LTSA. Future research should deal with possible risk factors such as health problems and organisational factors.

Regeneration of Russian wildrye foundation seed and its effect on genetic diversity and linkage disequilibrium

USDA-ARS?s Scientific Manuscript database

Maintaining the genetic integrity and performance of released cultivars over multiple generations of seed increase continues to be of concern in cross-pollinating grasses. It is not an uncommon practice when seed supplies are low or foundation seed is not available to designate registered seed as f...

Effect of Point-of-Care Diagnostics on Maternal Outcomes in Human Immunodeficiency Virus–Infected Women: Systematic Review and Meta-analysis

PubMed Central

Mashamba-Thompson, Tivani P; Morgan, Rebecca L; Sartorius, Benn; Dennis, Brittany; Drain, Paul K; Thabane, Lehana

2017-01-01

Introduction The World Health Organization advocates for increased accessibility of HIV-related point-of-care (POC) diagnostics in settings that lack laboratory infrastructure. The aim of this study is to assess the impact of POC diagnostics on maternal health outcomes in HIV-infected women. Methods A systematic literature review used multiple data sources as follows: Cochrane Infectious Disease Group Specialized Register; Cochrane Central Register of Control Trials, published in The Cochrane Library; PubMed; EBSCOhost and LILACS from January 2000 to October 2015. References of included studies were hand searched. Randomized controlled trials (RCTs) and observational studies examining health outcomes of HIV-infected women were eligible for inclusion in this review. The Cochrane Risk of Bias tool was used for bias assessment of the included studies. PRISMA guidelines were used for reporting. Results Of the 695 studies identified, six retrievable studies (five cross-sectional studies and one case control study) met the inclusion criteria and were included in this study. These studies examined a total of 167 HIV-infected women in different study settings. No studies reported evidence of CD4 count, viral load and TB, and the syphilis POC test impact on HIV-infected women was not found by this study. Included studies reported the impact of various HIV rapid tests across the following five maternal outcomes: timely receipt of results with pooled effect size (ES) = 1.00 (95% confidence interval [CI]: (0.98; 1.02); enabling partner testing, ES = 0.95 (0.85; 1.04); prevention of mother-to-child transmission of HIV, ES = 0.86 (0.79; 0.93); linkage to antiretroviral treatment (ART), ES = 0.76 (0.69; 0.84); and linkage to HIV care, ES = 0.50 (0.18; 0.82). No studies reported evidence of the impact of POC testing on maternal mortality or maternal and child morbidity of HIV-infected women. Conclusions The review provides an international overview of the impact of HIV POC diagnostics on maternal outcomes in HIV-infected women, showing the evidence that the HIV POC test is significantly associated with decreased mother-to-child transmission of HIV and increased linkage to ART and HIV care for HIV-infected women. It also revealed a gap in the literature aimed at assessing the impact of POC diagnostics on maternal morbidity and mortality in HIV-infected women. PMID:29242711

Association between registered nurse staffing and management outcomes of patients with type 2 diabetes within primary care: a cross-sectional linkage study

PubMed Central

Lukewich, Julia; Edge, Dana S.; VanDenKerkhof, Elizabeth; Williamson, Tyler; Tranmer, Joan

2016-01-01

Background: As the organization of primary care continues to evolve toward more interdisciplinary team structures, demonstrating effectiveness of care delivery is becoming important, particularly for nonphysician providers. Nurses are the most common nonphysician provider within primary care. The purpose of this study was to examine the relation between primary care delivery models that incorporate registered nurses and clinical outcomes of patients with type 2 diabetes. Methods: Patient data from the Canadian Primary Care Sentinel Surveillance Network were matched with survey data from 15 Family Health Team practices in southeastern Ontario. Included patients were adults with type 2 diabetes mellitus who had at least 1 primary care encounter at a Family Health Team practice that completed the organizational survey between Apr. 1, 2013, and Mar. 31, 2014. The clinical outcomes explored included hemoglobin A1c, fasting plasma glucose, blood pressure, low-density lipoprotein cholesterol and urine albumin:creatinine ratio. Results: Of the 15 practices, 13 (86.7%) had at least 1 registered nurse. The presence of 1 or more registered nurses in the practice was associated with increased odds of patients' having their hemoglobin A1c, fasting plasma glucose, blood pressure and low-density lipoprotein cholesterol values meet recommended targets. Practices with the lowest ratios of patients with diabetes to registered nurse had a significantly greater proportion of patients with hemoglobin A1c and fasting plasma glucose values on target than did practices with the highest ratios of patients to registered nurse (p < 0.01 and p = 0.03, respectively). Interpretation: The findings suggest that registered nurse staffing within primary care practice teams contributes to better diabetic care, as measured by diabetes management indicators. This study sets the groundwork for further exploration of nursing and organizational contributions to patient care in the primary care setting. PMID:27398372

Burnout as a predictor of all-cause mortality among industrial employees: a 10-year prospective register-linkage study.

PubMed

Ahola, Kirsi; Väänänen, Ari; Koskinen, Aki; Kouvonen, Anne; Shirom, Arie

2010-07-01

Burnout, a psychological consequence of prolonged work stress, has been shown to coexist with physical and mental disorders. The aim of this study was to investigate whether burnout is related to all-cause mortality among employees. In 1996, of 15,466 Finnish forest industry employees, 9705 participated in the 'Still Working' study and 8371 were subsequently identified from the National Population Register. Those who had been treated in a hospital for the most common causes of death prior to the assessment of burnout were excluded on the basis of the Hospital Discharge Register, resulting in a final study population of 7396 people. Burnout was measured using the Maslach Burnout Inventory-General Survey. Dates of death from 1996 to 2006 were extracted from the National Mortality Register. Mortality was predicted with Cox hazard regression models, controlling for baseline sociodemographic factors and register-based health status according to entitled medical reimbursement and prescribed medication for mental health problems, cardiac risk factors, and pain problems. During the 10-year 10-month follow-up, a total of 199 employees had died. The risk of mortality per one-unit increase in burnout was 35% higher (95% CI 1.07-1.71) for total score and 26% higher (0.99-1.60) for exhaustion, 29% higher for cynicism (1.03-1.62), and 22% higher for diminished professional efficacy (0.96-1.55) in participants who had been under 45 at baseline. After adjustments, only the associations regarding burnout and exhaustion were statistically significant. Burnout was not related to mortality among the older employees. Burnout, especially work-related exhaustion, may be a risk for overall survival. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Use of linkage to improve the completeness of the SIM and SINASC in the Brazilian capitals

PubMed Central

Maia, Lívia Teixeira de Souza; de Souza, Wayner Vieira; Mendes, Antonio da Cruz Gouveia; da Silva, Aline Galdino Soares

2017-01-01

ABSTRACT OBJECTIVE To analyze the contribution of linkage between databases of live births and infant mortality to improve the completeness of the variables common to the Mortality Information System (SIM) and the Live Birth Information System (SINASC) in Brazilian capitals in 2012. METHODS We studied 9,001 deaths of children under one year registered in the SIM in 2012 and 1,424,691 live births present in the SINASC in 2011 and 2012. The databases were related with linkage in two steps – deterministic and probabilistic. We calculated the percentage of incompleteness of the variables common to the SIM and SINASC before and after using the technique. RESULTS We could relate 90.8% of the deaths to their respective declarations of live birth, most of them paired deterministically. We found a higher percentage of pairs in Porto Alegre, Curitiba, and Campo Grande. In the capitals of the North region, the average of pairs was 84.2%; in the South region, this result reached 97.9%. The 11 variables common to the SIM and SINASC had 11,278 incomplete fields cumulatively, and we could recover 91.4% of the data after linkage. Before linkage, five variables presented excellent completeness in the SINASC in all Brazilian capitals, but only one variable had the same status in the SIM. After applying this technique, all 11 variables of the SINASC became excellent, while this occurred in seven variables of the SIM. The city of birth was significantly associated with the death component in the quality of the information. CONCLUSIONS Despite advances in the coverage and quality of the SIM and SINASC, problems in the completeness of the variables can still be identified, especially in the SIM. In this perspective, linkage can be used to qualify important information for the analysis of infant mortality. PMID:29211201

Acceptability and perceived barriers and facilitators to creating a national research register to enable ’direct to patient’ enrolment into research: the Scottish Health Research Register (SHARE)

PubMed Central

2013-01-01

Background Difficulties with recruitment pose a major, increasingly recognised challenge to the viability of research. We sought to explore whether a register of volunteers interested in research participation, with data linkage to electronic health records to identify suitable research participants, would prove acceptable to healthcare staff, patients and researchers. Methods We undertook a qualitative study in which a maximum variation sampling approach was adopted. Focus groups and interviews were conducted with patients, general practitioners (GP), practice managers and health service researchers in two Scottish health boards. Analysis was primarily thematic to identify a range of issues and concerns for all stakeholder groups. Results The concept of a national research register was, in general, acceptable to all stakeholder groups and was widely regarded as beneficial for research and for society. Patients, however, highlighted a number of conditions which should be met in the design of a register to expedite confidence and facilitate recruitment. They also gave their perceptions on how a register should operate and be promoted, favouring a range of media. GPs and practice managers were primarily concerned with the security and confidentiality of patient data and the impact a register may have on their workload. Researchers were supportive of the initiative seeing advantages in more rapid access to a wider pool of patients. They did raise concerns that GPs may be able to block access to personal patient data held in general practice clinical systems and that the register may not be representative of the whole population. Conclusions This work suggests that patients, healthcare staff and researchers have a favourable view of the potential benefits of a national register to identify people who are potentially eligible and willing to participate in health related research. It has highlighted a number of issues for the developers to incorporate in the design of research registers. PMID:24139174

Acceptability and perceived barriers and facilitators to creating a national research register to enable 'direct to patient' enrolment into research: the Scottish Health Research Register (SHARE).

PubMed

Grant, Aileen; Ure, Jenny; Nicolson, Donald J; Hanley, Janet; Sheikh, Aziz; McKinstry, Brian; Sullivan, Frank

2013-10-18

Difficulties with recruitment pose a major, increasingly recognised challenge to the viability of research. We sought to explore whether a register of volunteers interested in research participation, with data linkage to electronic health records to identify suitable research participants, would prove acceptable to healthcare staff, patients and researchers. We undertook a qualitative study in which a maximum variation sampling approach was adopted. Focus groups and interviews were conducted with patients, general practitioners (GP), practice managers and health service researchers in two Scottish health boards. Analysis was primarily thematic to identify a range of issues and concerns for all stakeholder groups. The concept of a national research register was, in general, acceptable to all stakeholder groups and was widely regarded as beneficial for research and for society. Patients, however, highlighted a number of conditions which should be met in the design of a register to expedite confidence and facilitate recruitment. They also gave their perceptions on how a register should operate and be promoted, favouring a range of media. GPs and practice managers were primarily concerned with the security and confidentiality of patient data and the impact a register may have on their workload. Researchers were supportive of the initiative seeing advantages in more rapid access to a wider pool of patients. They did raise concerns that GPs may be able to block access to personal patient data held in general practice clinical systems and that the register may not be representative of the whole population. This work suggests that patients, healthcare staff and researchers have a favourable view of the potential benefits of a national register to identify people who are potentially eligible and willing to participate in health related research. It has highlighted a number of issues for the developers to incorporate in the design of research registers.

The International Baccalaureate and a Framework for Class Consciousness: The Potential Outcomes of a "Class-for-Itself"

ERIC Educational Resources Information Center

Bunnell, Tristan

2010-01-01

The International Baccalaureate (IB) examination system in early 2010 was on offer in 2700 schools in 139 countries. Since 1999, the Geneva-registered IB has created a platform for image consolidation, product standardization, and technological linkage. Out of this has emerged a globally branded "IB World", educating the "IB Learner", using an…

Using probabilistic record linkage methods to identify Australian Indigenous women on the Queensland Pap Smear Register: the National Indigenous Cervical Screening Project.

PubMed

Whop, Lisa J; Diaz, Abbey; Baade, Peter; Garvey, Gail; Cunningham, Joan; Brotherton, Julia M L; Canfell, Karen; Valery, Patricia C; O'Connell, Dianne L; Taylor, Catherine; Moore, Suzanne P; Condon, John R

2016-02-12

To evaluate the feasibility and reliability of record linkage of existing population-based data sets to determine Indigenous status among women receiving Pap smears. This method may allow for the first ever population measure of Australian Indigenous women's cervical screening participation rates. A linked data set of women aged 20-69 in the Queensland Pap Smear Register (PSR; 1999-2011) and Queensland Cancer Registry (QCR; 1997-2010) formed the Initial Study Cohort. Two extracts (1995-2011) were taken from Queensland public hospitals data (Queensland Hospital Admitted Patient Data Collection, QHAPDC) for women, aged 20-69, who had ever been identified as Indigenous (extract 1) and had a diagnosis or procedure code relating to cervical cancer (extract 2). The Initial Study Cohort was linked to extract 1, and women with cervical cancer in the initial cohort were linked to extract 2. The proportion of women in the Initial Cohort who linked with the extracts (true -pairs) is reported, as well as the proportion of potential pairs that required clerical review. After assigning Indigenous status from QHAPDC to the PSR, the proportion of women identified as Indigenous was calculated using 4 algorithms, and compared. There were 28,872 women (2.1%) from the Initial Study Cohort who matched to an ever Indigenous record in extract 1 (n=76,831). Women with cervical cancer in the Initial Study Cohort linked to 1385 (71%) records in extract 2. The proportion of Indigenous women ranged from 2.00% to 2.08% when using different algorithms to define Indigenous status. The Final Study Cohort included 1,372,823 women (PSR n=1,374,401; QCR n=1955), and 5,062,118 records. Indigenous status in Queensland cervical screening data was successfully ascertained through record linkage, allowing for the crucial assessment of the current cervical screening programme for Indigenous women. Our study highlights the need to include Indigenous status on Pap smear request and report forms in any renewed and redesigned cervical screening programme in Australia. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

A Disease Register for ME/CFS: Report of a Pilot Study.

PubMed

Pheby, Derek; Lacerda, Eliana; Nacul, Luis; Drachler, Maria de Lourdes; Campion, Peter; Howe, Amanda; Poland, Fiona; Curran, Monica; Featherstone, Valerie; Fayyaz, Shagufta; Sakellariou, Dikaios; Leite, José Carlos de Carvalho

2011-05-09

The ME/CFS Disease Register is one of six subprojects within the National ME/CFS Observatory, a research programme funded by the Big Lottery Fund and sponsored by Action for ME. A pilot study in East Anglia, East Yorkshire, and London aimed to address the problem of identifying representative groups of subjects for research, in order to be able to draw conclusions applicable to the whole ME/CFS population.While not aiming for comprehensive population coverage, this pilot register sought to recruit participants with ME/CFS in an unbiased way from a large population base. Those recruited are constituting a cohort for long-term follow-up to shed light on prognosis, and a sampling frame for other studies. Patients with unidentified chronic fatigue were identified in GP databases using a READ-code based algorithm, and conformity to certain case definitions for ME/CFS determined. 29 practices, covering a population aged 18 to 64 of 143,153, participated.510 patients with unexplained chronic fatigue were identified. 265 of these conformed to one or more case definitions. 216 were invited to join the register; 160 agreed. 96.9% of participants conformed to the CDC 1994 (Fukuda) definition; the Canadian definition defined more precisely a subset of these. The addition of an epidemiological case definition increased case ascertainment by approximately 4%. A small-scale study in a specialist referral service in East Anglia was also undertaken.There was little difference in pattern of conformity to case definitions, age or sex among disease register participants compared with subjects in a parallel epidemiological study who declined to participate.One-year follow-up of 50 subjects showed little change in pain or fatigue scores. There were some changes in conformity to case definitions. Objective evaluation indicated that the aim of recruiting participants with ME/CFS to a Disease Register had been fulfilled, and confirmed the feasibility of our approach to case identification, data processing, transmission, storage, and analysis. Future developments should include expansion of the ME/CFS Register and its linkage to a tissue sample bank and post mortem tissue archive, to facilitate support for further research studies.

Comorbidities treated in primary care in children with chronic fatigue syndrome / myalgic encephalomyelitis: A nationwide registry linkage study from Norway.

PubMed

Bakken, Inger J; Tveito, Kari; Aaberg, Kari M; Ghaderi, Sara; Gunnes, Nina; Trogstad, Lill; Magnus, Per; Stoltenberg, Camilla; Håberg, Siri E

2016-09-02

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a complex condition. Causal factors are not established, although underlying psychological or immunological susceptibility has been proposed. We studied primary care diagnoses for children with CFS/ME, with children with another hospital diagnosis (type 1 diabetes mellitus [T1DM]) and the general child population as comparison groups. All Norwegian children born 1992-2012 constituted the study sample. Children with CFS/ME (n = 1670) or T1DM (n = 4937) were identified in the Norwegian Patient Register (NPR) (2008-2014). Children without either diagnosis constituted the general child population comparison group (n = 1337508). We obtained information on primary care diagnoses from the Norwegian Directorate of Health. For each primary care diagnosis, the proportion and 99 % confidence interval (CI) within the three groups was calculated, adjusted for sex and age by direct standardization. Children with CFS/ME were more often registered with a primary care diagnosis of weakness/general tiredness (89.9 % [99 % CI 88.0 to 91.8 %]) than children in either comparison group (T1DM: 14.5 % [99 % CI: 13.1 to 16.0 %], general child population: 11.1 % [99 % CI: 11.0 to 11.2 %]). Also, depressive disorder and anxiety disorder were more common in the CFS/ME group, as were migraine, muscle pain, and infections. In the 2 year period prior to the diagnoses, infectious mononucleosis was registered for 11.1 % (99 % CI 9.1 to 13.1 %) of children with CFS/ME and for 0.5 % (99 % CI (0.2 to 0.8 %) of children with T1DM. Of children with CFS/ME, 74.6 % (1292/1670) were registered with a prior primary care diagnosis of weakness / general tiredness. The time span from the first primary care diagnosis of weakness / general tiredness to the specialist health care diagnosis of CFS/ME was 1 year or longer for 47.8 %. This large nationwide registry linkage study confirms that the clinical picture in CFS/ME is complex. Children with CFS/ME were frequently diagnosed with infections, supporting the hypothesis that infections may be involved in the causal pathway. The long time span often observed from the first diagnosis of weakness / general tiredness to the diagnosis of CFS/ME might indicate that the treatment of these patients is sometimes not optimal.

Enrollment in HIV Care Two Years after HIV Diagnosis in the Kingdom of Swaziland: An Evaluation of a National Program of New Linkage Procedures.

PubMed

MacKellar, Duncan A; Williams, Daniel; Storer, Nosipho; Okello, Velephi; Azih, Charles; Drummond, Jennifer; Nuwagaba-Biribonwoha, Harriet; Preko, Peter; Morgan, Rebecca L; Dlamini, Makhosazana; Byrd, Johnita; Agolory, Simon; Baughman, Andrew L; McNairy, Margaret L; Sahabo, Ruben; Ehrenkranz, Peter

2016-01-01

To improve early enrollment in HIV care, the Swaziland Ministry of Health implemented new linkage procedures for persons HIV diagnosed during the Soka Uncobe male circumcision campaign (SOKA, 2011-2012) and the Swaziland HIV Incidence Measurement Survey (SHIMS, 2011). Abstraction of clinical records and telephone interviews of a retrospective cohort of HIV-diagnosed SOKA and SHIMS clients were conducted in 2013-2014 to evaluate compliance with new linkage procedures and enrollment in HIV care at 92 facilities throughout Swaziland. Of 1,105 clients evaluated, within 3, 12, and 24 months of diagnosis, an estimated 14.0%, 24.3%, and 37.0% enrolled in HIV care, respectively, after adjusting for lost to follow-up and non-response. Kaplan-Meier functions indicated lower enrollment probability among clients 14-24 (P = 0.0001) and 25-29 (P = 0.001) years of age compared with clients >35 years of age. At 69 facilities to which clients were referred for HIV care, compliance with new linkage procedures was low: referral forms were located for less than half (46.8%) of the clients, and few (9.6%) were recorded in the appointment register or called either before (0.3%) or after (4.9%) their appointment. Of over one thousand clients newly HIV diagnosed in Swaziland in 2011 and 2012, few received linkage services in accordance with national procedures and most had not enrolled in HIV care two years after their diagnosis. Our findings are a call to action to improve linkage services and early enrollment in HIV care in Swaziland.

[Italian national register of low etiological fraction occupational cancer pursuant to art. 244 of legislative decree n. 81/2008].

PubMed

Massari, S; Ippoliti, M; Menegozzo, S; Forastiere, F; Crosignani, P

2011-01-01

Legislative decree No. 81/2008 in the article n. 244 states that ISPESL, now INAIL, realizes a register of occupational cancers with low etiological fraction by means of a data collection method based exclusively on voluntary reports by GPs, healthcare and social security agencies (ReNaLOC) and a surveillance cancer monitoring system (OCCAM) based on linkage of routinely available data (cancer registries, hospital discharge records, Italian Social Security archives). ReNaLOC has produced a partial picture of the situation, it includes 1.584 cases as of June 2011. With OCCAM many situations of known risks were identified and others are worthy to be deepen.

A comparison of accuracy and computational feasibility of two record linkage algorithms in retrieving vital status information from HIV/AIDS patients registered in Brazilian public databases.

PubMed

de Paula, Adelzon Assis; Pires, Denise Franqueira; Filho, Pedro Alves; de Lemos, Kátia Regina Valente; Barçante, Eduardo; Pacheco, Antonio Guilherme

2018-06-01

While cross-referencing information from people living with HIV/AIDS (PLWHA) to the official mortality database is a critical step in monitoring the HIV/AIDS epidemic in Brazil, the accuracy of the linkage routine may compromise the validity of the final database, yielding to biased epidemiological estimates. We compared the accuracy and the total runtime of two linkage algorithms applied to retrieve vital status information from PLWHA in Brazilian public databases. Nominally identified records from PLWHA were obtained from three distinct government databases. Linkage routines included an algorithm in Python language (PLA) and Reclink software (RlS), a probabilistic software largely utilized in Brazil. Records from PLWHA 1 known to be alive were added to those from patients reported as deceased. Data were then searched into the mortality system. Scenarios where 5% and 50% of patients actually dead were simulated, considering both complete cases and 20% missing maternal names. When complete information was available both algorithms had comparable accuracies. In the scenario of 20% missing maternal names, PLA 2 and RlS 3 had sensitivities of 94.5% and 94.6% (p > 0.5), respectively; after manual reviewing, PLA sensitivity increased to 98.4% (96.6-100.0) exceeding that for RlS (p < 0.01). PLA had higher positive predictive value in 5% death proportion. Manual reviewing was intrinsically required by RlS in up to 14% register for people actually dead, whereas the corresponding proportion ranged from 1.5% to 2% for PLA. The lack of manual inspection did not alter PLA sensitivity when complete information was available. When incomplete data was available PLA sensitivity increased from 94.5% to 98.4%, thus exceeding that presented by RlS (94.6%, p < 0.05). RlS spanned considerably less processing time compared to PLA. Both linkage algorithms presented interchangeable accuracies in retrieving vital status data from PLWHA. RlS had a considerably lesser runtime but intrinsically required manually reviewing a fastidious proportion of the matched registries. On the other hand, PLA spent quite more runtime but spared manual reviewing at no expense of accuracy. Copyright © 2018 Elsevier B.V. All rights reserved.

Randomized evaluation and cost-effectiveness of HIV and sexual and reproductive health service referral and linkage models in Zambia.

PubMed

Hewett, Paul C; Nalubamba, Mutinta; Bozzani, Fiammetta; Digitale, Jean; Vu, Lung; Yam, Eileen; Nambao, Mary

2016-08-12

Provision of HIV prevention and sexual and reproductive health services in Zambia is largely characterized by discrete service provision with weak client referral and linkage. The literature reveals gaps in the continuity of care for HIV and sexual and reproductive health. This study assessed whether improved service delivery models increased the uptake and cost-effectiveness of HIV and sexual and reproductive health services. Adult clients 18+ years of age accessing family planning (females), HIV testing and counseling (females and males), and male circumcision services (males) were recruited, enrolled and individually randomized to one of three study arms: 1) the standard model of service provision at the entry point (N = 1319); 2) an enhanced counseling and referral to add-on service with follow-up (N = 1323); and 3) the components of study arm two, with the additional offer of an escort (N = 1321). Interviews were conducted with the same clients at baseline, six weeks and six months. Uptake of services for HIV, family planning, male circumcision, and cervical cancer screening at six weeks and six months were the primary endpoints. Pairwise chi-square and multivariable logistic regression statistical tests assessed differences across study arms, which were also assessed for incremental cost-efficiency and cost-effectiveness. A total of 3963 clients, 1920 males and 2043 females, were enrolled; 82 % of participants at six weeks were tracked and 81 % at six months; follow-up rates did not vary significantly by study arm. The odds of clients accessing HIV testing and counseling, cervical cancer screening services among females, and circumcision services among males varied significantly by study arm at six weeks and six months; less consistent findings were observed for HIV care and treatment. Client uptake of family planning services did not vary significantly by study arm. Integrated services were found to be more efficiently provided than vertical service provision; the cost-effectiveness for HIV/AIDS and cervical cancer was high in the enhanced service models. Study results provide evidence for increasing the linkages and integration of a selection of HIV and sexual and reproductive health services. The study provided cost-effective service delivery models that enhanced the likelihood of clients accessing some additional needed health services. ISRCTN84228514 Retrospectively registered. The study was retrospectively registered in the ISRCTN clinical trials registry on 06 October 2015. The first recruitment of participants occurred on 17 December 2013.

Cervical cancer screening in Middle Eastern and Asian migrants to Australia: a record linkage study.

PubMed

Aminisani, Nayyereh; Armstrong, Bruce K; Canfell, Karen

2012-12-01

Australia's organized cervical screening program recommends two-yearly screening for women aged 18-69 years and reminder letters are sent at 27 months. Cervical screening registers hold comprehensive information on screening, but not country of birth. A linkage study was performed in order to assess cervical screening behavior in migrants. To assess screening participation, we linked year 2000 records for 12,541 Middle Eastern/Asian-born women 20-54 years of age, and an age and area matched random sample of 12,143 Australian-born women in the New South Wales (NSW) Midwives Data Collection (MDC), which records country of birth, to screening register records. Screening behavior after 2000 was assessed in women without a recorded prior cervical abnormality. The odds ratios for being screened at least once within a 3 year period, with reference to Australian-born women and adjusted for age, parity, socioeconomic status and smoking, were 0.88 (95% CI: 0.81-0.97) and 0.74 (95% CI: 0.70-0.79) in women born in the Middle East and Asia, respectively. Screening increased with increasing socioeconomic status (SES), absence of smoking and greater parity in Australian-born women but little, if at all, in migrant women. In a sensitivity analysis in which hospital admitted patients were the source of population samples, some patterns were sufficiently different to suggest that selection for illness can affect the strength and direction of associations in linked data. Migrant women from Asian and Middle-eastern countries are less likely than Australian-born women to participate in cervical screening at the recommended interval. Their likelihood of screening is also less related to socioeconomic status, smoking and parity than that in Australian-born women. Copyright © 2012 Elsevier Ltd. All rights reserved.

Cardiac registers: the adult cardiac surgery register.

PubMed

Bridgewater, Ben

2010-09-01

AIMS OF THE SCTS ADULT CARDIAC SURGERY DATABASE: To measure the quality of care of adult cardiac surgery in GB and Ireland and provide information for quality improvement and research. Feedback of structured data to hospitals, publication of named hospital and surgeon mortality data, publication of benchmarked activity and risk adjusted clinical outcomes through intermittent comprehensive database reports, annual screening of all hospital and individual surgeon risk adjusted mortality rates by the professional society. All NHS hospitals in England, Scotland and Wales with input from some private providers and hospitals in Ireland. 1994-ongoing. Consecutive patients, unconsented. Current number of records: 400000. Adult cardiac surgery operations excluding cardiac transplantation and ventricular assist devices. 129 fields covering demographic factors, pre-operative risk factors, operative details and post-operative in-hospital outcomes. Entry onto local software systems by direct key board entry or subsequent transcription from paper records, with subsequent electronic upload to the central cardiac audit database. Non-financial incentives at hospital level. Local validation processes exist in the hospitals. There is currently no external data validation process. All cause mortality is obtained through linkage with Office for National Statistics. No other linkages exist at present. Available for research and audit by application to the SCTS database committee at http://www.scts.org.

The Use of Central Nervous System Active Drugs During Pregnancy

PubMed Central

Källén, Bengt; Borg, Natalia; Reis, Margareta

2013-01-01

CNS-active drugs are used relatively often during pregnancy. Use during early pregnancy may increase the risk of a congenital malformation; use during the later part of pregnancy may be associated with preterm birth, intrauterine growth disturbances and neonatal morbidity. There is also a possibility that drug exposure can affect brain development with long-term neuropsychological harm as a result. This paper summarizes the literature on such drugs used during pregnancy: opioids, anticonvulsants, drugs used for Parkinson’s disease, neuroleptics, sedatives and hypnotics, antidepressants, psychostimulants, and some other CNS-active drugs. In addition to an overview of the literature, data from the Swedish Medical Birth Register (1996–2011) are presented. The exposure data are either based on midwife interviews towards the end of the first trimester or on linkage with a prescribed drug register. An association between malformations and maternal use of anticonvulsants and notably valproic acid is well known from the literature and also demonstrated in the present study. Some other associations between drug exposure and outcome were found. PMID:24275849

Estimating the risk of crime and victimisation in people with intellectual disability: a data-linkage study.

PubMed

Nixon, Margaret; Thomas, Stuart D M; Daffern, Michael; Ogloff, James R P

2017-05-01

People with intellectual disability (PWID) appear more likely to be victims and perpetrators of crime. However, extant evidence pertaining to these risks is limited by methodological weaknesses and the absence of consistent operational definitions. This research aimed to estimate the prevalence of criminal histories and victimisation using a large, well-defined sample of PWID. A case-linkage study was conducted comprising 2220 PWID registered with disability services in Victoria, Australia, whose personal details were linked with a state-wide police database. Criminal charges and reports of victimisation were compared to a non-disabled community comparison sample (n = 2085). PWID were at increased risk of having a history of criminal charges, particularly for violent and sexual offences. Although the non-disabled comparison group had a greater risk of criminal victimisation overall, PWID had a greatly increased risk of sexual and violent crime victimisation. PWID are at increased risk of victimisation and perpetration of violent and sexual crimes. Risk of sex offending and victimisation is particularly elevated, and signalling the need for specialised interventions to prevent offending and to ensure victims is assisted with access to justice, support, and treatment.

In-Hospital Vital Status and Heart Transplants After Intervention for Congenital Heart Disease in the Pediatric Cardiac Care Consortium: Completeness of Ascertainment Using the National Death Index and United Network for Organ Sharing Datasets.

PubMed

Spector, Logan G; Menk, Jeremiah S; Vinocur, Jeffrey M; Oster, Matthew E; Harvey, Brian A; St Louis, James D; Moller, James; Kochilas, Lazaros K

2016-08-09

The long-term outcomes of patients undergoing interventions for congenital heart disease (CHD) remain largely unknown. We linked the Pediatric Cardiac Care Consortium (PCCC) with the National Death Index (NDI) and the United Network for Organ Sharing Dataset (UNOS) registries to study mortality and transplant occurring up to 32 years postintervention. The objective of the current analysis was to determine the sensitivity of this linkage in identifying patients who are known to have died or undergone heart transplant. We used direct identifiers from 59 324 subjects registered in the PCCC between 1982 and 2003 to test for completeness of case ascertainment of subjects with known vital and heart transplant status by linkage with the NDI and UNOS registries. Of the 4612 in-hospital deaths, 3873 were identified by the NDI as "true" matches for a sensitivity of 84.0% (95% CI, 82.9-85.0). There was no difference in sensitivity across 25 congenital cardiovascular conditions after adjustment for age, sex, race, presence of first name, death year, and residence at death. Of 455 known heart transplants in the PCCC, there were 408 matches in the UNOS registry, for a sensitivity of 89.7% (95% CI, 86.9-92.3). An additional 4851 deaths and 363 transplants that occurred outside the PCCC were identified through 2014. The linkage of the PCCC with the NDI and UNOS national registries is feasible with a satisfactory sensitivity. This linkage provides a conservative estimate of the long-term death and heart transplant events in this cohort. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

The SAIL databank: linking multiple health and social care datasets

PubMed Central

2009-01-01

Background Vast amounts of data are collected about patients and service users in the course of health and social care service delivery. Electronic data systems for patient records have the potential to revolutionise service delivery and research. But in order to achieve this, it is essential that the ability to link the data at the individual record level be retained whilst adhering to the principles of information governance. The SAIL (Secure Anonymised Information Linkage) databank has been established using disparate datasets, and over 500 million records from multiple health and social care service providers have been loaded to date, with further growth in progress. Methods Having established the infrastructure of the databank, the aim of this work was to develop and implement an accurate matching process to enable the assignment of a unique Anonymous Linking Field (ALF) to person-based records to make the databank ready for record-linkage research studies. An SQL-based matching algorithm (MACRAL, Matching Algorithm for Consistent Results in Anonymised Linkage) was developed for this purpose. Firstly the suitability of using a valid NHS number as the basis of a unique identifier was assessed using MACRAL. Secondly, MACRAL was applied in turn to match primary care, secondary care and social services datasets to the NHS Administrative Register (NHSAR), to assess the efficacy of this process, and the optimum matching technique. Results The validation of using the NHS number yielded specificity values > 99.8% and sensitivity values > 94.6% using probabilistic record linkage (PRL) at the 50% threshold, and error rates were < 0.2%. A range of techniques for matching datasets to the NHSAR were applied and the optimum technique resulted in sensitivity values of: 99.9% for a GP dataset from primary care, 99.3% for a PEDW dataset from secondary care and 95.2% for the PARIS database from social care. Conclusion With the infrastructure that has been put in place, the reliable matching process that has been developed enables an ALF to be consistently allocated to records in the databank. The SAIL databank represents a research-ready platform for record-linkage studies. PMID:19149883

The SAIL databank: linking multiple health and social care datasets.

PubMed

Lyons, Ronan A; Jones, Kerina H; John, Gareth; Brooks, Caroline J; Verplancke, Jean-Philippe; Ford, David V; Brown, Ginevra; Leake, Ken

2009-01-16

Vast amounts of data are collected about patients and service users in the course of health and social care service delivery. Electronic data systems for patient records have the potential to revolutionise service delivery and research. But in order to achieve this, it is essential that the ability to link the data at the individual record level be retained whilst adhering to the principles of information governance. The SAIL (Secure Anonymised Information Linkage) databank has been established using disparate datasets, and over 500 million records from multiple health and social care service providers have been loaded to date, with further growth in progress. Having established the infrastructure of the databank, the aim of this work was to develop and implement an accurate matching process to enable the assignment of a unique Anonymous Linking Field (ALF) to person-based records to make the databank ready for record-linkage research studies. An SQL-based matching algorithm (MACRAL, Matching Algorithm for Consistent Results in Anonymised Linkage) was developed for this purpose. Firstly the suitability of using a valid NHS number as the basis of a unique identifier was assessed using MACRAL. Secondly, MACRAL was applied in turn to match primary care, secondary care and social services datasets to the NHS Administrative Register (NHSAR), to assess the efficacy of this process, and the optimum matching technique. The validation of using the NHS number yielded specificity values > 99.8% and sensitivity values > 94.6% using probabilistic record linkage (PRL) at the 50% threshold, and error rates were < 0.2%. A range of techniques for matching datasets to the NHSAR were applied and the optimum technique resulted in sensitivity values of: 99.9% for a GP dataset from primary care, 99.3% for a PEDW dataset from secondary care and 95.2% for the PARIS database from social care. With the infrastructure that has been put in place, the reliable matching process that has been developed enables an ALF to be consistently allocated to records in the databank. The SAIL databank represents a research-ready platform for record-linkage studies.

Healthcare provision for HIV co-infected tuberculosis patients in rural Zambia: an observational cohort study at primary care centers

PubMed Central

2013-01-01

Background Linkage of healthcare services for tuberculosis (TB) and human immunodeficiency virus (HIV) remains a major challenge in resource-limited settings. Our operational research aimed to evaluate the linkage between TB and HIV services in a rural area of Zambia, and to explore factors associated with the enrolment of TB/HIV co-infected patients in HIV care services. Methods All TB patients newly diagnosed as HIV-positive in Chongwe district, Zambia between 2009 and 2010 were included. Data from TB registers and medical records were reviewed. Patient referral to HIV services and provision of antiretroviral therapy (ART) were further examined through HIV registers and records. Results Of 621 patients (median age 33.0 years, female 42.4%) who started anti-TB treatment, clinic records indicated that 297 patients were newly diagnosed as HIV-positive, and 176 (59.3%) of these were referred to an ART clinic. Analysis of records at the ART clinic found that only 85 (28.6%) of TB/HIV patients had actually been enrolled in HIV care, of whom only 58 (68.2%) had commenced ART. Logistic regression analyses demonstrated the following factors associated with lower enrolment: “male” sex (aOR, 0.45; 95% CI 0.26-0.78), “previous TB treatment” (aOR, 0.29; 95% CI, 0.11-0.75), “registration at sites that did not provide ART services (non-ART site)” (aOR, 0.10; 95% CI, 0.01-0.77) and “death on TB treatment outcome (aOR, 0.20; 95% CI, 0.06-0.65). However, patient registration at TB clinics in 2010 was associated with markedly higher enrolment in HIV care as compared to registration in 2009 (aOR, 2.80; 95% CI, 1.53-5.12). Conclusions HIV testing for TB patients has been successfully scaled up. However referrals of co-infected patients still remain a challenge due to poor linkage between TB and HIV healthcare services. Committed healthcare workers, a well-organized health services system and patient education are urgently required to ensure a higher rate of referral of TB/HIV co-infected patients for appropriate care. PMID:24103082

Coffee consumption during pregnancy and the risk of hyperkinetic disorder and ADHD: a prospective cohort study.

PubMed

Linnet, Karen Markussen; Wisborg, Kirsten; Secher, Niels Jørgen; Thomsen, Per Hove; Obel, Carsten; Dalsgaard, Søren; Henriksen, Tine Brink

2009-01-01

Based on hypotheses from experimental studies, we studied the association between intrauterine exposure to coffee and the risk of clinically verified hyperkinetic disorder and attention-deficit hyperactivity disorder (ADHD). A cohort study with prospectively collected data from the Aarhus Birth Cohort, Denmark. We included 24 068 singletons delivered between 1990 and 1998. Linkage was performed with three Danish longitudinal registers: The Danish Psychiatric Central Register, The Integrated Database for Labour Market Research and The Danish Civil Registration System. We identified 88 children with hyperkinetic disorder and ADHD. Information about coffee consumption during pregnancy was obtained at 16 weeks of gestation from self-administrated questionnaires. Potential confounding factors were evaluated using Cox regression analyses. We found that intrauterine exposure to 10 or more cups of coffee per day was associated with a threefold increased risk of hyperkinetic disorder and ADHD. After adjustments for a number of confounding factors, the risk decreased and became statistically insignificant (RR 2.3, 95% CI 0.9-5.9). Prenatal exposure to high levels of coffee did not significantly increase the risk of clinically verified hyperkinetic disorder and ADHD in childhood.

Cohort profile: the Italian Network of Longitudinal Metropolitan Studies (IN-LiMeS), a multicentre cohort for socioeconomic inequalities in health monitoring

PubMed Central

Giorgi Rossi, Paolo; Spadea, Teresa; Pacelli, Barbara; Broccoli, Serena; Ballotari, Paola; Costa, Giuseppe; Zengarini, Nicolás; Agabiti, Nera; Bargagli, Anna Maria; Cacciani, Laura; Canova, Cristina; Cestari, Laura; Biggeri, Annibale; Grisotto, Laura; Terni, Gianna; Costanzo, Gianfranco; Mirisola, Concetta; Petrelli, Alessio

2018-01-01

Purpose The Italian Network of Longitudinal Metropolitan Studies (IN-LiMeS) is a system of integrated data on health outcomes, demographic and socioeconomic information, and represents a powerful tool to study health inequalities. Participants IN-LiMeS is a multicentre and multipurpose pool of metropolitan population cohorts enrolled in nine Italian cities: Turin, Venice, Reggio Emilia, Modena, Bologna, Florence, Leghorn, Prato and Rome. Data come from record linkage of municipal population registries, the 2001 population census, mortality registers and hospital discharge archives. Depending on the source of enrolment, cohorts can be closed or open. The census-based closed cohort design includes subjects resident in any of the nine cities at the 2001 census day; 4 466 655 individuals were enrolled in 2001 in the nine closed cohorts. The open cohort design includes subjects resident in 2001 or subsequently registered by birth or immigration until the latest available follow-up (currently 31 December 2013). The open cohort design is available for Turin, Venice, Reggio Emilia, Modena, Bologna, Prato and Rome. Detailed socioeconomic data are available for subjects enrolled in the census-based cohorts; information on demographic characteristics, education and citizenship is available from population registries. Findings to date The first IN-LiMeS application was the study of differentials in mortality between immigrants and Italians. Either using a closed cohort design (nine cities) or an open one (Turin and Reggio Emilia), individuals from high migration pressure countries generally showed a lower mortality risk. However, a certain heterogeneity between the nine cities was noted, especially among men, and an excess mortality risk was reported for some macroareas of origin and specific causes of death. Future plans We are currently working on the linkage of the 2011 population census data, the expansion of geographical coverage and the implementation of the open design in all the participating cohorts. PMID:29678981

Social Conditions for People With Down Syndrome: A Register-Based Cohort Study in Denmark

PubMed Central

Zhu, Jin Liang; Obel, Carsten; Hasle, Henrik; Rasmussen, Sonja A.; Li, Jiong; Olsen, Jørn

2015-01-01

Today, most persons with Down syndrome (DS) survive into middle age, but information on their social conditions as adults is limited. We addressed this knowledge gap using data from national registers in Denmark. We identified a national cohort of 1,998 persons with DS who were born between 1968 and 2007 (1,852 with standard trisomy 21, 80 with Robertsonian translocations and 66 with mosaicism) using the Danish Cytogenetic Register. We followed this cohort from 1980 to 2007. Information on social conditions (education, employment, source of income, marital status, etc.) was obtained by linkages to national registers, including the Integrated Database for Longitudinal Labor Market Research. For those aged 18 and older, more than 80%of persons with DS attended 10 years of primary school, with about 2% completing secondary or post-secondary education. About 4% obtained a full-time job, whereas the remaining mainly received public support from the government. Only a few (1–2%) of persons with DS were married or had a child. No significant differences in these social conditions were seen between males and females. More persons with mosaic DS attended secondary or post-secondary education, had a full-time job, were married, or had a child (18%, 28%, 15%, and 7%, respectively), compared with persons with standard DS (1%, 2%, 1%, and 1%, respectively). These data may provide families with better insight into social conditions and society with a better understanding of the social support needed for persons with DS. PMID:24273114

The cascade of HIV care among refugees and nationals in Nakivale Refugee Settlement in Uganda.

PubMed

O'Laughlin, K N; Kasozi, J; Rabideau, D J; Parker, R A; Mulogo, E; Faustin, Z M; Greenwald, K E; Doraiswamy, S; Walensky, R P; Bassett, I V

2017-08-01

Refugees living in Uganda come from HIV-endemic countries, and many remain in refugee settlements for over a decade. Our objective was to evaluate the HIV care cascade in Nakivale Refugee Settlement and to assess correlates of linkage to care. We prospectively enrolled individuals accessing clinic-based HIV testing in Nakivale Refugee Settlement from March 2013 to July 2014. Newly HIV-diagnosed clients were followed for 3 months post-diagnosis. Clients underwent a baseline survey. The following outcomes were obtained from HIV clinic registers in Nakivale: clinic attendance ('linkage to HIV care'), CD4 testing, antiretroviral therapy (ART) eligibility, and ART initiation within 90 days of testing. Descriptive data were reported as frequency with 95% confidence interval (CI) or median with interquartile range (IQR). The impact of baseline variables on linkage to care was assessed with logistic regression models. Of 6850 adult clients tested for HIV, 276 (4%; CI: 3-5%) were diagnosed with HIV infection, 148 (54%; CI: 47-60%) of those were linked to HIV care, 54 (20%; CI: 15-25%) had a CD4 test, 22 (8%; CI: 5-12%) were eligible for ART, and 17 (6%; CI: 3-10%) initiated ART. The proportions of refugees and nationals at each step of the cascade were similar. We identified no significant predictors of linkage to care. Less than a quarter of newly HIV-diagnosed clients completed ART assessment, considerably lower than in other reports from sub-Saharan Africa. Understanding which factors hinder linkage to and engagement in care in the settlement will be important to inform interventions specific for this environment. © 2017 British HIV Association.

Towards non-conventional methods of designing register-based epidemiological studies: An application to pediatric research.

PubMed

Gong, Tong; Brew, Bronwyn; Sjölander, Arvid; Almqvist, Catarina

2017-07-01

Various epidemiological designs have been applied to investigate the causes and consequences of fetal growth restriction in register-based observational studies. This review seeks to provide an overview of several conventional designs, including cohort, case-control and more recently applied non-conventional designs such as family-based designs. We also discuss some practical points regarding the application and interpretation of family-based designs. Definitions of each design, the study population, the exposure and the outcome measures are briefly summarised. Examples of study designs are taken from the field of low birth-weight research for illustrative purposes. Also examined are relative advantages and disadvantages of each design in terms of assumptions, potential selection and information bias, confounding and generalisability. Kinship data linkage, statistical models and result interpretation are discussed specific to family-based designs. When all information is retrieved from registers, there is no evident preference of the case-control design over the cohort design to estimate odds ratios. All conventional designs included in the review are prone to bias, particularly due to residual confounding. Family-based designs are able to reduce such bias and strengthen causal inference. In the field of low birth-weight research, family-based designs have been able to confirm a negative association not confounded by genetic or shared environmental factors between low birth weight and the risk of asthma. We conclude that there is a broader need for family-based design in observational research as evidenced by the meaningful contributions to the understanding of the potential causal association between low birth weight and subsequent outcomes.

Bipolar disorder and criminal offending: a data linkage study.

PubMed

Daff, Elizabeth; Thomas, Stuart D M

2014-12-01

The current study explored criminal offending among people diagnosed with bipolar disorder with and without comorbid substance use and compared this with a community sample with no history of bipolar disorder. A case-linkage design was used to compare patterns of officially recorded criminal offending between 1,076 people with bipolar disorder drawn from a state-wide psychiatric case register with a community comparison group. Those with bipolar disorder were significantly more likely than community members to be charged with, convicted of, and be found guilty of, violent, non-violent and intermediate level criminal offences. Those with a comorbid substance use disorder were two times more likely than those without a substance use disorder to offend; both groups had a significantly higher chance of offending than the community sample. Females with bipolar disorder were significantly more likely to have been convicted of violent offences, irrespective of substance use. Significant interactions were found between bipolar disorder and substance use for males and females with respect to violent offending and for males with respect to non-violent offending. There is a statistically significant association between bipolar disorder and the likelihood of having a criminal history. Co-occurring substance use differentially impacts on the likelihood of criminal offending for males and females.

Linkage of Maternity Hospital Episode Statistics data to birth registration and notification records for births in England 2005–2014: Quality assurance of linkage of routine data for singleton and multiple births

PubMed Central

2018-01-01

Objectives To quality assure a Trusted Third Party linked data set to prepare it for analysis. Setting Birth registration and notification records from the Office for National Statistics for all births in England 2005–2014 linked to Maternity Hospital Episode Statistics (HES) delivery records by NHS Digital using mothers’ identifiers. Participants All 6 676 912 births that occurred in England from 1 January 2005 to 31 December 2014. Primary and secondary outcome measures Every link between a registered birth and an HES delivery record for the study period was categorised as either the same baby or a different baby to the same mother, or as a wrong link, by comparing common baby data items and valid values in key fields with stepwise deterministic rules. Rates of preserved and discarded links were calculated and which features were more common in each group were assessed. Results Ninety-eight per cent of births originally linked to HES were left with one preserved link. The majority of discarded links were due to duplicate HES delivery records. Of the 4854 discarded links categorised as wrong links, clerical checks found 85% were false-positives links, 13% were quality assurance false negatives and 2% were undeterminable. Births linked using a less reliable stage of the linkage algorithm, births at home and in the London region, and with birth weight or gestational age values missing in HES were more likely to have all links discarded. Conclusions Linkage error, data quality issues, and false negatives in the quality assurance procedure were uncovered. The procedure could be improved by allowing for transposition in date fields, and more discrimination between missing and differing values. The availability of identifiers in the datasets supported clerical checking. Other research using Trusted Third Party linkage should not assume the linked dataset is error-free or optimised for their analysis, and allow sufficient resources for this. PMID:29500200

A review of accessibility of administrative healthcare databases in the Asia-Pacific region.

PubMed

Milea, Dominique; Azmi, Soraya; Reginald, Praveen; Verpillat, Patrice; Francois, Clement

2015-01-01

We describe and compare the availability and accessibility of administrative healthcare databases (AHDB) in several Asia-Pacific countries: Australia, Japan, South Korea, Taiwan, Singapore, China, Thailand, and Malaysia. The study included hospital records, reimbursement databases, prescription databases, and data linkages. Databases were first identified through PubMed, Google Scholar, and the ISPOR database register. Database custodians were contacted. Six criteria were used to assess the databases and provided the basis for a tool to categorise databases into seven levels ranging from least accessible (Level 1) to most accessible (Level 7). We also categorised overall data accessibility for each country as high, medium, or low based on accessibility of databases as well as the number of academic articles published using the databases. Fifty-four administrative databases were identified. Only a limited number of databases allowed access to raw data and were at Level 7 [Medical Data Vision EBM Provider, Japan Medical Data Centre (JMDC) Claims database and Nihon-Chouzai Pharmacy Claims database in Japan, and Medicare, Pharmaceutical Benefits Scheme (PBS), Centre for Health Record Linkage (CHeReL), HealthLinQ, Victorian Data Linkages (VDL), SA-NT DataLink in Australia]. At Levels 3-6 were several databases from Japan [Hamamatsu Medical University Database, Medi-Trend, Nihon University School of Medicine Clinical Data Warehouse (NUSM)], Australia [Western Australia Data Linkage (WADL)], Taiwan [National Health Insurance Research Database (NHIRD)], South Korea [Health Insurance Review and Assessment Service (HIRA)], and Malaysia [United Nations University (UNU)-Casemix]. Countries were categorised as having a high level of data accessibility (Australia, Taiwan, and Japan), medium level of accessibility (South Korea), or a low level of accessibility (Thailand, China, Malaysia, and Singapore). In some countries, data may be available but accessibility was restricted based on requirements by data custodians. Compared with previous research, this study describes the landscape of databases in the selected countries with more granularity using an assessment tool developed for this purpose. A high number of databases were identified but most had restricted access, preventing their potential use to support research. We hope that this study helps to improve the understanding of the AHDB landscape, increase data sharing and database research in Asia-Pacific countries.

HIV screening among TB patients and level of antiretroviral therapy and co-trimoxazole preventive therapy for TB/HIV patients in Hawassa University Referral Hospital: a five year retrospective study.

PubMed

Simieneh, Asnake; Hailemariam, Mengistu; Amsalu, Anteneh

2017-01-01

Initiation of antiretroviral therapy (ART) and co-trimoxazole preventive therapy (CPT) is recommended for tuberculosis (TB)/human immunodeficiency virus (HIV) co-infected patients to prevent opportunistic infection. The aim of this study was to assess the prevalence of HIV among TB patients and initiation of ART and provision of CPT for TB/HIV co-infected patients in Hawassa university referral hospital. A five year document review was done on 1961 TB patients who are registered at TB clinic of Hawassa university referral hospital from September 2009 to august 2014. Data were collected using checklist. Data analysis was done by using SPSS version 20 software. Bivariate and multivariate logistic regression analysis was used to determine the predictors of TB/HIV co-infection. Among 1961 TB patients diagnosed in the hospital, 95% (1765) were screened for HIV. Of these, 13.9% (246) were HIV positive. Out of 246 TB/HIV co-infected patients 31.7% (78/246) and 37.4% (92/246) were enrolled to start ART and CPT respectively. Roughly the trends of TB/HIV co-infection decreased with increased linkage to CPT, while linkage to ART was not regular across the year. The rate of TB/HIV co-infection was significantly associated with type of TB. Although, trend of HIV among TB patients has decreased across the year, only a minority of co-infected patients was linked to start ART and CPT. Therefore, screening of all TB patients for HIV and linkage of co-infected patients to HIV care to start ART and CPT should be strengthened in-line with the national guidelines.

Breast cancer risk among women with psychiatric admission with affective or neurotic disorders: a nationwide cohort study in Denmark

PubMed Central

Hjerl, K; Andersen, E W; Keiding, N; Sawitz, A; Olsen, J H; Mortensen, P B; Jørgensen, T

1999-01-01

There is a considerable interest in the possible relationship between psychosocial factors and the onset of breast cancer. This cohort study was based upon two nationwide and population-based central registers: The Danish Psychiatric Central Register, which contains all cases of psychiatric admissions, and The Danish Cancer Registry, which contains all cases of cancer. The register-linkage was accomplished by using a personal identification number. The study population comprised all women admitted to psychiatric departments or psychiatric hospitals in Denmark between 1969 and 1993 with an affective or a neurotic disorder. Overall, 66 648 women comprising 199 910 admissions and 775 522 person-years were included. The incidence of breast cancer in the cohort was compared with the national breast cancer incidence rates adjusted for age and calendar time. In all, 1270 women with affective or neurotic disorders developed breast cancer subsequent to the first admission as compared with the 1242 women expected, standardized incidence ratio (SIR) = 1.02 (95% confidence interval 0.97–1.08). None of the hypothetical risk factors: type of diagnosis, age or calendar period at cohort entry, age at breast cancer, alcohol abuse, alcohol/drug abuse without further specification, total number of admissions, total length of admissions, or time from first admission showed a statistically significant effect on the relative risk of breast cancer. We found no support for the hypothesis that women admitted to a psychiatric department with an affective or a neurotic disorder subsequently have an increased risk of breast cancer. © 1999 Cancer Research Campaign PMID:10555767

Ascertainment of risk of serious adverse reactions associated with chemoprophylactic antimalarial drugs.

PubMed Central

Phillips-Howard, P. A.; Bjorkman, A. B.

1990-01-01

Serious adverse reactions during malaria chemoprophylaxis are reviewed. Three drugs considered to have caused serious reactions in recent years are pyrimethamine/sulfadoxine (Fansidar), pyrimethamine/dapsone (Maloprim) and amodiaquine. These reactions are principally independent of dose and cannot be determined during screening for optimal doses. However, host factors may precipitate dose-dependent reactions, some of which could be avoided with improvements in drug licensing. Since serious and life-threatening reactions are relatively rare (between 1:1000 and 1:20,000), Phase I to III trials cannot identify them. Reliance must therefore be placed on Phase IV post-marketing studies, including ongoing reviews of national registers, and specially tailored studies to identify the risk using prescription-event monitoring in high-risk populations. Occasionally, medical-record linkage, case-control and cohort studies may provide supportive data. Although large numbers of travellers must, of necessity, be exposed to a drug before relatively rare reactions are identified, the ascertainment of risk using post-marketing surveillance was prevented by the following five deficiencies: lack of awareness of early alerts, inadequate use of national registers, poor attention to epidemiological and statistical rigour, inadequate verification of denominators, and inadequacy of data records. Recommendations are given for minimizing such errors in the future. PMID:2208562

Cohort profile: the Italian Network of Longitudinal Metropolitan Studies (IN-LiMeS), a multicentre cohort for socioeconomic inequalities in health monitoring.

PubMed

Caranci, Nicola; Di Girolamo, Chiara; Giorgi Rossi, Paolo; Spadea, Teresa; Pacelli, Barbara; Broccoli, Serena; Ballotari, Paola; Costa, Giuseppe; Zengarini, Nicolás; Agabiti, Nera; Bargagli, Anna Maria; Cacciani, Laura; Canova, Cristina; Cestari, Laura; Biggeri, Annibale; Grisotto, Laura; Terni, Gianna; Costanzo, Gianfranco; Mirisola, Concetta; Petrelli, Alessio

2018-04-20

The Italian Network of Longitudinal Metropolitan Studies (IN-LiMeS) is a system of integrated data on health outcomes, demographic and socioeconomic information, and represents a powerful tool to study health inequalities. IN-LiMeS is a multicentre and multipurpose pool of metropolitan population cohorts enrolled in nine Italian cities: Turin, Venice, Reggio Emilia, Modena, Bologna, Florence, Leghorn, Prato and Rome. Data come from record linkage of municipal population registries, the 2001 population census, mortality registers and hospital discharge archives. Depending on the source of enrolment, cohorts can be closed or open. The census-based closed cohort design includes subjects resident in any of the nine cities at the 2001 census day; 4 466 655 individuals were enrolled in 2001 in the nine closed cohorts. The open cohort design includes subjects resident in 2001 or subsequently registered by birth or immigration until the latest available follow-up (currently 31 December 2013). The open cohort design is available for Turin, Venice, Reggio Emilia, Modena, Bologna, Prato and Rome. Detailed socioeconomic data are available for subjects enrolled in the census-based cohorts; information on demographic characteristics, education and citizenship is available from population registries. The first IN-LiMeS application was the study of differentials in mortality between immigrants and Italians. Either using a closed cohort design (nine cities) or an open one (Turin and Reggio Emilia), individuals from high migration pressure countries generally showed a lower mortality risk. However, a certain heterogeneity between the nine cities was noted, especially among men, and an excess mortality risk was reported for some macroareas of origin and specific causes of death. We are currently working on the linkage of the 2011 population census data, the expansion of geographical coverage and the implementation of the open design in all the participating cohorts. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

A locus for isolated cataract on human Xp

PubMed Central

Francis, P; Berry, V; Hardcastle, A; Maher, E; Moore, A; Bhattacharya, S

2002-01-01

Purpose: To genetically map the gene causing isolated X linked cataract in a large European pedigree. Methods: Using the patient registers at Birmingham Women's Hospital, UK, we identified and examined 23 members of a four generation family with nuclear cataract. Four of six affected males also had complex congenital heart disease. Pedigree data were collated and leucocyte DNA extracted from venous blood. Linkage analysis by PCR based microsatellite marker genotyping was used to identify the disease locus and mutations within candidate genes screened by direct sequencing. Results: The disease locus was genetically refined to chromosome Xp22, within a 3 cM linkage interval flanked by markers DXS9902 and DXS999 (Zmax=3.64 at θ=0 for marker DXS8036). Conclusions: This is the first report of a locus for isolated inherited cataract on the X chromosome. The disease interval lies within the Nance-Horan locus suggesting allelic heterogeneity. The apparent association with congenital cardiac anomalies suggests a possible new oculocardiac syndrome. PMID:11836358

A locus for isolated cataract on human Xp.

PubMed

Francis, P J; Berry, V; Hardcastle, A J; Maher, E R; Moore, A T; Bhattacharya, S S

2002-02-01

To genetically map the gene causing isolated X linked cataract in a large European pedigree. Using the patient registers at Birmingham Women's Hospital, UK, we identified and examined 23 members of a four generation family with nuclear cataract. Four of six affected males also had complex congenital heart disease. Pedigree data were collated and leucocyte DNA extracted from venous blood. Linkage analysis by PCR based microsatellite marker genotyping was used to identify the disease locus and mutations within candidate genes screened by direct sequencing. The disease locus was genetically refined to chromosome Xp22, within a 3 cM linkage interval flanked by markers DXS9902 and DXS999 (Zmax=3.64 at theta=0 for marker DXS8036). This is the first report of a locus for isolated inherited cataract on the X chromosome. The disease interval lies within the Nance-Horan locus suggesting allelic heterogeneity. The apparent association with congenital cardiac anomalies suggests a possible new oculocardiac syndrome.

Workplace bullying and subsequent psychotropic medication: a cohort study with register linkages

PubMed Central

Lallukka, Tea; Haukka, Jari; Partonen, Timo; Rahkonen, Ossi; Lahelma, Eero

2012-01-01

Objectives We aimed to examine longitudinally whether workplace bullying was associated with subsequent psychotropic medication among women and men. Design A cohort study. Setting Helsinki, Finland. Participants Employees of the City of Helsinki, Finland (n=6606, 80% women), 40–60 years at baseline in 2000–2002, and a register-based follow-up on medication. Primary and secondary outcome measures Workplace bullying comprised questions about current and earlier bullying as well as observing bullying. The Finnish Social Insurance Institution's register data on purchases of prescribed reimbursed psychotropic medication were linked with the survey data. All psychotropic medication 3 years prior to and 5 years after the baseline survey was included. Covariates included age, prior psychotropic medication, childhood bullying, occupational class, and body mass index. Cox proportional hazard models (HR, 95% CI) were fitted and days until the first purchase of prescribed psychotropic medication after baseline were used as the time axis. Results Workplace bullying was associated with subsequent psychotropic medication after adjusting for age and prior medication among both women (HR 1.51, 95% CI 1.18 to 1.93) and men (HR 2.15, 95% CI 1.36 to 3.41). Also observing bullying was associated with subsequent psychotropic medication among women (HR 1.53, 95% CI 1.25 to 1.88) and men (HR 1.92, 95% CI 1.23 to 2.99). The associations only modestly attenuated after full adjustment. Conclusions Our findings highlight the significance of workplace bullying to subsequent psychotropic medication reflecting medically confirmed mental problems. Tackling workplace bullying likely helps prevent mental problems among employees. PMID:23242240

Young adulthood cognitive ability predicts statin adherence in middle-aged men after first myocardial infarction: A Swedish National Registry study

PubMed Central

Lissåker, Claudia; Madison, Guy; Held, Claes; Olsson, Erik

2017-01-01

Background Cognitive ability (CA) is positively related to later health, health literacy, health behaviours and longevity. Accordingly, a lower CA is expected to be associated with poorer adherence to medication. We investigated the long-term role of CA in adherence to prescribed statins in male patients after a first myocardial infarction (MI). Methods CA was estimated at 18–20 years of age from Military Conscript Register data for first MI male patients (≤60 years) and was related to the one- and two-year post-MI statin adherence on average 30 years later. Background and clinical data were retrieved through register linkage with the unselected national quality register SWEDEHEART for acute coronary events (Register of Information and Knowledge about Swedish Heart Intensive Care Admissions) and secondary prevention (Secondary Prevention after Heart Intensive Care Admission). Previous and present statin prescription data were obtained from the Prescribed Drug Register and adherence was calculated as ≥80% of prescribed dispensations assuming standard dosage. Logistic regression was used to estimate crude and adjusted associations. The primary analyses used 2613 complete cases and imputing incomplete cases rendered a sample of 4061 cases for use in secondary (replicated) analyses. Results One standard deviation increase in CA was positively associated with both one-year (OR 1.15 (CI 1.01–1.31), P < 0.05) and two-year (OR 1.14 (CI 1.02–1.27), P < 0.05) adherence to prescribed statins. Only smoking attenuated the CA–adherence association after adjustment for a range of > 20 covariates. Imputed and complete case analyses yielded very similar results. Conclusions CA estimated on average 30 years earlier in young adulthood is a risk indicator for statin adherence in first MI male patients aged ≤60 years. Future research should include older and female patients and more socioeconomic variables. PMID:28195516

Sleep problems and disability retirement: a register-based follow-up study.

PubMed

Lallukka, Tea; Haaramo, Peija; Lahelma, Eero; Rahkonen, Ossi

2011-04-15

Among aging employees, sleep problems are prevalent, but they may have serious consequences that are poorly understood. This study examined whether sleep problems are associated with subsequent disability retirement. Baseline questionnaire survey data collected in 2000-2002 among employees of the city of Helsinki, Finland, were linked with register data on disability retirement diagnoses by the end of 2008 (n = 457) for those with written consent for such linkages (74%; N = 5,986). Sleep problems were measured by the Jenkins Sleep Questionnaire. Cox regression analysis was used to calculate hazard ratios and 95% confidence intervals for disability retirement. Gender- and age-adjusted frequent sleep problems predicted disability retirement due to all causes (hazard ratio (HR) = 3.22, 95% confidence interval (CI): 2.26, 4.60), mental disorders (HR = 9.06, 95% CI: 3.27, 25.10), and musculoskeletal disorders (HR = 3.27, 95% CI: 1.91, 5.61). Adjustments for confounders, that is, baseline sociodemographic factors, work arrangements, psychosocial working conditions, and sleep duration, had negligible effects on these associations, whereas baseline physical working conditions and health attenuated the associations. Health behaviors and obesity did not mediate the examined associations. In conclusion, sleep problems are associated with subsequent disability retirement. To prevent early exit from work, sleep problems among aging employees need to be addressed.

[The contribution of surveillance systems of occupational diseases and mesothelioma in environmental health studies].

PubMed

Marinaccio, A; Binazzi, A; Di Marzio, D; Massari, S; Scarselli, A; Iavicoli, S

2011-01-01

National surveillance systems of occupational diseases may contribute to evaluate the work-related component of diseases investigated in SENTIERI Project. For a description of SENTIERI, refer to the 2010 Supplement of Epidemiology & Prevention devoted to SENTIERI Project. The National Workers Compensation Authority (INAIL) archives all occupational diseases claims (more than 230 000 in the period 2000-2007) and is in charge of their compensation. The Italian National Mesothelioma Register (ReNaM) and the Sinonasal Cancer Register (ReNaTuNS) record high occupational etiological fraction neoplasms (i.e. mesothelioma and sinonasal cancers). The former has identified more than 10 000 mesothelioma cases until now, and covers almost the whole country; the latter is active only in three Italian regions, Piemonte, Lombardia and Toscana. The monitoring of cancer sites at lower occupational etiological fraction is based on a record-linkage procedure between population-based cancer registries and employment history data, available at the Italian National Institute for Social Security (INPS). Finally, the informative system Mal.Prof collects and classifies all the diseases possibly related to the work environment reported by the Prevention Services of the Local Health Units.

A Nested Case-Control Study of Intrauterine Exposure to Persistent Organochlorine Pollutants and the Risk of Hypospadias

PubMed Central

Rignell-Hydbom, Anna; Lindh, Christian H.; Dillner, Joakim; Jönsson, Bo A. G.; Rylander, Lars

2012-01-01

Background Environmental exposures to endocrine disrupting chemicals have been suggested as a risk factor for male genital abnormalities such as hypospadias. The aim of this case-control study was to investigate the association between fetal exposure to persistent organochlorine pollutants (POP) and the risk for hypospadias. Methodology/Principal Findings The Southern Sweden Maternity Cohort (SSMC) contains serum samples collected in early pregnancy among women in Southern Sweden. Linkages with the Medical Birth Register, the Malformation Register and the In-patient Register resulted in 390 SSMC mothers who had given birth to a boy with hypospadias in year 1986–2002 (mean 1995). For 237 of these (cases) sufficient amounts of serum for the chemical analyses were available. For each case, a control boy from the SSMC was randomly selected, matched for maternal age, birth year, parity and maternal smoking. PCB-153, p,p’-DDE and hexachlorbenzene (HCB) were used as biomarkers for POP exposure. The exposures were categorized into quartiles based on the distributions among the controls. There were no statistically significant trends between the a priori categorisation of the exposure variables and the risk for hypospadias. However, when the upper HCB quartile (>26 ng/ml) was compared to the other quartiles an odds ratio of 1.65 (95% CI 1.02 to 2.69) was obtained. p,p′-DDE levels above median (>1.0 ng/ml) compared to levels below 0.1 ng/ml gave an OR of 1.69 (95% CI 0.97 to 2.93). Conclusions The present study suggests that fetal exposure to HCB and p,p’-DDE may be a risk factor for hypospadias. PMID:23028613

The effects of HIV self-testing on the uptake of HIV testing and linkage to antiretroviral treatment among adults in Africa: a systematic review protocol.

PubMed

Njau, Bernard; Damian, Damian J; Abdullahi, Leila; Boulle, Andrew; Mathews, Catherine

2016-04-05

HIV is still a global public health problem. More than 75 % of HIV-infected people are in Africa, and most of them are unaware of their HIV status, which is a barrier to accessing antiretroviral treatment. Our review aims, firstly, to determine whether HIV self-testing is an effective method to increase the uptake of testing, the yield of new HIV-positive diagnoses, and the linkage to antiretroviral treatment. Secondly, we aim to review the factors that facilitate or impede the uptake of HIV self-testing. Participants will be adults living in Africa. For the first aim, the intervention will be HIV self-testing either alone or in addition to HIV testing standard of care. The comparison will be HIV testing standard of care. The primary outcomes will be (i) uptake of HIV testing and (ii) yield of new HIV-positive diagnoses. The secondary outcomes will be (a) linkage to antiretroviral (ARV) treatment and (b) incidence of social harms. For the second aim, we will review barriers and facilitators to the uptake of self-testing. We will search PubMed, Cochrane Central Register of Controlled Trials, Scopus, Web of Science, WHOLIS, Africa Wide, and CINAHL for eligible studies from 1998, with no language limits. We will check reference lists of included studies for other eligible reports. Eligible studies will include experimental and observational studies. Two authors will independently screen the search output, select studies, and extract data, resolving discrepancies by consensus and discussion. Two authors will use Cochrane risk of bias tools for experimental studies, the Newcastle-Ottawa Quality Assessment Scale for observational studies, and the Critical Appraisal Skills Programme (CASP) quality assessment tool for qualitative studies. Innovative and cost-effective community-based HIV testing strategies, such as self-testing, will contribute to universal coverage of HIV testing in Africa. The findings from this systematic review will guide development of self-testing policy in African countries. PROSPERO CRD42015023935.

[AIDS-related early mortality in Mexico between 2008 and 2012].

PubMed

Silverman-Retana, Omar; Bautista-Arredondo, Sergio; Serván-Mori, Edson; Lozano, Rafael

2015-01-01

To describe the distribution of AIDS-related mortality according to the time of occurrence since entry to the System for the Administration, Logistics and Surveillance of Antiretrovirals (SALVAR, in Spanish), among users of Ministry of Health facilities in Mexico. Descriptive analysis of AIDS mortality and the related clinical and demographic profile of 41847 patients registered in SALVAR. 3195 patients (8.1%) died within the study period, 59% of these deaths occurred within six months after treatment initiation. Among those patients, 87.3% were diagnosed late, given their CD4 levels (CD4cel<200 cel/ml³). Our results underscore the need to strengthen programs aimed to increase opportune HIV diagnosis and linkage to care, as a key component of universal access policy to antiretroviral treatment in Mexico.

A review of accessibility of administrative healthcare databases in the Asia-Pacific region

PubMed Central

Milea, Dominique; Azmi, Soraya; Reginald, Praveen; Verpillat, Patrice; Francois, Clement

2015-01-01

Objective We describe and compare the availability and accessibility of administrative healthcare databases (AHDB) in several Asia-Pacific countries: Australia, Japan, South Korea, Taiwan, Singapore, China, Thailand, and Malaysia. Methods The study included hospital records, reimbursement databases, prescription databases, and data linkages. Databases were first identified through PubMed, Google Scholar, and the ISPOR database register. Database custodians were contacted. Six criteria were used to assess the databases and provided the basis for a tool to categorise databases into seven levels ranging from least accessible (Level 1) to most accessible (Level 7). We also categorised overall data accessibility for each country as high, medium, or low based on accessibility of databases as well as the number of academic articles published using the databases. Results Fifty-four administrative databases were identified. Only a limited number of databases allowed access to raw data and were at Level 7 [Medical Data Vision EBM Provider, Japan Medical Data Centre (JMDC) Claims database and Nihon-Chouzai Pharmacy Claims database in Japan, and Medicare, Pharmaceutical Benefits Scheme (PBS), Centre for Health Record Linkage (CHeReL), HealthLinQ, Victorian Data Linkages (VDL), SA-NT DataLink in Australia]. At Levels 3–6 were several databases from Japan [Hamamatsu Medical University Database, Medi-Trend, Nihon University School of Medicine Clinical Data Warehouse (NUSM)], Australia [Western Australia Data Linkage (WADL)], Taiwan [National Health Insurance Research Database (NHIRD)], South Korea [Health Insurance Review and Assessment Service (HIRA)], and Malaysia [United Nations University (UNU)-Casemix]. Countries were categorised as having a high level of data accessibility (Australia, Taiwan, and Japan), medium level of accessibility (South Korea), or a low level of accessibility (Thailand, China, Malaysia, and Singapore). In some countries, data may be available but accessibility was restricted based on requirements by data custodians. Conclusions Compared with previous research, this study describes the landscape of databases in the selected countries with more granularity using an assessment tool developed for this purpose. A high number of databases were identified but most had restricted access, preventing their potential use to support research. We hope that this study helps to improve the understanding of the AHDB landscape, increase data sharing and database research in Asia-Pacific countries. PMID:27123180

Early life risk factors for testicular cancer: a case-cohort study based on the Copenhagen School Health Records Register.

PubMed

Piltoft, Johanne Spanggaard; Larsen, Signe Benzon; Dalton, Susanne Oksbjerg; Johansen, Christoffer; Baker, Jennifer L; Cederkvist, Luise; Andersen, Ingelise

2017-02-01

One established risk factors for testicular cancer is cryptorchidism. However, it remains unclear whether cryptorchidism is a risk factor in itself or whether the two conditions share common causes in early life (estrogen hypothesis), such as birth weight and birth order. The objective of this study is to utilize data from the Copenhagen School Health Records Register (CSHRR) to evaluate cryptorchidism, birth weight and birth order as risk factors for testicular cancer. The study population consisted of 408 cases of testicular cancer identified by a government issued identification number linkage of the entire CSHRR with the Danish Cancer Registry and a random subsample of 4819 males from the CSHRR. The study design was case-cohort and the period of follow-up between 2 April 1968 and 31 December 2003. Cryptorchidism was significantly associated with testicular cancer in crude analyses [hazard ratio (HR) = 3.60, 95% CI 2.79-4.65]. Birth weight was inversely associated with testicular cancer and no clear association with birth order was observed. The positive association between cryptorchidism and testicular cancer was only slightly attenuated controlling for birth weight and birth order and stratified on birth cohort (HR = 3.46, 95% CI 2.67-4.48). This study confirmed the robustness of the association between cryptorchidism and testicular cancer even after adjustment for birth weight and birth order. Furthermore, the study showed an inverse association between birth weight and testicular cancer.

Mortality and psychiatric disorders among public mental health care clients in Utrecht: a register-based cohort study.

PubMed

Termorshuizen, Fabian; van Bergen, Addi P L; Smit, Ronald B J; Smeets, Hugo M; van Ameijden, Erik J C

2014-08-01

Different studies have shown similar or even lower mortality among homeless persons with compared to homeless persons without a severe mental disorder. To clarify the association between presence of a psychiatric diagnosis and mortality among the socially marginalized. The Public Mental health care (PMHc) is a legal task of the municipal authority aiming at prevention and intervention in case of (imminent) homelessness among persons with a serious shortage of self-sufficiency. The data of PMHc clients (N=6,724) and personally matched controls (N=66,247) were linked to the registries of Statistics Netherlands and analysed in a Cox model. The increased mortality among PMHc clients, compared to the general population (HR=2.99, 95%-CI: 2.63-3.41), was associated with a broad range of death causes. Clients with a record linkage to the Psychiatric Case Registry Middle Netherlands ('PMHc+') had an increased risk of suicide (HR=2.63, 0.99-7.02, P=0.052), but a lower risk of natural death causes (HR=0.71, 0.54-0.92, P=0.011), compared to clients without this record linkage ('PMHc-'). Compared to controls, however, 'PMHc-' clients experienced substantially increased risks of suicide (HR=3.63, 1.42-9.26, P=0.007) and death associated with mental and behavioural disorders (ICD-10 Ch.V) (HR=7.85, 3.54-17.43, P<0.001). Psychiatric services may deliver an important contribution to the prevention of premature natural death among the socially marginalized. The earlier observed lower mortality among vulnerably housed and homeless persons with a psychiatric diagnosis compared to vulnerably housed and homeless persons without a psychiatric diagnosis appears to be due to a significantly lower risk of natural causes of death. Compared to controls from the general population, vulnerably housed and homeless persons without registered diagnosis at a local psychiatric service have a significantly increased mortality associated both with natural death causes and with suicide and death due to mental and behavioural disorders. Services for mental health care may deliver an important contribution to the prevention of premature death due to somatic disorders among the socially marginalized. © The Author(s) 2013.

Hypothyroidism is a predictor of disability pension and loss of labor market income: a Danish register-based study.

PubMed

Thvilum, Marianne; Brandt, Frans; Brix, Thomas Heiberg; Hegedüs, Laszlo

2014-09-01

Hypothyroidism is associated with an increased somatic and psychiatric disease burden. Whether there are any socioeconomic consequences of hypothyroidism, such as early retirement or loss of income, remains unclarified. Our aim was to examine, compared with a matched control group, the risk of receiving disability pension (before the age of 60) and the effect on labor market income in patients diagnosed with hypothyroidism. This was an observational register-based cohort study. By record linkage between different Danish health registers, 1745 hypothyroid singletons diagnosed before the age of 60 were each matched with 4 non-hypothyroid controls and followed for a mean of 5 (range 1-31) years. Additionally, we included 277 same-sex twin pairs discordant for hypothyroidism. The risk of disability pension was evaluated by the Cox regression analysis. Changes in labor market income progression over 5 years were evaluated using a difference in difference model. With a hazard ratio of 2.24 (95% confidence interval = 1.73-2.89), individuals diagnosed with hypothyroidism had a significantly increased risk of disability pension. This remained significant when adjusting for educational level and comorbidity (hazard ratio = 1.89; 95% confidence interval = 1.42-2.51). In an analysis of labor market income, 2 years before compared with 2 years after the diagnosis of hypothyroidism, the hypothyroid individuals had on average a €1605 poorer increase than their euthyroid controls (P < .001). Essentially similar results were found in the twin population. A diagnosis of hypothyroidism before the age of 60 is associated with loss of labor market income and an 89% increased risk of receiving a disability pension.

Prognosis of acute coronary events is worse in patients living alone: the FINAMI myocardial infarction register.

PubMed

Lammintausta, Aino; Airaksinen, Juhani K E; Immonen-Räihä, Pirjo; Torppa, Jorma; Kesäniemi, Antero Y; Ketonen, Matti; Koukkunen, Heli; Kärjä-Koskenkari, Päivi; Lehto, Seppo; Salomaa, Veikko

2014-08-01

Single living has been associated with a worse prognosis of acute coronary syndrome (ACS). We aimed to study the relation of sociodemographic characteristics to the morbidity, mortality, and case fatality (CF) of ACS in a large population-based ACS register. The population-based FINAMI myocardial infarction register recorded 15,330 cases of ACS among persons aged 35-99 years in Finland in 1993-2002. Record linkage with the files of Statistics Finland provided information on sociodemographic characteristics (marital status, household size). ACS incidence and 28-day mortality rate were higher in unmarried men and women in all age groups. The prehospital CF of incident ACS was higher in single living and/or unmarried 35-64-year-old people. The 28-day CF was 26% (95% confidence interval, CI, 24-29%) in married men, 42% (95% CI 37-47%) in men who had previously been married, and 51% (95% CI 46-57%) in never-married men. Among women, the corresponding figures were 20% (95% CI 15-24%), 32% (95% CI 25-39%), and 43% (95% CI 31-56%). Most of these CF differences were apparent already at the prehospital phase. The only difference in treatment was that middle-aged men living alone or unmarried received thrombolysis less often. The disparities in ACS morbidity and mortality by marital status tended to widen during the study period. Single living and/or being unmarried increases the risk of having a heart attack and worsens its prognosis both in men and women regardless of age. Most of the excess mortality appears already before the hospital admission and seems not to be related to differences in treatment of ACS. © The European Society of Cardiology 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Same day ART initiation versus clinic-based pre-ART assessment and counselling for individuals newly tested HIV-positive during community-based HIV testing in rural Lesotho - a randomized controlled trial (CASCADE trial).

PubMed

Labhardt, Niklaus Daniel; Ringera, Isaac; Lejone, Thabo Ishmael; Masethothi, Phofu; Thaanyane, T'sepang; Kamele, Mashaete; Gupta, Ravi Shankar; Thin, Kyaw; Cerutti, Bernard; Klimkait, Thomas; Fritz, Christiane; Glass, Tracy Renée

2016-04-14

Achievement of the UNAIDS 90-90-90 targets in Sub-Sahara Africa is challenged by a weak care-cascade with poor linkage to care and retention in care. Community-based HIV testing and counselling (HTC) is widely used in African countries. However, rates of linkage to care and initiation of antiretroviral therapy (ART) in individuals who tested HIV-positive are often very low. A frequently cited reason for non-linkage to care is the time-consuming pre-ART assessment often requiring several clinic visits before ART-initiation. This two-armed open-label randomized controlled trial compares in individuals tested HIV-positive during community-based HTC the proposition of same-day community-based ART-initiation to the standard of care pre-ART assessment at the clinic. Home-based HTC campaigns will be conducted in catchment areas of six clinics in rural Lesotho. Households where at least one individual tested HIV positive will be randomized. In the standard of care group individuals receive post-test counselling and referral to the nearest clinic for pre-ART assessment and counselling. Once they have started ART the follow-up schedule foresees monthly clinic visits. Individuals randomized to the intervention group receive on the spot point-of-care pre-ART assessment and adherence counselling with the proposition to start ART that same day. Once they have started ART, follow-up clinic visits will be less frequent. First primary outcome is linkage to care (individual presents at the clinic at least once within 3 months after the HIV test). The second primary outcome is viral suppression 12 months after enrolment in the study. We plan to enrol a minimum of 260 households with 1:1 allocation and parallel assignment into both arms. This trial will show if in individuals tested HIV-positive during community-based HTC campaigns the proposition of same-day ART initiation in the community, combined with less frequent follow-up visits at the clinic could be a pragmatic approach to improve the care cascade in similar settings. NCT02692027 , registered February 21, 2016.

Probabilistic record linkage

PubMed Central

Sayers, Adrian; Ben-Shlomo, Yoav; Blom, Ashley W; Steele, Fiona

2016-01-01

Abstract Studies involving the use of probabilistic record linkage are becoming increasingly common. However, the methods underpinning probabilistic record linkage are not widely taught or understood, and therefore these studies can appear to be a ‘black box’ research tool. In this article, we aim to describe the process of probabilistic record linkage through a simple exemplar. We first introduce the concept of deterministic linkage and contrast this with probabilistic linkage. We illustrate each step of the process using a simple exemplar and describe the data structure required to perform a probabilistic linkage. We describe the process of calculating and interpreting matched weights and how to convert matched weights into posterior probabilities of a match using Bayes theorem. We conclude this article with a brief discussion of some of the computational demands of record linkage, how you might assess the quality of your linkage algorithm, and how epidemiologists can maximize the value of their record-linked research using robust record linkage methods. PMID:26686842

A multiscale simulation technique for molecular electronics: design of a directed self-assembled molecular n-bit shift register memory device.

PubMed

Lambropoulos, Nicholas A; Reimers, Jeffrey R; Crossley, Maxwell J; Hush, Noel S; Silverbrook, Kia

2013-12-20

A general method useful in molecular electronics design is developed that integrates modelling on the nano-scale (using quantum-chemical software) and on the micro-scale (using finite-element methods). It is applied to the design of an n-bit shift register memory that could conceivably be built using accessible technologies. To achieve this, the entire complex structure of the device would be built to atomic precision using feedback-controlled lithography to provide atomic-level control of silicon devices, controlled wet-chemical synthesis of molecular insulating pillars above the silicon, and controlled wet-chemical self-assembly of modular molecular devices to these pillars that connect to external metal electrodes (leads). The shift register consists of n connected cells that read data from an input electrode, pass it sequentially between the cells under the control of two external clock electrodes, and deliver it finally to an output device. The proposed cells are trimeric oligoporphyrin units whose internal states are manipulated to provide functionality, covalently connected to other cells via dipeptide linkages. Signals from the clock electrodes are conveyed by oligoporphyrin molecular wires, and μ-oxo porphyrin insulating columns are used as the supporting pillars. The developed multiscale modelling technique is applied to determine the characteristics of this molecular device, with in particular utilization of the inverted region for molecular electron-transfer processes shown to facilitate latching and control using exceptionally low energy costs per logic operation compared to standard CMOS shift register technology.

A multiscale simulation technique for molecular electronics: design of a directed self-assembled molecular n-bit shift register memory device

NASA Astrophysics Data System (ADS)

Lambropoulos, Nicholas A.; Reimers, Jeffrey R.; Crossley, Maxwell J.; Hush, Noel S.; Silverbrook, Kia

2013-12-01

A general method useful in molecular electronics design is developed that integrates modelling on the nano-scale (using quantum-chemical software) and on the micro-scale (using finite-element methods). It is applied to the design of an n-bit shift register memory that could conceivably be built using accessible technologies. To achieve this, the entire complex structure of the device would be built to atomic precision using feedback-controlled lithography to provide atomic-level control of silicon devices, controlled wet-chemical synthesis of molecular insulating pillars above the silicon, and controlled wet-chemical self-assembly of modular molecular devices to these pillars that connect to external metal electrodes (leads). The shift register consists of n connected cells that read data from an input electrode, pass it sequentially between the cells under the control of two external clock electrodes, and deliver it finally to an output device. The proposed cells are trimeric oligoporphyrin units whose internal states are manipulated to provide functionality, covalently connected to other cells via dipeptide linkages. Signals from the clock electrodes are conveyed by oligoporphyrin molecular wires, and μ-oxo porphyrin insulating columns are used as the supporting pillars. The developed multiscale modelling technique is applied to determine the characteristics of this molecular device, with in particular utilization of the inverted region for molecular electron-transfer processes shown to facilitate latching and control using exceptionally low energy costs per logic operation compared to standard CMOS shift register technology.

[Registry of the Italian Institute for Occupational Prevention and Safety of local productive units: methodology and structure].

PubMed

Scarselli, A; Leva, A; Campo, G; Marconi, M; Nesti, M; Erba, P

2005-01-01

The Italian Institute for Occupational Prevention and Safety (ISPESL) carried out a register of enterprises operating in industry, services and agriculture sector to provide information on their location, economical activity and occupational data. This database has been built merging administrative files from the National Institute of Social Security (INPS) and the Computer Science Society of Italian Chambers of Commerce (InfoCamere). Enterprises have been classified by economic sector - in accordance with ISTAT (National Statistics Institute) "Ateco91" classification--and by accuracy level of the record linkage. In details, three different subsystems have been set up: (A) enterprises satisfying linkage; (B) enterprises in InfoCamere file not linked with INPS file; (C) enterprises in INPS file not linked with InfoCamere file. In the whole, 6.026.676 factories have been collected, of which 1.188.784 in group A, 4.543.091 in group B and 294.801 in group C. Establishing a database of information on industries may be useful to improve preventive programs and to plan health care surveillance systems.

Incidence of asthma among Finnish construction workers.

PubMed

Karjalainen, Antti; Martikainen, Rami; Oksa, Panu; Saarinen, Kimmo; Uitti, Jukka

2002-08-01

We wanted to explore the risk of asthma among male workers of the construction industry. All Finnish male construction industry workers and all those employed in administrative work were followed for asthma incidence through a register linkage in 1986 through 1998. Age-adjusted relative risks (RR) were estimated for 24 construction occupations. The risk was increased in nearly all construction occupations studied, but it was highest among welders and flame cutters (RR 2.34), asphalt roofing workers (RR 2.04), plumbers (RR 1.90), and brick layers and tile setters (RR 1.83). Only 45 (2%) of the cases of asthma among construction workers had been recognized as occupational asthma. Construction industry workers have an increased risk of adult-onset persistent asthma and cases of occupational asthma caused by well-established causative agents have only a minor contribution to this overall asthma excess.

Cancer incidence among male Swedish veterinarians and other workers of the veterinary industry: a record-linkage study.

PubMed

Travier, Noemie; Gridley, Gloria; Blair, Aaron; Dosemeci, Mustafa; Boffetta, Paolo

2003-08-01

To investigate the risk of cancer among veterinarians in a large record-linkage study from Sweden. We used the nationwide, Swedish Cancer Environment Registry III, which links the Cancer Register data for 1971-1989 to the national population censuses from 1960 and 1970, to compare the incidence of cancer among male veterinarians to that of the remaining part of the active population using multivariable Poisson regression models and standardized incidence ratios. One thousand one hundred and seventy eight men classified as veterinarians or workers in the veterinary industry at either census were identified. Veterinarians in the veterinary industry experienced increased risk of esophageal (relative risk (RR) 3.78, 95% confidence interval (CI) 1.42-10.09), colon (RR: 2.36, 95% CI: 1.42-3.91), pancreatic (RR: 2.10, 95% CI: 0.94-4.68) and brain (RR: 2.51, 95% CI: 1.04-6.03) cancers as well as melanoma of the skin (RR: 2.77, 95% CI: 1.24-6.17). Similar excess risks were observed when veterinarians were compared with individuals of similar socioeconomic status. The increased risks of esophageal, colon, pancreatic and brain cancers as well as melanoma observed among veterinarians did not seem to be explained by the high socio-economic status of this occupational group. Therefore, it is possible that some of these results reflect the carcinogenicity of occupational exposures, including animal viruses, solar or ionizing radiations and anesthetics.

Linking a pharmaceutical claims database with a birth defects registry to investigate birth defect rates of suspected teratogens.

PubMed

Colvin, Lyn; Slack-Smith, Linda; Stanley, Fiona J; Bower, Carol

2010-11-01

Data linkage of population administrative data is being investigated as a tool for pharmacovigilance in pregnancy in Australia. Records of prescriptions of known or suspected teratogens dispensed to pregnant women have been linked to a birth defects registry to determine if defects associated with medicine exposure can be detected. The Pharmaceutical Benefits Scheme is a national claims database that has been linked with population-based data to extract linkages for women with a pregnancy event in Western Australia from 2002 to 2005 (n = 106 074). Records of births to the women who were dispensed medicines in categories D or X of the Australian ADEC pregnancy risk category were linked to the Birth Defects Registry of Western Australia. Population rates of registered birth defects per 1000 births were calculated for each medicine. There were 47 medicines dispensed at least once during pregnancy with 23 associated with a registered birth defect to a woman dispensed the medicine. When the birth defect rate for each medicine was compared with the rate for all other women not dispensed that medicine, most medicines showed an increased risk. Medicines with the higher risks were medroxyprogesterone acetate (OR: 1.8; 95%CI: 1.4-2.3), follitropin alfa (OR: 2.5; 95%CI: 1.2-5.0), carbamazepine (OR: 3.1; 95%CI: 1.7-5.6) and enalapril maleate (OR: 8.1; 95%CI: 1.6-41.7). Many known associations between medicines and birth defects were identified, suggesting that linked administrative data could be an important means of pharmacovigilance in pregnancy in Australia. Copyright © 2010 John Wiley & Sons, Ltd.

Feasibility of trialling cord blood stem cell treatments for cerebral palsy in Australia.

PubMed

Crompton, Kylie E; Elwood, Ngaire; Kirkland, Mark; Clark, Pamela; Novak, Iona; Reddihough, Dinah

2014-07-01

Umbilical cord blood may have therapeutic benefit in children with cerebral palsy (CP), but further studies are required. On first appearance it seems that Australia is well placed for such a trial because we have excellence in CP research backed by extensive CP registers, and both public and private cord blood banks. We aimed to examine the possibilities of conducting a trial of autologous umbilical cord blood cells (UCBCs) as a treatment for children with CP in Australia. Data linkages between CP registers and cord blood banks were used to estimate potential participant numbers for a trial of autologous UCBCs for children with CP. As of early 2013, one Victorian child with CP had cord blood stored in the public bank, and between 1 and 3 children had their cord blood stored at Cell Care Australia (private cord blood bank). In New South Wales, we counted two children on the CP register who had their stored cord blood available in early 2013. We estimate that there are between 10 and 24 children with CP of any type who have autologous cord blood available across Australia. In nations with small populations like Australia, combined with Australia's relatively low per capita cord blood storage to date, it is not currently feasible to conduct trials of autologous UCBCs for children with CP. Other options must be explored, such as allogeneic UCBCs or prospective trials for neonates at risk of CP. © 2014 The Authors. Journal of Paediatrics and Child Health © 2014 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

Accuracy of reporting abortions with Down syndrome in England and Wales: a data linkage study.

PubMed

Morris, Joan K; Grinsted, Mary; Springett, Anna L

2016-03-01

The number of abortions of fetuses with Down syndrome in England and Wales reported by the Department of Health (DH) differs from that reported by the National Down Syndrome Cytogenetic Register (NDSCR). The aim of this study was to investigate the reasons for this. Abortions in 2011 and 2012 from DH were matched to those from NDSCR. The number of cases not reported to either source was estimated. An estimated 2240 abortions of fetuses with Down syndrome occurred in 2011/12; NDSCR estimated 2208 and DH 1100. One thousand and six abortions were identified in both data sets, including 145 (14%) which were not recorded by DH as having Down syndrome. Abortions in NDSCR that were not matched in DH occurred throughout England and Wales and at all gestational ages. An estimated 61 abortions of fetuses with Down syndrome were not reported to DH or NDSCR. The number of abortions of fetuses with Down syndrome reported by the NDSCR is more complete than that reported by the DH. DH data for abortions with other congenital anomalies are also likely to be underestimates, and more accurate estimates are available from BINOCAR regional congenital anomaly registers. © The Author 2015. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The relationship between sweetened beverage consumption and risk of heart failure in men.

PubMed

Rahman, Iffat; Wolk, Alicja; Larsson, Susanna C

2015-12-01

To investigate whether sweetened beverage consumption is associated with risk of heart failure (HF) in a large prospective population-based study of men. A population-based cohort comprising 42,400 men, 45-79 years of age, was followed from 1998 through 2010. Sweetened beverage consumption was assessed by utilising a food frequency questionnaire. Incident events of HF were identified through linkage to the Swedish National Patient Register and the Cause of Death Register. Cox regression analyses were implemented to investigate the association between sweetened beverage consumption and HF. During a mean follow-up time of 11.7 years, a total of 4113 HF events were identified. We observed a positive association between sweetened beverage consumption and risk of HF after adjustment for other risk factors (p for trend <0.001). Men who consumed two or more servings of sweetened beverages per day had a statistically significant higher risk of developing HF (23%, 95% CI 1.12 to 1.35) compared to men who were non-consumers. Our finding that sweetened beverage consumption is associated with higher risk of HF could have implications for HF prevention strategies. Additional prospective studies investigating the link between sweetened beverage consumption and HF are therefore needed. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Epilepsy in Sweden: health care costs and loss of productivity--a register-based approach.

PubMed

Bolin, Kristian; Lundgren, Anders; Berggren, Fredrik; Källén, Kristina

2012-12-01

The objective was to estimate health care costs and productivity losses due to epilepsy in Sweden and to compare these estimates to previously published estimates. Register data on health care utilisation, pharmaceutical sales, permanent disability and mortality were used to calculate health care costs and costs that accrue due to productivity losses. By linkage of register information, we were able to distinguish pharmaceuticals prescribed against epilepsy from prescriptions that were prompted by other indications. The estimated total cost of epilepsy in Sweden in 2009 was 441 million, which corresponds to an annual per-patient cost of 8,275. Health care accounted for about 16% of the estimated total cost, and drug costs accounted for about 7% of the total cost. The estimated health care cost corresponded to about 0.2% of the total health care cost in Sweden in 2009. Indirect costs were estimated at 370 million, 84% of which was due to sickness absenteeism. Costs resulting from epilepsy-attributable premature deaths or permanent disability to work accounted for about 1% of the total indirect cost in Sweden in 2009. The per-patient cost of epilepsy is substantial. Thus, even though the prevalence of the illness is relatively small, the aggregated cost that epilepsy incurs on society is significant.

The genetics of XX gonadal dysgenesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aittomaeki, K.

1994-05-01

In a nationwide population-based study of women born between 1950 and 1976, 75 patients with XX gonadal dysgenesis (XXGD) were identified in Finland. Patients were ascertained through hospital records and the registers of chromosome laboratories. In one family 4 daughters were affected; in six families 2 daughters were affected; and 57 cases were isolated. In one additional family the two affected females were in successive generations. Population records were utilized to trace ancestors of patients back to the beginning of the 19th century, in most cases. Consanguinity was detected in 8 (12%) of 66 families. When females only are considered,more » the segregation analyses yield a proportion of .23 affected. The relatively large number of affected individuals identified (incidence 1 in 8,300 live-born girls) implies a high gene frequency in the Finnish population. The geographic distribution was highly uneven, with most families originating in the sparsely populated north-central part of Finland. These findings support the existence of an autosomal recessive (XXGD) gene (locus designation [open quotes]ODG1[close quotes]) that is highly enriched in Finland. The multiplex families already identified will make it possible to map the ODG1 gene by a random search for linkage by using polymorphic markers. Linkage-disequilibrium analysis in the sporadic patients will then be used to test for genetic homogeneity versus heterogeneity. 27 refs., 3 figs.« less

Quantifying sources of bias in longitudinal data linkage studies of child abuse and neglect: measuring impact of outcome specification, linkage error, and partial cohort follow-up.

PubMed

Parrish, Jared W; Shanahan, Meghan E; Schnitzer, Patricia G; Lanier, Paul; Daniels, Julie L; Marshall, Stephen W

2017-12-01

Health informatics projects combining statewide birth populations with child welfare records have emerged as a valuable approach to conducting longitudinal research of child maltreatment. The potential bias resulting from linkage misspecification, partial cohort follow-up, and outcome misclassification in these studies has been largely unexplored. This study integrated epidemiological survey and novel administrative data sources to establish the Alaska Longitudinal Child Abuse and Neglect Linkage (ALCANLink) project. Using these data we evaluated and quantified the impact of non-linkage misspecification and single source maltreatment ascertainment use on reported maltreatment risk and effect estimates. The ALCANLink project integrates the 2009-2011 Alaska Pregnancy Risk Assessment Monitoring System (PRAMS) sample with multiple administrative databases through 2014, including one novel administrative source to track out-of-state emigration. For this project we limited our analysis to the 2009 PRAMS sample. We report on the impact of linkage quality, cohort follow-up, and multisource outcome ascertainment on the incidence proportion of reported maltreatment before age 6 and hazard ratios of selected characteristics that are often available in birth cohort linkage studies of maltreatment. Failure to account for out-of-state emigration biased the incidence proportion by 12% (from 28.3% w to 25.2% w ), and the hazard ratio (HR) by as much as 33% for some risk factors. Overly restrictive linkage parameters biased the incidence proportion downwards by 43% and the HR by as much as 27% for some factors. Multi-source linkages, on the other hand, were of little benefit for improving reported maltreatment ascertainment. Using the ALCANLink data which included a novel administrative data source, we were able to observe and quantify bias to both the incidence proportion and HR in a birth cohort linkage study of reported child maltreatment. Failure to account for out-of-state emigration and low-quality linkage methods may induce bias in longitudinal data linkage studies of child maltreatment which other researchers should be aware of. In this study multi-agency linkage did not lead to substantial increased detection of reported maltreatment. The ALCANLink methodology may be a practical approach for other states interested in developing longitudinal birth cohort linkage studies of maltreatment that requires limited resources to implement, provides comprehensive data elements, and can facilitate comparability between studies.

Evidence for a major retinitis pigmentosa locus on 19q13.4 (RP11), and association with a unique bimodal expressivity phenotype

DOE Office of Scientific and Technical Information (OSTI.GOV)

Al-Maghtheh, M.; Vithana, E.; Tarttelin, E.

Retinitis pigmentosa (RP) is the name given to a heterogeneous group of retinal degenerations mapping to at least 16 loci. The autosomal dominant form (adRP), accounting for {approximately}25% of cases, can be caused by mutations in two genes, rhodopsin and peripherin/RDS, and by at least six other loci identified by linkage analysis. The RP11 locus for adRP has previously been mapped to chromosome 19q13.4 in a large English family. This linkage has been independently confirmed in a Japanese family, and we now report three additional unrelated linked U.K. families, suggesting that this is a major locus for RP. Linkage analysismore » in the U.K. families refines the RP11 interval to 5 cM between markers D19S180 and AFMc001yb1. All linked families exhibit incomplete penetrance; some obligate gene carriers remain asymptomatic throughout their lives, whereas symptomatic individuals experience night blindness and visual field loss in their teens and are generally registered as blind by their 30s. This {open_quotes}bimodal expressivity{close_quotes} contrasts with the variable-expressivity RP mapping to chromosome 7p (RP9) in another family, which has implications for diagnosis and counseling of RP11 families. These results may also imply that a proportion of sporadic RP, previously assumed to be recessive, might result from mutations at this locus. 27 refs., 3 figs., 1 tab.« less

The Nightingale study: rationale, study design and baseline characteristics of a prospective cohort study on shift work and breast cancer risk among nurses.

PubMed

Pijpe, Anouk; Slottje, Pauline; van Pelt, Cres; Stehmann, Floor; Kromhout, Hans; van Leeuwen, Flora E; Vermeulen, Roel C H; Rookus, Matti A

2014-01-29

Evidence for the carcinogenicity of shift work in humans is limited because of significant heterogeneity of the results, thus more in-depth research in needed. The Nightingale Study is a nationwide prospective cohort study on occupational exposures and risks of chronic diseases among female nurses and focuses on the potential association between shift work and risk of breast cancer. The study design, methods, and baseline characteristics of the cohort are described. The source population for the cohort comprised 18 to 65 year old women who were registered as having completed training to be a nurse in the nationwide register for healthcare professionals in the Netherlands. Eligible women were invited to complete a web-based questionnaire including full job history, a detailed section on all domains of shift work (shift system, cumulative exposure, and shift intensity) and potential confounding factors, and an informed consent form for linkage with national (disease) registries. Women were also asked to donate toenail clippings as a source of DNA for genetic analyses. Between October 6, 2011 and February 1, 2012, 31% of the 192,931 women who were invited to participate completed the questionnaire, yielding a sample size of 59,947 cohort members. The mean age of the participants was 46.9 year (standard deviation 11.0 years). Toenail clippings were provided by 23,439 participants (39%). Results from the Nightingale Study will contribute to the scientific evidence of potential shift work-related health risks among nurses and will help develop preventive measures and policy aimed at reducing these risks.

Register based monitoring shows decreasing socioeconomic differences in Finnish perinatal health

PubMed Central

Gissler, M; Merilainen, J; Vuori, E; Hemminki, E

2003-01-01

Study objective: Several studies on differences in infant outcome by socioeconomic position have been done, but these have usually been based on ad hoc data linkages. The aim of this paper was to investigate whether socioeconomic differences in perinatal health in Finland could be regularly monitored using routinely collected data from one single register. Design and setting: Since October 1990, the Finnish Medical Birth Register (MBR) has included data on maternal occupation. A special computer program that converted the occupation name into an occupational code and into a socioeconomic position was prepared. Perinatal health was measured with five different indicators. The Finnish MBR data for years 1991 to 1999 (n=565 863 newborns) were used in the study. The study period was divided into three, three year periods to study time trends. Results: An occupational code was derived for 95% of women, but it was not possible to define a socioeconomic position for 22% of women, including, for example, students and housewives (the group "Others"). For the rest, the data showed socioeconomic differences in all perinatal health indicators. Maternal smoking explained up to half of the excess risk for adverse perinatal outcome in the lowest socioeconomic group. The socioeconomic differences narrowed during the 1990s: infant outcome improved in the lowest socioeconomic group, but remained at the same level or even deteriorated in other groups. When comparing the lowest group with the highest group, the odds ratios (OR) adjusted for maternal background characteristics at least halved for prematurity (from 1.32 (95% confidence intervals 1.24 to 1.43) in 1991–1993 to 1.16 (1.08 to 1.25) in 1997–1999), for low birth weight (from 1.49 (1.36 to 1.63) to 1.25 (1.17 to 1.40)), and for perinatal mortality (from 1.79 (1.44 to 2.21) to 1.33 (1.07 to 1.66)). Conclusions: Social inequality in perinatal health outcomes exists in Finland, but seems to have diminished in the 1990s. These data showed that routinely collected birth register data provide a good source for studies on socioeconomic health differences in the perinatal period, but that uncertainty, mainly attributable to the large group of women with difficult to classify socioeconomic status, remains. PMID:12775790

Occupational injuries in Italy.

PubMed

Baldasseroni, Alberto; Chellini, Elisabetta; Mantero, Silvia; Giovannetti, Lucia

2005-01-01

Data collected by the Italian Funds for Occupational Injuries and Diseases (INAIL) on incidence and mortality for occupational injuries in Italy during 1951-2001 are described with respect to the two main occupational sectors, Industry and Services, and Agriculture. Comparisons with other EU countries are included to place the current severe phenomenon in context. An ad hoc analysis aimed at verifying the completeness of the data on occupational fatal accidents collected by INAIL in Tuscany is reported: a linkage between the INAIL data and those registered by the Tuscan Regional Mortality Registry highlights that a number of working areas are not covered by INAIL, a problem whose solution would be useful for primary prevention.

Can statistical linkage of missing variables reduce bias in treatment effect estimates in comparative effectiveness research studies?

PubMed

Crown, William; Chang, Jessica; Olson, Melvin; Kahler, Kristijan; Swindle, Jason; Buzinec, Paul; Shah, Nilay; Borah, Bijan

2015-09-01

Missing data, particularly missing variables, can create serious analytic challenges in observational comparative effectiveness research studies. Statistical linkage of datasets is a potential method for incorporating missing variables. Prior studies have focused upon the bias introduced by imperfect linkage. This analysis uses a case study of hepatitis C patients to estimate the net effect of statistical linkage on bias, also accounting for the potential reduction in missing variable bias. The results show that statistical linkage can reduce bias while also enabling parameter estimates to be obtained for the formerly missing variables. The usefulness of statistical linkage will vary depending upon the strength of the correlations of the missing variables with the treatment variable, as well as the outcome variable of interest.

Data Linkage: A powerful research tool with potential problems

PubMed Central

2010-01-01

Background Policy makers, clinicians and researchers are demonstrating increasing interest in using data linked from multiple sources to support measurement of clinical performance and patient health outcomes. However, the utility of data linkage may be compromised by sub-optimal or incomplete linkage, leading to systematic bias. In this study, we synthesize the evidence identifying participant or population characteristics that can influence the validity and completeness of data linkage and may be associated with systematic bias in reported outcomes. Methods A narrative review, using structured search methods was undertaken. Key words "data linkage" and Mesh term "medical record linkage" were applied to Medline, EMBASE and CINAHL databases between 1991 and 2007. Abstract inclusion criteria were; the article attempted an empirical evaluation of methodological issues relating to data linkage and reported on patient characteristics, the study design included analysis of matched versus unmatched records, and the report was in English. Included articles were grouped thematically according to patient characteristics that were compared between matched and unmatched records. Results The search identified 1810 articles of which 33 (1.8%) met inclusion criteria. There was marked heterogeneity in study methods and factors investigated. Characteristics that were unevenly distributed among matched and unmatched records were; age (72% of studies), sex (50% of studies), race (64% of studies), geographical/hospital site (93% of studies), socio-economic status (82% of studies) and health status (72% of studies). Conclusion A number of relevant patient or population factors may be associated with incomplete data linkage resulting in systematic bias in reported clinical outcomes. Readers should consider these factors in interpreting the reported results of data linkage studies. PMID:21176171

Linkage and related analyses of Barrett's esophagus and its associated adenocarcinomas.

PubMed

Sun, Xiangqing; Elston, Robert; Falk, Gary W; Grady, William M; Faulx, Ashley; Mittal, Sumeet K; Canto, Marcia I; Shaheen, Nicholas J; Wang, Jean S; Iyer, Prasad G; Abrams, Julian A; Willis, Joseph E; Guda, Kishore; Markowitz, Sanford; Barnholtz-Sloan, Jill S; Chandar, Apoorva; Brock, Wendy; Chak, Amitabh

2016-07-01

Familial aggregation and segregation analysis studies have provided evidence of a genetic basis for esophageal adenocarcinoma (EAC) and its premalignant precursor, Barrett's esophagus (BE). We aim to demonstrate the utility of linkage analysis to identify the genomic regions that might contain the genetic variants that predispose individuals to this complex trait (BE and EAC). We genotyped 144 individuals in 42 multiplex pedigrees chosen from 1000 singly ascertained BE/EAC pedigrees, and performed both model-based and model-free linkage analyses, using S.A.G.E. and other software. Segregation models were fitted, from the data on both the 42 pedigrees and the 1000 pedigrees, to determine parameters for performing model-based linkage analysis. Model-based and model-free linkage analyses were conducted in two sets of pedigrees: the 42 pedigrees and a subset of 18 pedigrees with female affected members that are expected to be more genetically homogeneous. Genome-wide associations were also tested in these families. Linkage analyses on the 42 pedigrees identified several regions consistently suggestive of linkage by different linkage analysis methods on chromosomes 2q31, 12q23, and 4p14. A linkage on 15q26 is the only consistent linkage region identified in the 18 female-affected pedigrees, in which the linkage signal is higher than in the 42 pedigrees. Other tentative linkage signals are also reported. Our linkage study of BE/EAC pedigrees identified linkage regions on chromosomes 2, 4, 12, and 15, with some reported associations located within our linkage peaks. Our linkage results can help prioritize association tests to delineate the genetic determinants underlying susceptibility to BE and EAC.

Linkages between public and non-government sectors in healthcare: A case study from Uttar Pradesh, India.

PubMed

Srivastava, Aradhana; Bhattacharyya, Sanghita; Gautham, Meenakshi; Schellenberg, Joanna; Avan, Bilal I

2016-12-01

Effective utilisation of collaborative non-governmental organisation (NGO)-public health system linkages in pluralistic health systems of developing countries can substantially improve equity and quality of services. This study explores level and types of linkages between public health sector and NGOs in Uttar Pradesh (UP), an underprivileged state of India, using a social science model for the first time. It also identifies gaps and challenges for effective linkage. Two NGOs were selected as case studies. Data collection included semi-structured in-depth interviews with senior staff and review of records and reporting formats. Formal linkages of NGOs with the public health system related to registration, participation in district level meetings, workforce linkages and sharing information on government-supported programmes. Challenges included limited data sharing, participation in planning and limited monitoring of regulatory compliances. Linkage between public health system and NGOs in UP was moderate, marked by frequent interaction and some reciprocity in information and resource flows, but weak participation in policy and planning. The type of linkage could be described as 'complementarity', entailing information and resource sharing but not joint action. Stronger linkage is required for sustained and systematic collaboration, with joint planning, implementation and evaluation.

Physical and mental health functioning after all-cause and diagnosis-specific sickness absence: a register-linkage follow-up study among ageing employees.

PubMed

Mänty, Minna; Lallukka, Tea; Lahti, Jouni; Pietiläinen, Olli; Laaksonen, Mikko; Lahelma, Eero; Rahkonen, Ossi

2017-01-25

Sickness absence has been shown to be a risk marker for severe future health outcomes, such as disability retirement and premature death. However, it is poorly understood how all-cause and diagnosis-specific sickness absence is reflected in subsequent physical and mental health functioning over time. The aim of this study was to examine the association of all-cause and diagnosis-specific sickness absence with subsequent changes in physical and mental health functioning among ageing municipal employees. Prospective survey and register data from the Finnish Helsinki Health Study and the Social Insurance Institution of Finland were used. Register based records for medically certified all-cause and diagnostic-specific sickness absence spells (>14 consecutive calendar days) in 2004-2007 were examined in relation to subsequent physical and mental health functioning measured by Short-Form 36 questionnaire in 2007 and 2012. In total, 3079 respondents who were continuously employed over the sickness absence follow-up were included in the analyses. Repeated-measures analysis was used to examine the associations. During the 3-year follow-up, 30% of the participants had at least one spell of medically certified sickness absence. All-cause sickness absence was associated with lower subsequent physical and mental health functioning in a stepwise manner: the more absence days, the poorer the subsequent physical and mental health functioning. These differences remained but narrowed slightly during the follow-up. Furthermore, the adverse association for physical health functioning was strongest among those with sickness absence due to diseases of musculoskeletal or respiratory systems, and on mental functioning among those with sickness absence due to mental disorders. Sickness absence showed a persistent adverse stepwise association with subsequent physical and mental health functioning. Evidence on health-related outcomes after long-term sickness absence may provide useful information for targeted interventions to promote health and workability.

Continued antidepressant treatment and suicide in patients with depressive disorder.

PubMed

Søndergård, Lars; Lopez, Ana Garcia; Andersen, Per Kragh; Kessing, Lars Vedel

2007-01-01

Antidepressant use in Denmark, as in many developed countries, has substantially increased during recent years, coinciding with a decreasing suicide rate. In a nationwide observational cohort study with linkage of registers of all prescribed antidepressants and recorded suicides in Denmark from 1995 to 2000, we investigated the relation between continued treatment with antidepressants and suicide in a population of all patients discharged from hospital psychiatry with a diagnosis of depressive disorder. Patients discharged from hospital psychiatry with a diagnosis of depressive disorder had a highly increased rate of suicide. Those who continued treatment with antidepressants had a decreased rate of suicide compared with those who purchased antidepressants once (rate ratio: 0.31, 95% confidence interval: 0.26-0.36). Further, the rate of suicide decreased consistently with the number of prescriptions. On individualized data from a cohort of patients with a known history of depressive disorder, continued antidepressant treatment was associated with reduced risk of suicide.

Occupation and thyroid cancer risk in Sweden.

PubMed

Lope, Virginia; Pollán, Marina; Gustavsson, Per; Plato, Nils; Pérez-Gómez, Beatriz; Aragonés, Nuria; Suárez, Berta; Carrasco, José Miguel; Rodríguez, Silvia; Ramis, Rebeca; Boldo, Elena; López-Abente, Gonzalo

2005-09-01

The objective of this study was to identify occupations and industries with increased incidence of thyroid cancer in Swedish workers. Standardized incidence ratios were computed for each job and industry for the period 1971-1989 through record-linkage with the Swedish National Cancer and Death Registers. Age-, period-, geographically adjusted relative risks were calculated using Poisson models. Increased risks were found for teachers, construction carpenters, policemen, and prison/reformatory officials in men, and medical technicians, shop managers, tailors, and shoecutters among women. Industries with risk excess are manufacture of agricultural machinery, manufacture of computing/accessories, and public administration/police among men; and manufacture of prefabricated wooden buildings, electric installation work, and wholesale of live animals/fertilizers/oilseed/grain among women. Our results corroborate some previously reported increased risks. Further research is needed to assess the influence of specific chemical agents related with some of the highlighted work environments.

Linkage to HIV care after home-based HIV counselling and testing in sub-Saharan Africa: a systematic review.

PubMed

Ruzagira, Eugene; Baisley, Kathy; Kamali, Anatoli; Biraro, Samuel; Grosskurth, Heiner

2017-07-01

Home-based HIV counselling and testing (HBHCT) has the potential to increase HIV testing uptake in sub-Saharan Africa (SSA), but data on linkage to HIV care after HBHCT are scarce. We conducted a systematic review of linkage to care after HBHCT in SSA. Five databases were searched for studies published between 1st January 2000 and 19th August 2016 that reported on linkage to care among adults newly identified with HIV infection through HBHCT. Eligible studies were reviewed, assessed for risk of bias and findings summarised using the PRISMA guidelines. A total of 14 studies from six countries met the eligibility criteria; nine used specific strategies (point-of-care CD4 count testing, follow-up counselling, provision of transport funds to clinic and counsellor facilitation of HIV clinic visit) in addition to routine referral to facilitate linkage to care. Time intervals for ascertaining linkage ranged from 1 week to 12 months post-HBHCT. Linkage ranged from 8.2% [95% confidence interval (CI), 6.8-9.8%] to 99.1% (95% CI, 96.9-99.9%). Linkage was generally lower (<33%) if HBHCT was followed by referral only, and higher (>80%) if additional strategies were used. Only one study assessed linkage by means of a randomised trial. Five studies had data on cotrimoxazole (CTX) prophylaxis and 12 on ART eligibility and initiation. CTX uptake among those eligible ranged from 0% to 100%. The proportion of persons eligible for ART ranged from 16.5% (95% CI, 12.1-21.8) to 77.8% (95% CI, 40.0-97.2). ART initiation among those eligible ranged from 14.3% (95% CI, 0.36-57.9%) to 94.9% (95% CI, 91.3-97.4%). Additional linkage strategies, whilst seeming to increase linkage, were not associated with higher uptake of CTX and/or ART. Most of the studies were susceptible to risk of outcome ascertainment bias. A pooled analysis was not performed because of heterogeneity across studies with regard to design, setting and the key variable definitions. Only few studies from SSA investigated linkage to care among adults newly diagnosed with HIV through HBHCT. Linkage was often low after routine referral but higher if additional interventions were used to facilitate it. The effectiveness of linkage strategies should be confirmed through randomised controlled trials. © 2017 The Authors. Tropical Medicine & International Health Published by John Wiley & Sons Ltd.

Familial recurrence-pattern analysis of nonsyndromic isolated cleft palate - A Danish registry study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Christensen, K.; Mitchell, L.E.

1996-01-01

The finding of an association between genetic variation at the transforming growth-factor alpha (TGFA) locus and nonsyndromic isolated cleft palate (CP) represents a potentially important breakthrough in our understanding of this condition. The present study was undertaken to assess the feasibility of detecting linkage to putative CP-susceptibility loci, such as TGFA. To this end, the familial recurrence pattern for CP was evaluated to determine the most likely mode of inheritance for this condition. The study took advantage of the high ascertainment and uniform registration of CP in Denmark. In addition, the study utilized estimates of familial recurrence that were obtainedmore » by register linkage and, hence, were not subject to either recall bias or the potentially biasing influence of nonresponders. The recurrence risks for first-, second-, and third-degree relatives of 1,364 nonsyndromic CP probands were estimated to be 2.74% (72/2,628), 0.28% (3/1,068), and 0.00% (0/360), respectively. These estimates are close to published estimates based on questionnaire and interview data. The population prevalence for nonsyndromic CP was, however, found to be considerable higher than usually reported (0.058% [1,456/2,523,023]). Analyses of these and previously published data, using the method presented by Risch, indicated that major-locus or additive multilocus inheritance of CP is unlikely. The familial recurrence pattern was, however, consistent with CP being determined by several interacting loci. Under such a model, a single locus accounting for more than a sixfold increase in the risk to first-degree relatives of CP probands is unlikely, whereas a single locus accounting for a threefold increase provided a good fit to the data. Such a locus could be detected in a realistic sample of affected sib pairs. 26 refs., 3 tabs.« less

Retention of antiretroviral naïve patients registered in HIV care in a program clinic in Pune, India

PubMed Central

Ghate, Manisha V.; Zirpe, Sunil S.; Gurav, Nilam P.; Rewari, Bharat B.; Gangakhedkar, Raman R.; Paranjape, Ramesh S.

2014-01-01

Background: Retention in HIV care ensures delivery of services like secondary prevention, timely initiation of treatment, support, and care on a regular basis. The data on retention in pre antiretroviral therapy (ART) care in India is scanty. Materials and Methods: Antiretroviral naïve HIV-infected adult patients registered between January 2011 and March 2012 in HIV care (pre-ART) were included in the study. The follow-up procedures were done as per the national guidelines. Patients who did not report to the clinic for 1 year were considered as pre-ART lost to follow-up (pre-ART LFU). They were contacted either telephonically or by home visits. Logistic regression analysis was done to find out factors associated with pre-ART loss to follow-up. Results: A total of 689 antiretroviral naïve adult patients were registered in the HIV care. Fourteen (2%) patients died and 76 (11%) were LFU till March 2013. The multivariate analysis showed that baseline CD4 count >350 cells/mm3 (P < 0.01) and illiteracy (P = 0.044) were significantly associated with LFU. Of the total pre-ART LFUs, 35 (46.1%) informed that they would visit the clinic at their convenient time. NGOs that referred 16 female sex workers (FSWs) who were LFU (21.1%) informed that they would make efforts to refer them to the clinic. Conclusion: Higher CD4 count and illiteracy were significantly associated with lower retention in pre-ART care. Developing effective “retention package” for patients and strengthening linkage strategies between key sub-population such as FSWs and ART programming will help to plug the leaky cascade in HIV care. PMID:26396447

Chinese health care system and clinical epidemiology

PubMed Central

Sun, Yuelian; Gregersen, Hans; Yuan, Wei

2017-01-01

China has gone through a comprehensive health care insurance reform since 2003 and achieved universal health insurance coverage in 2011. The new health care insurance system provides China with a huge opportunity for the development of health care and medical research when its rich medical resources are fully unfolded. In this study, we review the Chinese health care system and its implication for medical research, especially within clinical epidemiology. First, we briefly review the population register system, the distribution of the urban and rural population in China, and the development of the Chinese health care system after 1949. In the following sections, we describe the current Chinese health care delivery system and the current health insurance system. We then focus on the construction of the Chinese health information system as well as several existing registers and research projects on health data. Finally, we discuss the opportunities and challenges of the health care system in regard to clinical epidemiology research. China now has three main insurance schemes. The Urban Employee Basic Medical Insurance (UEBMI) covers urban employees and retired employees. The Urban Residence Basic Medical Insurance (URBMI) covers urban residents, including children, students, elderly people without previous employment, and unemployed people. The New Rural Cooperative Medical Scheme (NRCMS) covers rural residents. The Chinese Government has made efforts to build up health information data, including electronic medical records. The establishment of universal health care insurance with linkage to medical records will provide potentially huge research opportunities in the future. However, constructing a complete register system at a nationwide level is challenging. In the future, China will demand increased capacity of researchers and data managers, in particular within clinical epidemiology, to explore the rich resources. PMID:28356772

Comorbidity of autoimmune thyroid disorders and psychiatric disorders during the postpartum period: a Danish nationwide register-based cohort study.

PubMed

Bergink, V; Pop, V J M; Nielsen, P R; Agerbo, E; Munk-Olsen, T; Liu, X

2018-06-01

The postpartum period is well-known risk period for the first onset of autoimmune thyroid disorders (AITDs) as well as first onset of psychiatric disorders. These two disorders are some of the most prevalent medical conditions postpartum, often misdiagnosed and disabling if left untreated. Our study was designed to explore the possible bidirectional association between AITDs and psychiatric disorders during the postpartum period. A population-based cohort study through linkage of Danish national registers, which comprised 312 779 women who gave birth to their first child during 1997-2010. We conducted Poisson regression analysis to estimate the incidence rate ratio (IRR) of psychiatric disorders among women with first-onset AITDs, the IRR of AITDs among women with first-onset psychiatric disorders as well as the overlap between these disorders using a comorbidity index. Women with first-onset AITDs postpartum were more likely to have first-onset psychiatric disorders than women who did not have postpartum AITDs (IRR = 1.88, 95% confidence interval (CI): 1.25-2.81). Women with first-onset postpartum psychiatric disorders had a higher risk of AITDs than women with no psychiatric disorders (IRR = 2.16, 95% CI: 1.45-3.20). The comorbidity index 2 years after delivery was 2.26 (95% CI: 1.61-2.90), indicating a comorbidity between first-onset AITDs and psychiatric disorders. First-onset AITDs and psychiatric disorders co-occur in the postpartum period, which has relevance to further studies on the etiologies of these disorders and why childbirth in particular triggers the onset.

Human Leukocyte Antigen-A, B, C, DRB1, and DQB1 Allele and Haplotype Frequencies in a Subset of 237 Donors in the South African Bone Marrow Registry

PubMed Central

Ingram, Charlotte; Schlaphoff, Terry; Borrill, Veronica; Christoffels, Alan

2018-01-01

Human leukocyte antigen- (HLA-) A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 allele and haplotype frequencies were studied in a subset of 237 volunteer bone marrow donors registered at the South African Bone Marrow Registry (SABMR). Hapl-o-Mat software was used to compute allele and haplotype frequencies from individuals typed at various resolutions, with some alleles in multiple allele code (MAC) format. Four hundred and thirty-eight HLA-A, 235 HLA-B, 234 HLA-DRB1, 41 HLA-DQB1, and 29 HLA-C alleles are reported. The most frequent alleles were A∗02:02g (0.096), B∗07:02g (0.082), C∗07:02g (0.180), DQB1∗06:02 (0.157), and DRB1∗15:01 (0.072). The most common haplotype was A∗03:01g~B∗07:02g~C∗07:02g~DQB1∗06:02~DRB1∗15:01 (0.067), which has also been reported in other populations. Deviations from Hardy-Weinberg equilibrium were observed in A, B, and DRB1 loci, with C~DQB1 being the only locus pair in linkage disequilibrium. This study describes allele and haplotype frequencies from a subset of donors registered at SABMR, the only active bone marrow donor registry in Africa. Although the sample size was small, our results form a key resource for future population studies, disease association studies, and donor recruitment strategies. PMID:29850621

Vaccination coverage according to doses received and timely administered based on an electronic immunization registry, Araraquara-SP, Brazil, 2012-2014.

PubMed

Tauil, Márcia de Cantuária; Sato, Ana Paula Sayuri; Costa, Ângela Aparecida; Inenami, Marta; Ferreira, Vinícius Leati de Rossi; Waldman, Eliseu Alves

2017-01-01

to describe vaccine coverage by type of vaccine at 12 and 24 months of age. descriptive cohort study with children born in 2012, living in Araraquara-SP, Brazil, recorded in the Information System on Live Births (Sinasc); a manual linkage of Sinasc data with an electronic immunization registry (EIR) was performed; the assessment was based on vaccination status according to São Paulo State recommendations, and on doses received and timely administered. 2,740 children were registered on Sinasc and 99.6% of them were included into EIR; among the 2,612 (95.3%) children studied, the triple viral vaccine (measles, mumps and rubella) had the lowest coverage at 12 months for received dose (74.8%) and at 24 months for timely vaccination (53.5%) and received doses (88.0%). coverage was higher than 90% for most vaccines; however, delayed vaccination was observed, which indicates the need to intensify actions aimed at timely vaccination.

Genome scan for linkage to asthma using a linkage disequilibrium-lod score test.

PubMed

Jiang, Y; Slager, S L; Huang, J

2001-01-01

We report a genome-wide linkage study of asthma on the German and Collaborative Study on the Genetics of Asthma (CSGA) data. Using a combined linkage and linkage disequilibrium test and the nonparametric linkage score, we identified 13 markers from the German data, 1 marker from the African American (CSGA) data, and 7 markers from the Caucasian (CSGA) data in which the p-values ranged between 0.0001 and 0.0100. From our analysis and taking into account previous published linkage studies of asthma, we suggest that three regions in chromosome 5 (around D5S418, D5S644, and D5S422), one region in chromosome 6 (around three neighboring markers D6S1281, D6S291, and D6S1019), one region in chromosome 11 (around D11S2362), and two regions in chromosome 12 (around D12S351 and D12S324) especially merit further investigation.

Comprehensive Care Plan Development Using Resident Assessment Instrument Framework: Past, Present, and Future Practices

PubMed Central

Dellefield, Mary Ellen; Corazzini, Kirsten

2015-01-01

Development of the comprehensive care plan (CCP) is a requirement for nursing homes participating in the federal Medicare and Medicaid programs, referred to as skilled nursing facilities. The plan must be developed within the context of the comprehensive interdisciplinary assessment framework—the Resident Assessment Instrument (RAI). Consistent compliance with this requirement has been difficult to achieve. To improve the quality of CCP development within this framework, an increased understanding of complex factors contributing to inconsistent compliance is required. In this commentary, we examine the history of the comprehensive care plan; its development within the RAI framework; linkages between the RAI and registered nurse staffing; empirical evidence of the CCP’s efficacy; and the limitations of extant standards of practices in CCP development. Because of the registered nurse’s educational preparation, professional practice standards, and licensure obligations, the essential contributions of professional nurses in CCP development are emphasized. Recommendations for evidence-based micro and macro level practice changes with the potential to improve the quality of CCP development and regulatory compliance are presented. Suggestions for future research are given. PMID:27417811

Racial misclassification of American Indians: its effect on injury rates in Oregon, 1989 through 1990.

PubMed Central

Sugarman, J R; Soderberg, R; Gordon, J E; Rivara, F P

1993-01-01

OBJECTIVES. We assessed the extent to which injury rates among American Indians in Oregon are underestimated owing to misclassification of race in a surveillance system. METHODS. The Oregon Injury Registry, a population-based surveillance system, was linked with the Indian Health Service patient registration file from Oregon, and injury rates for American Indians were calculated before and after correcting for racial misclassification. RESULTS. In 1989 and 1990, 301 persons in the Oregon registry were coded as American Indian. An additional 89 injured persons who were coded as a race other than American Indian in the registry were listed as American Indian in the Indian Health Service records. The age-adjusted annual injury rate for health service-registered American Indians was 6.9/1000, 68% higher than the rate calculated before data linkage. American Indian ancestry, female sex, and residence in metropolitan counties were associated with a higher likelihood of concordant racial classification in both data sets. CONCLUSION. Injury rates among American Indians in an Oregon surveillance system are substantially underestimated owing to racial misclassification. Linkage of disease registries and vital records with Indian Health Service records in other states may improve health-related data regarding American Indians. PMID:8484448

Genome-wide Linkage Scan of Antisocial Behavior, Depression and Impulsive Substance Use in the UCSF Family Alcoholism Study

PubMed Central

Gizer, Ian R.; Ehlers, Cindy L.; Vieten, Cassandra; Feiler, Heidi S.; Gilder, David A.; Wilhelmsen, Kirk C.

2012-01-01

OBJECTIVE Epidemiological and clinical studies suggest that rates of antisocial behavior, depression, and impulsive substance use are increased among individuals diagnosed with alcohol dependence relative to those who are not. Thus, the present study conducted genome-wide linkage scans of antisocial behavior, depression, and impulsive substance use in the University of California at San Francisco Family Alcoholism Study. METHODS Antisocial behavior, depressive symptoms, and impulsive substance use were assessed using three scales from the MMPI-2, the Antisocial Practices content scale (ASP), the Depression content scale (DEP), and the revised MacAndrew Alcoholism scale (MAC-R). Linkage analyses were conducted using a variance components approach. RESULTS Suggestive evidence of linkage to three genomic regions independent of alcohol and cannabis dependence diagnostic status was observed: the ASP scale showed evidence of linkage to chromosome 13 at 11 cM, the MAC-R scale showed evidence of linkage to chromosome 15 at 47 cM, and all 3 scales showed evidence of linkage to chromosome 17 at 57–58 cM. CONCLUSIONS Each of these regions has shown prior evidence of linkage and association to substance dependence as well as other psychiatric disorders such as mood and anxiety disorders, ADHD, and schizophrenia thus suggesting potentially broad relations between these regions and psychopathology. PMID:22517380

A New Method for Assessing How Sensitivity and Specificity of Linkage Studies Affects Estimation

PubMed Central

Moore, Cecilia L.; Amin, Janaki; Gidding, Heather F.; Law, Matthew G.

2014-01-01

Background While the importance of record linkage is widely recognised, few studies have attempted to quantify how linkage errors may have impacted on their own findings and outcomes. Even where authors of linkage studies have attempted to estimate sensitivity and specificity based on subjects with known status, the effects of false negatives and positives on event rates and estimates of effect are not often described. Methods We present quantification of the effect of sensitivity and specificity of the linkage process on event rates and incidence, as well as the resultant effect on relative risks. Formulae to estimate the true number of events and estimated relative risk adjusted for given linkage sensitivity and specificity are then derived and applied to data from a prisoner mortality study. The implications of false positive and false negative matches are also discussed. Discussion Comparisons of the effect of sensitivity and specificity on incidence and relative risks indicate that it is more important for linkages to be highly specific than sensitive, particularly if true incidence rates are low. We would recommend that, where possible, some quantitative estimates of the sensitivity and specificity of the linkage process be performed, allowing the effect of these quantities on observed results to be assessed. PMID:25068293

Estimation and test for linkage between markers: a comparison of lod score and χ (2) test in a linkage study of maritime pine (Pinus pinaster Ait.).

PubMed

Gerber, S; Rodolphe, F

1994-06-01

The first step in the construction of a linkage map involves the estimation and test for linkage between all possible pairs of markers. The lod score method is used in many linkage studies for the latter purpose. In contrast with classical statistical tests, this method does not rely on the choice of a first-type error level. We thus provide a comparison between the lod score and a χ (2) test on linkage data from a gymnosperm, the maritime pine. The lod score appears to be a very conservative test with the usual thresholds. Its severity depends on the type of data used.

Linked Records of Children with Traumatic Brain Injury. Probabilistic Linkage without Use of Protected Health Information.

PubMed

Bennett, T D; Dean, J M; Keenan, H T; McGlincy, M H; Thomas, A M; Cook, L J

2015-01-01

Record linkage may create powerful datasets with which investigators can conduct comparative effectiveness studies evaluating the impact of tests or interventions on health. All linkages of health care data files to date have used protected health information (PHI) in their linkage variables. A technique to link datasets without using PHI would be advantageous both to preserve privacy and to increase the number of potential linkages. We applied probabilistic linkage to records of injured children in the National Trauma Data Bank (NTDB, N = 156,357) and the Pediatric Health Information Systems (PHIS, N = 104,049) databases from 2007 to 2010. 49 match variables without PHI were used, many of them administrative variables and indicators for procedures recorded as International Classification of Diseases, 9th revision, Clinical Modification codes. We validated the accuracy of the linkage using identified data from a single center that submits to both databases. We accurately linked the PHIS and NTDB records for 69% of children with any injury, and 88% of those with severe traumatic brain injury eligible for a study of intervention effectiveness (positive predictive value of 98%, specificity of 99.99%). Accurate linkage was associated with longer lengths of stay, more severe injuries, and multiple injuries. In populations with substantial illness or injury severity, accurate record linkage may be possible in the absence of PHI. This methodology may enable linkages and, in turn, comparative effectiveness studies that would be unlikely or impossible otherwise.

The Nightingale study: rationale, study design and baseline characteristics of a prospective cohort study on shift work and breast cancer risk among nurses

PubMed Central

2014-01-01

Background Evidence for the carcinogenicity of shift work in humans is limited because of significant heterogeneity of the results, thus more in-depth research in needed. The Nightingale Study is a nationwide prospective cohort study on occupational exposures and risks of chronic diseases among female nurses and focuses on the potential association between shift work and risk of breast cancer. The study design, methods, and baseline characteristics of the cohort are described. Methods/Design The source population for the cohort comprised 18 to 65 year old women who were registered as having completed training to be a nurse in the nationwide register for healthcare professionals in the Netherlands. Eligible women were invited to complete a web-based questionnaire including full job history, a detailed section on all domains of shift work (shift system, cumulative exposure, and shift intensity) and potential confounding factors, and an informed consent form for linkage with national (disease) registries. Women were also asked to donate toenail clippings as a source of DNA for genetic analyses. Between October 6, 2011 and February 1, 2012, 31% of the 192,931 women who were invited to participate completed the questionnaire, yielding a sample size of 59,947 cohort members. The mean age of the participants was 46.9 year (standard deviation 11.0 years). Toenail clippings were provided by 23,439 participants (39%). Discussion Results from the Nightingale Study will contribute to the scientific evidence of potential shift work-related health risks among nurses and will help develop preventive measures and policy aimed at reducing these risks. PMID:24475944

Incidence of lip cancer in the male Norwegian agricultural population.

PubMed

Nordby, K C; Andersen, A; Kristensen, P

2004-08-01

To explore lip cancer (LC) associations with work environmental exposures in a record-linkage study of Norwegian farmers. We hypothesize immunosuppressive substances (e.g. mycotoxins, pesticides) to influence LC incidence. A cohort of 131,243 male Norwegian farmers born 1925-1971 was established by cross-linkage of national registers and followed up through 1999 for incident LC, (ICD-7 site 140) in the Cancer Registry of Norway. Farm production data from agricultural censuses 1969-1979 and meteorological data on solar radiation and fungal forecasts (events of wet and temperate conditions known to favour fungal growth and mycotoxin formation) served as exposure proxies. Adjusted rate ratios (RR) and 95% confidence intervals (CI) were estimated using Poisson regression. We identified 108 LC cases (rate 4.4 per 100,000 person-years). We found LC to be moderately associated with horses on the farm (RR = 1.6, CI = 1.0-2.4), construction work employment (RR = 1.7, CI = 1.1-2.6), pesticide use (RR = 0.7, CI = 0.4-1.0), grain production (RR = 1.3, CI = 0.9-2.1) and increasing levels of fungal forecasts (RR = 1.6, CI = 0.9-2.8 in the highest two quartiles). Moderate associations of LC with grain production and fungal forecasts and the negative association with pesticide could possibly be explained by exposure to immunosuppressive mycotoxins. Some of the associations observed could be explained by solar exposure. Copyright 2004 Kluwer Academic Publishers

Hybrid STTR intervention for heterosexuals using anonymous HIV testing and confidential linkage to care: a single arm exploratory trial using respondent-driven sampling.

PubMed

Gwadz, Marya; Cleland, Charles M; Leonard, Noelle R; Kutnick, Alexandra; Ritchie, Amanda S; Banfield, Angela; Hagan, Holly; Perlman, David C; McCright-Gill, Talaya; Sherpa, Dawa; Martinez, Belkis Y

2015-11-16

An estimated 14 % of the 1.2 million individuals living with HIV in the U.S. are unaware of their status. Yet this modest proportion of individuals with undiagnosed HIV is linked to 44-66 % of all new infections. Thus innovative intervention approaches are needed to seek out and test those with undiagnosed HIV, and link them to HIV treatment with high retention, an approach referred to as "Seek, Test, Treat, and Retain" (STTR). The present protocol describes a creative "hybrid" STTR approach that uses anonymous HIV testing followed by confidential care linkage, focused on heterosexuals at high risk (HHR) for HIV, who do not test as frequently as, and are diagnosed later, than other risk groups. This is a single-arm exploratory intervention efficacy trial. The study has two phases: one to seek out and test HHR, and another to link those found infected to HIV treatment in a timely fashion, with high retention. We will recruit African American/Black and Latino adult HHR who reside in urban locations with high poverty and HIV prevalence. Participants will be recruited with respondent-driven sampling, a peer recruitment method. The "Seek and Test" phase is comprised of a brief, convenient, single-session, anonymous HIV counseling and testing session. The "Treat and Retain" component will engage those newly diagnosed with HIV into a confidential research phase and use a set of procedures called care navigation to link them to HIV primary care. Participants will be followed for 6 months with objective assessment of outcomes (using medical records and biomarkers). Undiagnosed HIV infection is a major public health problem. While anonymous HIV testing is an important part of the HIV testing portfolio, it does not typically include linkage to care. The present study has potential to produce an innovative, brief, cost-effective, and replicable STTR intervention, and thereby reduce racial/ethnic disparities in HIV/AIDS. ClinicalTrials.gov, NCT02421159 , Registered April 15, 2015.

Evaluation of record linkage of two large administrative databases in a middle income country: stillbirths and notifications of dengue during pregnancy in Brazil.

PubMed

Paixão, Enny S; Harron, Katie; Andrade, Kleydson; Teixeira, Maria Glória; Fiaccone, Rosemeire L; Costa, Maria da Conceição N; Rodrigues, Laura C

2017-07-17

Due to the increasing availability of individual-level information across different electronic datasets, record linkage has become an efficient and important research tool. High quality linkage is essential for producing robust results. The objective of this study was to describe the process of preparing and linking national Brazilian datasets, and to compare the accuracy of different linkage methods for assessing the risk of stillbirth due to dengue in pregnancy. We linked mothers and stillbirths in two routinely collected datasets from Brazil for 2009-2010: for dengue in pregnancy, notifications of infectious diseases (SINAN); for stillbirths, mortality (SIM). Since there was no unique identifier, we used probabilistic linkage based on maternal name, age and municipality. We compared two probabilistic approaches, each with two thresholds: 1) a bespoke linkage algorithm; 2) a standard linkage software widely used in Brazil (ReclinkIII), and used manual review to identify further links. Sensitivity and positive predictive value (PPV) were estimated using a subset of gold-standard data created through manual review. We examined the characteristics of false-matches and missed-matches to identify any sources of bias. From records of 678,999 dengue cases and 62,373 stillbirths, the gold-standard linkage identified 191 cases. The bespoke linkage algorithm with a conservative threshold produced 131 links, with sensitivity = 64.4% (68 missed-matches) and PPV = 92.5% (8 false-matches). Manual review of uncertain links identified an additional 37 links, increasing sensitivity to 83.7%. The bespoke algorithm with a relaxed threshold identified 132 true matches (sensitivity = 69.1%), but introduced 61 false-matches (PPV = 68.4%). ReclinkIII produced lower sensitivity and PPV than the bespoke linkage algorithm. Linkage error was not associated with any recorded study variables. Despite a lack of unique identifiers for linking mothers and stillbirths, we demonstrate a high standard of linkage of large routine databases from a middle income country. Probabilistic linkage and manual review were essential for accurately identifying cases for a case-control study, but this approach may not be feasible for larger databases or for linkage of more common outcomes.

Significant linkage disequilibrium between the Huntington disease gene and the loci D4S10 and D4S95 in the Dutch population

DOE Office of Scientific and Technical Information (OSTI.GOV)

Skraastad, M.I.; Van de Vosse, E.; Belfroid, R.

1992-10-01

Significant linkage disequilibrium has been found between the Huntington disease (HD) gene and DNA markers located around D4S95 and D4S98. The linkage-disequilibrium studies favor the proximal location of the HD gene, in contrast to the conflicting results of recombination analyses. The authors have analyzed 45 Dutch HD families with 19 DNA markers and have calculated the strength of linkage disequilibrium. Highly significant linkage disequilibrium has been detected with D4S95, consistent with the studies in other populations. In contrast with most other studies, however, the area of linkage disequilibrium extends from D4S10 proximally to D4S95, covering 1,100 kb. These results confirmmore » that the HD gene most likely maps near D4S95. 28 refs., 1 fig., 2 tabs.« less

A Simple Sequence Repeat- and Single-Nucleotide Polymorphism-Based Genetic Linkage Map of the Brown Planthopper, Nilaparvata lugens

PubMed Central

Jairin, Jirapong; Kobayashi, Tetsuya; Yamagata, Yoshiyuki; Sanada-Morimura, Sachiyo; Mori, Kazuki; Tashiro, Kosuke; Kuhara, Satoru; Kuwazaki, Seigo; Urio, Masahiro; Suetsugu, Yoshitaka; Yamamoto, Kimiko; Matsumura, Masaya; Yasui, Hideshi

2013-01-01

In this study, we developed the first genetic linkage map for the major rice insect pest, the brown planthopper (BPH, Nilaparvata lugens). The linkage map was constructed by integrating linkage data from two backcross populations derived from three inbred BPH strains. The consensus map consists of 474 simple sequence repeats, 43 single-nucleotide polymorphisms, and 1 sequence-tagged site, for a total of 518 markers at 472 unique positions in 17 linkage groups. The linkage groups cover 1093.9 cM, with an average distance of 2.3 cM between loci. The average number of marker loci per linkage group was 27.8. The sex-linkage group was identified by exploiting X-linked and Y-specific markers. Our linkage map and the newly developed markers used to create it constitute an essential resource and a useful framework for future genetic analyses in BPH. PMID:23204257

Individual Data Linkage of Survey Data with Claims Data in Germany—An Overview Based on a Cohort Study

PubMed Central

March, Stefanie

2017-01-01

Research based on health insurance data has a long tradition in Germany. By contrast, data linkage of survey data with such claims data is a relatively new field of research with high potential. Data linkage opens up new opportunities for analyses in the field of health services research and public health. Germany has comprehensive rules and regulations of data protection that have to be followed. Therefore, a written informed consent is needed for individual data linkage. Additionally, the health system is characterized by heterogeneity of health insurance. The lidA-living at work-study is a cohort study on work, age and health, which linked survey data with claims data of a large number of statutory health insurance data. All health insurance funds were contacted, of whom a written consent was given. This paper will give an overview of individual data linkage of survey data with German claims data on the example of the lidA-study results. The challenges and limitations of data linkage will be presented. Despite heterogeneity, such kind of studies is possible with a negligibly small influence of bias. The experience we gain in lidA will be shown and provide important insights for other studies focusing on data linkage. PMID:29232834

Individual Data Linkage of Survey Data with Claims Data in Germany-An Overview Based on a Cohort Study.

PubMed

March, Stefanie

2017-12-09

Research based on health insurance data has a long tradition in Germany. By contrast, data linkage of survey data with such claims data is a relatively new field of research with high potential. Data linkage opens up new opportunities for analyses in the field of health services research and public health. Germany has comprehensive rules and regulations of data protection that have to be followed. Therefore, a written informed consent is needed for individual data linkage. Additionally, the health system is characterized by heterogeneity of health insurance. The lidA-living at work-study is a cohort study on work, age and health, which linked survey data with claims data of a large number of statutory health insurance data. All health insurance funds were contacted, of whom a written consent was given. This paper will give an overview of individual data linkage of survey data with German claims data on the example of the lidA-study results. The challenges and limitations of data linkage will be presented. Despite heterogeneity, such kind of studies is possible with a negligibly small influence of bias. The experience we gain in lidA will be shown and provide important insights for other studies focusing on data linkage.

Past and present socioeconomic circumstances and psychotropic medication: a register-linkage study.

PubMed

Mauramo, Elina; Lallukka, Tea; Laaksonen, Mikko; Martikainen, Pekka; Rahkonen, Ossi; Lahelma, Eero

2012-12-01

Various domains of socioeconomic circumstances are associated with self-reported mental health, but we lack evidence from studies using medically confirmed mental health outcomes. This longitudinal study aimed to examine the associations of multiple domains of socioeconomic circumstances with subsequent prescribed psychotropic medication among Finnish public sector employees. Baseline survey data among 40-60-year-old employees of City of Helsinki were linked with Social Insurance Institution of Finland register data on psychotropic medication purchases (n=5563). HRs were calculated using Cox regression to examine associations of parental and own education, childhood and current economic difficulties, occupational class, household income and housing tenure with antidepressants, sleeping pills and sedatives and any psychotropic medication during a 5-year follow-up. In age and previous psychotropic medication adjusted models, the risk of antidepressant medication was higher in those with childhood (women: HR=1.29, men: HR=1.64) and current economic difficulties (women: HR=1.30-1.54), rented housing (women: HR=1.20, men: HR=1.45) and the second lowest income group (men: HR=1.71). Gradual adjustments had little effect on the associations. For sleeping pills and sedatives, similar associations were found in women for current economic difficulties, and in men for housing tenure. Results for any psychotropic medication reflected those observed for antidepressants. Past and present economic difficulties and housing tenure were more important determinants of subsequent psychotropic medication among employees than the conventional socioeconomic determinants. The associations were somewhat inconsistent between the medication groups and the sexes. The results support the importance of examining multiple domains of socioeconomic circumstances simultaneously.

Joint associations of smoking and physical activity with disability retirement: a register-linked cohort study.

PubMed

Lallukka, Tea; Rahkonen, Ossi; Lahelma, Eero; Lahti, Jouni

2015-07-29

We examined the risk of disability retirement by smoking and physical activity, and particularly whether the risk due to smoking is affected by the level of physical activity. Additionally, the contribution of baseline health, sociodemographic and work-related factors to the joint associations of smoking and physical activity with disability retirement was considered. Cohort study. Helsinki, Finland. Employees of the City of Helsinki, aged 40-60 years at baseline in 2000-2002, were followed up using complete register data from the Finnish Centre of Pensions until the end of 2010 (n=6390, with a consent to register linkage from 74%). All-cause disability retirement (ICD-10). Altogether, 608 employees (9.5%) retired due to disability during the follow-up. Cox regression models were fitted to examine the joint associations of smoking and physical activity with subsequent disability retirement. Never-smokers, ex-smokers and moderate smokers who were inactive or moderately active had an increased risk of disability retirement, but if they were vigorously active, they had no excess risk. Instead, all heavy smokers (15 or more cigarettes per day among women, and 20 or more among men), irrespective of physical activity, had an increased risk of disability retirement. The examined associations attenuated but remained for ex-smokers and heavy smokers after adjustments for gender, age, socioeconomic position, mental and physical workload, problem drinking, body mass index and self-rated health. No gender interactions were found. Vigorous physical activity might help prevent disability retirement not only among never-smokers, but even among ex-smokers and moderate smokers. However, among heavy smokers, physical activity is not sufficient to eliminate the adverse effects of smoking on health and work ability. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Type, number or both? A population-based matched case-control study on the risk of fall injuries among older people and number of medications beyond fall-inducing drugs.

PubMed

Laflamme, Lucie; Monárrez-Espino, Joel; Johnell, Kristina; Elling, Berty; Möller, Jette

2015-01-01

Drug use is a modifiable risk factor for fall-related injuries in older people. Whereas the injurious effect of polypharmacy is established, that of low numbers of medications has not been fully ascertained. Neither do we know whether it is the number per se or the type of medications that actually matters. We assessed this question for fall injuries leading to hospitalization. National register-based, population-based, matched case-control study. Community dwellers aged 65+ years living in Sweden between March 2006 and December 2009. Cases (n = 64,399) were identified in the national inpatient register and four controls per case were randomly matched by gender, date of birth and residential area. The association between number of prescribed medications, assessed through linkage with the Swedish prescribed drug register, and the risk of injurious falls was estimated with odds ratios with 95% confidence intervals using conditional logistic regression, adjusted for demographic and health status. The number of medications was associated with an increased risk of fall injury in a dose-response fashion, even after adjustment for marital status, comorbidity and number of fall-risk-inducing drugs (FRIDs). Using ten or more medications was associated with an almost two-fold higher risk (adjusted OR: 1.76, 95% CI: 1.66 to 1.88). When stratified by use (or not) of at least one FRID, the association weakened slightly among both non-users (adjusted OR: 1.50, 95% CI: 1.34 to 1.67) and users (adjusted OR: 1.67, 95% CI: 1.58 to 1.77). In older people, not only large but also small numbers of medications may affect the risk for them to sustain injurious falls. Although the mechanisms lying behind this are complex, the finding challenges the prevention strategies targeting either specific types of medications (FRIDs) or high numbers of them.

Morbidity before and after the diagnosis of hyperthyroidism: a nationwide register-based study.

PubMed

Brandt, Frans; Thvilum, Marianne; Almind, Dorthe; Christensen, Kaare; Green, Anders; Hegedüs, Laszlo; Brix, Thomas Heiberg

2013-01-01

Hyperthyroidism has been linked with different morbidities, like atrial fibrillation, stroke and diabetes mellitus. However, our knowledge regarding the extent and temporal relation between hyperthyroidism and other diseases is fragmented. Here, we aimed at evaluating various morbidities before and after the diagnosis of hyperthyroidism. Observational cohort study. From nationwide Danish health registers 2631 hyperthyroid singletons and 375 twin pairs discordant for hyperthyroidism were identified and followed for an average of 6 years (range 0-13). Data on the occurrence of cardiovascular diseases, lung diseases, diabetes mellitus, rheumatic diseases and malignant diseases was obtained by person-to-person record linkage with the National Danish Patient Register and/or the Danish National Prescription Registry (lung diseases and diabetes mellitus). Logistic and Cox regression models were used to assess the risk of morbidity before and after the diagnosis of hyperthyroidism, respectively. All Cox regression analyses were adjusted for the degree of co-morbidity preceding the diagnosis of hyperthyroidism, using the Charlson score. Hyperthyroid individuals had a significantly higher risk of being diagnosed with cardiovascular diseases (odds ratio (OR) 1.65; 95% confidence interval (CI): 1.45-1.87), lung diseases (OR 1.53; 95% CI: 1.29-1.60), and diabetes mellitus (OR 1.43, 95% CI: 1.20-1.72), but not with malignant diseases (OR 1.16, 95% CI: 0.99-1.36) prior to the diagnosis of hyperthyroidism. After the diagnosis of hyperthyroidism, subjects had a significantly higher risk of being diagnosed with cardiovascular diseases (hazard ratio (HR) 1.34; 95% CI: 1.15-1.56), lung diseases (HR 1.28; 95% CI: 1.10-1.49), and diabetes mellitus (HR 1.46; 95% CI: 1.16-1.84), but not with rheumatic diseases (HR 1.39, 95% CI: 0.92-2.09) or malignant diseases (HR 1.18, 95% CI 0.97-1.42). We demonstrate a significantly increased burden of morbidity, both before and after the diagnosis of hyperthyroidism.

Sleep Apnea, Disability Pensions, and Cause-Specific Mortality: A Swedish Nationwide Register Linkage Study.

PubMed

Rod, Naja Hulvej; Kjeldgård, Linnea; Åkerstedt, Torbjörn; Ferrie, Jane E; Salo, Paula; Vahtera, Jussi; Alexanderson, Kristina

2017-09-15

Sleep apnea is a common problem affecting daily functioning and health. We evaluated associations between sleep apnea and receipt of a disability pension and mortality in a prospective study of 74,543 cases of sleep apnea (60,125 outpatient, 14,418 inpatient) from the Swedish Patient Register (2000-2009 inclusive). Cases were matched to 5 noncases (n = 371,592) and followed from diagnosis/inclusion to December 31, 2010, via nationwide registers. During a mean follow-up period of 5.1 (standard deviation, 2.7) years, 13% of men and 21% of women with inpatient sleep apnea received a disability pension. Inpatient sleep apnea was associated with higher total mortality (for men, hazard ratio (HR) = 1.71, 95% confidence interval (CI): 1.59, 1.84; for women, HR = 2.33, 95% CI: 2.04, 2.67), with associations being strongest for deaths due to ischemic heart disease (for men, HR = 2.27, 95% CI: 1.94, 2.65; for women, HR = 5.27, 95% CI: 3.78, 7.34), respiratory disorders (for men, HR = 3.29, 95% CI: 2.45, 4.42; for women, HR= 5.24, 95% CI: 3.52, 7.81), and suicide (for men, HR = 1.76, 95% CI: 1.19, 2.60; for women, HR = 4.33, 95% CI: 1.96, 9.56). There were no associations of inpatient sleep apnea with cancer mortality. Outpatient sleep apnea was associated with a higher risk of receiving a disability pension but not higher total mortality. In conclusion, inpatient sleep apnea is related to a higher risk of disability pension receipt and mortality a decade after diagnosis. © The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The population-based Occupational and Environmental Health Prospective Cohort Study (AMIGO) in The Netherlands.

PubMed

Slottje, Pauline; Yzermans, C Joris; Korevaar, Joke C; Hooiveld, Mariëtte; Vermeulen, Roel C H

2014-11-26

Occupational and environmental exposures remain important modifiable risk factors of public health. Existing cohort studies are often limited by the level of detail of data collected on these factors and health. It is also often assumed that the more healthy group is over-represented in cohort studies, which is of concern for their external validity. In this cohort profile, we describe how we set up the population-based Occupational and Environmental Health Cohort Study (AMIGO) to longitudinally study occupational and environmental determinants of diseases and well-being from a multidisciplinary and life course point of view. Reviewed by the Medical Ethics Research Committee of the University Medical Center Utrecht (protocol 10-268/C). All cohort members participate voluntarily and gave informed consent prior to their inclusion. 14,829 adult cohort members (16% of those invited) consented and filled in the online baseline questionnaire. Determinants include chemical, biological, physical (eg, electromagnetic fields), and psychosocial factors. Priority health outcomes include cancer, neurological, cardiovascular and respiratory diseases and non-specific symptoms. Owing to the recruitment strategy via general practitioners of an established network, we also collect longitudinal data registered in their electronic medical records including symptoms, diagnosis and treatments. Besides the advantage of health outcomes that cannot be easily captured longitudinally by other means, this created a unique opportunity to assess health-related participation bias by comparing general practitioner-registered prevalence rates in the cohort and its source population. We found no indications of such a systematic bias. The major assets of the AMIGO approach are its detailed occupational and environmental determinants in combination with the longitudinal health data registered in general practice besides linkage to cancer and mortality registries and self-reported health. We are now in the phase of prospective follow-up, with the aim of continuing this for as long as possible (20+ years), pending future funding. Findings will be disseminated through scientific conferences and peer-reviewed journals, and through newsletters and the project website to participants, stakeholders and the wider public. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Improving record linkage performance in the presence of missing linkage data.

PubMed

Ong, Toan C; Mannino, Michael V; Schilling, Lisa M; Kahn, Michael G

2014-12-01

Existing record linkage methods do not handle missing linking field values in an efficient and effective manner. The objective of this study is to investigate three novel methods for improving the accuracy and efficiency of record linkage when record linkage fields have missing values. By extending the Fellegi-Sunter scoring implementations available in the open-source Fine-grained Record Linkage (FRIL) software system we developed three novel methods to solve the missing data problem in record linkage, which we refer to as: Weight Redistribution, Distance Imputation, and Linkage Expansion. Weight Redistribution removes fields with missing data from the set of quasi-identifiers and redistributes the weight from the missing attribute based on relative proportions across the remaining available linkage fields. Distance Imputation imputes the distance between the missing data fields rather than imputing the missing data value. Linkage Expansion adds previously considered non-linkage fields to the linkage field set to compensate for the missing information in a linkage field. We tested the linkage methods using simulated data sets with varying field value corruption rates. The methods developed had sensitivity ranging from .895 to .992 and positive predictive values (PPV) ranging from .865 to 1 in data sets with low corruption rates. Increased corruption rates lead to decreased sensitivity for all methods. These new record linkage algorithms show promise in terms of accuracy and efficiency and may be valuable for combining large data sets at the patient level to support biomedical and clinical research. Copyright © 2014 Elsevier Inc. All rights reserved.

Data cleaning and management protocols for linked perinatal research data: a good practice example from the Smoking MUMS (Maternal Use of Medications and Safety) Study.

PubMed

Tran, Duong Thuy; Havard, Alys; Jorm, Louisa R

2017-07-11

Data cleaning is an important quality assurance in data linkage research studies. This paper presents the data cleaning and preparation process for a large-scale cross-jurisdictional Australian study (the Smoking MUMS Study) to evaluate the utilisation and safety of smoking cessation pharmacotherapies during pregnancy. Perinatal records for all deliveries (2003-2012) in the States of New South Wales (NSW) and Western Australia were linked to State-based data collections including hospital separation, emergency department and death data (mothers and babies) and congenital defect notifications (babies in NSW) by State-based data linkage units. A national data linkage unit linked pharmaceutical dispensing data for the mothers. All linkages were probabilistic. Twenty two steps assessed the uniqueness of records and consistency of items within and across data sources, resolved discrepancies in the linkages between units, and identified women having records in both States. State-based linkages yielded a cohort of 783,471 mothers and 1,232,440 babies. Likely false positive links relating to 3703 mothers were identified. Corrections of baby's date of birth and age, and parity were made for 43,578 records while 1996 records were flagged as duplicates. Checks for the uniqueness of the matches between State and national linkages detected 3404 ID clusters, suggestive of missed links in the State linkages, and identified 1986 women who had records in both States. Analysis of content data can identify inaccurate links that cannot be detected by data linkage units that have access to personal identifiers only. Perinatal researchers are encouraged to adopt the methods presented to ensure quality and consistency among studies using linked administrative data.

Effectiveness of service linkages in primary mental health care: a narrative review part 1

PubMed Central

2011-01-01

Background With the move to community care and increased involvement of generalist health care providers in mental health, the need for health service partnerships has been emphasised in mental health policy. Within existing health system structures the active strategies that facilitate effective partnership linkages are not clear. The objective of this study was to examine the evidence from peer reviewed literature regarding the effectiveness of service linkages in primary mental health care. Methods A narrative and thematic review of English language papers published between 1998 and 2009. Studies of analytic, descriptive and qualitative designs from Australia, New Zealand, UK, Europe, USA and Canada were included. Data were extracted to examine what service linkages have been used in studies of collaboration in primary mental health care. Findings from the randomised trials were tabulated to show the proportion that demonstrated clinical, service delivery and economic benefits. Results A review of 119 studies found ten linkage types. Most studies used a combination of linkage types and so the 42 RCTs were grouped into four broad linkage categories for meaningful descriptive analysis of outcomes. Studies that used multiple linkage strategies from the suite of "direct collaborative activities" plus "agreed guidelines" plus "communication systems" showed positive clinical (81%), service (78%) and economic (75%) outcomes. Most evidence of effectiveness came from studies of depression. Long term benefits were attributed to medication concordance and the use of case managers with a professional background who received expert supervision. There were fewer randomised trials related to collaborative care of people with psychosis and there were almost none related to collaboration with the wider human service sectors. Because of the variability of study types we did not exclude on quality or attempt to weight findings according to power or effect size. Conclusion There is strong evidence to support collaborative primary mental health care for people with depression when linkages involve "direct collaborative activity", plus "agreed guidelines" and "communication systems". PMID:21481236

A guide to evaluating linkage quality for the analysis of linked data.

PubMed

Harron, Katie L; Doidge, James C; Knight, Hannah E; Gilbert, Ruth E; Goldstein, Harvey; Cromwell, David A; van der Meulen, Jan H

2017-10-01

Linked datasets are an important resource for epidemiological and clinical studies, but linkage error can lead to biased results. For data security reasons, linkage of personal identifiers is often performed by a third party, making it difficult for researchers to assess the quality of the linked dataset in the context of specific research questions. This is compounded by a lack of guidance on how to determine the potential impact of linkage error. We describe how linkage quality can be evaluated and provide widely applicable guidance for both data providers and researchers. Using an illustrative example of a linked dataset of maternal and baby hospital records, we demonstrate three approaches for evaluating linkage quality: applying the linkage algorithm to a subset of gold standard data to quantify linkage error; comparing characteristics of linked and unlinked data to identify potential sources of bias; and evaluating the sensitivity of results to changes in the linkage procedure. These approaches can inform our understanding of the potential impact of linkage error and provide an opportunity to select the most appropriate linkage procedure for a specific analysis. Evaluating linkage quality in this way will improve the quality and transparency of epidemiological and clinical research using linked data. © The Author 2017. Published by Oxford University Press on behalf of the International Epidemiological Association.

Antisocial personality disorder as a predictor of criminal behaviour in a longitudinal study of a cohort of abusers of several classes of drugs: relation to type of substance and type of crime.

PubMed

Fridell, Mats; Hesse, Morten; Jaeger, Mads Meier; Kühlhorn, Eckart

2008-06-01

Mixed findings have been made with regard to the long-term predictive validity of antisocial personality disorder (ASPD) on criminal behaviour in samples of substance abusers. A longitudinal record-linkage study of a cohort of 1052 drug abusers admitted 1977-1995 was undertaken. Subjects were recruited from a detoxification and short-term rehabilitation unit in Lund, Sweden, and followed through criminal justice registers from their first treatment episode to death or to the year 2004. In a ML multinomial random effects regression, subjects diagnosed with antisocial personality disorders were 2.16 times more likely to be charged with theft only (p<0.001), and 2.44 times more likely to be charged committing multiple types of crime during an observation year (p<0.001). The findings of the current study support the predictive validity of the DSM-III-R diagnosis of ASPD. ASPD should be taken seriously in drug abusers, and be targeted in treatment to prevent crime in society.

The acceptability of conducting data linkage research without obtaining consent: lay people's views and justifications.

PubMed

Xafis, Vicki

2015-11-17

A key ethical issue arising in data linkage research relates to consent requirements. Patients' consent preferences in the context of health research have been explored but their consent preferences regarding data linkage specifically have been under-explored. In addition, the views on data linkage are often those of patient groups. As a result, little is known about lay people's views and their preferences about consent requirements in the context of data linkage. This study explores lay people's views and justifications regarding the acceptability of conducting data linkage research without obtaining consent. A qualitative study explored lay people's views regarding consent requirements in data linkage via four hypothetical data linkage scenarios of increasing complexity. Prior to considering the scenarios, participants were provided with information regarding best practice data linkage processes via discussion and a diagrammatic representation of the process. Lay people were able to understand the intricate processes involved in data linkage and the key protections afforded within a short amount of time. They were supportive of data linkage research and, on the whole, believed it should be conducted without consent provided a data linkage organization de-identifies the data used so that researchers do not handle identifiable data. Many thought that de-identified data holds a different status to identifiable data and should be used without specific consent in research that aims to benefit society. In weighing up conflicting values and interests, participants shifted consent preferences before arriving at their final consent preference for each scenario and provided justifications for their choices. They considered the protection of people's information, societal benefits, and the nature and constraints of research and recognized that these need to be balanced. With some exposure to the features of data linkage, lay people have the capacity to understand the processes sufficiently in order to consider ethical issues associated with consent preferences. Shifts in views reveal the complexity of such decisions. While privacy protection remained an important consideration for most participants, adequate protection measures adopted in best practice data linkage were viewed by most as protection enough for data linkage to proceed without specific individual consent.

Annotated genetic linkage maps of Pinus pinaster Ait. from a Central Spain population using microsatellite and gene based markers.

PubMed

de Miguel, Marina; de Maria, Nuria; Guevara, M Angeles; Diaz, Luis; Sáez-Laguna, Enrique; Sánchez-Gómez, David; Chancerel, Emilie; Aranda, Ismael; Collada, Carmen; Plomion, Christophe; Cabezas, José-Antonio; Cervera, María-Teresa

2012-10-04

Pinus pinaster Ait. is a major resin producing species in Spain. Genetic linkage mapping can facilitate marker-assisted selection (MAS) through the identification of Quantitative Trait Loci and selection of allelic variants of interest in breeding populations. In this study, we report annotated genetic linkage maps for two individuals (C14 and C15) belonging to a breeding program aiming to increase resin production. We use different types of DNA markers, including last-generation molecular markers. We obtained 13 and 14 linkage groups for C14 and C15 maps, respectively. A total of 211 and 215 markers were positioned on each map and estimated genome length was between 1,870 and 2,166 cM respectively, which represents near 65% of genome coverage. Comparative mapping with previously developed genetic linkage maps for P. pinaster based on about 60 common markers enabled aligning linkage groups to this reference map. The comparison of our annotated linkage maps and linkage maps reporting QTL information revealed 11 annotated SNPs in candidate genes that co-localized with previously reported QTLs for wood properties and water use efficiency. This study provides genetic linkage maps from a Spanish population that shows high levels of genetic divergence with French populations from which segregating progenies have been previously mapped. These genetic maps will be of interest to construct a reliable consensus linkage map for the species. The importance of developing functional genetic linkage maps is highlighted, especially when working with breeding populations for its future application in MAS for traits of interest.

Annotated genetic linkage maps of Pinus pinaster Ait. from a Central Spain population using microsatellite and gene based markers

PubMed Central

2012-01-01

Background Pinus pinaster Ait. is a major resin producing species in Spain. Genetic linkage mapping can facilitate marker-assisted selection (MAS) through the identification of Quantitative Trait Loci and selection of allelic variants of interest in breeding populations. In this study, we report annotated genetic linkage maps for two individuals (C14 and C15) belonging to a breeding program aiming to increase resin production. We use different types of DNA markers, including last-generation molecular markers. Results We obtained 13 and 14 linkage groups for C14 and C15 maps, respectively. A total of 211 and 215 markers were positioned on each map and estimated genome length was between 1,870 and 2,166 cM respectively, which represents near 65% of genome coverage. Comparative mapping with previously developed genetic linkage maps for P. pinaster based on about 60 common markers enabled aligning linkage groups to this reference map. The comparison of our annotated linkage maps and linkage maps reporting QTL information revealed 11 annotated SNPs in candidate genes that co-localized with previously reported QTLs for wood properties and water use efficiency. Conclusions This study provides genetic linkage maps from a Spanish population that shows high levels of genetic divergence with French populations from which segregating progenies have been previously mapped. These genetic maps will be of interest to construct a reliable consensus linkage map for the species. The importance of developing functional genetic linkage maps is highlighted, especially when working with breeding populations for its future application in MAS for traits of interest. PMID:23036012

Identifying core NANDA-I nursing diagnoses, NIC interventions, NOC outcomes, and NNN linkages for heart failure.

PubMed

Park, Hyejin

2014-02-01

The purpose of the study was to identify the core nursing diagnoses, interventions, outcomes, and linkages using standardized nursing terminologies for patients with heart failure (HF). For this study a retrospective descriptive design was used. The frequently used NANDA-I, NIC, NOC, and NNN linkages were identified through 272 inpatient records of patients discharged with HF in a midwestern community. The findings indicate that the top 10 NANDA-I, NIC, and NOC accounted for more than 50% of nursing diagnoses, interventions, and outcomes. The most frequently used top 10 NNN linkages were identified for patients with HF. The identified core NANDA-I, NIC, NOC, and NNN linkages for HF from this study provide scope of practice of nurses working in HF clinics. © 2013 NANDA International, Inc.

Association and linkage studies of candidate genes involved in GABAergic neurotransmission in lithium-responsive bipolar disorder.

PubMed Central

Duffy, A; Turecki, G; Grof, P; Cavazzoni, P; Grof, E; Joober, R; Ahrens, B; Berghöfer, A; Müller-Oerlinghausen, B; Dvoráková, M; Libigerová, E; Vojtĕchovský, M; Zvolský, P; Nilsson, A; Licht, R W; Rasmussen, N A; Schou, M; Vestergaard, P; Holzinger, A; Schumann, C; Thau, K; Robertson, C; Rouleau, G A; Alda, M

2000-01-01

OBJECTIVE: To test for genetic linkage and association with GABAergic candidate genes in lithium-responsive bipolar disorder. DESIGN: Polymorphisms located in genes that code for GABRA3, GABRA5 and GABRB3 subunits of the GABAA receptor were investigated using association and linkage strategies. PARTICIPANTS: A total of 138 patients with bipolar 1 disorder with a clear response to lithium prophylaxis, selected from specialized lithium clinics in Canada and Europe that are part of the International Group for the Study of Lithium-Treated Patients, and 108 psychiatrically healthy controls. Families of 24 probands were suitable for linkage analysis. OUTCOME MEASURES: The association between the candidate genes and patients with bipolar disorder versus that of controls and genetic linkage within families. RESULTS: There was no significant association or linkage found between lithium-responsive bipolar disorder and the GABAergic candidate genes investigated. CONCLUSIONS: This study does not support a major role for the GABAergic candidate genes tested in lithium-responsive bipolar disorder. PMID:11022400

Academia-Industry-Government Linkages in Tanzania: Trends, Challenges and Prospects

ERIC Educational Resources Information Center

Mpehongwa, Gasper

2013-01-01

This paper analyzed trends, challenges and prospects of academia-industry-government linkages in Tanzania. Using case study design, and documentary review to gather the required data, the study sought to answer three research questions: (1) what are the trends of academia-industry-government linkages in Tanzania?, (2) what are the challenges…

Napping and the risk of type 2 diabetes: a population-based prospective study.

PubMed

Hublin, Christer; Lehtovirta, Mikko; Partinen, Markku; Koskenvuo, Markku; Kaprio, Jaakko

2016-01-01

Some studies indicate an association between napping and increased risk of type 2 diabetes. We studied this prospectively in a sample representative of general population. A questionnaire was administered to the Finnish Twin Cohort in 1990 (response rate 77%, age 33-60 years). The study population included 12,244 subjects who replied to the question "Do you sleep during the daytime (take naps)?" with five response alternatives ranging from "no need" to "every or almost every day." Information on incident cases of diabetes was obtained by linkage to nationwide registers. Logistic regression models were used to obtain odds ratios (ORs) (95% confidence intervals) for incident type 2 diabetes risk in 1991-2004 by napping category. Adjustments were made for 11 socio-demographic and lifestyle covariates. For subjects aged 33-45 years at baseline, a questionnaire in 2011 provided information on prevalent diabetes. Thirty-four per cent had no need for napping, and 15% did so on ≥3 days weekly. There were 356 incident type 2 diabetes cases during the follow-up. Using the 'no need' category as the reference, the risk of type 2 diabetes was significantly increased only among those napping most frequently [OR 1.86 (1.29-2.67), age- and sex-adjusted]. After adjusting for other covariates, the results were essentially the same, but when adjusted for body mass index, the association decreased (to about 1.3) and was statistically non-significant. Analysis of 2011 self-reported type 2 diabetes was in line with the register data. Frequent napping is associated with future risk of type 2 diabetes. This association is largely explained by obesity. Copyright © 2015 Elsevier B.V. All rights reserved.

Suicide in children and young adolescents: a 25-year database on suicides from Northern Finland.

PubMed

Lahti, Anniina; Harju, Aleksi; Hakko, Helinä; Riala, Kaisa; Räsänen, Pirkko

2014-11-01

Despite the large amount of research on adolescent suicidality, there are few detailed studies illustrating the characteristics of child and adolescent completed suicide. Our study presents the characteristics of child and adolescent suicides occurring over a period of 25 years within a large geographical area in Northern Finland, with a special focus on gender differences. The study sample included all 58 suicides among children and adolescents (<18 years) occurring in the province of Oulu in Finland between 1988 and 2012. The data is based on documents pertaining to establish the cause of death from forensic autopsy investigations. A register linkage to the data from the Finnish Hospital Discharge Register (FHDR) was also made. 79% of the suicide victims were male. Violent suicide methods predominated in both genders (males 98%, females 83%). While symptoms of mental illness were common, only a minority (15% of males and 17% of females) had a previous history of psychiatric hospitalization. 17% of females but none of the males had been hospitalized previously due to self-poisoning. A greater proportion of females than males had a history of self-cutting (33% vs. 7%) and previous suicide attempts (25% vs. 4%). 48% of males and 58% of females were under the influence of alcohol at the time of their suicide, and alcohol intoxication was related to suicides during the night. One fifth of the adolescents screened positive for substances other than alcohol. The results of this study indicate that there are similarities but also some differences in the characteristics of male and female suicides in adolescents. Copyright © 2014 Elsevier Ltd. All rights reserved.

Long working hours and use of psychotropic medicine: a follow-up study with register linkage.

PubMed

Hannerz, Harald; Albertsen, Karen

2016-03-01

This study aimed to investigate the possibility of a prospective association between long working hours and use of psychotropic medicine. Survey data drawn from random samples of the general working population of Denmark in the time period 1995-2010 were linked to national registers covering all inhabitants. The participants were followed for first occurrence of redeemed prescriptions for psychotropic medicine. The primary analysis included 25,959 observations (19,259 persons) and yielded a total of 2914 new cases of psychotropic drug use in 99,018 person-years at risk. Poisson regression was used to model incidence rates of redeemed prescriptions for psychotropic medicine as a function of working hours (32-40, 41-48, >48 hours/week). The analysis was controlled for gender, age, sample, shift work, and socioeconomic status. A likelihood ratio test was used to test the null hypothesis, which stated that the incidence rates were independent of weekly working hours. The likelihood ratio test did not reject the null hypothesis (P=0.085). The rate ratio (RR) was 1.04 [95% confidence interval (95% CI) 0.94-1.15] for the contrast 41-48 versus 32-40 work hours/week and 1.15 (95% CI 1.02-1.30) for >48 versus 32-40 hours/week. None of the rate ratios that were estimated in the present study were statistically significant after adjustment for multiple testing. However, stratified analyses, in which 30 RR were estimated, generated the hypothesis that overtime work (>48 hours/week) might be associated with an increased risk among night or shift workers (RR=1.51, 95% CI 1.15-1.98). The present study did not find a statistically significant association between long working hours and incidence of psychotropic drug usage among Danish employees.

Prognosis of 1169 hepatitis C chronically infected patients with decompensated cirrhosis in the predirect-acting antiviral era.

PubMed

McDonald, S A; Innes, H A; Aspinall, E; Hayes, P C; Alavi, M; Valerio, H; Goldberg, D J; Hutchinson, S J

2017-04-01

At a population level, little is known regarding the risk of liver- and nonliver-related mortality and hospitalization and the development of hepatocellular carcinoma (HCC) in hepatitis C virus (HCV)-infected patients with decompensated cirrhosis (DC). This large-scale national record-linkage study estimates these outcomes following first hospital admission for DC. Record-linkages between national HCV diagnosis and clinical databases and the national inpatient hospital episode database and mortality register were conducted to follow-up the disease course of all identified HCV-diagnosed and chronically infected persons. The study population consisted of 1169 HCV chronically infected persons who had a first hospital admission for DC within the period 1994-2013. We observed an overall average annual percentage change of 12.6% in new DC patients (from 63 in 1994-1999 to 541 in 2009-2013), with no evidence for any improvement in the relative risks of liver-related or all-cause death over time. Between 1 January 1994 and 31 May 2014, 722 and 95 DC patients had died of a liver- and a nonliver-related cause, respectively, and 106 patients had a subsequent first admission for HCC. The 5-year cumulative incidence of liver-related mortality, nonliver-related mortality and first subsequent HCC admission was 61.3%, 8.2% and 8.8%, respectively. The health burden in HCV-infected patients associated with development of decompensated cirrhosis has increased dramatically over the last 20 years. Our findings establish the baseline mortality and HCC progression rates in DC patients against which the impact of new antiviral therapies can be measured. © 2016 John Wiley & Sons Ltd.

Linkage mechanisms in the vertebrate skull: Structure and function of three-dimensional, parallel transmission systems.

PubMed

Olsen, Aaron M; Westneat, Mark W

2016-12-01

Many musculoskeletal systems, including the skulls of birds, fishes, and some lizards consist of interconnected chains of mobile skeletal elements, analogous to linkage mechanisms used in engineering. Biomechanical studies have applied linkage models to a diversity of musculoskeletal systems, with previous applications primarily focusing on two-dimensional linkage geometries, bilaterally symmetrical pairs of planar linkages, or single four-bar linkages. Here, we present new, three-dimensional (3D), parallel linkage models of the skulls of birds and fishes and use these models (available as free kinematic simulation software), to investigate structure-function relationships in these systems. This new computational framework provides an accessible and integrated workflow for exploring the evolution of structure and function in complex musculoskeletal systems. Linkage simulations show that kinematic transmission, although a suitable functional metric for linkages with single rotating input and output links, can give misleading results when applied to linkages with substantial translational components or multiple output links. To take into account both linear and rotational displacement we define force mechanical advantage for a linkage (analogous to lever mechanical advantage) and apply this metric to measure transmission efficiency in the bird cranial mechanism. For linkages with multiple, expanding output points we propose a new functional metric, expansion advantage, to measure expansion amplification and apply this metric to the buccal expansion mechanism in fishes. Using the bird cranial linkage model, we quantify the inaccuracies that result from simplifying a 3D geometry into two dimensions. We also show that by combining single-chain linkages into parallel linkages, more links can be simulated while decreasing or maintaining the same number of input parameters. This generalized framework for linkage simulation and analysis can accommodate linkages of differing geometries and configurations, enabling novel interpretations of the mechanics of force transmission across a diversity of vertebrate feeding mechanisms and enhancing our understanding of musculoskeletal function and evolution. J. Morphol. 277:1570-1583, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Linkages between ACE Vocational Provision and Mainstream VET.

ERIC Educational Resources Information Center

Saunders, John

A study investigated linkages between adult community education (ACE) and mainstream vocational education and training (VET) in Australia, which enable people to move between the two sectors in their pursuit of vocational learning, and the ways in which linkages might be improved or new ones developed. The data from the study were derived from 69…

No evidence of a causal relationship between hypothyroidism and glaucoma: A Danish nationwide register-based cohort study.

PubMed

Thvilum, Marianne; Brandt, Frans; Brix, Thomas Heiberg; Hegedüs, Laszlo

2018-01-01

An interrelationship between hypothyroidism and glaucoma, due to a shared autoimmune background or based on deposition of mucopolysaccharides in the trabecular meshwork in the eye, has been suggested but is at present unsubstantiated. Therefore, our objective was to investigate, at a nationwide and population-based level, whether there is such an association. Observational cohort study using record-linkage data from nationwide Danish health registers. 121,799 individuals diagnosed with a first episode of hypothyroidism were identified and were matched with 4 non-hypothyroid controls according to age and sex. Prevalence of glaucoma was recorded and cases and controls were followed over a mean of 7.1 years (range 0-17). Logistic and Cox regression models were used to assess the risk of glaucoma before and after the diagnosis of hypothyroidism, respectively. Overall, we found a higher prevalence of glaucoma in subjects with hypothyroidism as compared to controls (4.6% vs. 4.3%, p < 0.001). Prior to the diagnosis of hypothyroidism, the odds ratio (OR) was significantly increased for glaucoma [1.09; 95% confidence interval (CI): 1.04-1.13]. Based on the Cox regression model, there was no increased risk of glaucoma after the diagnosis of hypothyroidism [hazard ratio (HR) 1.00; 95% CI: 0.96-1.06], and the HR decreased further after adjusting for pre-existing co-morbidity (0.88; 95% CI: 0.84-0.93). There was an increased risk of glaucoma before but not after the diagnosis of hypothyroidism, suggesting that screening for glaucoma in hypothyroid individuals is unwarranted.

Overweight among international adoptees in Sweden: a population-based study.

PubMed

Johansson-Kark, M; Rasmussen, F; Hjern, A

2002-01-01

This study investigated the prevalence of overweight [body mass index (BMI) > or = 25 kg m-2] in young adulthood among international adoptees. The prevalence of overweight among adoptees from various countries of origin was compared with that in a large group of non-adopted individuals. All 275,026 young men born in 1973-1977 and living in Sweden at 17 y of age were included. A record linkage was made between the Military Service Conscription Register and several population registers. Data on BMI at 18 y of age were obtained from military conscription examinations conducted in 1991-1995. BMI was missing for 12.7% of 2400 adoptees and 10.8% of 263,173 non-adoptees. Among 623 adoptees from Latin America 21.5% (95% confidence interval 18.3-24.7) were overweight, with a particularly high prevalence of overweight among the 266 adoptees from Chile (28.6%, 23.1-34.0). Among 502 adoptees from the Indian subcontinent 8.4% (5.9-10.8) were overweight and the prevalence of overweight was 8.8% (5.7-12.0) among 317 adoptees from India. Among 817 adoptees from the Far East 12.0% (9.8-14.2) were overweight and the prevalence of overweight was 10.9% (7.9-13.9) among 404 from South Korea. The corresponding figure was 14.1% (14.0-14.2) among the non-adopted individuals. These differences in prevalence of overweight between various groups of adoptees and between adopted and non-adopted subjects are remarkable and are probably due to diversity in genetic susceptibility to overweight.

Linkage of Type 2 Diabetes on Chromosome 9p24 in Mexican Americans: Additional Evidence from the Veterans Administration Genetic Epidemiology Study (VAGES)

PubMed Central

Farook, Vidya S.; Coletta, Dawn K.; Puppala, Sobha; Schneider, Jennifer; Chittoor, Geetha; Hu, Shirley L.; Winnier, Deidre A.; Norton, Luke; Dyer, Thomas D.; Arya, Rector; Cole, Shelley A.; Carless, Melanie; Göring, Harald H.; Almasy, Laura; Mahaney, Michael C.; Comuzzie, Anthony G.; Curran, Joanne E.; Blangero, John; Duggirala, Ravindranath; Lehman, Donna M.; Jenkinson, Christopher P.; DeFronzo, Ralph A.

2014-01-01

Objective Type 2 diabetes (T2DM) is a complex metabolic disease and is more prevalent in certain ethnic groups such as the Mexican Americans. The goal of our study was to perform a genome-wide linkage analysis to localize T2DM susceptibility loci in Mexican Americans. Methods We used the phenotypic and genotypic data from 1,122 Mexican American individuals (307 families) who participated in the Veterans Administration Genetic Epidemiology Study (VAGES). Genome-wide linkage analysis was performed, using the variance components approach. Data from two additional Mexican American family studies, the San Antonio Family Heart Study (SAFHS) and the San Antonio Family Diabetes/Gallbladder Study (SAFDGS), were combined with the VAGES data to test for improved linkage evidence. Results After adjusting for covariate effects, T2DM was found to be under significant genetic influences (h2 = 0.62, P = 2.7 × 10−6). The strongest evidence for linkage of T2DM occurred between markers D9S1871 and D9S2169 on chromosome 9p24.2-p24.1 (LOD = 1.8). Given that we previously reported suggestive evidence for linkage of T2DM at this region in SAFDGS also, we found the significant and increased linkage evidence (LOD = 4.3, empirical P = 1.0 × 10−5, genome-wide P = 1.6 × 10−3) for T2DM at the same chromosomal region when we performed genome-wide linkage analysis of the VAGES data combined with SAFHS and SAFDGS data. Conclusion Significant T2DM linkage evidence was found on chromosome 9p24 in Mexican Americans. Importantly, the chromosomal region of interest in this study overlaps with several recent genome-wide association studies (GWASs) involving T2DM related traits. Given its overlap with such findings and our own initial T2DM association findings in the 9p24 chromosomal region, high throughput sequencing of the linked chromosomal region could identify the potential causal T2DM genes. PMID:24060607

Development and characterization of microsatellite markers for the Pacific abalone ( Haliotis discus) via EST database mining

NASA Astrophysics Data System (ADS)

Zhan, Aibin; Bao, Zhenmin; Wang, Mingling; Chang, Dan; Yuan, Jian; Wang, Xiaolong; Hu, Xiaoli; Liang, Chengzhu; Hu, Jingjie

2008-05-01

The EST database of the Pacific abalone ( Haliotis discus) was mined for developing microsatellite markers. A total of 1476 EST sequences were registered in GenBank when data mining was performed. Fifty sequences (approximately 3.4%) were found to contain one or more microsatellites. Based on the length and GC content of the flanking regions, cluster analysis and BLASTN, 13 microsatellite-containing ESTs were selected for PCR primer design. The results showed that 10 out of 13 primer pairs could amplify scorable PCR products and showed polymorphism. The number of alleles ranged from 2 to 13 and the values of H o and H e varied from 0.1222 to 0.8611 and 0.2449 to 0.9311, respectively. No significant linkage disequilibrium (LD) between any pairs of these loci was found, and 6 of 10 loci conformed to the Hardy-Weinberg equilibrium (HWE). These EST-SSRs are therefore potential tools for studies of intraspecies variation and hybrid identification.

A system for endobronchial video analysis

NASA Astrophysics Data System (ADS)

Byrnes, Patrick D.; Higgins, William E.

2017-03-01

Image-guided bronchoscopy is a critical component in the treatment of lung cancer and other pulmonary disorders. During bronchoscopy, a high-resolution endobronchial video stream facilitates guidance through the lungs and allows for visual inspection of a patient's airway mucosal surfaces. Despite the detailed information it contains, little effort has been made to incorporate recorded video into the clinical workflow. Follow-up procedures often required in cancer assessment or asthma treatment could significantly benefit from effectively parsed and summarized video. Tracking diagnostic regions of interest (ROIs) could potentially better equip physicians to detect early airway-wall cancer or improve asthma treatments, such as bronchial thermoplasty. To address this need, we have developed a system for the postoperative analysis of recorded endobronchial video. The system first parses an input video stream into endoscopic shots, derives motion information, and selects salient representative key frames. Next, a semi-automatic method for CT-video registration creates data linkages between a CT-derived airway-tree model and the input video. These data linkages then enable the construction of a CT-video chest model comprised of a bronchoscopy path history (BPH) - defining all airway locations visited during a procedure - and texture-mapping information for rendering registered video frames onto the airwaytree model. A suite of analysis tools is included to visualize and manipulate the extracted data. Video browsing and retrieval is facilitated through a video table of contents (TOC) and a search query interface. The system provides a variety of operational modes and additional functionality, including the ability to define regions of interest. We demonstrate the potential of our system using two human case study examples.

Robustness of linkage strategy that leads to large-scale cooperation.

PubMed

Inaba, Misato; Takahashi, Nobuyuki; Ohtsuki, Hisashi

2016-11-21

One of the most well-known models to characterize cooperation among unrelated individuals is Social dilemma (SD). However there is no consensus about how to solve the SD by itself. Since SDs are often embedded in other social interactions, including indirect reciprocity games (IR), human can coordinate their behaviors across multiple games. Such coordination is called 'linkage'. Recently linkage has been considered as a promising solution to resolve SDs, since excluding SD defectors (i.e. those who defected in SD) from indirectly reciprocal relationships functions as a costless sanction. A previous study performed mathematical modeling and revealed that a linkage strategy, which cooperates in SD and engages in the Standing strategy in IR based on the recipients' behaviors in both SD and IR, was an ESS against a non-linkage strategy which defects in SD and engages in the Standing strategy in IR based on recipients' behaviors only in IR (Panchanathan and Boyd, 2004). In order to investigate the robustness of the linkage strategy, we devised a non-linkage strategy, which cooperates in SD but does not link two games. First, we conducted a mathematical analysis and demonstrated that the linkage strategy was not an ESS against cooperating non-linkage strategy. Second, we conducted a series of agent-based computer simulations to examine how the strategies perform in situations in which various types of errors can occur. Our results showed that the linkage strategy was an ESS only when there are implementation errors in SD. However, the equilibrium of the linkage strategy was unstable when there are perception errors. Since we know that humans are not free from perception errors in their social life, future studies will need to show how perception errors can be overcome in order to provide support for the conclusion that linkage is a plausible solution to SDs. Copyright © 2016 Elsevier Ltd. All rights reserved.

Individuals motivated to participate in adherence, care and treatment (imPACT): development of a multi-component intervention to help HIV-infected recently incarcerated individuals link and adhere to HIV care.

PubMed

Golin, Carol E; Knight, Kevin; Carda-Auten, Jessica; Gould, Michele; Groves, Jennifer; L White, Becky; Bradley-Bull, Steve; Amola, Kemi; Fray, Niasha; Rosen, David L; Mugavaro, Michael J; Pence, Brian W; Flynn, Patrick M; Wohl, David

2016-09-06

Policy-makers promote a seek, test, treat and retain (STTR) strategy to expand HIV testing, support linkage and engagement in care, and enhance the continuous use of antiretroviral therapy for those HIV-infected. This HIV prevention strategy is particularly appropriate in correctional settings where HIV screening and treatment are routinely available yet many HIV-infected individuals have difficulty sustaining sufficient linkage and engagement in care, disease management, and viral suppression after prison release. Our research team developed Project imPACT (individuals motivated to Participate in Adherence, Care and Treatment), a multi-component approach for HIV-Infected recently incarcerated individuals that specifically targets their care linkage, retention, and medication adherence by addressing multiple barriers to care engagement after release. The ultimate goals of this intervention are to improve the health of HIV-infected individuals recently released from prison and reduce HIV transmission to their communities by maintaining viral suppression. This paper describes the intervention and technology development processes, based on best practices for intervention development and process evaluation. These processes included: 1) identifying the target population; 2) clarifying the theoretical basis for intervention design; 3) describing features of its foundational interventions; 4) conducting formative qualitative research; 5) integrating and adapting foundational interventions to create and refine intervention content based on target audience feedback. These stages along with the final intervention product are described in detail. The intervention is currently being evaluation and a two arm randomized, controlled trial in two US state prison systems. Based on a literature review, qualitative research, integration of proven interventions and behavioral theory, the final imPACT intervention focused on the transition period two to three months before and three months after prison release. It emphasized pre-release readiness, pre- and post-release supportive non-judgmental counseling, linking individuals to a HIV care clinic and technological supports through videos and text messages. This article provides a useful model for how researchers can develop, test, and refine multi-component interventions to address HIV care linkage, retention and adherence. NCT01629316 , first registered 6-4-2012; last updated 6-9-2015.

Genetic studies of stuttering in a founder population.

PubMed

Wittke-Thompson, Jacqueline K; Ambrose, Nicoline; Yairi, Ehud; Roe, Cheryl; Cook, Edwin H; Ober, Carole; Cox, Nancy J

2007-01-01

Genome-wide linkage and association analyses were conducted to identify genetic determinants of stuttering in a founder population in which 48 individuals affected with stuttering are connected in a single 232-person genealogy. A novel approach was devised to account for all necessary relationships to enable multipoint linkage analysis. Regions with nominal evidence for linkage were found on chromosomes 3 (P=0.013, 208.8 centiMorgans (cM)), 13 (P=0.012, 52.6 cM), and 15 (P=0.02, 100 cM). Regions with nominal evidence for association with stuttering that overlapped with a linkage signal are located on chromosomes 3 (P=0.0047, 195 cM), 9 (P=0.0067, 46.5 cM), and 13 (P=0.0055, 52.6 cM). We also conducted the first meta-analysis for stuttering using results from linkage studies in the Hutterites and The Illinois International Genetics of Stuttering Project and identified regions with nominal evidence for linkage on chromosomes 2 (P=0.013, 180-195 cM) and 5 (P=0.0051, 105-120 cM; P=0.015, 120-135 cM). None of the linkage signals detected in the Hutterite sample alone, or in the meta-analysis, meet genome-wide criteria for significance, although some of the stronger signals overlap linkage mapping signals previously reported for other speech and language disorders. After reading this article, the reader will be able to: (1) summarize information about the background of common disorders and methodology of genetic studies; (2) evaluate the role of genetics in stuttering; (3) discuss the value of using founder populations in genetic studies; (4) articulate the importance of combining several studies in a meta-analysis; (5) discuss the overlap of genetic signals identified in stuttering with other speech and language disorders.

A high-density SNP linkage scan with 142 combined subtype ADHD sib pairs identifies linkage regions on chromosomes 9 and 16.

PubMed

Asherson, P; Zhou, K; Anney, R J L; Franke, B; Buitelaar, J; Ebstein, R; Gill, M; Altink, M; Arnold, R; Boer, F; Brookes, K; Buschgens, C; Butler, L; Cambell, D; Chen, W; Christiansen, H; Feldman, L; Fleischman, K; Fliers, E; Howe-Forbes, R; Goldfarb, A; Heise, A; Gabriëls, I; Johansson, L; Lubetzki, I; Marco, R; Medad, S; Minderaa, R; Mulas, F; Müller, U; Mulligan, A; Neale, B; Rijsdijk, F; Rabin, K; Rommelse, N; Sethna, V; Sorohan, J; Uebel, H; Psychogiou, L; Weeks, A; Barrett, R; Xu, X; Banaschewski, T; Sonuga-Barke, E; Eisenberg, J; Manor, I; Miranda, A; Oades, R D; Roeyers, H; Rothenberger, A; Sergeant, J; Steinhausen, H-C; Taylor, E; Thompson, M; Faraone, S V

2008-05-01

As part of the International Multi-centre ADHD Genetics project we completed an affected sibling pair study of 142 narrowly defined Diagnostic and Statistical Manual of Mental Disorders, fourth edition combined type attention deficit hyperactivity disorder (ADHD) proband-sibling pairs. No linkage was observed on the most established ADHD-linked genomic regions of 5p and 17p. We found suggestive linkage signals on chromosomes 9 and 16, respectively, with the highest multipoint nonparametric linkage signal on chromosome 16q23 at 99 cM (log of the odds, LOD=3.1) overlapping data published from the previous UCLA (University of California, Los Angeles) (LOD>1, approximately 95 cM) and Dutch (LOD>1, approximately 100 cM) studies. The second highest peak in this study was on chromosome 9q22 at 90 cM (LOD=2.13); both the previous UCLA and German studies also found some evidence of linkage at almost the same location (UCLA LOD=1.45 at 93 cM; German LOD=0.68 at 100 cM). The overlap of these two main peaks with previous findings suggests that loci linked to ADHD may lie within these regions. Meta-analysis or reanalysis of the raw data of all the available ADHD linkage scan data may help to clarify whether these represent true linked loci.

DNA linkage studies of degenerative retinal diseases.

PubMed

Daiger, S P; Heckenlively, J R; Lewis, R A; Pelias, M Z

1987-01-01

DNA linkage studies of human genetic diseases have led to rapid characterization of a number of otherwise intractable disease loci. Detection of a linked DNA marker, the first step in "reverse genetics", has permitted cloning of the genes for Duchenne muscular dystrophy, retinoblastoma and chronic granulomatosis disease, among others. Thus, the case for applying these techniques to retinitis pigmentosa and related diseases, and the urgency in capitalizing on molecular developments, is justified and compelling. The first major success regarding RP was in demonstrating linkage of the DNA marker DXS7 (L1.28) to XRP. For autosomal forms of the disease, conventional linkage studies have provided tentative evidence for linkage of ADRP to the Rh blood group on chromosome lp and for linkage of Usher's syndrome to Gc and 4q. These provisional assignments are, at least, an important starting point for DNA analysis. The Support Program for DNA Linkage Studies of Degenerative Retinal Diseases was established to provide access for the scientific community to appropriate families, using the resources of the Human Genetic Mutant Cell Repository to prepare, store and distribute lymphoblast lines. To date, two extensive, well-characterized families are included in the program: the autosomal dominant RP family UCLA-RP01, and the Usher's syndrome families LSU-US01. It is highly likely that rapid progress will be made in mapping and characterizing the inherited retinal dystrophies. We believe the support program will facilitate this progress.

Genetics of recurrent early-onset major depression (GenRED): significant linkage on chromosome 15q25-q26 after fine mapping with single nucleotide polymorphism markers.

PubMed

Levinson, Douglas F; Evgrafov, Oleg V; Knowles, James A; Potash, James B; Weissman, Myrna M; Scheftner, William A; Depaulo, J Raymond; Crowe, Raymond R; Murphy-Eberenz, Kathleen; Marta, Diana H; McInnis, Melvin G; Adams, Philip; Gladis, Madeline; Miller, Erin B; Thomas, Jo; Holmans, Peter

2007-02-01

The authors studied a dense map of single nucleotide polymorphism (SNP) DNA markers on chromosome 15q25-q26 to maximize the informativeness of genetic linkage analyses in a region where they previously reported suggestive evidence for linkage of recurrent early-onset major depressive disorder. In 631 European-ancestry families with multiple cases of recurrent early-onset major depressive disorder, 88 SNPs were genotyped, and multipoint allele-sharing linkage analyses were carried out. Marker-marker linkage disequilibrium was minimized, and a simulation study with founder haplotypes from these families suggested that linkage scores were not inflated by linkage disequilibrium. The dense SNP map increased the information content of the analysis from around 0.7 to over 0.9. The maximum evidence for linkage was the Z likelihood ratio score statistic of Kong and Cox (Z(LR))=4.69 at 109.8 cM. The exact p value was below the genomewide significance threshold. By contrast, in the genome scan with microsatellite markers at 9 cM spacing, the maximum Z(LR) for European-ancestry families was 3.43 (106.53 cM). It was estimated that the linked locus or loci in this region might account for a 20% or less populationwide increase in risk to siblings of cases. This region has produced modestly positive evidence for linkage to depression and related traits in other studies. These results suggest that DNA sequence variations in one or more genes in the 15q25-q26 region can increase susceptibility to major depression and that efforts are warranted to identify these genes.

To what extent is the familial risk of rheumatoid arthritis explained by established rheumatoid arthritis risk factors?

PubMed

Jiang, Xia; Frisell, Thomas; Askling, Johan; Karlson, Elizabeth W; Klareskog, Lars; Alfredsson, Lars; Källberg, Henrik

2015-02-01

Family history of rheumatoid arthritis (RA) is one of the strongest risk factors for developing RA, and information on family history is, therefore, routinely collected in clinical practice. However, as more genetic and environmental risk factors shared by relatives are identified, the importance of family history may diminish. The aim of this study was to determine how much of the familial risk of RA can be explained by established genetic and nongenetic risk factors. History of RA among first-degree relatives of individuals in the Epidemiological Investigation of Rheumatoid Arthritis case-control study was assessed through linkage to the Swedish Multigeneration Register and the Swedish Patient Register. We used logistic regression models to investigate the decrease in familial risk after successive adjustment for combinations of nongenetic risk factors (smoking, alcohol intake, parity, silica exposure, body mass index, fatty fish consumption, and education), and genetic risk factors (shared epitope [SE] and 76 single-nucleotide polymorphisms [SNPs]). Established nongenetic risk factors did not explain familial risk of either seropositive or seronegative RA to any significant degree. Genetic risk factors accounted for a limited proportion of the familial risk of seropositive RA (unadjusted odds ratio [OR] 4.10, SE-adjusted OR 3.72, SNP-adjusted OR 3.46, and SE and SNP-adjusted OR 3.35). Established risk factors only provided an explanation for familial risk of RA in minor part, suggesting that many (familial) risk factors remain to be identified, in particular for seronegative RA. Family history of RA therefore remains an important clinical risk factor for RA, the value of which has not yet been superseded by other information. There is thus a need for further etiologic studies of both seropositive and seronegative RA. Copyright © 2015 by the American College of Rheumatology.

Adherence to the Danish food-based dietary guidelines and risk of myocardial infarction: a cohort study.

PubMed

Hansen, Camilla Plambeck; Overvad, Kim; Tetens, Inge; Tjønneland, Anne; Parner, Erik Thorlund; Jakobsen, Marianne Uhre; Dahm, Christina Catherine

2018-05-01

A direct way to evaluate food-based dietary guidelines is to assess if adherence is associated with development of non-communicable diseases. Thus, the objective was to develop an index to assess adherence to the 2013 Danish food-based dietary guidelines and to investigate the association between adherence to the index and risk of myocardial infarction (MI). Population-based cohort study with recruitment of participants in 1993-1997. Information on dietary intake was collected at baseline using an FFQ and an index ranging from 0 to 6 points was created to assess adherence to the 2013 Danish food-based dietary guidelines. MI cases were identified by record linkage to the Danish National Patient Register and the Causes of Death Register. Cox proportional hazards models were used to estimate hazard ratios (HR) of MI. Greater areas of Aarhus and Copenhagen, Denmark. Men and women aged 50-64 years (n 55 021) from the Diet, Cancer and Health study. A total of 3046 participants were diagnosed with first-time MI during a median follow-up of 16·9 years. A higher Danish Dietary Guidelines Index score was associated with a lower risk of MI. After adjustment for potential confounders, the hazard of MI was 13 % lower among men with a score of 3-<4 (HR=0·87; 95 % CI 0·78, 0·96) compared with men with a score of <3. The corresponding HR among women was 0·76 (95 % CI 0·63, 0·93). Adherence to the 2013 Danish food-based dietary guidelines was inversely associated with risk of MI.

Hyperthyroidism and psychiatric morbidity: evidence from a Danish nationwide register study.

PubMed

Brandt, Frans; Thvilum, Marianne; Almind, Dorthe; Christensen, Kaare; Green, Anders; Hegedüs, Laszlo; Brix, Thomas Heiberg

2014-02-01

Thyroid hormones are essential for the normal development of the fetal brain, while hyperthyroidism in adults is associated with mood symptoms and reduced quality of life. In this study, we aimed to investigate the association and temporal relationship between hyperthyroidism and psychiatric morbidity. Register-based nationwide cohort study. Data on hyperthyroidism and psychiatric morbidity were obtained by record linkage of the Danish National Patient Registry and the Danish National Prescription Registry. A total of 2631 hyperthyroid individuals were identified and matched 1:4 with non-hyperthyroid controls and followed for a mean duration of 6 years (range 0-13). Logistic and Cox regression models were used to assess the risk of psychiatric morbidity before and after the diagnosis of hyperthyroidism respectively. BEFORE THE DIAGNOSIS OF HYPERTHYROIDISM, SUCH INDIVIDUALS HAD AN INCREASED RISK OF BEING HOSPITALIZED WITH PSYCHIATRIC DIAGNOSES (ODDS RATIO (OR): 1.33; 95% CI: 0.98-1.80) and an increased risk of being treated with antipsychotics (OR: 1.17; 95% CI: 1.00-1.38), antidepressants (OR: 1.13; 95% CI: 1.01-1.27), or anxiolytics (OR: 1.28; 95% CI: 1.16-1.42). After the diagnosis of hyperthyroidism, there was a higher risk of being hospitalized with psychiatric diagnoses (hazard ratio (HR): 1.51; 95% CI: 1.11-2.05) and an increased risk of being treated with antipsychotics (HR: 1.46; 95% CI: 1.20-1.79), antidepressants (HR: 1.54; 95% CI: 1.36-1.74), or anxiolytics (HR: 1.47; 95% CI: 1.27-1.69). Hyperthyroid individuals have an increased risk of being hospitalized with psychiatric diagnoses and being treated with antipsychotics, antidepressants, and anxiolytics, both before and after the diagnosis of hyperthyroidism.

Linking ClinicalTrials.gov and PubMed to Track Results of Interventional Human Clinical Trials

PubMed Central

Huser, Vojtech; Cimino, James J.

2013-01-01

Objective In an effort to understand how results of human clinical trials are made public, we analyze a large set of clinical trials registered at ClinicalTrials.gov, the world’s largest clinical trial registry. Materials and Methods We considered two trial result artifacts: (1) existence of a trial result journal article that is formally linked to a registered trial or (2) the deposition of a trial’s basic summary results within the registry. Results The study sample consisted of 8907 completed, interventional, phase 2-or-higher clinical trials that were completed in 2006-2009. The majority of trials (72.2%) had no structured trial-article link present. A total of 2367 trials (26.6%) deposited basic summary results within the registry. Of those , 969 trials (10.9%) were classified as trials with extended results and 1398 trials (15.7%) were classified as trials with only required basic results. The majority of the trials (54.8%) had no evidence of results, based on either linked result articles or basic summary results (silent trials), while a minimal number (9.2%) report results through both registry deposition and publication. Discussion Our study analyzes the body of linked knowledge around clinical trials (which we refer to as the “trialome”). Our results show that most trials do not report results and, for those that do, there is minimal overlap in the types of reporting. We identify several mechanisms by which the linkages between trials and their published results can be increased. Conclusion Our study shows that even when combining publications and registry results, and despite availability of several information channels, trial sponsors do not sufficiently meet the mandate to inform the public either via a linked result publication or basic results submission. PMID:23874614

Mental distress and subsequent use of psychotropic drugs among adolescents-a prospective register linkage study.

PubMed

Steffenak, Anne Kjersti Myhrene; Nordström, Gun; Wilde-Larsson, Bodil; Skurtveit, Svetlana; Furu, Kari; Hartz, Ingeborg

2012-06-01

To investigate the association between mental distress, other factors, and subsequent use of psychotropic drugs in adolescents aged 15-16 years. This study is based on information retrieved from the Norwegian Youth Health Surveys (2000-2003) and linked to prescription data from the Norwegian Prescription Database (2004-2009). The study population included 11,620 adolescents aged 15-16 (87% response rate) years. Self-reported mental distress (Hopkins Symptom Checklist-10 score 1.85) was recorded along with health and lifestyle habits, education plans, and family economics. Incident psychotropic drug use (outcome measure) was defined ≥1 prescriptions of one of the following psychotropic drugs: anxiolytics, hypnotics, antidepressants, or phenothiazines registered in the Norwegian Prescription Database. Overall, 15.5% of the adolescents reported mental distress, 75% of them were girls. For both genders, incident psychotropic use was significantly higher among those reporting mental distresses at baseline, compared with the rest of the participants. The highest psychotropic drug use was observed among mentally distressed girls (27.7%). Mental distress was significantly associated with incident use of psychotropic drugs (odds ratio: 2.25, 95% confidence interval: 1.97-2.55). After adjustment for confounding factors and inclusion of potential mediating factors, the odds ratio attenuated to 1.59 (95% confidence interval: 1.35-1.86). The prevalence of mental distress among adolescents may have consequences for health promotion. Public health nurses in Norway, working in health centers and schools, have a responsibility to promote health and prevent health problems. They have the opportunity and a responsibility to identify vulnerable young people. Copyright © 2012 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Evolution of educational inequalities in site-specific cancer mortality among Belgian men between the 1990s and 2000s using a "fundamental cause" perspective.

PubMed

Vanthomme, Katrien; Vandenheede, Hadewijch; Hagedoorn, Paulien; Gadeyne, Sylvie

2017-07-05

According to the "fundamental cause" theory, emerging knowledge on health-enhancing behaviours and technologies results in health disparities. This study aims to assess (trends in) educational inequalities in site-specific cancer mortality in Belgian men in the 1990s and the 2000s using this framework. Data were derived from record linkage between the Belgian censuses of 1991 and 2001 and register data on mortality. The study population comprised all Belgian men aged 50-79 years during follow-up. Both absolute and relative inequality measures have been calculated. Despite an overall downward trend in cancer mortality, educational differences are observed for the majority of cancer sites in the 2000s. Generally, inequalities are largest for mortality from preventable cancers. Trends over time in inequalities are rather stable compared with the 1990s. Educational differences in site-specific cancer mortality persist in the 2000s in Belgium, mainly for cancers related to behavioural change and medical interventions. Policy efforts focussing on behavioural change and healthcare utilization remain crucial in order to tackle these increasing inequalities.

HLA-F polymorphisms in a Euro-Brazilian population from Southern Brazil.

PubMed

Manvailer, L F S; Wowk, P F; Mattar, S B; da Siva, J S; da Graça Bicalho, M; Roxo, V M M S

2014-12-01

HLA-F is a non-classical major histocompatibility complex (MHC) gene. It codes class Ib MHC molecules with restricted distribution and less nucleotide variations than MHC class Ia genes. Of the 22 alleles registered on the IMGT database only four alleles encode for proteins that differ in their primary structure. To estimate genotype and allele frequencies, this study targeted on known protein coding regions of the HLA-F gene. Genotyping was performed by Sequence Base Typing (SBT). The sample was composed by 199-unrelated bone marrow donors from the Brazilian Bone Marrow Donor Registry (REDOME), Euro-Brazilians, from Southern Brazil. About 1673 bp were analyzed. The most frequent allele was HLA-F*01:01 (87.19%), followed by HLA-F*01:03 (12.31%), HLA-F*01:02 (0.25%) and HLA-F*01:04 (0.25%). Significant linkage disequilibrium (LD) was verified between HLA-F and HLA classes I and II alleles. This is the first study regarding HLA-F polymorphisms in a Euro-Brazilian population contributing to the Southern Brazilian genetic characterization. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Testing association and linkage using affected-sib-parent study designs.

PubMed

Millstein, Joshua; Siegmund, Kimberly D; Conti, David V; Gauderman, W James

2005-11-01

We have developed a method for jointly testing linkage and association using data from affected sib pairs and their parents. We specify a conditional logistic regression model with two covariates, one that quantifies association (either direct association or indirect association via linkage disequilibrium), and a second that quantifies linkage. The latter covariate is computed based on expected identity-by-descend (ibd) sharing of marker alleles between siblings. In addition to a joint test of linkage and association, our general framework can be used to obtain a linkage test comparable to the mean test (Blackwelder and Elston [1985] Genet. Epidemiol. 2:85-97), and an association test comparable to the Family-Based Association Test (FBAT; Rabinowitz and Laird [2000] Hum. Hered. 50:211-223). We present simulation results demonstrating that our joint test can be more powerful than some standard tests of linkage or association. For example, with a relative risk of 2.7 per variant allele at a disease locus, the estimated power to detect a nearby marker with a modest level of LD was 58.1% by the mean test (linkage only), 69.8% by FBAT, and 82.5% by our joint test of linkage and association. Our model can also be used to obtain tests of linkage conditional on association and association conditional on linkage, which can be helpful in fine mapping. Copyright 2005 Wiley-Liss, Inc.

Meta-analysis of 32 genome-wide linkage studies of schizophrenia

PubMed Central

Ng, MYM; Levinson, DF; Faraone, SV; Suarez, BK; DeLisi, LE; Arinami, T; Riley, B; Paunio, T; Pulver, AE; Irmansyah; Holmans, PA; Escamilla, M; Wildenauer, DB; Williams, NM; Laurent, C; Mowry, BJ; Brzustowicz, LM; Maziade, M; Sklar, P; Garver, DL; Abecasis, GR; Lerer, B; Fallin, MD; Gurling, HMD; Gejman, PV; Lindholm, E; Moises, HW; Byerley, W; Wijsman, EM; Forabosco, P; Tsuang, MT; Hwu, H-G; Okazaki, Y; Kendler, KS; Wormley, B; Fanous, A; Walsh, D; O’Neill, FA; Peltonen, L; Nestadt, G; Lasseter, VK; Liang, KY; Papadimitriou, GM; Dikeos, DG; Schwab, SG; Owen, MJ; O’Donovan, MC; Norton, N; Hare, E; Raventos, H; Nicolini, H; Albus, M; Maier, W; Nimgaonkar, VL; Terenius, L; Mallet, J; Jay, M; Godard, S; Nertney, D; Alexander, M; Crowe, RR; Silverman, JM; Bassett, AS; Roy, M-A; Mérette, C; Pato, CN; Pato, MT; Roos, J Louw; Kohn, Y; Amann-Zalcenstein, D; Kalsi, G; McQuillin, A; Curtis, D; Brynjolfson, J; Sigmundsson, T; Petursson, H; Sanders, AR; Duan, J; Jazin, E; Myles-Worsley, M; Karayiorgou, M; Lewis, CM

2009-01-01

A genome scan meta-analysis (GSMA) was carried out on 32 independent genome-wide linkage scan analyses that included 3255 pedigrees with 7413 genotyped cases affected with schizophrenia (SCZ) or related disorders. The primary GSMA divided the autosomes into 120 bins, rank-ordered the bins within each study according to the most positive linkage result in each bin, summed these ranks (weighted for study size) for each bin across studies and determined the empirical probability of a given summed rank (PSR) by simulation. Suggestive evidence for linkage was observed in two single bins, on chromosomes 5q (142-168 Mb) and 2q (103-134 Mb). Genome-wide evidence for linkage was detected on chromosome 2q (119-152 Mb) when bin boundaries were shifted to the middle of the previous bins. The primary analysis met empirical criteria for ‘aggregate’ genome-wide significance, indicating that some or all of 10 bins are likely to contain loci linked to SCZ, including regions of chromosomes 1, 2q, 3q, 4q, 5q, 8p and 10q. In a secondary analysis of 22 studies of European-ancestry samples, suggestive evidence for linkage was observed on chromosome 8p (16-33 Mb). Although the newer genome-wide association methodology has greater power to detect weak associations to single common DNA sequence variants, linkage analysis can detect diverse genetic effects that segregate in families, including multiple rare variants within one locus or several weakly associated loci in the same region. Therefore, the regions supported by this meta-analysis deserve close attention in future studies. PMID:19349958

Mapping loci influencing blood pressure in the Framingham pedigrees using model-free LOD score analysis of a quantitative trait.

PubMed

Knight, Jo; North, Bernard V; Sham, Pak C; Curtis, David

2003-12-31

This paper presents a method of performing model-free LOD-score based linkage analysis on quantitative traits. It is implemented in the QMFLINK program. The method is used to perform a genome screen on the Framingham Heart Study data. A number of markers that show some support for linkage in our study coincide substantially with those implicated in other linkage studies of hypertension. Although the new method needs further testing on additional real and simulated data sets we can already say that it is straightforward to apply and may offer a useful complementary approach to previously available methods for the linkage analysis of quantitative traits.

Mapping loci influencing blood pressure in the Framingham pedigrees using model-free LOD score analysis of a quantitative trait

PubMed Central

Knight, Jo; North, Bernard V; Sham, Pak C; Curtis, David

2003-01-01

This paper presents a method of performing model-free LOD-score based linkage analysis on quantitative traits. It is implemented in the QMFLINK program. The method is used to perform a genome screen on the Framingham Heart Study data. A number of markers that show some support for linkage in our study coincide substantially with those implicated in other linkage studies of hypertension. Although the new method needs further testing on additional real and simulated data sets we can already say that it is straightforward to apply and may offer a useful complementary approach to previously available methods for the linkage analysis of quantitative traits. PMID:14975142

Linkage analysis of quantitative refraction and refractive errors in the Beaver Dam Eye Study.

PubMed

Klein, Alison P; Duggal, Priya; Lee, Kristine E; Cheng, Ching-Yu; Klein, Ronald; Bailey-Wilson, Joan E; Klein, Barbara E K

2011-07-13

Refraction, as measured by spherical equivalent, is the need for an external lens to focus images on the retina. While genetic factors play an important role in the development of refractive errors, few susceptibility genes have been identified. However, several regions of linkage have been reported for myopia (2q, 4q, 7q, 12q, 17q, 18p, 22q, and Xq) and for quantitative refraction (1p, 3q, 4q, 7p, 8p, and 11p). To replicate previously identified linkage peaks and to identify novel loci that influence quantitative refraction and refractive errors, linkage analysis of spherical equivalent, myopia, and hyperopia in the Beaver Dam Eye Study was performed. Nonparametric, sibling-pair, genome-wide linkage analyses of refraction (spherical equivalent adjusted for age, education, and nuclear sclerosis), myopia and hyperopia in 834 sibling pairs within 486 extended pedigrees were performed. Suggestive evidence of linkage was found for hyperopia on chromosome 3, region q26 (empiric P = 5.34 × 10(-4)), a region that had shown significant genome-wide evidence of linkage to refraction and some evidence of linkage to hyperopia. In addition, the analysis replicated previously reported genome-wide significant linkages to 22q11 of adjusted refraction and myopia (empiric P = 4.43 × 10(-3) and 1.48 × 10(-3), respectively) and to 7p15 of refraction (empiric P = 9.43 × 10(-4)). Evidence was also found of linkage to refraction on 7q36 (empiric P = 2.32 × 10(-3)), a region previously linked to high myopia. The findings provide further evidence that genes controlling refractive errors are located on 3q26, 7p15, 7p36, and 22q11.

Genome-wide scan of IQ finds significant linkage to a quantitative trait locus on 2q.

PubMed

Luciano, M; Wright, M J; Duffy, D L; Wainwright, M A; Zhu, G; Evans, D M; Geffen, G M; Montgomery, G W; Martin, N G

2006-01-01

A genome-wide linkage scan of 795 microsatellite markers (761 autosomal, 34 X chromosome) was performed on Multidimensional Aptitude Battery subtests and verbal, performance and full scale scores, the WAIS-R Digit Symbol subtest, and two word-recognition tests (Schonell Graded Word Reading Test, Cambridge Contextual Reading Test) highly predictive of IQ. The sample included 361 families comprising 2-5 siblings who ranged in age from 15.7 to 22.2 years; genotype, but not phenotype, data were available for 81% of parents. A variance components analysis which controlled for age and sex effects showed significant linkage for the Cambridge reading test and performance IQ to the same region on chromosome 2, with respective LOD scores of 4.15 and 3.68. Suggestive linkage (LOD score>2.2) for various measures was further supported on chromosomes 6, 7, 11, 14, 21 and 22. Where location of linkage peaks converged for IQ subtests within the same scale, the overall scale score provided increased evidence for linkage to that region over any individual subtest. Association studies of candidate genes, particularly those involved in neural transmission and development, will be directed to genes located under the linkage peaks identified in this study.

A genome-wide search for linkage of estimated glomerular filtration rate (eGFR) in the Family Investigation of Nephropathy and Diabetes (FIND).

PubMed

Thameem, Farook; Igo, Robert P; Freedman, Barry I; Langefeld, Carl; Hanson, Robert L; Schelling, Jeffrey R; Elston, Robert C; Duggirala, Ravindranath; Nicholas, Susanne B; Goddard, Katrina A B; Divers, Jasmin; Guo, Xiuqing; Ipp, Eli; Kimmel, Paul L; Meoni, Lucy A; Shah, Vallabh O; Smith, Michael W; Winkler, Cheryl A; Zager, Philip G; Knowler, William C; Nelson, Robert G; Pahl, Madeline V; Parekh, Rulan S; Kao, W H Linda; Rasooly, Rebekah S; Adler, Sharon G; Abboud, Hanna E; Iyengar, Sudha K; Sedor, John R

2013-01-01

Estimated glomerular filtration rate (eGFR), a measure of kidney function, is heritable, suggesting that genes influence renal function. Genes that influence eGFR have been identified through genome-wide association studies. However, family-based linkage approaches may identify loci that explain a larger proportion of the heritability. This study used genome-wide linkage and association scans to identify quantitative trait loci (QTL) that influence eGFR. Genome-wide linkage and sparse association scans of eGFR were performed in families ascertained by probands with advanced diabetic nephropathy (DN) from the multi-ethnic Family Investigation of Nephropathy and Diabetes (FIND) study. This study included 954 African Americans (AA), 781 American Indians (AI), 614 European Americans (EA) and 1,611 Mexican Americans (MA). A total of 3,960 FIND participants were genotyped for 6,000 single nucleotide polymorphisms (SNPs) using the Illumina Linkage IVb panel. GFR was estimated by the Modification of Diet in Renal Disease (MDRD) formula. The non-parametric linkage analysis, accounting for the effects of diabetes duration and BMI, identified the strongest evidence for linkage of eGFR on chromosome 20q11 (log of the odds [LOD] = 3.34; P = 4.4 × 10(-5)) in MA and chromosome 15q12 (LOD = 2.84; P = 1.5 × 10(-4)) in EA. In all subjects, the strongest linkage signal for eGFR was detected on chromosome 10p12 (P = 5.5 × 10(-4)) at 44 cM near marker rs1339048. A subsequent association scan in both ancestry-specific groups and the entire population identified several SNPs significantly associated with eGFR across the genome. The present study describes the localization of QTL influencing eGFR on 20q11 in MA, 15q21 in EA and 10p12 in the combined ethnic groups participating in the FIND study. Identification of causal genes/variants influencing eGFR, within these linkage and association loci, will open new avenues for functional analyses and development of novel diagnostic markers for DN.

A Genome-Wide Search for Linkage of Estimated Glomerular Filtration Rate (eGFR) in the Family Investigation of Nephropathy and Diabetes (FIND)

PubMed Central

Thameem, Farook; Igo, Robert P.; Freedman, Barry I.; Langefeld, Carl; Hanson, Robert L.; Schelling, Jeffrey R.; Elston, Robert C.; Duggirala, Ravindranath; Nicholas, Susanne B.; Goddard, Katrina A. B.; Divers, Jasmin; Guo, Xiuqing; Ipp, Eli; Kimmel, Paul L.; Meoni, Lucy A.; Shah, Vallabh O.; Smith, Michael W.; Winkler, Cheryl A.; Zager, Philip G.; Knowler, William C.; Nelson, Robert G.; Pahl, Madeline V.; Parekh, Rulan S.; Kao, W. H. Linda; Rasooly, Rebekah S.; Adler, Sharon G.; Abboud, Hanna E.; Iyengar, Sudha K.; Sedor, John R.

2013-01-01

Objective Estimated glomerular filtration rate (eGFR), a measure of kidney function, is heritable, suggesting that genes influence renal function. Genes that influence eGFR have been identified through genome-wide association studies. However, family-based linkage approaches may identify loci that explain a larger proportion of the heritability. This study used genome-wide linkage and association scans to identify quantitative trait loci (QTL) that influence eGFR. Methods Genome-wide linkage and sparse association scans of eGFR were performed in families ascertained by probands with advanced diabetic nephropathy (DN) from the multi-ethnic Family Investigation of Nephropathy and Diabetes (FIND) study. This study included 954 African Americans (AA), 781 American Indians (AI), 614 European Americans (EA) and 1,611 Mexican Americans (MA). A total of 3,960 FIND participants were genotyped for 6,000 single nucleotide polymorphisms (SNPs) using the Illumina Linkage IVb panel. GFR was estimated by the Modification of Diet in Renal Disease (MDRD) formula. Results The non-parametric linkage analysis, accounting for the effects of diabetes duration and BMI, identified the strongest evidence for linkage of eGFR on chromosome 20q11 (log of the odds [LOD] = 3.34; P = 4.4×10−5) in MA and chromosome 15q12 (LOD = 2.84; P = 1.5×10−4) in EA. In all subjects, the strongest linkage signal for eGFR was detected on chromosome 10p12 (P = 5.5×10−4) at 44 cM near marker rs1339048. A subsequent association scan in both ancestry-specific groups and the entire population identified several SNPs significantly associated with eGFR across the genome. Conclusion The present study describes the localization of QTL influencing eGFR on 20q11 in MA, 15q21 in EA and 10p12 in the combined ethnic groups participating in the FIND study. Identification of causal genes/variants influencing eGFR, within these linkage and association loci, will open new avenues for functional analyses and development of novel diagnostic markers for DN. PMID:24358131

RNF8- and Ube2S-Dependent Ubiquitin Lysine 11-Linkage Modification in Response to DNA Damage.

PubMed

Paul, Atanu; Wang, Bin

2017-05-18

Ubiquitin modification of proteins plays pivotal roles in the cellular response to DNA damage. Given the complexity of ubiquitin conjugation due to the formation of poly-conjugates of different linkages, functional roles of linkage-specific ubiquitin modification at DNA damage sites are largely unclear. We identify that Lys11-linkage ubiquitin modification occurs at DNA damage sites in an ATM-dependent manner, and ubiquitin-modifying enzymes, including Ube2S E2-conjugating enzyme and RNF8 E3 ligase, are responsible for the assembly of Lys11-linkage conjugates on damaged chromatin, including histone H2A/H2AX. We show that RNF8- and Ube2S-dependent Lys11-linkage ubiquitin conjugation plays an important role in regulating DNA damage-induced transcriptional silencing, distinct from the role of Lys63-linkage ubiquitin in the recruitment of DNA damage repair proteins 53BP1 and BRCA1. Thus, our study highlights the importance of linkage-specific ubiquitination at DNA damage sites, and it reveals that Lys11-linkage ubiquitin modification plays a crucial role in the DNA damage response. Copyright © 2017 Elsevier Inc. All rights reserved.

Risk of congenital anomalies after exposure to asthma medication in the first trimester of pregnancy - a cohort linkage study.

PubMed

Garne, E; Vinkel Hansen, A; Morris, J; Jordan, S; Klungsøyr, K; Engeland, A; Tucker, D; Thayer, D S; Davies, G I; Nybo Andersen, A-M; Dolk, H

2016-09-01

To examine the effect of maternal exposure to asthma medications on the risk of congenital anomalies. Meta-analysis of aggregated data from three cohort studies. Linkage between healthcare databases and EUROCAT congenital anomaly registries. 519 242 pregnancies in Norway (2004-2010), Wales (2000-2010) and Funen, Denmark (2000-2010). Exposure defined as having at least one prescription for asthma medications issued (Wales) or dispensed (Norway, Denmark) from 91 days before to 91 days after the pregnancy start date. Odds ratios (ORs) were estimated separately for each register and combined in meta-analyses. ORs for all congenital anomalies and specific congenital anomalies. Overall exposure prevalence was 3.76%. For exposure to asthma medication in general, the adjusted OR (adjOR) for a major congenital anomaly was 1.21 (99% CI 1.09-1.34) after adjustment for maternal age and socioeconomic position. The OR of anal atresia was significantly increased in pregnancies exposed to inhaled corticosteroids (3.40; 99% CI 1.15-10.04). For severe congenital heart defects, an increased OR (1.97; 1.12-3.49) was associated with exposure to combination treatment with inhaled corticosteroids and long-acting beta-2-agonists. Associations with renal dysplasia were driven by exposure to short-acting beta-2-agonists (2.37; 1.20-4.67). The increased risk of congenital anomalies for women taking asthma medication is small with little confounding by maternal age or socioeconomic status. The study confirmed the association of inhaled corticosteroids with anal atresia found in earlier research and found potential new associations with combination treatment. The potential new associations should be interpreted with caution due to the large number of comparisons undertaken. This cohort study found a small increased risk of congenital anomalies for women taking asthma medication. © 2016 The Authors. BJOG An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd on behalf of Royal College of Obstetricians and Gynaecologists.

An association between autumn birth and clozapine treatment in patients with schizophrenia: a population-based analysis.

PubMed

Sørensen, Holger J; Foldager, Leslie; Røge, Rasmus; Pristed, Sofie Gry; Andreasen, Jesper T; Nielsen, Jimmi

2014-08-01

Numerous studies on seasonality of birth and schizophrenia risk have been published but it is uncertain whether, among those with schizophrenia, refractory illness exhibits any predilection for birth month. We hypothesized and examined whether a season of birth effect was present in patients with schizophrenia with a history of clozapine treatment. Using record linkage with Danish registers, we examined patients with schizophrenia born between 1950 and 1970, and between 1995 and 2009 and Cox regression analysis was used to examine season of birth in relation to history of clozapine treatment. In a study population corresponding to 60,062 person-years from 5328 individuals with schizophrenia of which 1223 (23%) received at least one clozapine prescription, birth in the autumn (September-November) was associated with clozapine treatment (HR = 1.24; 95% CI 1.07-1.46) when compared with birth in the spring (March-May). Although replication studies are needed, this is the first evidence from a nationwide study suggesting a possible season-associated risk of clozapine treatment in schizophrenia. The reasons for this relationship remain to be further investigated but might be partially explained by early exposures such as winter flu season and low vitamin D levels.

Genetic Studies of Stuttering in a Founder Population

PubMed Central

Wittke-Thompson, Jacqueline K.; Ambrose, Nicoline; Yairi, Ehud; Roe, Cheryl; Cook, Edwin H.; Ober, Carole; Cox, Nancy J.

2007-01-01

Genome-wide linkage and association analyses were conducted to identify genetic determinants of stuttering in a founder population in which 48 individuals affected with stuttering are connected in a single 232-person genealogy. A novel approach was devised to account for all necessary relationships to enable multipoint linkage analysis. Regions with nominal evidence for linkage were found on chromosomes 3 (P=0.013, 208.8 centiMorgans (cM)), 13 (P=0.012, 52.6 cM), and 15 (P=0.02, 100 cM). Regions with nominal evidence for association with stuttering that overlapped with a linkage signal are located on chromosomes 3 (P=0.0047, 195 cM), 9 (P=0.0067, 46.5 cM), and 13 (P=0.0055, 52.6 cM). We also conducted the first meta-analysis for stuttering using results from linkage studies in the Hutterites and The Illinois International Genetics of Stuttering Project and identified regions with nominal evidence for linkage on chromosomes 2 (P=0.013, 180–195 cM) and 5 (P=0.0051, 105–120 cM; P=0.015, 120–135 cM). None of the linkage signals detected in the Hutterite sample alone, or in the meta-analysis, meet genome-wide criteria for significance, although some of the stronger signals overlap linkage mapping signals previously reported for other speech and language disorders. PMID:17276504

Failure to find a chromosome 18 pericentric linkage in families with schizophrenia

DOE Office of Scientific and Technical Information (OSTI.GOV)

De Lisi, L.E.; Shields, G.; Lehner, T.

1995-12-18

A recent report of a possible linkage of bipolar affective disorder to a pericentric region of chromosome 18 initiated the present investigation to search for a similar linkage in 32 families with schizophrenia. The results of a study using 5 markers mapped to this region show negative lod scores and only weak evidence for any linkage by nonparametric analyses. If the previously reported finding is a true positive linkage for bipolar disorder, then either it is unlikely to be related to the genetics of schizophrenia, or the proportion of families linked to this region is small. 12 refs., 4 tabs.

Prospective Industrial Linkage at Aqaba University College, Jordan

ERIC Educational Resources Information Center

Abu-Hamatteh, Zeid; Al-Amyan, Mozfi; Al-Azzam, Farouq

2008-01-01

The present study intends to examine the overall situation and the environment of Aqaba University College (AUC) in relation to industrial-educational interaction, and to discuss existing and possible future industrial linkage strategies. This article presents observations from AUC, as well as suggestions for action on industrial linkage. The…

Validity of deterministic record linkage using multiple indirect personal identifiers: linking a large registry to claims data.

PubMed

Setoguchi, Soko; Zhu, Ying; Jalbert, Jessica J; Williams, Lauren A; Chen, Chih-Ying

2014-05-01

Linking patient registries with administrative databases can enhance the utility of the databases for epidemiological and comparative effectiveness research. However, registries often lack direct personal identifiers, and the validity of record linkage using multiple indirect personal identifiers is not well understood. Using a large contemporary national cardiovascular device registry and 100% Medicare inpatient data, we linked hospitalization-level records. The main outcomes were the validity measures of several deterministic linkage rules using multiple indirect personal identifiers compared with rules using both direct and indirect personal identifiers. Linkage rules using 2 or 3 indirect, patient-level identifiers (ie, date of birth, sex, admission date) and hospital ID produced linkages with sensitivity of 95% and specificity of 98% compared with a gold standard linkage rule using a combination of both direct and indirect identifiers. Ours is the first large-scale study to validate the performance of deterministic linkage rules without direct personal identifiers. When linking hospitalization-level records in the absence of direct personal identifiers, provider information is necessary for successful linkage. © 2014 American Heart Association, Inc.

Accuracy of Definitions for Linkage to Care in Persons Living with HIV

PubMed Central

KELLER, Sara C.; YEHIA, Baligh R.; EBERHART, Michael G.; BRADY, Kathleen A.

2013-01-01

Objective To compare the accuracy of linkage to care metrics for patients diagnosed with HIV using retention in care and virologic suppression as the gold standards of effective linkage. Design A retrospective cohort study of patients aged 18 and over with newly-diagnosed HIV infection in the City of Philadelphia, 2007 to 2008. Methods Times from diagnosis to clinic visits or laboratory testing were used as linkage measures. Outcome variables included being retained in care and achieving virologic suppression, 366-730 days after diagnosis. Positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC) for each linkage measure and retention and virologic suppression outcomes are described. Results Of the 1781 patients in the study, 503 (28.2%) were retained in care in the Ryan White system and 418 (23.5%) achieved virologic suppression 366-730 days after diagnosis. The linkage measure with the highest PPV for retention was having two clinic visits within 365 days of diagnosis, separated by 90 days (74.2%). Having a clinic visit between 21 and 365 days after diagnosis had both the highest NPV for retention (94.5%) and the highest adjusted AUC for retention (0.872). Having two tests within 365 days of diagnosis, separated by 90 days, had the highest adjusted AUC for virologic suppression (0.780). Conclusions Linkage measures associated with clinic visits had higher PPV and NPV for retention, while linkage measures associated with laboratory testing had higher PPV and NPV for retention. Linkage measures should be chosen based on the outcome of interest. PMID:23614992

Linkage to care among adults being investigated for tuberculosis in South Africa: pilot study of a case manager intervention.

PubMed

Maraba, Noriah; Chihota, Violet; McCarthy, Kerrigan; Churchyard, Gavin J; Grant, Alison D

2018-05-24

We piloted an intervention to determine if support from a case manager would assist adults being investigated for tuberculosis (TB) to link into TB and HIV care. Pilot interventional cohort study. Patients identified by primary healthcare clinic staff in South Africa as needing TB investigations were enrolled. Participants were supported for 3 months by case managers who facilitated the care pathway by promoting HIV testing, getting laboratory results, calling patients to return for results and facilitating treatment initiation. Linkage to TB care was defined as starting TB treatment within 28 days in those with a positive test result; linkage to HIV care, for HIV-positive people, was defined as having blood taken for CD4 count and, for those eligible, starting antiretroviral therapy within 3 months. Intervention implementation was measured by number of attempts to contact participants. Among 562 participants (307 (54.6%) female, median age: 36 years (IQR 29-44)), most 477 (84.8%) had previously tested for HIV; of these, 328/475 (69.1%) self-reported being HIV-positive. Overall, 189/562 (33.6%) participants needed linkage to care (132 HIV care linkage only; 35 TB treatment linkage only; 22 both). Of 555 attempts to contact these 189 participants, 407 were to facilitate HIV care linkage, 78 for TB treatment linkage and 70 for both. At the end of 3-month follow-up, 40 participants had not linked to care (29 of the 132 (22.0%) participants needing linkage to HIV care only, 4 of the 35 (11.4%) needing to start on TB treatment only and 7 of the 22 (31.8%) needing both). Many people testing for TB need linkage to care. Despite case manager support, non-linkage into HIV care remained higher than desirable, suggesting a need to modify this intervention before implementation. Innovative strategies to enable linkage to care are needed. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

[Fatal occupational accidents: updating of data from a mortality register].

PubMed

Mantero, Silvia; Baldasseroni, A; Chellini, Elisabetta; Giovanetti, Lucia

2005-01-01

In Italy, almost one thousand deaths due to occupational accidents are usually registered by INAIL each year. Case registration by INAIL has merely administrative purposes and therefore it is necessary to use other sources for case ascertainment in order to better estimate the real number of deaths related to occupational accidents, as shown also by previous papers. Evaluation of the contribution of another data source, namely the Tuscany Regional Mortality Registry, to obtain the correct figure for occupational accident deaths through the use of a place-of-occurrence notation on the death certificate. Cases that occurred in residents in Tuscany in 2000-2001 were considered. They were identified from : a) the Tuscany Regional Mortality Registry (RMR) using the E code of the ICD LX code of death, the year and place of occurrence; b) the INAIL archive using the year of event, the type of definition and management. The INAIL source was without doubt the most informative but was only 51% complete, whereas the RMR source, although less informative, was more complete (82.4%) and allowed identification of cases not registered by INAIL, that had occurred for instance in the Armed Forces and in the National Railway Company. However, the vast majority of RMR extra-cases occurred in subjects aged 65+, in agriculture and in the building industry. It is currently possible to plan a systematic linkage of the two sources due to the new possibilities that are available: the place-of-occurrence in the death certificate and the availability of individual data in the INAIL source.

Validation of an instrument to measure inter-organisational linkages in general practice.

PubMed

Amoroso, Cheryl; Proudfoot, Judith; Bubner, Tanya; Jayasinghe, Upali W; Holton, Christine; Winstanley, Julie; Beilby, Justin; Harris, Mark F

2007-12-03

Linkages between general medical practices and external services are important for high quality chronic disease care. The purpose of this research is to describe the development, evaluation and use of a brief tool that measures the comprehensiveness and quality of a general practice's linkages with external providers for the management of patients with chronic disease. In this study, clinical linkages are defined as the communication, support, and referral arrangements between services for the care and assistance of patients with chronic disease. An interview to measure surgery-level (rather than individual clinician-level) clinical linkages was developed, piloted, reviewed, and evaluated with 97 Australian general practices. Two validated survey instruments were posted to patients, and a survey of locally available services was developed and posted to participating Divisions of General Practice (support organisations). Hypotheses regarding internal validity, association with local services, and patient satisfaction were tested using factor analysis, logistic regression and multilevel regression models. The resulting General Practice Clinical Linkages Interview (GP-CLI) is a nine-item tool with three underlying factors: referral and advice linkages, shared care and care planning linkages, and community access and awareness linkages. Local availability of chronic disease services has no affect on the comprehensiveness of services with which practices link, however, comprehensiveness of clinical linkages has an association with patient assessment of access, receptionist services, and of continuity of care in their general practice. The GP-CLI may be useful to researchers examining comparable health care systems for measuring the comprehensiveness and quality of linkages at a general practice-level with related services, possessing both internal and external validity. The tool can be used with large samples exploring the impact, outcomes, and facilitators of high quality clinical linkages in general practice.

Particle swarm optimization with recombination and dynamic linkage discovery.

PubMed

Chen, Ying-Ping; Peng, Wen-Chih; Jian, Ming-Chung

2007-12-01

In this paper, we try to improve the performance of the particle swarm optimizer by incorporating the linkage concept, which is an essential mechanism in genetic algorithms, and design a new linkage identification technique called dynamic linkage discovery to address the linkage problem in real-parameter optimization problems. Dynamic linkage discovery is a costless and effective linkage recognition technique that adapts the linkage configuration by employing only the selection operator without extra judging criteria irrelevant to the objective function. Moreover, a recombination operator that utilizes the discovered linkage configuration to promote the cooperation of particle swarm optimizer and dynamic linkage discovery is accordingly developed. By integrating the particle swarm optimizer, dynamic linkage discovery, and recombination operator, we propose a new hybridization of optimization methodologies called particle swarm optimization with recombination and dynamic linkage discovery (PSO-RDL). In order to study the capability of PSO-RDL, numerical experiments were conducted on a set of benchmark functions as well as on an important real-world application. The benchmark functions used in this paper were proposed in the 2005 Institute of Electrical and Electronics Engineers Congress on Evolutionary Computation. The experimental results on the benchmark functions indicate that PSO-RDL can provide a level of performance comparable to that given by other advanced optimization techniques. In addition to the benchmark, PSO-RDL was also used to solve the economic dispatch (ED) problem for power systems, which is a real-world problem and highly constrained. The results indicate that PSO-RDL can successfully solve the ED problem for the three-unit power system and obtain the currently known best solution for the 40-unit system.

Genetic linkage map and comparative genome analysis for the estuarine Atlantic killifish (Fundulus heteroclitus)

EPA Pesticide Factsheets

Genetic linkage maps are valuable tools in evolutionary biology; however, their availability for wild populations is extremely limited. Fundulus heteroclitus (Atlantic killifish) is a non-migratory estuarine fish that exhibits high allelic and phenotypic diversity partitioned among subpopulations that reside in disparate environmental conditions. An ideal candidate model organism for studying gene-environment interactions, the molecular toolbox for F. heteroclitus is limited. We identified hundreds of novel microsatellites which, when combined with existing microsatellites and single nucleotide polymorphisms (SNPs), were used to construct the first genetic linkage map for this species. By integrating independent linkage maps from three genetic crosses, we developed a consensus map containing 24 linkage groups, consistent with the number of chromosomes reported for this species. These linkage groups span 2300 centimorgans (cM) of recombinant genomic space, intermediate in size relative to the current linkage maps for the teleosts, medaka and zebrafish. Comparisons between fish genomes support a high degree of synteny between the consensus F. heteroclitus linkage map and the medaka and (to a lesser extent) zebrafish physical genome assemblies.This dataset is associated with the following publication:Waits , E., J. Martinson , B. Rinner, S. Morris, D. Proestou, D. Champlin , and D. Nacci. Genetic linkage map and comparative genome analysis for the estuarine Atlanti

Privacy-preserving record linkage on large real world datasets.

PubMed

Randall, Sean M; Ferrante, Anna M; Boyd, James H; Bauer, Jacqueline K; Semmens, James B

2014-08-01

Record linkage typically involves the use of dedicated linkage units who are supplied with personally identifying information to determine individuals from within and across datasets. The personally identifying information supplied to linkage units is separated from clinical information prior to release by data custodians. While this substantially reduces the risk of disclosure of sensitive information, some residual risks still exist and remain a concern for some custodians. In this paper we trial a method of record linkage which reduces privacy risk still further on large real world administrative data. The method uses encrypted personal identifying information (bloom filters) in a probability-based linkage framework. The privacy preserving linkage method was tested on ten years of New South Wales (NSW) and Western Australian (WA) hospital admissions data, comprising in total over 26 million records. No difference in linkage quality was found when the results were compared to traditional probabilistic methods using full unencrypted personal identifiers. This presents as a possible means of reducing privacy risks related to record linkage in population level research studies. It is hoped that through adaptations of this method or similar privacy preserving methods, risks related to information disclosure can be reduced so that the benefits of linked research taking place can be fully realised. Copyright © 2013 Elsevier Inc. All rights reserved.

Linkage studies in primary open angle glaucoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Avramopoulos, D.; Grigoriadu, M.; Kitsos, G.

1994-09-01

Glaucoma is a leading cause of blindness worldwide. The majority of glaucoma is associated with an open, normal appearing anterior chamber angle and is termed primary open angle glaucoma (POAG, MIM 137760). It is characterized by elevated intraocular pressure and onset in middle age or later. A subset of POAG with juvenile onset has recently been linked to chromosome 1q in two families with autosomal dominant inheritance. Eleven pedigrees with autosomal dominant POG (non-juvenile-onset) have been identified in Epirus, Greece. In the present study DNA samples have been collected from 50 individuals from one large pedigree, including 12 affected individuals.more » Preliminary results of linkage analysis with chromosome 1 microsatellites using the computer program package LINKAGE Version 5.1 showed no linkage with the markers previously linked to juvenile-onset POAG. Further linkage analysis is being pursued, and the results will be presented.« less

Linkage disequilibrium fine mapping of quantitative trait loci: A simulation study

PubMed Central

Abdallah, Jihad M; Goffinet, Bruno; Cierco-Ayrolles, Christine; Pérez-Enciso, Miguel

2003-01-01

Recently, the use of linkage disequilibrium (LD) to locate genes which affect quantitative traits (QTL) has received an increasing interest, but the plausibility of fine mapping using linkage disequilibrium techniques for QTL has not been well studied. The main objectives of this work were to (1) measure the extent and pattern of LD between a putative QTL and nearby markers in finite populations and (2) investigate the usefulness of LD in fine mapping QTL in simulated populations using a dense map of multiallelic or biallelic marker loci. The test of association between a marker and QTL and the power of the test were calculated based on single-marker regression analysis. The results show the presence of substantial linkage disequilibrium with closely linked marker loci after 100 to 200 generations of random mating. Although the power to test the association with a frequent QTL of large effect was satisfactory, the power was low for the QTL with a small effect and/or low frequency. More powerful, multi-locus methods may be required to map low frequent QTL with small genetic effects, as well as combining both linkage and linkage disequilibrium information. The results also showed that multiallelic markers are more useful than biallelic markers to detect linkage disequilibrium and association at an equal distance. PMID:12939203

Current and future developments in patents for quantitative trait loci in dairy cattle.

PubMed

Weller, Joel I

2007-01-01

Many studies have proposed that rates of genetic gain in dairy cattle can be increased by direct selection on the individual quantitative loci responsible for the genetic variation in these traits, or selection on linked genetic markers. The development of DNA-level genetic markers has made detection of QTL nearly routine in all major livestock species. The studies that attempted to detect genes affecting quantitative traits can be divided into two categories: analysis of candidate genes, and genome scans based on within-family genetic linkage. To date, 12 patent cooperative treaty (PCT) and US patents have been registered for DNA sequences claimed to be associated with effects on economic traits in dairy cattle. All claim effects on milk production, but other traits are also included in some of the claims. Most of the sequences found by the candidate gene approach are of dubious validity, and have been repeated in only very few independent studies. The two missense mutations on chromosomes 6 and 14 affecting milk concentration derived from genome scans are more solidly based, but the claims are also disputed. A few PCT in dairy cattle are commercialized as genetic tests where commercial dairy farmers are the target market.

Morbidity before and after the Diagnosis of Hyperthyroidism: A Nationwide Register-Based Study

PubMed Central

Brandt, Frans; Thvilum, Marianne; Almind, Dorthe; Christensen, Kaare; Green, Anders; Hegedüs, Laszlo; Brix, Thomas Heiberg

2013-01-01

Background Hyperthyroidism has been linked with different morbidities, like atrial fibrillation, stroke and diabetes mellitus. However, our knowledge regarding the extent and temporal relation between hyperthyroidism and other diseases is fragmented. Here, we aimed at evaluating various morbidities before and after the diagnosis of hyperthyroidism. Methods Observational cohort study. From nationwide Danish health registers 2631 hyperthyroid singletons and 375 twin pairs discordant for hyperthyroidism were identified and followed for an average of 6 years (range 0–13). Data on the occurrence of cardiovascular diseases, lung diseases, diabetes mellitus, rheumatic diseases and malignant diseases was obtained by person-to-person record linkage with the National Danish Patient Register and/or the Danish National Prescription Registry (lung diseases and diabetes mellitus). Logistic and Cox regression models were used to assess the risk of morbidity before and after the diagnosis of hyperthyroidism, respectively. All Cox regression analyses were adjusted for the degree of co-morbidity preceding the diagnosis of hyperthyroidism, using the Charlson score. Results Hyperthyroid individuals had a significantly higher risk of being diagnosed with cardiovascular diseases (odds ratio (OR) 1.65; 95% confidence interval (CI): 1.45–1.87), lung diseases (OR 1.53; 95% CI: 1.29–1.60), and diabetes mellitus (OR 1.43, 95% CI: 1.20–1.72), but not with malignant diseases (OR 1.16, 95% CI: 0.99–1.36) prior to the diagnosis of hyperthyroidism. After the diagnosis of hyperthyroidism, subjects had a significantly higher risk of being diagnosed with cardiovascular diseases (hazard ratio (HR) 1.34; 95% CI: 1.15–1.56), lung diseases (HR 1.28; 95% CI: 1.10–1.49), and diabetes mellitus (HR 1.46; 95% CI: 1.16–1.84), but not with rheumatic diseases (HR 1.39, 95% CI: 0.92–2.09) or malignant diseases (HR 1.18, 95% CI 0.97–1.42). Conclusions We demonstrate a significantly increased burden of morbidity, both before and after the diagnosis of hyperthyroidism. PMID:23818961

High Hospitalization Rates in Survivors of Childhood Cancer: A Longitudinal Follow-Up Study Using Medical Record Linkage

PubMed Central

Sieswerda, Elske; Font-Gonzalez, Anna; Reitsma, Johannes B.; Dijkgraaf, Marcel G. W.; Heinen, Richard C.; Jaspers, Monique W.; van der Pal, Helena J.; van Leeuwen, Flora E.; Caron, Huib N.

2016-01-01

Hospitalization rates over time of childhood cancer survivors (CCS) provide insight into the burden of unfavorable health conditions on CCS and health care resources. The objective of our study was to examine trends in hospitalizations of CCS and risk factors in comparison with the general population. We performed a medical record linkage study of a cohort of 1564 ≥five-year CCS with national registers. We obtained a random sample of the general population matched on year of birth, gender and calendar year per CCS retrieved. We quantified and compared hospitalization rates of CCS and reference persons from 1995 until 2005, and we analyzed risk factors for hospitalization within the CCS cohort with multivariable Poisson models. We retrieved hospitalization information from 1382 CCS and 25583 reference persons. The overall relative hospitalization rate (RHR) was 2.2 (95%CI:1.9–2.5) for CCS compared to reference persons. CCS with central nervous system and solid tumors had highest RHRs. Hospitalization rates in CCS were increased compared to reference persons up to at least 30 years after primary diagnosis, with highest rates 5–10 and 20–30 years after primary cancer. RHRs were highest for hospitalizations due to neoplasms (10.7; 95%CI:7.1–16.3) and endocrine/nutritional/metabolic disorders (7.3; 95%CI:4.6–11.7). Female gender (P<0.001), radiotherapy to head and/or neck (P<0.001) or thorax and/or abdomen (P = 0.03) and surgery (P = 0.01) were associated with higher hospitalization rates in CCS. In conclusion, CCS have increased hospitalization rates compared to the general population, up to at least 30 years after primary cancer treatment. These findings imply a high and long-term burden of unfavorable health conditions after childhood cancer on survivors and health care resources. PMID:27433937

High Hospitalization Rates in Survivors of Childhood Cancer: A Longitudinal Follow-Up Study Using Medical Record Linkage.

PubMed

Sieswerda, Elske; Font-Gonzalez, Anna; Reitsma, Johannes B; Dijkgraaf, Marcel G W; Heinen, Richard C; Jaspers, Monique W; van der Pal, Helena J; van Leeuwen, Flora E; Caron, Huib N; Geskus, Ronald B; Kremer, Leontien C

2016-01-01

Hospitalization rates over time of childhood cancer survivors (CCS) provide insight into the burden of unfavorable health conditions on CCS and health care resources. The objective of our study was to examine trends in hospitalizations of CCS and risk factors in comparison with the general population. We performed a medical record linkage study of a cohort of 1564 ≥five-year CCS with national registers. We obtained a random sample of the general population matched on year of birth, gender and calendar year per CCS retrieved. We quantified and compared hospitalization rates of CCS and reference persons from 1995 until 2005, and we analyzed risk factors for hospitalization within the CCS cohort with multivariable Poisson models. We retrieved hospitalization information from 1382 CCS and 25583 reference persons. The overall relative hospitalization rate (RHR) was 2.2 (95%CI:1.9-2.5) for CCS compared to reference persons. CCS with central nervous system and solid tumors had highest RHRs. Hospitalization rates in CCS were increased compared to reference persons up to at least 30 years after primary diagnosis, with highest rates 5-10 and 20-30 years after primary cancer. RHRs were highest for hospitalizations due to neoplasms (10.7; 95%CI:7.1-16.3) and endocrine/nutritional/metabolic disorders (7.3; 95%CI:4.6-11.7). Female gender (P<0.001), radiotherapy to head and/or neck (P<0.001) or thorax and/or abdomen (P = 0.03) and surgery (P = 0.01) were associated with higher hospitalization rates in CCS. In conclusion, CCS have increased hospitalization rates compared to the general population, up to at least 30 years after primary cancer treatment. These findings imply a high and long-term burden of unfavorable health conditions after childhood cancer on survivors and health care resources.

Linking Swedish health data registers to establish a research database and a shared decision-making tool in hip replacement.

PubMed

Cnudde, Peter; Rolfson, Ola; Nemes, Szilard; Kärrholm, Johan; Rehnberg, Clas; Rogmark, Cecilia; Timperley, John; Garellick, Göran

2016-10-04

Sweden offers a unique opportunity to researchers to construct comprehensive databases that encompass a wide variety of healthcare related data. Statistics Sweden and the National Board of Health and Welfare collect individual level data for all Swedish residents that ranges from medical diagnoses to socioeconomic information. In addition to the information collected by governmental agencies the medical profession has initiated nationwide Quality Registers that collect data on specific diagnoses and interventions. The Quality Registers analyze activity within healthcare institutions, with the aims of improving clinical care and fostering clinical research. The Swedish Hip Arthroplasty Register (SHAR) has been collecting data since 1979. Joint replacement in general and hip replacement in particular is considered a success story with low mortality and complication rate. It is credited to the pioneering work of the SHAR that the revision rate following hip replacement surgery in Sweden is amongst the lowest in the world. This has been accomplished by the diligent follow-up of patients with feedback of outcomes to the providers of the healthcare along with post market surveillance of individual implant performance. During its existence SHAR has experienced a constant organic growth. One major development was the introduction of the Patient Reported Outcome Measures program, giving a voice to the patients in healthcare performance evaluation. The next aim for SHAR is to integrate patients' wishes and expectations with the surgeons' expertise in the form of a Shared Decision-Making (SDM) instrument. The first step in building such an instrument is to assemble the necessary data. This involves linking the SHARs database with the two aforementioned governmental agencies. The linkage is done by the 10-digit personal identity number assigned at birth (or immigration) for every Swedish resident. The anonymized data is stored on encrypted serves and can only be accessed after double identification. This data will serve as starting point for several research projects and clinical improvement work.

Correlation between quantitative traits and correlation between corresponding LOD scores: detection of pleiotropic effects.

PubMed

Ulgen, Ayse; Han, Zhihua; Li, Wentian

2003-12-31

We address the question of whether statistical correlations among quantitative traits lead to correlation of linkage results of these traits. Five measured quantitative traits (total cholesterol, fasting glucose, HDL cholesterol, blood pressure, and triglycerides), and one derived quantitative trait (total cholesterol divided by the HDL cholesterol) are used for phenotype correlation studies. Four of them are used for linkage analysis. We show that although correlation among phenotypes partially reflects the correlation among linkage analysis results, the LOD-score correlations are on average low. The most significant peaks found by using different traits do not often overlap. Studying covariances at specific locations in LOD scores may provide clues for further bivariate linkage analyses.

Combined linkage and association analyses identify a novel locus for obesity near PROX1 in Asians.

PubMed

Kim, Hyun-Jin; Yoo, Yun Joo; Ju, Young Seok; Lee, Seungbok; Cho, Sung-Il; Sung, Joohon; Kim, Jong-Il; Seo, Jeong-Sun

2013-11-01

Although genome-wide association studies (GWAS) have substantially contributed to understanding the genetic architecture, unidentified variants for complex traits remain an issue. One of the efficient approaches is the improvement of the power of GWAS scan by weighting P values with prior linkage signals. Our objective was to identify the novel candidates for obesity in Asian populations by using genemapping strategies that combine linkage and association analyses. To obtain linkage information for body mass index (BMI) and waist circumference (WC), we performed a multipoint genome-wide linkage study in an isolated Mongolian sample of 1,049 individuals from 74 families. Next, a family-based GWAS, which integrates within- and between-family components, was performed using the genotype data of 756 individuals of the Mongolian sample, and P values for association were weighted using linkage information obtained previously. For both BMI (LOD = 3.3) and WC (LOD = 2.6), the highest linkage peak was discovered at chromosome 10q11.22. In family-based GWAS combined with linkage information, six single-nucleotide polymorphisms (SNPs) for BMI and five SNPs for WC reached a significant level of association (linkage weighted P < 1 × 10(-5) ). Of these, only one of the SNPs associated with WC (rs1704198) was replicated in 327 Korean families comprising 1,301 individuals. This SNP was located in the proximity of the prosperorelated homeobox 1 (PROX1) gene, the function of which was validated previously in a mouse model. Our powerful strategic analysis enabled the discovery of a novel candidate gene, PROX1, associated with WC in an Asian population. Copyright © 2012 The Obesity Society.

No evidence of a causal relationship between hypothyroidism and glaucoma: A Danish nationwide register-based cohort study

PubMed Central

2018-01-01

Background An interrelationship between hypothyroidism and glaucoma, due to a shared autoimmune background or based on deposition of mucopolysaccharides in the trabecular meshwork in the eye, has been suggested but is at present unsubstantiated. Therefore, our objective was to investigate, at a nationwide and population-based level, whether there is such an association. Subjects and methods Observational cohort study using record-linkage data from nationwide Danish health registers. 121,799 individuals diagnosed with a first episode of hypothyroidism were identified and were matched with 4 non-hypothyroid controls according to age and sex. Prevalence of glaucoma was recorded and cases and controls were followed over a mean of 7.1 years (range 0–17). Logistic and Cox regression models were used to assess the risk of glaucoma before and after the diagnosis of hypothyroidism, respectively. Results Overall, we found a higher prevalence of glaucoma in subjects with hypothyroidism as compared to controls (4.6% vs. 4.3%, p < 0.001). Prior to the diagnosis of hypothyroidism, the odds ratio (OR) was significantly increased for glaucoma [1.09; 95% confidence interval (CI): 1.04–1.13]. Based on the Cox regression model, there was no increased risk of glaucoma after the diagnosis of hypothyroidism [hazard ratio (HR) 1.00; 95% CI: 0.96–1.06], and the HR decreased further after adjusting for pre-existing co-morbidity (0.88; 95% CI: 0.84–0.93). Conclusions There was an increased risk of glaucoma before but not after the diagnosis of hypothyroidism, suggesting that screening for glaucoma in hypothyroid individuals is unwarranted. PMID:29444121

Comorbidities, treatment patterns and cost-of-illness of acromegaly in Sweden: a register-linkage population-based study.

PubMed

Lesén, Eva; Granfeldt, Daniel; Houchard, Aude; Dinet, Jérôme; Berthon, Anthony; Olsson, Daniel S; Björholt, Ingela; Johannsson, Gudmundur

2017-02-01

Acromegaly is a complex endocrine disease with multiple comorbidities. Treatment to obtain biochemical remission includes surgery, medical therapy and radiation. We aimed to describe comorbidities, treatment patterns and cost-of-illness in patients with acromegaly in Sweden. A nationwide population-based study. Patients with acromegaly were identified and followed in national registers in Sweden. Longitudinal treatment patterns were assessed in patients diagnosed between July 2005 and December 2013. The cost-of-illness during 2013 was estimated from a societal perspective among patients diagnosed between 1987 and 2013. Among 358 patients with acromegaly (48% men, mean age at diagnosis 50.0 (s.d. 15.3) years) at least one comorbidity was reported in 81% (n = 290). The most common comorbidities were hypertension (40%, n = 142), neoplasms outside the pituitary (30%, n = 109), hypopituitarism (22%, n = 80) and diabetes mellitus (17%, n = 61). Acromegaly treatment was initiated on average 3.7 (s.d. 6.9) months after diagnosis. Among the 301 treated patients, the most common first-line treatments were surgery (60%, n = 180), somatostatin analogues (21%, n = 64) and dopamine agonists (14%, n = 41). After primary surgery, 24% (n = 44) received somatostatin analogues. The annual per-patient cost was €12 000; this was €8700 and €16 000 if diagnosed before or after July 2005, respectively. The cost-of-illness for acromegaly and its comorbidities was 77% from direct costs and 23% from production loss. The prevalence of comorbidity is high in patients with acromegaly. The most common first-line treatment in acromegalic patients was surgery followed by somatostatin analogues. The annual per-patient cost of acromegaly and its comorbidities was €12 000. © 2017 European Society of Endocrinology.

Discrepancy in term calculation from second trimester ultrasound scan versus last menstrual period in women with type 1 diabetes.

PubMed

Eidem, Ingvild; Vangen, Siri; Henriksen, Tore; Vollset, Stein E; Hanssen, Kristian F; Joner, Geir; Stene, Lars C

2014-08-01

To study differences in ultrasound-based compared to menstrual-based term estimation in women with type 1 diabetes. Nationwide register study. Norway. Deliveries in Norway 1999-2004 by women registered in the Norwegian Childhood Diabetes Registry (n = 342) and the background population (n = 307 248), with data on both ultrasound-based and menstrual-based gestational age notified in the Birth Registry of Norway. Births with major malformations were excluded. Linkage of two nationwide registries, the Medical Birth Registry of Norway and the Norwegian Childhood Diabetes Registry. Estimated gestational age at delivery based on routine second trimester ultrasound measurements and last menstrual period. In women with type 1 diabetes, the distribution of gestational age at delivery was shifted considerably towards a lower gestational age when using second trimester ultrasound data for estimation, compared with last menstrual period data. The difference between the two estimation methods was larger among women with type 1 diabetes, although also evident in the general population. One in four women with diabetes and a certain last menstrual period date had their ultrasound-calculated term postponed 1 week or more, while one in 10 had it postponed 2 weeks or more. Corresponding numbers in the background population were one in five and one in 20. We found a systematic postponement of ultrasound-based compared with menstrual-based term estimation in women with type 1 diabetes. Relying solely on routine ultrasound-based term calculation for delivery decision may imply a risk of going beyond an optimal pregnancy length. © 2014 Nordic Federation of Societies of Obstetrics and Gynecology.

A cohort study of low Apgar scores and cognitive outcomes

PubMed Central

Odd, D E; Rasmussen, F; Gunnell, D; Lewis, G; Whitelaw, A

2008-01-01

Objective: To investigate the association of brief (0–5 minutes) and prolonged (>5 minutes) low Apgar scores (<7) in non-encephalopathic infants with educational achievement at age 15–16 and intelligence quotients (IQs) at age 18. Design: Population-based record-linkage cohort study of 176 524 male infants born throughout Sweden between 1973 and 1976. Patients and methods: Data from the Medical Birth Register were linked to Population and Housing Censuses, conscription medical records (IQ), and school registers (summary school grade). Infants were classified according to the time for their Apgar score to reach 7 or above. Premature infants and those with encephalopathy were excluded. Results: Infants with brief (OR = 1.14 (1.03–1.27)) or prolonged (OR = 1.35 (1.07–1.69)) low Apgar scores were more likely to have a low IQ score. There was an increased risk of a low IQ score (p = 0.003) the longer it took the infant to achieve a normal Apgar score. There was no association between brief (OR = 0.96 (0.87–1.06)) or prolonged (OR = 1.01 (0.81–1.26)) low Apgar scores and a low summary school grade at age 15–16, or evidence for a trend in the risk of a low school grade (p = 0.61). The estimated proportion with an IQ score below 81 due to transiently low Apgar scores was only 0.7%. Conclusions: Infants in poor condition at birth have increased risk of poor functioning in cognitive tests in later life. This supports the idea of a “continuum of reproductive casualty”, although the small individual effect suggests that these mild degrees of fetal compromise are not of clinical importance. PMID:17916594

A Simple Sampling Method for Estimating the Accuracy of Large Scale Record Linkage Projects.

PubMed

Boyd, James H; Guiver, Tenniel; Randall, Sean M; Ferrante, Anna M; Semmens, James B; Anderson, Phil; Dickinson, Teresa

2016-05-17

Record linkage techniques allow different data collections to be brought together to provide a wider picture of the health status of individuals. Ensuring high linkage quality is important to guarantee the quality and integrity of research. Current methods for measuring linkage quality typically focus on precision (the proportion of incorrect links), given the difficulty of measuring the proportion of false negatives. The aim of this work is to introduce and evaluate a sampling based method to estimate both precision and recall following record linkage. In the sampling based method, record-pairs from each threshold (including those below the identified cut-off for acceptance) are sampled and clerically reviewed. These results are then applied to the entire set of record-pairs, providing estimates of false positives and false negatives. This method was evaluated on a synthetically generated dataset, where the true match status (which records belonged to the same person) was known. The sampled estimates of linkage quality were relatively close to actual linkage quality metrics calculated for the whole synthetic dataset. The precision and recall measures for seven reviewers were very consistent with little variation in the clerical assessment results (overall agreement using the Fleiss Kappa statistics was 0.601). This method presents as a possible means of accurately estimating matching quality and refining linkages in population level linkage studies. The sampling approach is especially important for large project linkages where the number of record pairs produced may be very large often running into millions.

Linkage Analysis of Quantitative Refraction and Refractive Errors in the Beaver Dam Eye Study

PubMed Central

Duggal, Priya; Lee, Kristine E.; Cheng, Ching-Yu; Klein, Ronald; Bailey-Wilson, Joan E.; Klein, Barbara E. K.

2011-01-01

Purpose. Refraction, as measured by spherical equivalent, is the need for an external lens to focus images on the retina. While genetic factors play an important role in the development of refractive errors, few susceptibility genes have been identified. However, several regions of linkage have been reported for myopia (2q, 4q, 7q, 12q, 17q, 18p, 22q, and Xq) and for quantitative refraction (1p, 3q, 4q, 7p, 8p, and 11p). To replicate previously identified linkage peaks and to identify novel loci that influence quantitative refraction and refractive errors, linkage analysis of spherical equivalent, myopia, and hyperopia in the Beaver Dam Eye Study was performed. Methods. Nonparametric, sibling-pair, genome-wide linkage analyses of refraction (spherical equivalent adjusted for age, education, and nuclear sclerosis), myopia and hyperopia in 834 sibling pairs within 486 extended pedigrees were performed. Results. Suggestive evidence of linkage was found for hyperopia on chromosome 3, region q26 (empiric P = 5.34 × 10−4), a region that had shown significant genome-wide evidence of linkage to refraction and some evidence of linkage to hyperopia. In addition, the analysis replicated previously reported genome-wide significant linkages to 22q11 of adjusted refraction and myopia (empiric P = 4.43 × 10−3 and 1.48 × 10−3, respectively) and to 7p15 of refraction (empiric P = 9.43 × 10−4). Evidence was also found of linkage to refraction on 7q36 (empiric P = 2.32 × 10−3), a region previously linked to high myopia. Conclusions. The findings provide further evidence that genes controlling refractive errors are located on 3q26, 7p15, 7p36, and 22q11. PMID:21571680

Quantification of NSW Ambulance Record Linkages with Multiple External Datasets.

PubMed

Carroll, Therese; Muecke, Sandy; Simpson, Judy; Irvine, Katie; Jenkins, André

2015-01-01

This study has two aims: 1) to describe linkage rates between ambulance data and external datasets for "episodes of care" and "patient only" linkages in New South Wales (NSW), Australia; and 2) to detect and report any systematic issues with linkage that relate to patients, and operational or clinical variables that may introduce bias in subsequent studies if not adequately addressed. During 2010-11, the Centre for Health Record Linkage (CHeReL) in NSW, linked the records for patients attended by NSW Ambulance paramedics for the period July 2006 to June 2009, with four external datasets: Emergency Department Data Collection; Admitted Patient Data Collection; NSW Registry of Births, Deaths and Marriages death registration data; and the Australian Bureau of Statistics mortality data. This study reports linkage rates in terms of those "expected" to link and those who were "not expected" to link with external databases within 24 hours of paramedic attendance. Following thorough data preparation processes, 2,041,728 NSW Ambulance care episodes for 1,116,509 patients fulfilled the inclusion criteria. The overall episode-specific hospital linkage rate was 97.2%. Where a patient was not transported to hospital following paramedic care, 8.6% of these episodes resulted in an emergency department attendance within 24 hours. For all care episodes, 5.2% linked to a death record at some time within the 3-year period, with 2.4% of all death episodes occurring within 7 days of a paramedic encounter. For NSW Ambulance episodes of care that were expected to link to an external dataset but did not, nonlinkage to hospital admission records tended to decrease with age. For all other variables, issues relating to rates of linkage and nonlinkage were more indiscriminate. This quantification of the limitations of this large linked dataset will underpin the interpretation and results of ensuing studies that will inform future clinical and operational policies and practices at NSW Ambulance.

Young people's views about consenting to data linkage: findings from the PEARL qualitative study.

PubMed

Audrey, Suzanne; Brown, Lindsey; Campbell, Rona; Boyd, Andy; Macleod, John

2016-03-21

Electronic administrative data exist in several domains which, if linked, are potentially useful for research. However, benefits from data linkage should be considered alongside risks such as the threat to privacy. Avon Longitudinal Study of Parents and Children (ALSPAC) is a birth cohort study. The Project to Enhance ALSPAC through Record Linkage (PEARL) was established to enrich the ALSPAC resource through linkage between ALSPAC participants and routine sources of health and social data. Qualitative research was incorporated in the PEARL study to examine participants' views about data linkage and inform approaches to information sharing. This paper focusses on issues of consent. Digitally recorded interviews were conducted with 55 participants aged 17-19 years. Terms and processes relating to consent, anonymization and data linkage were explained to interviewees. Scenarios were used to prompt consideration of linking different sources of data, and whether consent should be requested. Interview recordings were fully transcribed. Thematic analysis was undertaken using the Framework approach. Participant views on data linkage appeared to be most influenced by: considerations around the social sensitivity of the research question, and; the possibility of tangible health benefits in the public interest. Some participants appeared unsure about the effectiveness of anonymization, or did not always view effective anonymization as making consent unnecessary. This was related to notions of ownership of personal information and etiquette around asking permission for secondary use. Despite different consent procedures being explained, participants tended to equate consent with 'opt-in' consent through which participants are 'asked' if their data can be used for a specific study. Participants raising similar concerns came to differing conclusions about whether consent was needed. Views changed when presented with different scenarios, and were sometimes inconsistent. Findings from this study question the validity of 'informed consent' as a cornerstone of good governance, and the extent to which potential research participants understand different types of consent and what they are consenting, or not consenting, to. Pragmatic, imaginative and flexible approaches are needed if research using data linkage is to successfully realise its potential for public good without undermining public trust in the research process.

A microsatellite genetic linkage map of black rockfish ( Sebastes schlegeli)

NASA Astrophysics Data System (ADS)

Chu, Guannan; Jiang, Liming; He, Yan; Yu, Haiyang; Wang, Zhigang; Jiang, Haibin; Zhang, Quanqi

2014-12-01

Ovoviviparous black rockfish ( Sebastes schlegeli) is an important marine fish species for aquaculture and fisheries in China. Genetic information of this species is scarce because of the lack of microsatellite markers. In this study, a large number of microsatellite markers of black rockfish were isolated by constructing microsatellite-enriched libraries. Female- and male-specific genetic linkage maps were constructed using 435 microsatellite markers genotyped in a full-sib family of the fish species. The female linkage map contained 140 microsatellite markers, in which 23 linkage groups had a total genetic length of 1334.1 cM and average inter-marker space of 13.3 cM. The male linkage map contained 156 microsatellite markers, in which 25 linkage groups had a total genetic length of 1359.6 cM and average inter-marker distance of 12.4 cM. The genome coverage of the female and male linkage maps was 68.6% and 69.3%, respectively. The female-to-male ratio of the recombination rate was approximately 1.07:1 in adjacent microsatellite markers. This paper presents the first genetic linkage map of microsatellites in black rockfish. The collection of polymorphic markers and sex-specific linkage maps of black rockfish could be useful for further investigations on parental assignment, population genetics, quantitative trait loci mapping, and marker-assisted selection in related breeding programs.

Construction of a BAC library and mapping BAC clones to the linkage map of Barramundi, Lates calcarifer.

PubMed

Wang, Chun Ming; Lo, Loong Chueng; Feng, Felicia; Gong, Ping; Li, Jian; Zhu, Ze Yuan; Lin, Grace; Yue, Gen Hua

2008-03-25

Barramundi (Lates calcarifer) is an important farmed marine food fish species. Its first generation linkage map has been applied to map QTL for growth traits. To identify genes located in QTL responsible for specific traits, genomic large insert libraries are of crucial importance. We reported herein a bacterial artificial chromosome (BAC) library and the mapping of BAC clones to the linkage map. This BAC library consisted of 49,152 clones with an average insert size of 98 kb, representing 6.9-fold haploid genome coverage. Screening the library with 24 microsatellites and 15 ESTs/genes demonstrated that the library had good genome coverage. In addition, 62 novel microsatellites each isolated from 62 BAC clones were mapped onto the first generation linkage map. A total of 86 BAC clones were anchored on the linkage map with at least one BAC clone on each linkage group. We have constructed the first BAC library for L. calcarifer and mapped 86 BAC clones to the first generation linkage map. This BAC library and the improved linkage map with 302 DNA markers not only supply an indispensable tool to the integration of physical and linkage maps, the fine mapping of QTL and map based cloning genes located in QTL of commercial importance, but also contribute to comparative genomic studies and eventually whole genome sequencing.

Death on a strange isle: the mortality of the stone workers of Purbeck in the nineteenth century.

PubMed

Hinde, Andrew; Edgar, Michael

2010-01-01

This paper analyses the mortality of a group of rural workers in an extractive industry, the stone quarriers of the Isle of Purbeck in the southern English county of Dorset. The analysis uses a database created by nominal record linkage of the census enumerators' books and the Church of England baptism and burial registers to estimate age-specific death rates at all ages for males and females, and hence statistics such as the expectation of life at birth. The results are compared with mortality statistics published by the Registrar General of England and Wales (on the basis of the civil registers of deaths) for the registration district of Wareham, in which Purbeck is situated. The stone quarriers had heavier mortality levels than the rest of the population of Purbeck. Closer inspection, however, reveals that their high mortality was confined to males, and was almost entirely due to especially high mortality among boys aged less than five years. In contrast to the experience of coal and metal ore miners, adult male mortality among stone workers was no higher than that among the general population. The final section of the paper considers possible explanations for these results, and suggests that excess mortality among boys in Purbeck from lung diseases might have been responsible.

Genome-wide linkage and association analysis of cardiometabolic phenotypes in Hispanic Americans.

PubMed

Hellwege, Jacklyn N; Palmer, Nicholette D; Dimitrov, Latchezar; Keaton, Jacob M; Tabb, Keri L; Sajuthi, Satria; Taylor, Kent D; Ng, Maggie C Y; Speliotes, Elizabeth K; Hawkins, Gregory A; Long, Jirong; Ida Chen, Yii-Der; Lorenzo, Carlos; Norris, Jill M; Rotter, Jerome I; Langefeld, Carl D; Wagenknecht, Lynne E; Bowden, Donald W

2017-02-01

Linkage studies of complex genetic diseases have been largely replaced by genome-wide association studies, due in part to limited success in complex trait discovery. However, recent interest in rare and low-frequency variants motivates re-examination of family-based methods. In this study, we investigated the performance of two-point linkage analysis for over 1.6 million single-nucleotide polymorphisms (SNPs) combined with single variant association analysis to identify high impact variants, which are both strongly linked and associated with cardiometabolic traits in up to 1414 Hispanics from the Insulin Resistance Atherosclerosis Family Study (IRASFS). Evaluation of all 50 phenotypes yielded 83 557 000 LOD (logarithm of the odds) scores, with 9214 LOD scores ⩾3.0, 845 ⩾4.0 and 89 ⩾5.0, with a maximal LOD score of 6.49 (rs12956744 in the LAMA1 gene for tumor necrosis factor-α (TNFα) receptor 2). Twenty-seven variants were associated with P<0.005 as well as having an LOD score >4, including variants in the NFIB gene under a linkage peak with TNFα receptor 2 levels on chromosome 9. Linkage regions of interest included a broad peak (31 Mb) on chromosome 1q with acute insulin response (max LOD=5.37). This region was previously documented with type 2 diabetes in family-based studies, providing support for the validity of these results. Overall, we have demonstrated the utility of two-point linkage and association in comprehensive genome-wide array-based SNP genotypes.

A SNP based high-density linkage map of Apis cerana reveals a high recombination rate similar to Apis mellifera.

PubMed

Shi, Yuan Yuan; Sun, Liang Xian; Huang, Zachary Y; Wu, Xiao Bo; Zhu, Yong Qiang; Zheng, Hua Jun; Zeng, Zhi Jiang

2013-01-01

The Eastern honey bee, Apis cerana Fabricius, is distributed in southern and eastern Asia, from India and China to Korea and Japan and southeast to the Moluccas. This species is also widely kept for honey production besides Apis mellifera. Apis cerana is also a model organism for studying social behavior, caste determination, mating biology, sexual selection, and host-parasite interactions. Few resources are available for molecular research in this species, and a linkage map was never constructed. A linkage map is a prerequisite for quantitative trait loci mapping and for analyzing genome structure. We used the Chinese honey bee, Apis cerana cerana to construct the first linkage map in the Eastern honey bee. F2 workers (N = 103) were genotyped for 126,990 single nucleotide polymorphisms (SNPs). After filtering low quality and those not passing the Mendel test, we obtained 3,000 SNPs, 1,535 of these were informative and used to construct a linkage map. The preliminary map contains 19 linkage groups, we then mapped the 19 linkage groups to 16 chromosomes by comparing the markers to the genome of A. mellfiera. The final map contains 16 linkage groups with a total of 1,535 markers. The total genetic distance is 3,942.7 centimorgans (cM) with the largest linkage group (180 loci) measuring 574.5 cM. Average marker interval for all markers across the 16 linkage groups is 2.6 cM. We constructed a high density linkage map for A. c. cerana with 1,535 markers. Because the map is based on SNP markers, it will enable easier and faster genotyping assays than randomly amplified polymorphic DNA or microsatellite based maps used in A. mellifera.

Lack of genetic linkage evidence for a trans-acting factor having a large effect on plasma lipoprotein[a] levels in African Americans.

PubMed

Barkley, Ruth Ann; Brown, Andrew C; Hanis, Craig L; Kardia, Sharon L; Turner, Stephen T; Boerwinkle, Eric

2003-07-01

The distribution of plasma lipoprotein[a] (Lp[a]) concentrations, a risk factor for cardiovascular disease, varies greatly among racial groups, with African Americans having values that are shifted toward higher levels than those of whites. The underlying cause of this heterogeneity is unknown, but a role for "trans-acting" factors has been hypothesized. This study used genetic linkage analysis to localize genetic factors influencing Lp[a] levels in African Americans that were absent in other populations; linkage results were analyzed separately in non-Hispanic whites, Hispanic whites, and African Americans. As expected, all three samples showed highly significant linkage at the approximate location of the lysophosphatidic acid locus. The white populations also independently had regions of significant linkage on chromosome 19 (LOD 3.80) and suggestive linkage on chromosomes 12 (LOD 1.60), 14 (LOD 2.56), and 19 (LOD 2.52). No linkage evidence was found to support the hypothesis of another single gene with large effects specifically segregating in African Americans that may account for their elevated Lp[a] levels.

Heritability of Addison's disease and prevalence of associated autoimmunity in a cohort of 112,100 Swedish twins.

PubMed

Skov, Jakob; Höijer, Jonas; Magnusson, Patrik K E; Ludvigsson, Jonas F; Kämpe, Olle; Bensing, Sophie

2017-12-01

The pathophysiology behind autoimmune Addison's disease (AAD) is poorly understood, and the relative influence of genetic and environmental factors remains unclear. In this study, we examined the heritability of AAD and explored disease-associated autoimmune comorbidity among Swedish twins. A population-based longitudinal cohort of 112,100 Swedish twins was used to calculate the heritability of AAD, and to explore co-occurrence of 10 organ-specific autoimmune disorders in twin pairs with AAD. Diagnoses were collected 1964-2012 through linkage to the Swedish National Patient Register. The Swedish Prescribed Drug Register was used for additional diagnostic precision. When available, biobank serum samples were used to ascertain the AAD diagnosis through identification of 21-hydroxylase autoantibodies. We identified 29 twins with AAD. Five out of nine (5/9) monozygotic pairs and zero out of fifteen (0/15) dizygotic pairs were concordant for AAD. The probandwise concordance for monozygotic twins was 0.71 (95% CI 0.40-0.90) and the heritability 0.97 (95% CI 0.88-99). Autoimmune disease patterns of monozygotic twin pairs affected by AAD displayed a higher degree of similarity than those of dizygotic twins, with an incidence rate ratio of 15 (95% CI 1.8-116) on the number of shared autoimmune diagnoses within pairs. The heritability of AAD appears to be very high, emphasizing the need for further research on the genetic etiology of the disease. Monozygotic twin concordance for multiple autoimmune manifestations suggests strong genetic influence on disease specificity in organ-specific autoimmunity.

Cancer Incidence among Patients with Anorexia Nervosa from Sweden, Denmark and Finland

PubMed Central

Mellemkjaer, Lene; Papadopoulos, Fotios C.; Pukkala, Eero; Ekbom, Anders; Gissler, Mika; Christensen, Jane; Olsen, Jørgen H.

2015-01-01

A diet with restricted energy content reduces the occurrence of cancer in animal experiments. It is not known if the underlying mechanism also exists in human beings. To determine whether cancer incidence is reduced among patients with anorexia nervosa who tend to have a low intake of energy, we carried out a retrospective cohort study of 22 654 women and 1678 men diagnosed with anorexia nervosa at ages 10-50 years during 1968-2010 according to National Hospital Registers in Sweden, Denmark and Finland. The comparison group consisted of randomly selected persons from population registers who were similar to the anorexia nervosa patients in respect to sex, year of birth and place of residence. Patients and population comparisons were followed for cancer by linkage to Cancer Registries. Incidence rate ratios (IRR) were estimated using Poisson models. In total, 366 cases of cancer (excluding non-melanoma skin cancer) were seen among women with anorexia nervosa, and the IRR for all cancer sites was 0.97 (95% CI = 0.87-1.08) adjusted for age, parity and age at first child. There were 76 breast cancers corresponding to an adjusted IRR of 0.61 (95% CI = 0.49-0.77). Significantly increased IRRs were observed for esophageal, lung, and liver cancer. Among men with anorexia nervosa, there were 23 cases of cancer (age-adjusted IRR = 1.08; 95% CI = 0.71-1.66). There seems to be no general reduction in cancer occurrence among patients with anorexia nervosa, giving little support to the energy restriction hypothesis. PMID:26000630

Maternal deaths in the Nordic countries.

PubMed

Vangen, Siri; Bødker, Birgit; Ellingsen, Liv; Saltvedt, Sissel; Gissler, Mika; Geirsson, Reynir T; Nyfløt, Lill T

2017-09-01

Despite the seriousness of the event, maternal deaths are substantially underreported. There is often a missed opportunity to learn from such tragedies. The aim of the study was to identify maternal deaths in the five Nordic countries, to classify causes of death based on internationally acknowledged criteria, and to identify areas that would benefit from further teaching, training or research to possibly reduce the number of maternal deaths. We present data for the years 2005-2013. National audit groups collected data by linkage of registers and direct reporting from hospitals. Each case was then assessed to determine the cause of death, and level of care provided. Potential improvements to care were evaluated. We registered 168 maternal deaths, 90 direct and 78 indirect cases. The maternal mortality ratio was 7.2/100 000 live births ranging from 6.8 to 8.1 between the countries. Cardiac disease (n = 29) was the most frequent cause of death, followed by preeclampsia (n = 24), thromboembolism (n = 20) and suicide (n = 20). Improvements to care which could potentially have made a difference to the outcome were identified in one-third of the deaths, i.e. in as many as 60% of preeclamptic, 45% of thromboembolic, and 32% of the deaths from cardiac disease. Direct deaths exceeded indirect maternal deaths in the Nordic countries. To reduce maternal deaths, increased efforts to better implement existing clinical guidelines seem warranted, particularly for preeclampsia, thromboembolism and cardiac disease. More knowledge is also needed about what contributes to suicidal maternal deaths. © 2017 Nordic Federation of Societies of Obstetrics and Gynecology.

[Occupational mortality in Italy during 1992, assessed through record-linkage between pension records and death certificates].

PubMed

d'Errico, A; Filippi, M; Demaria, M; Picanza, Grazia; Crialesi, Roberta; Costa, G; Campo, G; Passerini, M

2005-01-01

The creation of a surveillance system of occupational mortality in Italy is limited by the low quality of information on occupation in death certificates, since the information is often incomplete or lacking and because only the occupation at the time of death is registered. To evaluate the possible use of INPS (National Institute of Social Security) records for the purpose of surveillance of occupational mortality, in terms of feasibility of setting up a system and of validity of the results obtained. Death records of 218,510 subjects aged 18-74, deceased in the 12 months following the 1991 census, were obtained from ISTAT (Central Statistics Institute). These were combined through record-linkage with the INPS social security archives, which contain the employment records by economic sector going back to 1974, in order to assign these deaths the sector in which they had worked the longest. Mortality by specific causes was evaluated by industry by means of a proportional mortality analysis stratified by sex and occupational status, and adjusted for age, education, marital status, geographical area of birth, drawing a disability pension, employment status at the time of death and work instability. Record-linkage allowed attribution of the longest held job to 70% of the deaths recorded. Results are presented and discussed only on mortality in men due to asbestosis and silicosis, and causes of death with a substantial proportion attributable to occupation: chronic obstructive pulmonary disease (COPD); cancers of the bladder, nasal cavity, larynx, lung and pleura; leukaemia and lymphoma; accidental causes. Among the economic sectors with a significant excess mortality, the following are well documented in the literature: mortality due to COPD in the coal and peat-bog sectors; due to leukaemia among farmers; due to sino-nasal tumours in wood-working and furniture production; due to cancer of the larynx, lung, and pleura in occupations where there was probable exposure to asbestos (fishing and maritime transport, non-metal mining, building industry, and naval, train and aircraft construction); due to silicosis in industries with potential exposure to crystalline silica; due to accidental causes in the building industry and farming. Other mortality excesses and deficits, especially those due to bladder and lympho-haemopoietic cancers, appear to be only partly consistent with those described by other authors. The feasibility of developing a surveillance system of occupational mortality based on the INPS source was found to be good, and, at least among males, for 75% of the deceased subjects historical information existed concerning the economic sectors registered in the INPS records. The results obtained would appear to indicate that the system is capable of highlighting risk excesses due to widespread exposure in the industries examined, regarding diseases for which there is a strong association with exposure. On the other hand, due to the inherent limits of the study's design (lack of a complete work history and of precise information on the jobs held) its use is not recommended in the surveillance of diseases with a low proportion attributable to a risk factor, or with wide exposure variability in a given sector among the various jobs.

Significant Linkage for Tourette Syndrome in a Large French Canadian Family

PubMed Central

Mérette, Chantal; Brassard, Andrée; Potvin, Anne; Bouvier, Hélène; Rousseau, François; Émond, Claudia; Bissonnette, Luc; Roy, Marc-André; Maziade, Michel; Ott, Jurg; Caron, Chantal

2000-01-01

Family and twin studies provide strong evidence that genetic factors are involved in the transmission of Gilles de la Tourette syndrome (TS) and related psychiatric disorders. To detect the underlying susceptibility gene(s) for TS, we performed linkage analysis in one large French Canadian family (127 members) from the Charlevoix region, in which 20 family members were definitely affected by TS and 20 others showed related tic disorders. Using model-based linkage analysis, we observed a LOD score of 3.24 on chromosome 11 (11q23). This result was obtained in a multipoint approach involving marker D11S1377, the marker for which significant linkage disequilibrium with TS recently has been detected in an Afrikaner population. Altogether, 25 markers were studied, and, for level of significance, we derived a criterion that took into account the multiple testing arising from the use of three phenotype definitions and three modes of inheritance, a procedure that yielded a LOD score of 3.18. Hence, even after adjustment for multiple testing, the present study shows statistically significant evidence for genetic linkage with TS. PMID:10986045

Genome-wide scan for genes involved in bipolar affective disorder in 70 European families ascertained through a bipolar type I early-onset proband: supportive evidence for linkage at 3p14

PubMed Central

Etain, Bruno; Mathieu, Flavie; Rietschel, Marcella; Maier, Wolfgang; Albus, Margot; Mckeon, Patrick; Roche, S.; Kealey, Carmel; Blackwood, Douglas; Muir, Walter; Bellivier, Franc; Henry, C.; Dina, Christian; Gallina, Sophie; Gurling, H.; Malafosse, Alain; Preisig, Martin; Ferrero, François; Cichon, Sven; Schumacher, J.; Ohlraun, Stéphanie; Borrmann-Hassenbach, M.; Propping, Peter; Abou Jamra, Rami; Schulze, Thomas G.; Marusic, Andrej; Dernovsek, Mojca Z.; Giros, Bruno; Bourgeron, Thomas; Lemainque, Arnaud; Bacq, Delphine; Betard, Christine; Charon, Céline; Nöthen, Markus M.; Lathrop, Mark; Leboyer, Marion

2006-01-01

Summary Preliminary studies suggested that age at onset (AAO) may help to define homogeneous bipolar affective disorder (BPAD) subtypes. This candidate symptom approach might be useful to identify vulnerability genes. Thus, the probability of detecting major disease-causing genes might be increased by focusing on families with early-onset BPAD type I probands. This study was conducted as part of the European Collaborative Study of Early Onset BPAD (France, Germany, Ireland, Scotland, Switzerland, England, Slovenia). We performed a genome-wide search with 384 microsatellite markers using non parametric linkage analysis in 87 sib-pairs ascertained through an early-onset BPAD type I proband (age at onset of 21 years or below). Non parametric multi-point analysis suggested eight regions of linkage with p-values <0.01 (2p21, 2q14.3, 3p14, 5q33, 7q36, 10q23, 16q23 and 20p12). The 3p14 region showed the most significant linkage (genome-wide p-value estimated over 10.000 simulated replicates of 0.015 [0.01–0.02]). After genome-wide search analysis, we performed additional linkage analyses with increase marker density using markers in four regions suggestive for linkage and having an information contents lower than 75% (3p14, 10q23, 16q23 and 20p12). For these regions, the information content improved by about 10%. In chromosome 3, the non parametric linkage score increased from 3.51 to 3.83. This study is the first to use early onset bipolar type I probands in an attempt to increase sample homogeneity. These preliminary findings require confirmation in independent panels of families. PMID:16534504

Testing for linkage disequilibrium in the New Zealand radiata pine breeding population

Treesearch

S. Kumar; Craig Echt; P.L. Wilcox; T.E. Richardson

2004-01-01

Linkage analysis is commonly uscd to find marker-trait associations within the full-sib families of forest tree and other species. Study of marker-trait associations at the population level is termed linkage-disequilibrium (LD) mapping. A female-tester design comprising 200 full-sib families generated by crossing 40 pollen parents with five female parents was used to...

Saturation of an intra-gene pool linkage map: toward unified consensus linkage map in common bean

USDA-ARS?s Scientific Manuscript database

Map-based cloning to find genes of interest and marker assisted selection (MAS) requires good genetic maps with high reproducible markers. In this study, we saturated the linkage map of the intra-gene pool population of common bean DOR364×BAT477 (DB) by evaluating 2,706 molecular markers in includin...

Irish study of high-density Schizophrenia families: Field methods and power to detect linkage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kendler, K.S.; Straub, R.E.; MacLean, C.J.

Large samples of multiplex pedigrees will probably be needed to detect susceptibility loci for schizophrenia by linkage analysis. Standardized ascertainment of such pedigrees from culturally and ethnically homogeneous populations may improve the probability of detection and replication of linkage. The Irish Study of High-Density Schizophrenia Families (ISHDSF) was formed from standardized ascertainment of multiplex schizophrenia families in 39 psychiatric facilities covering over 90% of the population in Ireland and Northern Ireland. We here describe a phenotypic sample and a subset thereof, the linkage sample. Individuals were included in the phenotypic sample if adequate diagnostic information, based on personal interview and/ormore » hospital record, was available. Only individuals with available DNA were included in the linkage sample. Inclusion of a pedigree into the phenotypic sample required at least two first, second, or third degree relatives with non-affective psychosis (NAP), one of whom had schizophrenia (S) or poor-outcome schizoaffective disorder (PO-SAD). Entry into the linkage sample required DNA samples on at least two individuals with NAP, of whom at least one had S or PO-SAD. Affection was defined by narrow, intermediate, and broad criteria. 75 refs., 6 tabs.« less

Genome-wide linkage scan for contraction velocity characteristics of knee musculature in the Leuven Genes for Muscular Strength Study.

PubMed

De Mars, Gunther; Windelinckx, An; Huygens, Wim; Peeters, Maarten W; Beunen, Gaston P; Aerssens, Jeroen; Vlietinck, Robert; Thomis, Martine A I

2008-09-17

The torque-velocity relationship is known to be affected by ageing, decreasing its protective role in the prevention of falls. Interindividual variability in this torque-velocity relationship is partly determined by genetic factors (h(2): 44-67%). As a first attempt, this genome-wide linkage study aimed to identify chromosomal regions linked to the torque-velocity relationship of the knee flexors and extensors. A selection of 283 informative male siblings (17-36 yr), belonging to 105 families, was used to conduct a genome-wide SNP-based (Illumina Linkage IVb panel) multipoint linkage analysis for the torque-velocity relationship of the knee flexors and extensors. The strongest evidence for linkage was found at 15q23 for the torque-velocity slope of the knee extensors (TVSE). Other interesting linkage regions with LOD scores >2 were found at 7p12.3 [logarithm of the odds ratio (LOD) = 2.03, P = 0.0011] for the torque-velocity ratio of the knee flexors (TVRF), at 2q14.3 (LOD = 2.25, P = 0.0006) for TVSE, and at 4p14 and 18q23 for the torque-velocity ratio of the knee extensors TVRE (LOD = 2.23 and 2.08; P = 0.0007 and 0.001, respectively). We conclude that many small contributing genes are involved in causing variation in the torque-velocity relationship of the knee flexor and extensor muscles. Several earlier reported candidate genes for muscle strength and muscle mass and new candidates are harbored within or in close vicinity of the linkage regions reported in the present study.

Dosage Transmission Disequilibrium Test (dTDT) for Linkage and Association Detection

PubMed Central

Zhang, Zhehao; Wang, Jen-Chyong; Howells, William; Lin, Peng; Agrawal, Arpana; Edenberg, Howard J.; Tischfield, Jay A.; Schuckit, Marc A.; Bierut, Laura J.; Goate, Alison; Rice, John P.

2013-01-01

Both linkage and association studies have been successfully applied to identify disease susceptibility genes with genetic markers such as microsatellites and Single Nucleotide Polymorphisms (SNPs). As one of the traditional family-based studies, the Transmission/Disequilibrium Test (TDT) measures the over-transmission of an allele in a trio from its heterozygous parents to the affected offspring and can be potentially useful to identify genetic determinants for complex disorders. However, there is reduced information when complete trio information is unavailable. In this study, we developed a novel approach to “infer” the transmission of SNPs by combining both the linkage and association data, which uses microsatellite markers from families informative for linkage together with SNP markers from the offspring who are genotyped for both linkage and a Genome-Wide Association Study (GWAS). We generalized the traditional TDT to process these inferred dosage probabilities, which we name as the dosage-TDT (dTDT). For evaluation purpose, we developed a simulation procedure to assess its operating characteristics. We applied the dTDT to the simulated data and documented the power of the dTDT under a number of different realistic scenarios. Finally, we applied our methods to a family study of alcohol dependence (COGA) and performed individual genotyping on complete families for the top signals. One SNP (rs4903712 on chromosome 14) remained significant after correcting for multiple testing Methods developed in this study can be adapted to other platforms and will have widespread applicability in genomic research when case-control GWAS data are collected in families with existing linkage data. PMID:23691058

A population-based study of familial Alzheimer disease: linkage to chromosomes 14, 19, and 21.

PubMed

van Duijn, C M; Hendriks, L; Farrer, L A; Backhovens, H; Cruts, M; Wehnert, A; Hofman, A; Van Broeckhoven, C

1994-10-01

Linkage of Alzheimer disease (AD) to DNA markers on chromosomes 14, 19, and 21 was studied in 10 families in which the disease was apparently inherited as an autosomal dominant trait. Families were derived from a Dutch population-based epidemiologic study of early-onset AD. Although in all probands the onset of AD was at or before age 65 years, the mean age at onset was after age 65 years in four families (referred to as "LOAD"). Among the six families with early-onset AD (referred to as "EOAD," i.e., mean age of onset of AD of relatives was at or before age 65 years), conclusive linkage to 14q24.3 was found in one family with a very early onset (around 47 years), while linkage to the same region was excluded in two other families. For the LOAD families, predominantly negative lod scores were obtained, and the overall lod score excluded linkage to chromosome 14. The results with markers on chromosome 19 and chromosome 21 were not conclusive for EOAD and LOAD. The findings of our study confirm genetic heterogeneity within familial EOAD.

Army Active Duty Members’ Linkage to Veterans Health Administration Services After Deployments to Iraq or Afghanistan and Following Separation

PubMed Central

Vanneman, Megan E.; Harris, Alex H. S.; Chen, Cheng; Mohr, Beth A.; Adams, Rachel Sayko; Williams, Thomas V.; Larson, Mary Jo

2015-01-01

This study described the rate and predictors of Operation Enduring Freedom/Operation Iraqi Freedom active duty Army members’ enrollment in and use of Veterans Health Administration (VHA) services (linkage), as well as variation in linkage rates by VHA facility. We used a multivariate mixed effect regression model to predict linkage to VHA, and also calculated linkage rates in the catchment areas of each facility (n = 158). The sample included 151,122 active duty members who deployed to Iraq or Afghanistan and then separated from the Army between fiscal years 2008 and 2012. Approximately 48% of the active duty members separating utilized VHA as an enrollee within one year. There was significant variation in linkage rates by VHA facilities (31–72%). The most notable variables associated with greater linkage included probable serious injury during index deployment (odds ratio = 1.81), separation because of disability (odds ratio = 2.86), and various measures of receipt of VHA care before and after separation. Information about the individual characteristics that predict greater or lesser linkage to VHA services can be used to improve delivery of health care services at VHA as well as outreach efforts to active duty Army members. PMID:26444467

Linkage Analysis of a Model Quantitative Trait in Humans: Finger Ridge Count Shows Significant Multivariate Linkage to 5q14.1

PubMed Central

Medland, Sarah E; Loesch, Danuta Z; Mdzewski, Bogdan; Zhu, Gu; Montgomery, Grant W; Martin, Nicholas G

2007-01-01

The finger ridge count (a measure of pattern size) is one of the most heritable complex traits studied in humans and has been considered a model human polygenic trait in quantitative genetic analysis. Here, we report the results of the first genome-wide linkage scan for finger ridge count in a sample of 2,114 offspring from 922 nuclear families. Both univariate linkage to the absolute ridge count (a sum of all the ridge counts on all ten fingers), and multivariate linkage analyses of the counts on individual fingers, were conducted. The multivariate analyses yielded significant linkage to 5q14.1 (Logarithm of odds [LOD] = 3.34, pointwise-empirical p-value = 0.00025) that was predominantly driven by linkage to the ring, index, and middle fingers. The strongest univariate linkage was to 1q42.2 (LOD = 2.04, point-wise p-value = 0.002, genome-wide p-value = 0.29). In summary, the combination of univariate and multivariate results was more informative than simple univariate analyses alone. Patterns of quantitative trait loci factor loadings consistent with developmental fields were observed, and the simple pleiotropic model underlying the absolute ridge count was not sufficient to characterize the interrelationships between the ridge counts of individual fingers. PMID:17907812

A SSR-based composite genetic linkage map for the cultivated peanut (Arachis hypogaea L.) genome

PubMed Central

2010-01-01

Background The construction of genetic linkage maps for cultivated peanut (Arachis hypogaea L.) has and continues to be an important research goal to facilitate quantitative trait locus (QTL) analysis and gene tagging for use in a marker-assisted selection in breeding. Even though a few maps have been developed, they were constructed using diploid or interspecific tetraploid populations. The most recently published intra-specific map was constructed from the cross of cultivated peanuts, in which only 135 simple sequence repeat (SSR) markers were sparsely populated in 22 linkage groups. The more detailed linkage map with sufficient markers is necessary to be feasible for QTL identification and marker-assisted selection. The objective of this study was to construct a genetic linkage map of cultivated peanut using simple sequence repeat (SSR) markers derived primarily from peanut genomic sequences, expressed sequence tags (ESTs), and by "data mining" sequences released in GenBank. Results Three recombinant inbred lines (RILs) populations were constructed from three crosses with one common female parental line Yueyou 13, a high yielding Spanish market type. The four parents were screened with 1044 primer pairs designed to amplify SSRs and 901 primer pairs produced clear PCR products. Of the 901 primer pairs, 146, 124 and 64 primer pairs (markers) were polymorphic in these populations, respectively, and used in genotyping these RIL populations. Individual linkage maps were constructed from each of the three populations and a composite map based on 93 common loci were created using JoinMap. The composite linkage maps consist of 22 composite linkage groups (LG) with 175 SSR markers (including 47 SSRs on the published AA genome maps), representing the 20 chromosomes of A. hypogaea. The total composite map length is 885.4 cM, with an average marker density of 5.8 cM. Segregation distortion in the 3 populations was 23.0%, 13.5% and 7.8% of the markers, respectively. These distorted loci tended to cluster on LG1, LG3, LG4 and LG5. There were only 15 EST-SSR markers mapped due to low polymorphism. By comparison, there were potential synteny, collinear order of some markers and conservation of collinear linkage groups among the maps and with the AA genome but not fully conservative. Conclusion A composite linkage map was constructed from three individual mapping populations with 175 SSR markers in 22 composite linkage groups. This composite genetic linkage map is among the first "true" tetraploid peanut maps produced. This map also consists of 47 SSRs that have been used in the published AA genome maps, and could be used in comparative mapping studies. The primers described in this study are PCR-based markers, which are easy to share for genetic mapping in peanuts. All 1044 primer pairs are provided as additional files and the three RIL populations will be made available to public upon request for quantitative trait loci (QTL) analysis and linkage map improvement. PMID:20105299

Uptake of Home-Based HIV Testing, Linkage to Care, and Community Attitudes about ART in Rural KwaZulu-Natal, South Africa: Descriptive Results from the First Phase of the ANRS 12249 TasP Cluster-Randomised Trial

PubMed Central

Okesola, Nonhlanhla; Tanser, Frank; Thiebaut, Rodolphe; Rekacewicz, Claire; Newell, Marie-Louise

2016-01-01

Background The 2015 WHO recommendation of antiretroviral therapy (ART) for all immediately following HIV diagnosis is partially based on the anticipated impact on HIV incidence in the surrounding population. We investigated this approach in a cluster-randomised trial in a high HIV prevalence setting in rural KwaZulu-Natal. We present findings from the first phase of the trial and report on uptake of home-based HIV testing, linkage to care, uptake of ART, and community attitudes about ART. Methods and Findings Between 9 March 2012 and 22 May 2014, five clusters in the intervention arm (immediate ART offered to all HIV-positive adults) and five clusters in the control arm (ART offered according to national guidelines, i.e., CD4 count ≤ 350 cells/μl) contributed to the first phase of the trial. Households were visited every 6 mo. Following informed consent and administration of a study questionnaire, each resident adult (≥16 y) was asked for a finger-prick blood sample, which was used to estimate HIV prevalence, and offered a rapid HIV test using a serial HIV testing algorithm. All HIV-positive adults were referred to the trial clinic in their cluster. Those not linked to care 3 mo after identification were contacted by a linkage-to-care team. Study procedures were not blinded. In all, 12,894 adults were registered as eligible for participation (5,790 in intervention arm; 7,104 in control arm), of whom 9,927 (77.0%) were contacted at least once during household visits. HIV status was ever ascertained for a total of 8,233/9,927 (82.9%), including 2,569 ascertained as HIV-positive (942 tested HIV-positive and 1,627 reported a known HIV-positive status). Of the 1,177 HIV-positive individuals not previously in care and followed for at least 6 mo in the trial, 559 (47.5%) visited their cluster trial clinic within 6 mo. In the intervention arm, 89% (194/218) initiated ART within 3 mo of their first clinic visit. In the control arm, 42.3% (83/196) had a CD4 count ≤ 350 cells/μl at first visit, of whom 92.8% initiated ART within 3 mo. Regarding attitudes about ART, 93% (8,802/9,460) of participants agreed with the statement that they would want to start ART as soon as possible if HIV-positive. Estimated baseline HIV prevalence was 30.5% (2,028/6,656) (95% CI 25.0%, 37.0%). HIV prevalence, uptake of home-based HIV testing, linkage to care within 6 mo, and initiation of ART within 3 mo in those with CD4 count ≤ 350 cells/μl did not differ significantly between the intervention and control clusters. Selection bias related to noncontact could not be entirely excluded. Conclusions Home-based HIV testing was well received in this rural population, although men were less easily contactable at home; immediate ART was acceptable, with good viral suppression and retention. However, only about half of HIV-positive people accessed care within 6 mo of being identified, with nearly two-thirds accessing care by 12 mo. The observed delay in linkage to care would limit the individual and public health ART benefits of universal testing and treatment in this population. Trial registration ClinicalTrials.gov NCT01509508 PMID:27504637

Uptake of Home-Based HIV Testing, Linkage to Care, and Community Attitudes about ART in Rural KwaZulu-Natal, South Africa: Descriptive Results from the First Phase of the ANRS 12249 TasP Cluster-Randomised Trial.

PubMed

Iwuji, Collins C; Orne-Gliemann, Joanna; Larmarange, Joseph; Okesola, Nonhlanhla; Tanser, Frank; Thiebaut, Rodolphe; Rekacewicz, Claire; Newell, Marie-Louise; Dabis, Francois

2016-08-01

The 2015 WHO recommendation of antiretroviral therapy (ART) for all immediately following HIV diagnosis is partially based on the anticipated impact on HIV incidence in the surrounding population. We investigated this approach in a cluster-randomised trial in a high HIV prevalence setting in rural KwaZulu-Natal. We present findings from the first phase of the trial and report on uptake of home-based HIV testing, linkage to care, uptake of ART, and community attitudes about ART. Between 9 March 2012 and 22 May 2014, five clusters in the intervention arm (immediate ART offered to all HIV-positive adults) and five clusters in the control arm (ART offered according to national guidelines, i.e., CD4 count ≤ 350 cells/μl) contributed to the first phase of the trial. Households were visited every 6 mo. Following informed consent and administration of a study questionnaire, each resident adult (≥16 y) was asked for a finger-prick blood sample, which was used to estimate HIV prevalence, and offered a rapid HIV test using a serial HIV testing algorithm. All HIV-positive adults were referred to the trial clinic in their cluster. Those not linked to care 3 mo after identification were contacted by a linkage-to-care team. Study procedures were not blinded. In all, 12,894 adults were registered as eligible for participation (5,790 in intervention arm; 7,104 in control arm), of whom 9,927 (77.0%) were contacted at least once during household visits. HIV status was ever ascertained for a total of 8,233/9,927 (82.9%), including 2,569 ascertained as HIV-positive (942 tested HIV-positive and 1,627 reported a known HIV-positive status). Of the 1,177 HIV-positive individuals not previously in care and followed for at least 6 mo in the trial, 559 (47.5%) visited their cluster trial clinic within 6 mo. In the intervention arm, 89% (194/218) initiated ART within 3 mo of their first clinic visit. In the control arm, 42.3% (83/196) had a CD4 count ≤ 350 cells/μl at first visit, of whom 92.8% initiated ART within 3 mo. Regarding attitudes about ART, 93% (8,802/9,460) of participants agreed with the statement that they would want to start ART as soon as possible if HIV-positive. Estimated baseline HIV prevalence was 30.5% (2,028/6,656) (95% CI 25.0%, 37.0%). HIV prevalence, uptake of home-based HIV testing, linkage to care within 6 mo, and initiation of ART within 3 mo in those with CD4 count ≤ 350 cells/μl did not differ significantly between the intervention and control clusters. Selection bias related to noncontact could not be entirely excluded. Home-based HIV testing was well received in this rural population, although men were less easily contactable at home; immediate ART was acceptable, with good viral suppression and retention. However, only about half of HIV-positive people accessed care within 6 mo of being identified, with nearly two-thirds accessing care by 12 mo. The observed delay in linkage to care would limit the individual and public health ART benefits of universal testing and treatment in this population. ClinicalTrials.gov NCT01509508.

A new method of linkage analysis using LOD scores for quantitative traits supports linkage of monoamine oxidase activity to D17S250 in the Collaborative Study on the Genetics of Alcoholism pedigrees.

PubMed

Curtis, David; Knight, Jo; Sham, Pak C

2005-09-01

Although LOD score methods have been applied to diseases with complex modes of inheritance, linkage analysis of quantitative traits has tended to rely on non-parametric methods based on regression or variance components analysis. Here, we describe a new method for LOD score analysis of quantitative traits which does not require specification of a mode of inheritance. The technique is derived from the MFLINK method for dichotomous traits. A range of plausible transmission models is constructed, constrained to yield the correct population mean and variance for the trait but differing with respect to the contribution to the variance due to the locus under consideration. Maximized LOD scores under homogeneity and admixture are calculated, as is a model-free LOD score which compares the maximized likelihoods under admixture assuming linkage and no linkage. These LOD scores have known asymptotic distributions and hence can be used to provide a statistical test for linkage. The method has been implemented in a program called QMFLINK. It was applied to data sets simulated using a variety of transmission models and to a measure of monoamine oxidase activity in 105 pedigrees from the Collaborative Study on the Genetics of Alcoholism. With the simulated data, the results showed that the new method could detect linkage well if the true allele frequency for the trait was close to that specified. However, it performed poorly on models in which the true allele frequency was much rarer. For the Collaborative Study on the Genetics of Alcoholism data set only a modest overlap was observed between the results obtained from the new method and those obtained when the same data were analysed previously using regression and variance components analysis. Of interest is that D17S250 produced a maximized LOD score under homogeneity and admixture of 2.6 but did not indicate linkage using the previous methods. However, this region did produce evidence for linkage in a separate data set, suggesting that QMFLINK may have been able to detect a true linkage which was not picked up by the other methods. The application of model-free LOD score analysis to quantitative traits is novel and deserves further evaluation of its merits and disadvantages relative to other methods.

Large-scale SNP discovery and construction of a high-density genetic map of Colossoma macropomum through genotyping-by-sequencing

PubMed Central

Nunes, José de Ribamar da Silva; Liu, Shikai; Pértille, Fábio; Perazza, Caio Augusto; Villela, Priscilla Marqui Schmidt; de Almeida-Val, Vera Maria Fonseca; Hilsdorf, Alexandre Wagner Silva; Liu, Zhanjiang; Coutinho, Luiz Lehmann

2017-01-01

Colossoma macropomum, or tambaqui, is the largest native Characiform species found in the Amazon and Orinoco river basins, yet few resources for genetic studies and the genetic improvement of tambaqui exist. In this study, we identified a large number of single-nucleotide polymorphisms (SNPs) for tambaqui and constructed a high-resolution genetic linkage map from a full-sib family of 124 individuals and their parents using the genotyping by sequencing method. In all, 68,584 SNPs were initially identified using minimum minor allele frequency (MAF) of 5%. Filtering parameters were used to select high-quality markers for linkage analysis. We selected 7,734 SNPs for linkage mapping, resulting in 27 linkage groups with a minimum logarithm of odds (LOD) of 8 and maximum recombination fraction of 0.35. The final genetic map contains 7,192 successfully mapped markers that span a total of 2,811 cM, with an average marker interval of 0.39 cM. Comparative genomic analysis between tambaqui and zebrafish revealed variable levels of genomic conservation across the 27 linkage groups which allowed for functional SNP annotations. The large-scale SNP discovery obtained here, allowed us to build a high-density linkage map in tambaqui, which will be useful to enhance genetic studies that can be applied in breeding programs. PMID:28387238

Health Care Utilisation and Attitudes towards Health Care in Subjects Reporting Environmental Annoyance from Electricity and Chemicals

PubMed Central

Eek, Frida; Merlo, Juan; Gerdtham, Ulf; Lithman, Thor

2009-01-01

Environmentally intolerant persons report decreased self-rated health and daily functioning. However, it remains unclear whether this condition also results in increased health care costs. The aim of this study was to describe the health care consumption and attitudes towards health care in subjects presenting subjective environmental annoyance in relation to the general population, as well as to a group with a well-known disorder as treated hypertension (HT). Methods. Postal questionnaire (n = 13 604) and record linkage with population-based register on health care costs. Results. Despite significantly lower subjective well being and health than both the general population and HT group, the environmentally annoyed subjects had lower health care costs than the hypertension group. In contrast to the hypertension group, the environmentally annoyed subjects expressed more negative attitudes toward the health care than the general population. Conclusions. Despite their impaired subjective health and functional capacity, health care utilisation costs were not much increased for the environmentally annoyed group. This may partly depend on negative attitudes towards the health care in this group. PMID:19936124

The effectiveness of measles-mumps-rubella (MMR) vaccination in the prevention of pediatric hospitalizations for targeted and untargeted infections: A retrospective cohort study.

PubMed

La Torre, Giuseppe; Saulle, Rosella; Unim, Brigid; Meggiolaro, Angela; Barbato, Angelo; Mannocci, Alice; Spadea, Antonietta

2017-08-03

To evaluate the effectiveness of the measles-mumps-rubella (MMR) vaccine in reducing hospitalizations for infectious disease, targeted and not targeted, as well as from respiratory diseases in children in Rome. The cohort was recomposed through record linkage of 2 archives (vaccination register and hospital discharge records. The analysis included 11,004 children. 20.9% did not receive the MMR vaccination, 49% and 30.1% received one and 2 doses. There were no hospitalizations for rubella, 2 for mumps, and 12 for measles. The vaccine was highly protective against measles and mumps hospitalizations (HR = 0.10; 95% CI: 0.03.0.34). Regarding all infectious diseases there were 414 hospitalizations, and the vaccine was protective (HR = 0.29; 95% CI: 0.25 to 0.34). Concerning respiratory diseases, there were 809 admissions (7.4%), and the vaccine was highly protective (HR: 0.18; 95% CI: 0.07 to 0.48). MMR vaccination is effective for the primary prevention of target and not targeted infectious diseases and may also limit hospitalizations for respiratory diseases.

The association of indicators of fetal growth with visual acuity and hearing among conscripts.

PubMed

Olsen, J; Sørensen, H T; Steffensen, F H; Sabroe, S; Gillman, M W; Fischer, P; Rothman, K J

2001-03-01

Impaired fetal growth is associated with increased susceptibility to several chronic diseases. We studied the association between birth weight, indicators of disproportional fetal growth, and impaired visual acuity and hearing in 4,300 conscripts from a well-defined region in Denmark from August 1, 1993, to July 31, 1994. From the standard health examination for conscripts, we obtained data on sight based on the Snellen's chart and data on hearing acuity based on audiometry. By means of record linkage, we obtained data on outcomes for the conscripts at birth from the Medical Birth Registry. From this registry, we have data on birth weight, gestational age, and birth length that were recorded from existing computerized registers based on the records of midwives. A birth weight of less than 3,000 gm and a body mass index at birth of less than 3.4 were associated with reduced visual acuity and impaired hearing. The results could be due to fetal brain programming or due to confounding, by early birth trauma or other factors.

Pregnancy outcomes among female hairdressers who participated in the Danish National Birth Cohort.

PubMed

Zhu, Jin Liang; Vestergaard, Mogens; Hjollund, Niels Henrik; Olsen, Jørn

2006-02-01

The Danish National Birth Cohort (DNBC) was used to examine pregnancy outcomes among female hairdressers and neurodevelopment in their offspring. A population-based cohort study was conducted of 550 hairdressers and 3216 shop assistants (reference group) by using data from the Danish National Birth Cohort between 1997 and 2003. Information on job characteristics was reported by the women in the first interview (around 17 weeks of gestation). Pregnancy outcomes were obtained by linkage to the national registers. Developmental milestones were reported by the mother at the fourth interview, when the child was approximately 19 months old. Cox regression was applied to analyze fetal loss and congenital malformation. Logistic regression was used to analyze other pregnancy outcomes and developmental milestones. We found no significant differences in fetal loss, multiple births, gender ratio, preterm birth, small-for-gestational age, congenital malformations, or achievement of developmental milestones among the children of hairdressers and shop assistants. The results do not indicate that children of hairdressers in Denmark currently have a high risk of fetal impairment or delayed psychomotor development.

A second-generation anchored genetic linkage map of the tammar wallaby (Macropus eugenii)

PubMed Central

2011-01-01

Background The tammar wallaby, Macropus eugenii, a small kangaroo used for decades for studies of reproduction and metabolism, is the model Australian marsupial for genome sequencing and genetic investigations. The production of a more comprehensive cytogenetically-anchored genetic linkage map will significantly contribute to the deciphering of the tammar wallaby genome. It has great value as a resource to identify novel genes and for comparative studies, and is vital for the ongoing genome sequence assembly and gene ordering in this species. Results A second-generation anchored tammar wallaby genetic linkage map has been constructed based on a total of 148 loci. The linkage map contains the original 64 loci included in the first-generation map, plus an additional 84 microsatellite loci that were chosen specifically to increase coverage and assist with the anchoring and orientation of linkage groups to chromosomes. These additional loci were derived from (a) sequenced BAC clones that had been previously mapped to tammar wallaby chromosomes by fluorescence in situ hybridization (FISH), (b) End sequence from BACs subsequently FISH-mapped to tammar wallaby chromosomes, and (c) tammar wallaby genes orthologous to opossum genes predicted to fill gaps in the tammar wallaby linkage map as well as three X-linked markers from a published study. Based on these 148 loci, eight linkage groups were formed. These linkage groups were assigned (via FISH-mapped markers) to all seven autosomes and the X chromosome. The sex-pooled map size is 1402.4 cM, which is estimated to provide 82.6% total coverage of the genome, with an average interval distance of 10.9 cM between adjacent markers. The overall ratio of female/male map length is 0.84, which is comparable to the ratio of 0.78 obtained for the first-generation map. Conclusions Construction of this second-generation genetic linkage map is a significant step towards complete coverage of the tammar wallaby genome and considerably extends that of the first-generation map. It will be a valuable resource for ongoing tammar wallaby genetic research and assembling the genome sequence. The sex-pooled map is available online at http://compldb.angis.org.au/. PMID:21854616

A second-generation anchored genetic linkage map of the tammar wallaby (Macropus eugenii).

PubMed

Wang, Chenwei; Webley, Lee; Wei, Ke-jun; Wakefield, Matthew J; Patel, Hardip R; Deakin, Janine E; Alsop, Amber; Marshall Graves, Jennifer A; Cooper, Desmond W; Nicholas, Frank W; Zenger, Kyall R

2011-08-19

The tammar wallaby, Macropus eugenii, a small kangaroo used for decades for studies of reproduction and metabolism, is the model Australian marsupial for genome sequencing and genetic investigations. The production of a more comprehensive cytogenetically-anchored genetic linkage map will significantly contribute to the deciphering of the tammar wallaby genome. It has great value as a resource to identify novel genes and for comparative studies, and is vital for the ongoing genome sequence assembly and gene ordering in this species. A second-generation anchored tammar wallaby genetic linkage map has been constructed based on a total of 148 loci. The linkage map contains the original 64 loci included in the first-generation map, plus an additional 84 microsatellite loci that were chosen specifically to increase coverage and assist with the anchoring and orientation of linkage groups to chromosomes. These additional loci were derived from (a) sequenced BAC clones that had been previously mapped to tammar wallaby chromosomes by fluorescence in situ hybridization (FISH), (b) End sequence from BACs subsequently FISH-mapped to tammar wallaby chromosomes, and (c) tammar wallaby genes orthologous to opossum genes predicted to fill gaps in the tammar wallaby linkage map as well as three X-linked markers from a published study. Based on these 148 loci, eight linkage groups were formed. These linkage groups were assigned (via FISH-mapped markers) to all seven autosomes and the X chromosome. The sex-pooled map size is 1402.4 cM, which is estimated to provide 82.6% total coverage of the genome, with an average interval distance of 10.9 cM between adjacent markers. The overall ratio of female/male map length is 0.84, which is comparable to the ratio of 0.78 obtained for the first-generation map. Construction of this second-generation genetic linkage map is a significant step towards complete coverage of the tammar wallaby genome and considerably extends that of the first-generation map. It will be a valuable resource for ongoing tammar wallaby genetic research and assembling the genome sequence. The sex-pooled map is available online at http://compldb.angis.org.au/.

Population structure and its effect on haplotype diversity and linkage disequilibrium surrounding the xa5 locus of rice (Oryza sativa L.).

PubMed Central

Garris, Amanda J; McCouch, Susan R; Kresovich, Stephen

2003-01-01

To assess the usefulness of linkage disequilibrium mapping in an autogamous, domesticated species, we have characterized linkage disequilibrium in the candidate region for xa5, a recessive gene conferring race-specific resistance to bacterial blight in rice. This trait and locus have good mapping information, a tractable phenotype, and available sequence data, but no cloned gene. We sampled 13 short segments from the 70-kb candidate region in 114 accessions of Oryza sativa. Five additional segments were sequenced from the adjacent 45-kb region in resistant accessions to estimate the distance at which linkage disequilibrium decays. The data show significant linkage disequilibrium between sites 100 kb apart. The presence of the xa5 resistant reaction in two ecotypes and in accessions with different haplotypes in the candidate region may indicate multiple origins or genetic heterogeneity for resistance. In addition, genetic differentiation between ecotypes emphasizes the need for controlling for population structure in the design of linkage disequilibrium studies in rice. PMID:14573486

Exclusion of linkage between cleft lip with or without cleft palate and markers on chromosomes 4 and 6

DOE Office of Scientific and Technical Information (OSTI.GOV)

Blanton, S.H.; Malcolm, S.; Winter, R.

1996-01-01

Nonsyndromic cleft lip with or without associate cleft palate (CLP) is a common craniofacial defect, occurring in {approximately}1/1,000 live births. While the defect generally occurs sporadically, multiplex families have been reported. Segregation analyses have demonstrated that, in some families, CLP is inherited as an autosomal dominant/codominant disorder with low penetrance. Several clefting loci have been proposed on multiple chromosomes, including 6p24, 4q, and 19q13.1. Association studies and linkage studies suggested a locus that mapped to 6p24. We were unable to confirm this in a linkage study of 12 multigenerational families. A subsequent linkage study by Carinci et al., however, foundmore » evidence for linkage to this region in 14 of 21 clefting families. Additionally, Davies et al. studied the chromosomes of three individuals with cleft lip and palate, all of whom had a rearrangement involving 6p24. Their investigation supported a locus at 6p24. Carinci et al. reported that the most likely position for a clefting locus was at D6S89, which is centromeric to EDN1. This is in contrast to the findings of Davies et al., who suggested a placement telomeric to EDN1. F13A, which had been implicated in the initial association studies, is telomeric to EDN1. Thus, the region between F13A and D6S89 encompasses the regions proposed by both Davies et al. and Carinci et al. A second clefting locus, at 4q, was proposed by Beiraghi et al., who studied a single multigenerational family by linkage analysis. Their data suggested a locus near D4S175 and D4S192. 10 refs., 1 tab.« less

Excess Mortality in Hyperthyroidism: The Influence of Preexisting Comorbidity and Genetic Confounding: A Danish Nationwide Register-Based Cohort Study of Twins and Singletons

PubMed Central

Brandt, Frans; Almind, Dorthe; Christensen, Kaare; Green, Anders; Brix, Thomas Heiberg

2012-01-01

Context: Hyperthyroidism is associated with severe comorbidity, such as stroke, and seems to confer increased mortality. However, it is unknown whether this increased mortality is explained by hyperthyroidism per se, comorbidity, and/or genetic confounding. Objective: The objective of the study was to investigate whether hyperthyroidism is associated with an increased mortality and, if so, whether the association is influenced by comorbidity and/or genetic confounding. Methods: This was an observational cohort study using record-linkage data from nationwide Danish health registers. We identified 4850 singletons and 926 twins from same-sex pairs diagnosed with hyperthyroidism. Each case was matched with four controls for age and gender. The Charlson score was calculated from discharge diagnoses on an individual level to measure comorbidity. Cases and controls were followed up for a mean of 10 yr (range 0–31 yr), and the hazard ratio (HR) for mortality was calculated using Cox regression analyses. Results: In singletons there was a significantly higher mortality in individuals diagnosed with hyperthyroidism than in controls [HR 1.37; 95% confidence interval (CI) 1.30–1.46]. This persisted after adjustment for preexisting comorbidity (HR 1,28; 95% CI 1.21–1.36). In twin pairs discordant for hyperthyroidism (625 pairs), the twin with hyperthyroidism had an increased mortality compared with the corresponding cotwin (HR 1.43; 95% CI 1.09–1.88). However, this was found only in dizygotic pairs (HR 1.80; 95% CI 1.27–2.55) but not in monozygotic pairs (HR 0.95; 95% CI 0.60–1.50). Conclusions: Hyperthyroidism is associated with an increased mortality independent of preexisting comorbidity. The study of twin pairs discordant for hyperthyroidism suggests that genetic confounding influences the association between hyperthyroidism and mortality. PMID:22930783

Housing wealth and mortality: A register linkage study of the Finnish population.

PubMed

Laaksonen, Mikko; Tarkiainen, Lasse; Martikainen, Pekka

2009-09-01

In many countries home ownership is the main form of property and covers a major part of people's possessions. Since overall wealth is difficult to measure, many health studies have used home ownership as an indicator of wealth and material resources. However, most studies have measured housing wealth with a simple dichotomous measure of home ownership. We examined the associations between three different measures of housing wealth and overall mortality, separating subsidized renters and private renters, and using floor area and the number of rooms as measures of dwelling size. We further examined whether other socioeconomic factors, level of urbanisation of the region of residence, and household composition account for the found associations. Finns aged 35-79 years at the end of 1999 were followed up until the end of 2004. Data were drawn from various registers combined by Statistics Finland and linked with death records. The age-adjusted hazard ratio for mortality among subsidized renters compared to owner-occupiers was 2.26 in men and 1.87 in women. However, also private renters had clearly higher mortality than owner-occupiers, with the excess mortality of 92% in men and 61% in women. Both measures of home size were also strongly associated with mortality, with the excess risk of 1.7-3.0 in the lowest home size quintile compared to the highest. Adjusting for socioeconomic factors and mutually for all housing wealth measures considerably attenuated the associations. Further adjustment for urbanisation had no effect whereas adjustment for household size, marital status and living arrangements attenuated the associations of the two home size measures and mortality. However, a clear association remained between all housing wealth measures and mortality after all adjustments. Housing wealth summarises one's material circumstances over a prolonged period of time. Measures of housing wealth may therefore provide useful social classifications for studies on poor health and mortality especially in older age groups where most deaths occur.

Robust LOD scores for variance component-based linkage analysis.

PubMed

Blangero, J; Williams, J T; Almasy, L

2000-01-01

The variance component method is now widely used for linkage analysis of quantitative traits. Although this approach offers many advantages, the importance of the underlying assumption of multivariate normality of the trait distribution within pedigrees has not been studied extensively. Simulation studies have shown that traits with leptokurtic distributions yield linkage test statistics that exhibit excessive Type I error when analyzed naively. We derive analytical formulae relating the deviation from the expected asymptotic distribution of the lod score to the kurtosis and total heritability of the quantitative trait. A simple correction constant yields a robust lod score for any deviation from normality and for any pedigree structure, and effectively eliminates the problem of inflated Type I error due to misspecification of the underlying probability model in variance component-based linkage analysis.

Two-trait-locus linkage analysis: A powerful strategy for mapping complex genetic traits

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schork, N.J.; Boehnke, M.; Terwilliger, J.D.

1993-11-01

Nearly all diseases mapped to date follow clear Mendelian, single-locus segregation patterns. In contrast, many common familial diseases such as diabetes, psoriasis, several forms of cancer, and schizophrenia are familial and appear to have a genetic component but do not exhibit simple Mendelian transmission. More complex models are required to explain the genetics of these important diseases. In this paper, the authors explore two-trait-locus, two-marker-locus linkage analysis in which two trait loci are mapped simultaneously to separate genetic markers. The authors compare the utility of this approach to standard one-trait-locus, one-marker-locus linkage analysis with and without allowance for heterogeneity. Themore » authors also compare the utility of the two-trait-locus, two-marker-locus analysis to two-trait-locus, one-marker-locus linkage analysis. For common diseases, pedigrees are often bilineal, with disease genes entering via two or more unrelated pedigree members. Since such pedigrees often are avoided in linkage studies, the authors also investigate the relative information content of unilineal and bilineal pedigrees. For the dominant-or-recessive and threshold models that the authors consider, the authors find that two-trait-locus, two-marker-locus linkage analysis can provide substantially more linkage information, as measured by expected maximum lod score, than standard one-trait-locus, one-marker-locus methods, even allowing for heterogeneity, while, for a dominant-or-dominant generating model, one-locus models that allow for heterogeneity extract essentially as much information as the two-trait-locus methods. For these three models, the authors also find that bilineal pedigrees provide sufficient linkage information to warrant their inclusion in such studies. The authors discuss strategies for assessing the significance of the two linkages assumed in two-trait-locus, two-marker-locus models. 37 refs., 1 fig., 4 tabs.« less

Factors associated with linkage to HIV care and TB treatment at community-based HIV testing services in Cape Town, South Africa.

PubMed

Meehan, Sue-Ann; Sloot, Rosa; Draper, Heather R; Naidoo, Pren; Burger, Ronelle; Beyers, Nulda

2018-01-01

Diagnosing HIV and/or TB is not sufficient; linkage to care and treatment is conditional to reduce the burden of disease. This study aimed to determine factors associated with linkage to HIV care and TB treatment at community-based services in Cape Town, South Africa. This retrospective cohort study utilized routinely collected data from clients who utilized stand-alone (fixed site not attached to a health facility) and mobile HIV testing services in eight communities in the City of Cape Town Metropolitan district, between January 2008 and June 2012. Clients were included in the analysis if they were ≥12 years and had a known HIV status. Generalized estimating equations (GEE) logistic regression models were used to assess the association between determinants (sex, age, HIV testing service and co-infection status) and self-reported linkage to HIV care and/or TB treatment. Linkage to HIV care was 3 738/5 929 (63.1%). Linkage to HIV care was associated with the type of HIV testing service. Clients diagnosed with HIV at mobile services had a significantly reduced odds of linking to HIV care (aOR 0.7 (CI 95%: 0.6-0.8), p<0.001. Linkage to TB treatment was 210/275 (76.4%). Linkage to TB treatment was not associated with sex and service type, but was associated with age. Clients in older age groups were less likely to link to TB treatment compared to clients in the age group 12-24 years (all, p-value<0.05). A large proportion of clients diagnosed with HIV at mobile services did not link to care. Almost a quarter of clients diagnosed with TB did not link to treatment. Integrated community-based HIV and TB testing services are efficient in diagnosing HIV and TB, but strategies to improve linkage to care are required to control these epidemics.

The Italian Register of Cardiovascular Diseases: Attack Rates and Case Fatality for Cerebrovascular Events

PubMed Central

Palmieri, L.; Barchielli, A.; Cesana, G.; de Campora, E.; Goldoni, C.A.; Spolaore, P.; Uguccioni, M.; Vancheri, F.; Vanuzzo, D.; Ciccarelli, P.; Giampaoli, S.

2007-01-01

Background The Italian register of cardiovascular diseases is a surveillance system of fatal and nonfatal cardiovascular events in the general population aged 35–74 years. It was launched in Italy at the end of the 1990s with the aim of estimating periodically the occurrence and case fatality rate of coronary and cerebrovascular events in the different geographical areas of the country. This paper presents data for cerebrovascular events. Methods Currentevents were assessed through record linkage between two sources of information: death certificates and hospital discharge diagnosis records. Events were identified through the ICD codes and duration. To calculate the number of estimated events, current events were multiplied by the positive predictive value of each specific mortality or discharge code derived from the validation of a sample of suspected events. Attack rates were calculated by dividing estimatedevents by resident population, and case fatality rate at 28 days was determined from the ratio of estimated fatal to total events. Results Attack rates were found to be higher in men than in women: mean age-standardized attack rate was 21.9/10,000 in men and 12.5/10,000 in women; age-standardized 28-day case fatality rate was higher in women (17.1%) than in men (14.5%). Significant geographical differences were found in attack rates of both men and women. Case fatality was significantly heterogeneous in both men and women. Conclusions Differences still exist in the geographical distribution of attack and case fatality rates of cerebrovascular events, regardless of the north-south gradient. These data show the feasibility of implementing a population-based register using a validated routine database, necessary for monitoring cardiovascular diseases. PMID:17971632

Chorionicity and Heritability Estimates from Twin Studies: The Prenatal Environment of Twins and Their Resemblance Across a Large Number of Traits.

PubMed

van Beijsterveldt, C E M; Overbeek, L I H; Rozendaal, L; McMaster, M T B; Glasner, T J; Bartels, M; Vink, J M; Martin, N G; Dolan, C V; Boomsma, D I

2016-05-01

There are three types of monozygotic (MZ) twins. MZ twins can either share one chorion and one amnion, each twin can have its own amnion, or MZ twins can-like dizygotic twins-each have their own chorion and amnion. Sharing the same chorion may create a more similar/dissimilar prenatal environment and bias heritability estimates, but most twin studies do not distinguish between these three types of MZ twin pairs. The aim of this paper is to investigate the effect of chorion sharing on the similarity within MZ twin pairs for a large number of traits. Information on chorion status was obtained for the Netherlands twin register (NTR) by linkage to the records from the database of the dutch pathological anatomy national automated archive (PALGA). Record linkage was successful for over 9000 pairs. Effect of chorion type was tested by comparing the within-pair similarity between monochorionic (MC) and dichorionic (DC) MZ twins on 66 traits including weight, height, motor milestones, child problem behaviors, cognitive function, wellbeing and personality. For only 10 traits, within-pair similarity differed between MCMZ and DCMZ pairs. For traits influenced by birth weight (e.g. weight and height in young children) we expected that MC twins would be more discordant. This was found for 5 out of 13 measures. When looking at traits where blood supply is important, we saw MCMZ twins to be more concordant than DCMZ's for 3 traits. We conclude that the influence on the MZ twin correlation of the intra-uterine prenatal environment, as measured by sharing a chorion type, is small and limited to a few phenotypes. This implies that the assumption of equal prenatal environment of mono- and DC MZ twins, which characterizes the classical twin design, is largely tenable.

Genome-wide linkage scans for type 2 diabetes mellitus in four ethnically diverse populations-significant evidence for linkage on chromosome 4q in African Americans: the Family Investigation of Nephropathy and Diabetes Research Group.

PubMed

Malhotra, Alka; Igo, Robert P; Thameem, Farook; Kao, W H Linda; Abboud, Hanna E; Adler, Sharon G; Arar, Nedal H; Bowden, Donald W; Duggirala, Ravindranath; Freedman, Barry I; Goddard, Katrina A B; Ipp, Eli; Iyengar, Sudha K; Kimmel, Paul L; Knowler, William C; Kohn, Orly; Leehey, David; Meoni, Lucy A; Nelson, Robert G; Nicholas, Susanne B; Parekh, Rulan S; Rich, Stephen S; Chen, Yii-Der I; Saad, Mohammed F; Scavini, Marina; Schelling, Jeffrey R; Sedor, John R; Shah, Vallabh O; Taylor, Kent D; Thornley-Brown, Denyse; Zager, Philip G; Horvath, Amanda; Hanson, Robert L

2009-11-01

Previous studies have shown that in addition to environmental influences, type 2 diabetes mellitus (T2DM) has a strong genetic component. The goal of the current study is to identify regions of linkage for T2DM in ethnically diverse populations. Phenotypic and genotypic data were obtained from African American (AA; total number of individuals [N] = 1004), American Indian (AI; N = 883), European American (EA; N = 537), and Mexican American (MA; N = 1634) individuals from the Family Investigation of Nephropathy and Diabetes. Non-parametric linkage analysis, using an average of 4404 SNPs, was performed in relative pairs affected with T2DM in each ethnic group. In addition, family-based tests were performed to detect association with T2DM. Statistically significant evidence for linkage was observed on chromosome 4q21.1 (LOD = 3.13; genome-wide p = 0.04) in AA. In addition, a total of 11 regions showed suggestive evidence for linkage (estimated at LOD > 1.71), with the highest LOD scores on chromosomes 12q21.31 (LOD = 2.02) and 22q12.3 (LOD = 2.38) in AA, 2p11.1 (LOD = 2.23) in AI, 6p12.3 (LOD = 2.77) in EA, and 13q21.1 (LOD = . 2.24) in MA. While no region overlapped across all ethnic groups, at least five loci showing LOD > 1.71 have been identified in previously published studies. The results from this study provide evidence for the presence of genes affecting T2DM on chromosomes 4q, 12q, and 22q in AA; 6p in EA; 2p in AI; and 13q in MA. The strong evidence for linkage on chromosome 4q in AA provides important information given the paucity of diabetes genetic studies in this population.

Significant linkage to airway responsiveness on chromosome 12q24 in families of children with asthma in Costa Rica.

PubMed

Celedón, Juan C; Soto-Quiros, Manuel E; Avila, Lydiana; Lake, Stephen L; Liang, Catherine; Fournier, Eduardo; Spesny, Mitzi; Hersh, Craig P; Sylvia, Jody S; Hudson, Thomas J; Verner, Andrei; Klanderman, Barbara J; Freimer, Nelson B; Silverman, Edwin K; Weiss, Scott T

2007-01-01

Although asthma is a major public health problem in certain Hispanic subgroups in the United States and Latin America, only one genome scan for asthma has included Hispanic individuals. Because of small sample size, that study had limited statistical power to detect linkage to asthma and its intermediate phenotypes in Hispanic participants. To identify genomic regions that contain susceptibility genes for asthma and airway responsiveness in an isolated Hispanic population living in the Central Valley of Costa Rica, we conducted a genome-wide linkage analysis of asthma (n = 638) and airway responsiveness (n = 488) in members of eight large pedigrees of Costa Rican children with asthma. Nonparametric multipoint linkage analysis of asthma was conducted by the NPL-PAIR allele-sharing statistic, and variance component models were used for the multipoint linkage analysis of airway responsiveness as a quantitative phenotype. All linkage analyses were repeated after exclusion of the phenotypic data of former and current smokers. Chromosome 12q showed some evidence of linkage to asthma, particularly in nonsmokers (P < 0.01). Among nonsmokers, there was suggestive evidence of linkage to airway responsiveness on chromosome 12q24.31 (LOD = 2.33 at 146 cM). After genotyping 18 additional short-tandem repeat markers on chromosome 12q, there was significant evidence of linkage to airway responsiveness on chromosome 12q24.31 (LOD = 3.79 at 144 cM), with a relatively narrow 1.5-LOD unit support interval for the observed linkage peak (142-147 cM). Our results suggest that chromosome 12q24.31 contains a locus (or loci) that influence a critical intermediate phenotype of asthma (airway responsiveness) in Costa Ricans.

Mental illness and psychiatric treatment amongst firesetters, other offenders and the general community.

PubMed

Ducat, Lauren; Ogloff, James R P; McEwan, Troy

2013-10-01

Firesetting is often reported to be associated with psychopathology, but frequently these conclusions are based on studies reliant on selective forensic psychiatric samples without the use of comparison groups. The aim of the study was to examine the rates of mental illness, substance use disorders, personality pathology and psychiatric service usage in a population of convicted firesetters compared with other offenders and community controls. Using a data-linkage design, the study examined the psychiatric histories and usage of public mental health services by 1328 arsonists convicted between 2000 and 2009 in Victoria, Australia. These were compared with 1328 matched community controls and 421 non-firesetting offenders. Firesetters were significantly more likely to have been registered with psychiatric services (37%) compared with other offenders (29.3%) and community controls (8.7%). The firesetters were also more likely to have utilised a diverse range of public mental health services. Firesetters attracted psychiatric diagnoses more often than community controls and other offenders, particularly affective, substance use, and personality disorders. This study confirms that there is a link between firesetting and psychopathology, suggesting that there is a role for the psychiatric screening of known firesetters, and a need to consider psychopathology in formulating the risk for further firesetting.

Technology use in linking criminal justice reentrants to HIV care in the community: a qualitative formative research study.

PubMed

Peterson, James; Cota, Michelle; Gray, Holly; Bazerman, Lauri; Kuo, Irene; Kurth, Ann; Beckwith, Curt

2015-01-01

Innovative interventions increasing linkage, adherence, and retention in care among HIV-infected persons in the criminal justice system are needed. The authors conducted a qualitative study to investigate technology-based tools to facilitate linkage to community-based care and viral suppression for HIV-infected jail detainees on antiretroviral medications being released to the community. The authors conducted 24 qualitative interview-12 in Rhode Island and 12 in Washington, DC-among recently incarcerated HIV-infected persons to elicit their perceptions on the use of technology tools to support linkage to HIV care among criminal justice populations. This article discusses participants' perceptions of the acceptability of technological tools such as (a) a computer-based counseling and (b) text messaging interventions. The participants reported positive experiences when previewing the technology-based tools to facilitate linkage to HIV care and adherence to HIV medications. Successful linkage to care has been shown to improve HIV-associated and non-HIV-associated health outcomes, as well as prevent criminal recidivism and facilitate reentrants' successful and meaningful transition. These findings can be used to inform the implementation of interventions aimed at promoting adherence to antiretroviral medications and linkage to care for HIV-infected persons being released from the correctional setting.

Genome survey and high-density genetic map construction provide genomic and genetic resources for the Pacific White Shrimp Litopenaeus vannamei

PubMed Central

Yu, Yang; Zhang, Xiaojun; Yuan, Jianbo; Li, Fuhua; Chen, Xiaohan; Zhao, Yongzhen; Huang, Long; Zheng, Hongkun; Xiang, Jianhai

2015-01-01

The Pacific white shrimp Litopenaeus vannamei is the dominant crustacean species in global seafood mariculture. Understanding the genome and genetic architecture is useful for deciphering complex traits and accelerating the breeding program in shrimp. In this study, a genome survey was conducted and a high-density linkage map was constructed using a next-generation sequencing approach. The genome survey was used to identify preliminary genome characteristics and to generate a rough reference for linkage map construction. De novo SNP discovery resulted in 25,140 polymorphic markers. A total of 6,359 high-quality markers were selected for linkage map construction based on marker coverage among individuals and read depths. For the linkage map, a total of 6,146 markers spanning 4,271.43 cM were mapped to 44 sex-averaged linkage groups, with an average marker distance of 0.7 cM. An integration analysis linked 5,885 genome scaffolds and 1,504 BAC clones to the linkage map. Based on the high-density linkage map, several QTLs for body weight and body length were detected. This high-density genetic linkage map reveals basic genomic architecture and will be useful for comparative genomics research, genome assembly and genetic improvement of L. vannamei and other penaeid shrimp species. PMID:26503227

Localization of genes involved in the metabolic syndrome using multivariate linkage analysis.

PubMed

Olswold, Curtis; de Andrade, Mariza

2003-12-31

There are no well accepted criteria for the diagnosis of the metabolic syndrome. However, the metabolic syndrome is identified clinically by the presence of three or more of these five variables: larger waist circumference, higher triglyceride levels, lower HDL-cholesterol concentrations, hypertension, and impaired fasting glucose. We use sets of two or three variables, which are available in the Framingham Heart Study data set, to localize genes responsible for this syndrome using multivariate quantitative linkage analysis. This analysis demonstrates the applicability of using multivariate linkage analysis and how its use increases the power to detect linkage when genes are involved in the same disease mechanism.

A novel metadata management model to capture consent for record linkage in longitudinal research studies.

PubMed

McMahon, Christiana; Denaxas, Spiros

2017-11-06

Informed consent is an important feature of longitudinal research studies as it enables the linking of the baseline participant information with administrative data. The lack of standardized models to capture consent elements can lead to substantial challenges. A structured approach to capturing consent-related metadata can address these. a) Explore the state-of-the-art for recording consent; b) Identify key elements of consent required for record linkage; and c) Create and evaluate a novel metadata management model to capture consent-related metadata. The main methodological components of our work were: a) a systematic literature review and qualitative analysis of consent forms; b) the development and evaluation of a novel metadata model. We qualitatively analyzed 61 manuscripts and 30 consent forms. We extracted data elements related to obtaining consent for linkage. We created a novel metadata management model for consent and evaluated it by comparison with the existing standards and by iteratively applying it to case studies. The developed model can facilitate the standardized recording of consent for linkage in longitudinal research studies and enable the linkage of external participant data. Furthermore, it can provide a structured way of recording consent-related metadata and facilitate the harmonization and streamlining of processes.

A population-based study of familial Alzheimer disease: Linkage to chromosomes 14, 19, and 21

DOE Office of Scientific and Technical Information (OSTI.GOV)

Duijn, C.M. van; Hofman, A.; Hendriks, L.

1994-10-01

Linkage of Alzheimer disease (AD) to DNA markers on chromosomes 14, 19, and 21 was studied in 10 families in which the disease was apparently inherited as an autosomal dominant trait. Families were derived from a Dutch population-based epidemiologic study of early-onset AD. Although in all probands the onset of AD was at or before age 65 years, the mean age at onset was after age 65 years in four families (referred to as {open_quotes}LOAD{close_quotes}). Among the six families with early-onset AD (referred to as {open_quotes}EOAD,{close_quotes} i.e., mean age of onset of AD of relatives was at or before agemore » 65 years), conclusive linkage to 14q24.3 was found in one family with a very early onset (around 47 years), while linkage to the same region was excluded in two other families. For the LOAD families, predominantly negative lod scores were obtained, and the overall lod score excluded linkage to chromosome 14. The results with markers on chromosome 19 and chromosome 21 were not conclusive for EOAD and LOAD. The findings of our study confirm genetic heterogeneity within familial EOAD. 50 refs., 7 figs., 2 tabs.« less

Genome-Wide Linkage and Positional Association Analyses Identify Associations of Novel AFF3 and NTM Genes with Triglycerides: The GenSalt Study

PubMed Central

Li, Changwei; Bazzano, Lydia A.L.; Rao, Dabeeru C.; Hixson, James E.; He, Jiang; Gu, Dongfeng; Gu, Charles C.; Shimmin, Lawrence C.; Jaquish, Cashell E.; Schwander, Karen; Liu, De-Pei; Huang, Jianfeng; Lu, Fanghong; Cao, Jie; Chong, Shen; Lu, Xiangfeng; Kelly, Tanika N.

2016-01-01

We conducted a genome-wide linkage scan and positional association study to identify genes and variants influencing blood lipid levels among participants of the Genetic Epidemiology Network of Salt-Sensitivity (GenSalt) study. The GenSalt study was conducted among 1906 participants from 633 Han Chinese families. Lipids were measured from overnight fasting blood samples using standard methods. Multipoint quantitative trait genome-wide linkage scans were performed on the high-density lipoprotein, low-density lipoprotein, and log-transformed triglyceride phenotypes. Using dense panels of single nucleotide polymorphisms (SNPs), single-marker and gene-based association analyses were conducted to follow-up on promising linkage signals. Additive associations between each SNP and lipid phenotypes were tested using mixed linear regression models. Gene-based analyses were performed by combining P-values from single-marker analyses within each gene using the truncated product method (TPM). Significant associations were assessed for replication among 777 Asian participants of the Multi-ethnic Study of Atherosclerosis (MESA). Bonferroni correction was used to adjust for multiple testing. In the GenSalt study, suggestive linkage signals were identified at 2p11.2–2q12.1 [maximum multipoint LOD score (MML) = 2.18 at 2q11.2] and 11q24.3–11q25 (MML = 2.29 at 11q25) for the log-transformed triglyceride phenotype. Follow-up analyses of these two regions revealed gene-based associations of charged multivesicular body protein 3 (CHMP3), ring finger protein 103 (RNF103), AF4/FMR2 family, member 3 (AFF3), and neurotrimin (NTM ) with triglycerides (P = 4 × 10−4, 1.00 × 10−5, 2.00 × 10−5, and 1.00 × 10−7, respectively). Both the AFF3 and NTM triglyceride associations were replicated among MESA study participants (P = 1.00 × 10−7 and 8.00 × 10−5, respectively). Furthermore, NTM explained the linkage signal on chromosome 11. In conclusion, we identified novel genes associated with lipid phenotypes in linkage regions on chromosomes 2 and 11. PMID:25819087

Construction of a reference genetic linkage map for carnation (Dianthus caryophyllus L.)

PubMed Central

2013-01-01

Background Genetic linkage maps are important tools for many genetic applications including mapping of quantitative trait loci (QTLs), identifying DNA markers for fingerprinting, and map-based gene cloning. Carnation (Dianthus caryophyllus L.) is an important ornamental flower worldwide. We previously reported a random amplified polymorphic DNA (RAPD)-based genetic linkage map derived from Dianthus capitatus ssp. andrezejowskianus and a simple sequence repeat (SSR)-based genetic linkage map constructed using data from intraspecific F2 populations; however, the number of markers was insufficient, and so the number of linkage groups (LGs) did not coincide with the number of chromosomes (x = 15). Therefore, we aimed to produce a high-density genetic map to improve its usefulness for breeding purposes and genetic research. Results We improved the SSR-based genetic linkage map using SSR markers derived from a genomic library, expression sequence tags, and RNA-seq data. Linkage analysis revealed that 412 SSR loci (including 234 newly developed SSR loci) could be mapped to 17 linkage groups (LGs) covering 969.6 cM. Comparison of five minor LGs covering less than 50 cM with LGs in our previous RAPD-based genetic map suggested that four LGs could be integrated into two LGs by anchoring common SSR loci. Consequently, the number of LGs corresponded to the number of chromosomes (x = 15). We added 192 new SSRs, eight RAPD, and two sequence-tagged site loci to refine the RAPD-based genetic linkage map, which comprised 15 LGs consisting of 348 loci covering 978.3 cM. The two maps had 125 SSR loci in common, and most of the positions of markers were conserved between them. We identified 635 loci in carnation using the two linkage maps. We also mapped QTLs for two traits (bacterial wilt resistance and anthocyanin pigmentation in the flower) and a phenotypic locus for flower-type by analyzing previously reported genotype and phenotype data. Conclusions The improved genetic linkage maps and SSR markers developed in this study will serve as reference genetic linkage maps for members of the genus Dianthus, including carnation, and will be useful for mapping QTLs associated with various traits, and for improving carnation breeding programs. PMID:24160306

Construction of a reference genetic linkage map for carnation (Dianthus caryophyllus L.).

PubMed

Yagi, Masafumi; Yamamoto, Toshiya; Isobe, Sachiko; Hirakawa, Hideki; Tabata, Satoshi; Tanase, Koji; Yamaguchi, Hiroyasu; Onozaki, Takashi

2013-10-26

Genetic linkage maps are important tools for many genetic applications including mapping of quantitative trait loci (QTLs), identifying DNA markers for fingerprinting, and map-based gene cloning. Carnation (Dianthus caryophyllus L.) is an important ornamental flower worldwide. We previously reported a random amplified polymorphic DNA (RAPD)-based genetic linkage map derived from Dianthus capitatus ssp. andrezejowskianus and a simple sequence repeat (SSR)-based genetic linkage map constructed using data from intraspecific F2 populations; however, the number of markers was insufficient, and so the number of linkage groups (LGs) did not coincide with the number of chromosomes (x = 15). Therefore, we aimed to produce a high-density genetic map to improve its usefulness for breeding purposes and genetic research. We improved the SSR-based genetic linkage map using SSR markers derived from a genomic library, expression sequence tags, and RNA-seq data. Linkage analysis revealed that 412 SSR loci (including 234 newly developed SSR loci) could be mapped to 17 linkage groups (LGs) covering 969.6 cM. Comparison of five minor LGs covering less than 50 cM with LGs in our previous RAPD-based genetic map suggested that four LGs could be integrated into two LGs by anchoring common SSR loci. Consequently, the number of LGs corresponded to the number of chromosomes (x = 15). We added 192 new SSRs, eight RAPD, and two sequence-tagged site loci to refine the RAPD-based genetic linkage map, which comprised 15 LGs consisting of 348 loci covering 978.3 cM. The two maps had 125 SSR loci in common, and most of the positions of markers were conserved between them. We identified 635 loci in carnation using the two linkage maps. We also mapped QTLs for two traits (bacterial wilt resistance and anthocyanin pigmentation in the flower) and a phenotypic locus for flower-type by analyzing previously reported genotype and phenotype data. The improved genetic linkage maps and SSR markers developed in this study will serve as reference genetic linkage maps for members of the genus Dianthus, including carnation, and will be useful for mapping QTLs associated with various traits, and for improving carnation breeding programs.

Estimating parameters for probabilistic linkage of privacy-preserved datasets.

PubMed

Brown, Adrian P; Randall, Sean M; Ferrante, Anna M; Semmens, James B; Boyd, James H

2017-07-10

Probabilistic record linkage is a process used to bring together person-based records from within the same dataset (de-duplication) or from disparate datasets using pairwise comparisons and matching probabilities. The linkage strategy and associated match probabilities are often estimated through investigations into data quality and manual inspection. However, as privacy-preserved datasets comprise encrypted data, such methods are not possible. In this paper, we present a method for estimating the probabilities and threshold values for probabilistic privacy-preserved record linkage using Bloom filters. Our method was tested through a simulation study using synthetic data, followed by an application using real-world administrative data. Synthetic datasets were generated with error rates from zero to 20% error. Our method was used to estimate parameters (probabilities and thresholds) for de-duplication linkages. Linkage quality was determined by F-measure. Each dataset was privacy-preserved using separate Bloom filters for each field. Match probabilities were estimated using the expectation-maximisation (EM) algorithm on the privacy-preserved data. Threshold cut-off values were determined by an extension to the EM algorithm allowing linkage quality to be estimated for each possible threshold. De-duplication linkages of each privacy-preserved dataset were performed using both estimated and calculated probabilities. Linkage quality using the F-measure at the estimated threshold values was also compared to the highest F-measure. Three large administrative datasets were used to demonstrate the applicability of the probability and threshold estimation technique on real-world data. Linkage of the synthetic datasets using the estimated probabilities produced an F-measure that was comparable to the F-measure using calculated probabilities, even with up to 20% error. Linkage of the administrative datasets using estimated probabilities produced an F-measure that was higher than the F-measure using calculated probabilities. Further, the threshold estimation yielded results for F-measure that were only slightly below the highest possible for those probabilities. The method appears highly accurate across a spectrum of datasets with varying degrees of error. As there are few alternatives for parameter estimation, the approach is a major step towards providing a complete operational approach for probabilistic linkage of privacy-preserved datasets.

Patterns of linkage disequilibrium at PARK16 may explain variances in genetic association studies.

PubMed

Li, Huihua; Teo, Yik-Ying; Tan, Eng-King

2015-09-01

Reproducing genomewide association studies findings in different populations is challenging, because the reproducibility fundamentally relies on the similar patterns of linkage disequilibrium between the unknown causal variants and the genotyped single-nucleotide polymorphisms (SNPs). The PARK16 locus was reported to alter the risk of Parkinson's disease (PD) in genomewide association studies in Japanese and Caucasians. We evaluated the regional linkage disequilibrium pattern at PARK16 locus in Caucasians, Japanese, and Chinese from HapMap and Chinese, Malays, and Indians from the Singapore Genome Variation Project, using the traditional heatmaps and targeted analysis of PARK16 gene via Monte Carlo simulation through varLD scores of these ethnic groups. One hundred SNPs in Caucasians, 95 SNPs in Chinese, 78 SNPs in Japanese from HapMap, 86 SNPs in Chinese, 99 SNPs in Indians, and 97 SNPs in Malays from the Singapore Genome Variation Project were included. Our targeted analysis showed that the linkage disequilibrium pattern of SNPs close to rs947211 was similar in Caucasians and Asians, including Chinese, Japanese, and Malay (all P > 0.0001), whereas different linkage disequilibrium patterns around rs823128, rs823156, and rs708730 were found between Caucasians and these Asian groups (all P < 0.0001). Our study suggests a higher chance to detect the association between rs947211 and PD in Chinese, Malay, and other Caucasian groups because of the similar linkage disequilibrium pattern around rs947211. The associations between rs823128/rs823156/rs708730 and PD are more likely to be replicated in Chinese and Malay populations. © 2015 International Parkinson and Movement Disorder Society.

Synthesis and properties of ApA analogues with shortened phosphonate internucleotide linkage.

PubMed

Králíková, Sárka; Buděšínský, Miloš; Barvík, Ivan; Masojídková, Milena; Točík, Zdeněk; Rosenberg, Ivan

2011-01-01

A complete series of the 2 '-5 ' and 3 '-5 ' regioisomeric types of r(ApA) and 2 '-d(ApA) analogues with the α-hydroxy-phosphonate C3 '-O-P-CH(OH)-C4 ″ internucleotide linkage, isopolar but non-isosteric with the phosphodiester one, were synthesized and their hybridization properties with polyU studied. Due to the chirality on the 5 '-carbon atom of the modified internucleotide linkage bearing phosphorus and hydroxy moieties, each regioisomeric type of ApA dimer is split into epimeric pairs. To examine the role of the 5 '-hydroxyl of the α-hydroxy-phosphonate moiety during hybridization, the appropriate r(ApA) analogues with 3 '(2 ')-O-P-CH(2)-C4 ″ linkage lacking the 5 '-hydroxyl were synthesized. Nuclear magnetic resonance (NMR) spectroscopy study on the conformation of the modified sugar-phosphate backbone, along with the hybridization measurements, revealed remarkable differences in the stability of complexes with polyU, depending on the 5 '-carbon atom configuration. Potential usefulness of the α-hydroxy-phosphonate linkage in modified oligoribonucleotides is discussed.

[Genetics of bipolar affective disorders. Current status of research for identification of susceptibility genes].

PubMed

Schumacher, J; Cichon, S; Rietschel, M; Nöthen, M M; Propping, P

2002-07-01

Bipolar affective disorder is a highly heritable condition, as evidenced by twin, family, and adoption studies. However, the mode of inheritance is complex and linkage findings have been difficult to replicate. Despite these limitations, consistent linkage findings have emerged for several chromosomes, notably 3p12-p14, 4p16, 10q25-q26, and 12q23-q24. Three additional areas, 13q32-q33, 18p11-q11, and 22q12-q13, have shown linkage in regions that appear to overlap with linkage findings in schizophrenia. These chromosomal regions might harbour genes that contribute to the development of bipolar affective disorder. Recent candidate gene studies include some positive results for the serotonin transporter gene (5-HTT) on 17q11-q12 and the catechol-O-methyltransferase gene (COMT) on 22q11. New methods are being developed for linkage disequilibrium mapping and candidate gene approaches. One can be optimistic that over the next few years bipolar susceptibility genes will be identified.

Genomewide scan in families with schizophrenia from the founder population of Afrikaners reveals evidence for linkage and uniparental disomy on chromosome 1.

PubMed

Abecasis, Gonçalo R; Burt, Rachel A; Hall, Diana; Bochum, Sylvia; Doheny, Kimberly F; Lundy, S Laura; Torrington, Marie; Roos, J Louw; Gogos, Joseph A; Karayiorgou, Maria

2004-03-01

We report on our initial genetic linkage studies of schizophrenia in the genetically isolated population of the Afrikaners from South Africa. A 10-cM genomewide scan was performed on 143 small families, 34 of which were informative for linkage. Using both nonparametric and parametric linkage analyses, we obtained evidence for a small number of disease loci on chromosomes 1, 9, and 13. These results suggest that few genes of substantial effect exist for schizophrenia in the Afrikaner population, consistent with our previous genealogical tracing studies. The locus on chromosome 1 reached genomewide significance levels (nonparametric LOD score of 3.30 at marker D1S1612, corresponding to an empirical P value of.012) and represents a novel susceptibility locus for schizophrenia. In addition to providing evidence for linkage for chromosome 1, we also identified a proband with a uniparental disomy (UPD) of the entire chromosome 1. This is the first time a UPD has been described in a patient with schizophrenia, lending further support to involvement of chromosome 1 in schizophrenia susceptibility in the Afrikaners.

Short Communication: Genetic linkage map of Cucurbita maxima with molecular and morphological markers.

PubMed

Ge, Y; Li, X; Yang, X X; Cui, C S; Qu, S P

2015-05-22

Cucurbita maxima is one of the most widely cultivated vegetables in China and exhibits distinct morphological characteristics. In this study, genetic linkage analysis with 57 simple-sequence repeats, 21 amplified fragment length polymorphisms, 3 random-amplified polymorphic DNA, and one morphological marker revealed 20 genetic linkage groups of C. maxima covering a genetic distance of 991.5 cM with an average of 12.1 cM between adjacent markers. Genetic linkage analysis identified the simple-sequence repeat marker 'PU078072' 5.9 cM away from the locus 'Rc', which controls rind color. The genetic map in the present study will be useful for better mapping, tagging, and cloning of quantitative trait loci/gene(s) affecting economically important traits and for breeding new varieties of C. maxima through marker-assisted selection.

Searching susceptibility loci for bipolar disorder: a sib pair study on chromosome 12.

PubMed

Lorenzi, Cristina; Delmonte, Dario; Pirovano, Adele; Marino, Elena; Bongiorno, Fanny; Catalano, Marco; Colombo, Cristina; Bramanti, Placido; Smeraldi, Enrico

2010-01-01

Several linkage studies demonstrated that different chromosomal regions are involved in the susceptibility to bipolar disorder. In particular, some genome scans evidenced the role of chromosome 12. For this reason, our group chose this chromosome for a preliminary genome scan on a sample of 137 Italian sib pairs, including at least 1 bipolar subject. The analyses were carried out by means of DNA extracted from whole blood. DNA samples were genotyped by 19 simple tandem repeat markers (microsatellites). Starting from the genetic data, we performed two- and multipoint linkage analyses (both parametric and nonparametric) by means of Easy Linkage plus package (version 5.05). The multipoint linkage analyses pointed out a region suggestive of linkage between the markers D12S310 and D12S364, at locus 12p12. In particular, we reached the best evidence of linkage performing multipoint analyses and assuming a recessive model, under the hypothesis of genetic heterogeneity (heterogeneity LOD score = 2.01 and alpha = 0.77). It is interesting to notice that the region at the marker D12S364 is located inside the gene coding for the glutamatergic receptor GRIN2B. Therefore, our finding not only confirmed the role of genetics in determining liability to bipolar disorder, but suggested glutamatergic transmission impairment as a possible cause. Nevertheless, we acknowledge that our study is heavily underpowered. Therefore, independent replication is needed. (c) 2009 S. Karger AG, Basel.

The Family Investigation of Nephropathy and Diabetes (FIND): design and methods.

PubMed

Knowler, William C; Coresh, Josef; Elston, Robert C; Freedman, Barry I; Iyengar, Sudha K; Kimmel, Paul L; Olson, Jane M; Plaetke, Rosemarie; Sedor, John R; Seldin, Michael F

2005-01-01

The Family Investigation of Nephropathy and Diabetes (FIND) is a multicenter study designed to identify genetic determinants of diabetic nephropathy. It is conducted in eight U.S. clinical centers and a coordinating center, and with four ethnic groups (European Americans, African Americans, Mexican Americans, and American Indians). Two strategies are used to localize susceptibility genes: a family-based linkage study and a case-control study using mapping by admixture linkage disequilibrium (MALD). In the family-based study, probands with diabetic nephropathy are recruited with their parents and selected siblings. Linkage analyses will be conducted to identify chromosomal regions containing genes that influence the development of diabetic nephropathy or related quantitative traits such as serum creatinine concentration, urinary albumin excretion, and plasma glucose concentrations. Regions showing evidence of linkage will be examined further with both genetic linkage and association studies to identify genes that influence diabetic nephropathy or related traits. Two types of MALD studies are being done. One is a case-control study of unrelated individuals of Mexican American heritage in which both cases and controls have diabetes, but only the case has nephropathy. The other is a case-control study of African American patients with nephropathy (cases) and their spouses (controls) unaffected by diabetes and nephropathy; offspring are genotyped when available to provide haplotype data. Identification of genes that influence susceptibility to diabetic nephropathy will lead to a better understanding of how nephropathy develops. This should eventually lead to improved treatment and prevention.

Rural Job Creation. Case Studies of CETA Linkage with Economic Development.

ERIC Educational Resources Information Center

Bruno, A. Lee; Wright, L. M., Jr.

This collection contains 20 case studies illustrating some of the contributions Comprehensive Employment and Training Act (CETA) programs have made to economic development and job creation efforts in rural areas. The collection is a companion volume to the monograph entitled "Rural Job Creation--a Study of CETA Linkages with Economic…

Refined genetic mapping of X-linked Charcot-Marie-Tooth neuropathy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fain, P.R.; Barker, D.F.; Chance, P.F.

1994-02-01

Genetic linkage studies were conducted in four multigenerational families with X-linked Charcot-Marie-Tooth disease (CMTX), using 12 highly polymorphic short-tandem-repeat markers for the pericentromeric region of the X Chromosome. Pairwise linkage analysis with individual markers confirmed tight linkage of CMTX to the pericentromeric region in each family. Multipoint analyses strongly support the order DXS337-CMTX-DXS441-(DXS56, PGK1). 38 refs., 2 figs., 1 tab.

Meta-analysis of genome-wide linkage studies in BMI and obesity.

PubMed

Saunders, Catherine L; Chiodini, Benedetta D; Sham, Pak; Lewis, Cathryn M; Abkevich, Victor; Adeyemo, Adebowale A; de Andrade, Mariza; Arya, Rector; Berenson, Gerald S; Blangero, John; Boehnke, Michael; Borecki, Ingrid B; Chagnon, Yvon C; Chen, Wei; Comuzzie, Anthony G; Deng, Hong-Wen; Duggirala, Ravindranath; Feitosa, Mary F; Froguel, Philippe; Hanson, Robert L; Hebebrand, Johannes; Huezo-Dias, Patricia; Kissebah, Ahmed H; Li, Weidong; Luke, Amy; Martin, Lisa J; Nash, Matthew; Ohman, Miina; Palmer, Lyle J; Peltonen, Leena; Perola, Markus; Price, R Arlen; Redline, Susan; Srinivasan, Sathanur R; Stern, Michael P; Stone, Steven; Stringham, Heather; Turner, Stephen; Wijmenga, Cisca; Collier, David A

2007-09-01

The objective was to provide an overall assessment of genetic linkage data of BMI and BMI-defined obesity using a nonparametric genome scan meta-analysis. We identified 37 published studies containing data on over 31,000 individuals from more than >10,000 families and obtained genome-wide logarithm of the odds (LOD) scores, non-parametric linkage (NPL) scores, or maximum likelihood scores (MLS). BMI was analyzed in a pooled set of all studies, as a subgroup of 10 studies that used BMI-defined obesity, and for subgroups ascertained through type 2 diabetes, hypertension, or subjects of European ancestry. Bins at chromosome 13q13.2- q33.1, 12q23-q24.3 achieved suggestive evidence of linkage to BMI in the pooled analysis and samples ascertained for hypertension. Nominal evidence of linkage to these regions and suggestive evidence for 11q13.3-22.3 were also observed for BMI-defined obesity. The FTO obesity gene locus at 16q12.2 also showed nominal evidence for linkage. However, overall distribution of summed rank p values <0.05 is not different from that expected by chance. The strongest evidence was obtained in the families ascertained for hypertension at 9q31.1-qter and 12p11.21-q23 (p < 0.01). Despite having substantial statistical power, we did not unequivocally implicate specific loci for BMI or obesity. This may be because genes influencing adiposity are of very small effect, with substantial genetic heterogeneity and variable dependence on environmental factors. However, the observation that the FTO gene maps to one of the highest ranking bins for obesity is interesting and, while not a validation of this approach, indicates that other potential loci identified in this study should be investigated further.

A genome-wide linkage scan for dietary energy and nutrient intakes: the Health, Risk Factors, Exercise Training, and Genetics (HERITAGE) Family Study.

PubMed

Collaku, Agron; Rankinen, Tuomo; Rice, Treva; Leon, Arthur S; Rao, D C; Skinner, James S; Wilmore, Jack H; Bouchard, Claude

2004-05-01

A poor diet is a risk factor for chronic diseases such as obesity, cardiovascular disease, hypertension, and some cancers. Twin and family studies suggest that genetic factors potentially influence energy and nutrient intakes. We sought to identify genomic regions harboring genes affecting total energy, carbohydrate, protein, and fat intakes. We performed a genomic scan in 347 white sibling pairs and 99 black sibling pairs. Dietary energy and nutrient intakes were assessed by using Willett's food-frequency questionnaire. Single-point and multipoint Haseman-Elston regression techniques were used to test for linkage. These subjects were part of the Health, Risk Factors, Exercise Training, and Genetics (HERITAGE) Family Study, a multicenter project undertaken by 5 laboratories. In the whites, the strongest evidence of linkage appeared for dietary energy and nutrient intakes on chromosomes 1p21.2 (P = 0.0002) and 20q13.13 (P = 0.00007), and that for fat intake appeared on chromosome 12q14.1 (P = 0.0013). The linkage evidence on chromosomes 1 and 20 related to total energy intake rather than to the intake of specific macronutrients. In the blacks, promising linkages for macronutrient intakes occurred on chromosomes 12q23-q24.21, 1q32.1, and 7q11.1. Several potential candidate genes are encoded in and around the linkage regions on chromosomes 1p21.2, 12q14.1, and 20q13.13. These are the first reported human quantitative trait loci for dietary energy and macronutrient intakes. Further study may refine these quantitative trait loci to identify potential candidate genes for energy and specific macronutrient intakes that would be amenable to more detailed molecular studies.

Viral Linkage in HIV-1 Seroconverters and Their Partners in an HIV-1 Prevention Clinical Trial

PubMed Central

Campbell, Mary S.; Mullins, James I.; Hughes, James P.; Celum, Connie; Wong, Kim G.; Raugi, Dana N.; Sorensen, Stefanie; Stoddard, Julia N.; Zhao, Hong; Deng, Wenjie; Kahle, Erin; Panteleeff, Dana; Baeten, Jared M.; McCutchan, Francine E.; Albert, Jan; Leitner, Thomas; Wald, Anna; Corey, Lawrence; Lingappa, Jairam R.

2011-01-01

Background Characterization of viruses in HIV-1 transmission pairs will help identify biological determinants of infectiousness and evaluate candidate interventions to reduce transmission. Although HIV-1 sequencing is frequently used to substantiate linkage between newly HIV-1 infected individuals and their sexual partners in epidemiologic and forensic studies, viral sequencing is seldom applied in HIV-1 prevention trials. The Partners in Prevention HSV/HIV Transmission Study (ClinicalTrials.gov #NCT00194519) was a prospective randomized placebo-controlled trial that enrolled serodiscordant heterosexual couples to determine the efficacy of genital herpes suppression in reducing HIV-1 transmission; as part of the study analysis, HIV-1 sequences were examined for genetic linkage between seroconverters and their enrolled partners. Methodology/Principal Findings We obtained partial consensus HIV-1 env and gag sequences from blood plasma for 151 transmission pairs and performed deep sequencing of env in some cases. We analyzed sequences with phylogenetic techniques and developed a Bayesian algorithm to evaluate the probability of linkage. For linkage, we required monophyletic clustering between enrolled partners' sequences and a Bayesian posterior probability of ≥50%. Adjudicators classified each seroconversion, finding 108 (71.5%) linked, 40 (26.5%) unlinked, and 3 (2.0%) indeterminate transmissions, with linkage determined by consensus env sequencing in 91 (84%). Male seroconverters had a higher frequency of unlinked transmissions than female seroconverters. The likelihood of transmission from the enrolled partner was related to time on study, with increasing numbers of unlinked transmissions occurring after longer observation periods. Finally, baseline viral load was found to be significantly higher among linked transmitters. Conclusions/Significance In this first use of HIV-1 sequencing to establish endpoints in a large clinical trial, more than one-fourth of transmissions were unlinked to the enrolled partner, illustrating the relevance of these methods in the design of future HIV-1 prevention trials in serodiscordant couples. A hierarchy of sequencing techniques, analysis methods, and expert adjudication contributed to the linkage determination process. PMID:21399681

Evaluation of the Tsima community mobilization intervention to improve engagement in HIV testing and care in South Africa: study protocol for a cluster randomized trial.

PubMed

Lippman, Sheri A; Pettifor, Audrey; Rebombo, Dumisani; Julien, Aimée; Wagner, Ryan G; Kang Dufour, Mi-Suk; Kabudula, Chodziwadziwa Whiteson; Neilands, Torsten B; Twine, Rhian; Gottert, Ann; Gómez-Olivé, F Xavier; Tollman, Stephen M; Sanne, Ian; Peacock, Dean; Kahn, Kathleen

2017-01-17

HIV transmission can be decreased substantially by reducing the burden of undiagnosed HIV infection and expanding early and consistent use of antiretroviral therapy (ART). Treatment as prevention (TasP) has been proposed as key to ending the HIV epidemic. To activate TasP in high prevalence countries, like South Africa, communities must be motivated to know their status, engage in care, and remain in care. Community mobilization (CM) has the potential to significantly increase uptake testing, linkage to and retention in care by addressing the primary social barriers to engagement with HIV care-including poor understanding of HIV care; fear and stigma associated with infection, clinic attendance and disclosure; lack of social support; and gender norms that deter men from accessing care. Using a cluster randomized trial design, we are implementing a 3-year-theory-based CM intervention and comparing gains in HIV testing, linkage, and retention in care among individuals residing in 8 intervention communities to that of individuals residing in 7 control communities. Eligible communities include 15 villages within a health and demographic surveillance site (HDSS) in rural Mpumalanga, South Africa, that were not exposed to previous CM efforts. CM activities conducted in the 8 intervention villages map onto six mobilization domains that comprise the key components for community mobilization around HIV prevention. To evaluate the intervention, we will link a clinic-based electronic clinical tracking system in all area clinics to the HDSS longitudinal census data, thus creating an open, population-based cohort with over 30,000 18-49-year-old residents. We will estimate the marginal effect of the intervention on individual outcomes using generalized estimating equations. In addition, we will evaluate CM processes by conducting baseline and endline surveys among a random sample of 1200 community residents at each time point to monitor intervention exposure and community level change using validated measures of CM. Given the known importance of community social factors with regard to uptake of testing and HIV care, and the lack of rigorously evaluated community-level interventions effective in improving testing uptake, linkage and retention, the proposed study will yield much needed data to understand the potential of CM to improve the prevention and care cascade. Further, our work in developing a CM framework and domain measures will permit validation of a CM conceptual framework and process, which should prove valuable for community programming in Africa. NCT02197793 Registered July 21, 2014.

Identification of Multiple QTL Hotspots in Sockeye Salmon (Oncorhynchus nerka) Using Genotyping-by-Sequencing and a Dense Linkage Map.

PubMed

Larson, Wesley A; McKinney, Garrett J; Limborg, Morten T; Everett, Meredith V; Seeb, Lisa W; Seeb, James E

2016-03-01

Understanding the genetic architecture of phenotypic traits can provide important information about the mechanisms and genomic regions involved in local adaptation and speciation. Here, we used genotyping-by-sequencing and a combination of previously published and newly generated data to construct sex-specific linkage maps for sockeye salmon (Oncorhynchus nerka). We then used the denser female linkage map to conduct quantitative trait locus (QTL) analysis for 4 phenotypic traits in 3 families. The female linkage map consisted of 6322 loci distributed across 29 linkage groups and was 4082 cM long, and the male map contained 2179 loci found on 28 linkage groups and was 2291 cM long. We found 26 QTL: 6 for thermotolerance, 5 for length, 9 for weight, and 6 for condition factor. QTL were distributed nonrandomly across the genome and were often found in hotspots containing multiple QTL for a variety of phenotypic traits. These hotspots may represent adaptively important regions and are excellent candidates for future research. Comparing our results with studies in other salmonids revealed several regions with overlapping QTL for the same phenotypic trait, indicating these regions may be adaptively important across multiple species. Altogether, our study demonstrates the utility of genomic data for investigating the genetic basis of important phenotypic traits. Additionally, the linkage map created here will enable future research on the genetic basis of phenotypic traits in salmon. © The American Genetic Association 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Sex-specific genetic architecture of human fatness in Chinese: the SAPPHIRe Study.

PubMed

Chiu, Y-F; Chuang, L-M; Kao, H-Y; Shih, K-C; Lin, M-W; Lee, W-J; Quertermous, T; Curb, J D; Chen, I; Rodriguez, B L; Hsiung, C A

2010-11-01

To dissect the genetic architecture of sexual dimorphism in obesity-related traits, we evaluated the sex-genotype interaction, sex-specific heritability and genome-wide linkages for seven measurements related to obesity. A total of 1,365 non-diabetic Chinese subjects from the family study of the Stanford Asia-Pacific Program of Hypertension and Insulin Resistance were used to search for quantitative trait loci (QTLs) responsible for the obesity-related traits. Pleiotropy and co-incidence effects from the QTLs were also examined using the bivariate linkage approach. We found that sex-specific differences in heritability and the genotype-sex interaction effects were substantially significant for most of these traits. Several QTLs with strong linkage evidence were identified after incorporating genotype by sex (G × S) interactions into the linkage mapping, including one QTL for hip circumference [maximum LOD score (MLS) = 4.22, empirical p = 0.000033] and two QTLs: for BMI on chromosome 12q with MLS 3.37 (empirical p = 0.0043) and 3.10 (empirical p = 0.0054). Sex-specific analyses demonstrated that these linkage signals all resulted from females rather than males. Most of these QTLs for obesity-related traits replicated the findings in other ethnic groups. Bivariate linkage analyses showed several obesity traits were influenced by a common set of QTLs. All regions with linkage signals were observed in one gender, but not in the whole sample, suggesting the genetic architecture of obesity-related traits does differ by gender. These findings are useful for further identification of the liability genes for these phenotypes through candidate genes or genome-wide association analysis.

A general model for likelihood computations of genetic marker data accounting for linkage, linkage disequilibrium, and mutations.

PubMed

Kling, Daniel; Tillmar, Andreas; Egeland, Thore; Mostad, Petter

2015-09-01

Several applications necessitate an unbiased determination of relatedness, be it in linkage or association studies or in a forensic setting. An appropriate model to compute the joint probability of some genetic data for a set of persons given some hypothesis about the pedigree structure is then required. The increasing number of markers available through high-density SNP microarray typing and NGS technologies intensifies the demand, where using a large number of markers may lead to biased results due to strong dependencies between closely located loci, both within pedigrees (linkage) and in the population (allelic association or linkage disequilibrium (LD)). We present a new general model, based on a Markov chain for inheritance patterns and another Markov chain for founder allele patterns, the latter allowing us to account for LD. We also demonstrate a specific implementation for X chromosomal markers that allows for computation of likelihoods based on hypotheses of alleged relationships and genetic marker data. The algorithm can simultaneously account for linkage, LD, and mutations. We demonstrate its feasibility using simulated examples. The algorithm is implemented in the software FamLinkX, providing a user-friendly GUI for Windows systems (FamLinkX, as well as further usage instructions, is freely available at www.famlink.se ). Our software provides the necessary means to solve cases where no previous implementation exists. In addition, the software has the possibility to perform simulations in order to further study the impact of linkage and LD on computed likelihoods for an arbitrary set of markers.

Linkages Between Clinical Practices and Community Organizations for Prevention: A Literature Review and Environmental Scan

PubMed Central

Hinnant, Laurie W.; Kane, Heather; Horne, Joseph; McAleer, Kelly; Roussel, Amy

2012-01-01

Objectives. We conducted a literature review and environmental scan to develop a framework for interventions that utilize linkages between clinical practices and community organizations for the delivery of preventive services, and to identify and characterize these efforts. Methods. We searched 4 major health services and social science electronic databases and conducted an Internet search to identify examples of linkage interventions in the areas of tobacco cessation, obesity, nutrition, and physical activity. Results. We identified 49 interventions, of which 18 examples described their evaluation methods or reported any intervention outcomes. Few conducted evaluations that were rigorous enough to capture changes in intermediate or long-term health outcomes. Outcomes in these evaluations were primarily patient-focused and did not include organizational or linkage characteristics. Conclusions. An attractive option to increase the delivery of preventive services is to link primary care practices to community organizations; evidence is not yet conclusive, however, that such linkage interventions are effective. Findings provide recommendations to researchers and organizations that fund research, and call for a framework and metrics to study linkage interventions. PMID:22690974

The score statistic of the LD-lod analysis: detecting linkage adaptive to linkage disequilibrium.

PubMed

Huang, J; Jiang, Y

2001-01-01

We study the properties of a modified lod score method for testing linkage that incorporates linkage disequilibrium (LD-lod). By examination of its score statistic, we show that the LD-lod score method adaptively combines two sources of information: (a) the IBD sharing score which is informative for linkage regardless of the existence of LD and (b) the contrast between allele-specific IBD sharing scores which is informative for linkage only in the presence of LD. We also consider the connection between the LD-lod score method and the transmission-disequilibrium test (TDT) for triad data and the mean test for affected sib pair (ASP) data. We show that, for triad data, the recessive LD-lod test is asymptotically equivalent to the TDT; and for ASP data, it is an adaptive combination of the TDT and the ASP mean test. We demonstrate that the LD-lod score method has relatively good statistical efficiency in comparison with the ASP mean test and the TDT for a broad range of LD and the genetic models considered in this report. Therefore, the LD-lod score method is an interesting approach for detecting linkage when the extent of LD is unknown, such as in a genome-wide screen with a dense set of genetic markers. Copyright 2001 S. Karger AG, Basel

Linkage of A-to-I RNA Editing in Metazoans and the Impact on Genome Evolution

PubMed Central

Duan, Yuange; Dou, Shengqian; Zhang, Hong; Wu, Changcheng; Wu, Mingming

2018-01-01

Abstract The adenosine-to-inosine (A-to-I) RNA editomes have been systematically characterized in various metazoan species, and many editing sites were found in clusters. However, it remains unclear whether the clustered editing sites tend to be linked in the same RNA molecules or not. By adopting a method originally designed to detect linkage disequilibrium of DNA mutations, we examined the editomes of ten metazoan species and detected extensive linkage of editing in Drosophila and cephalopods. The prevalent linkages of editing in these two clades, many of which are conserved between closely related species and might be associated with the adaptive proteomic recoding, are maintained by natural selection at the cost of genome evolution. Nevertheless, in worms and humans, we only detected modest proportions of linked editing events, the majority of which were not conserved. Furthermore, the linkage of editing in coding regions of worms and humans might be overall deleterious, which drives the evolution of DNA sites to escape promiscuous editing. Altogether, our results suggest that the linkage landscape of A-to-I editing has evolved during metazoan evolution. This present study also suggests that linkage of editing should be considered in elucidating the functional consequences of RNA editing. PMID:29048557

An AFLP genetic linkage map of pacific abalone ( Haliotis discus hannai)

NASA Astrophysics Data System (ADS)

Qi, Li; Yanhong, Xu; Ruihai, Yu; Akihiro, Kijima

2007-07-01

A genetic linkage map of Pacific abalone ( Haliotis discus hannai) was constructed using AFLP markers based on a two-way pseudo-testeross strategy in a full-sib family. With 33 primer combinations, a total of 455 markers (225 from the female parent and 230 from the male parent) segregated in a 1:1 ratio, corresponding to DNA polymorphism: heterozygous in one parent and null in the other. The female framework map consisted of 174 markers distributed in 18 linkage groups, equivalent to the H. discus hannai haploid chromosome number, and spanning a total length of 2031.4 cM, with an average interval of 13.0 cM between adjacent markers. The male framework map consisted of 195 markers mapped on 19 linkage groups, spanning a total length of 2273.4 cM, with an average spacing of 12.9 cM between adjacent markers. The estimated coverage for the framework linkage maps was 81.2% for the female and 82.1% for the male, on the basis of two estimates of genome length. Fifty-two markers (11.4%) remained unlinked. The level of segregation distortion observed in this cross was 20.4%. These linkage maps will serve as a starting point for linkage studies in the Pacific abalone with potential application for marker-assisted selection in breeding programs.

A procedure for linking psychosocial job characteristics data to health surveys.

PubMed Central

Schwartz, J E; Pieper, C F; Karasek, R A

1988-01-01

A system is presented for linking information about psychosocial characteristics of job situations to national health surveys. Job information can be imputed to individuals on surveys that contain three-digit US Census occupation codes. Occupational mean scores on psychosocial job characteristics-control over task situation (decision latitude), psychological work load, physical exertion, and other measures-for the linkage system are derived from US national surveys of working conditions (Quality of Employment Surveys 1969, 1972, and 1977). This paper discusses a new method for reducing the biases in multivariate analyses that are likely to arise when utilizing linkage systems based on mean scores. Such biases are reduced by modifying the linkage system to adjust imputed individual scores for demographic factors such as age, education, race, marital status and, implicitly, sex (since men and women have separate linkage data bases). Statistics on the linkage system's efficiency and reliability are reported. All dimensions have high inter-survey reproducibility. Despite their psychosocial nature, decision latitude and physical exertion can be more efficiently imputed with the linkage system than earnings (a non-psychosocial job characteristic). The linkage system presented here is a useful tool for initial epidemiological studies of the consequences of psychosocial job characteristics and constitutes the methodological basis for the subsequent paper. PMID:3389426

Interface of culture, insecurity and HIV and AIDS: Lessons from displaced communities in Pader District, Northern Uganda.

PubMed

Rujumba, Joseph; Kwiringira, Japheth

2010-11-22

Northern Uganda unlike other rural regions has registered high HIV prevalence rates comparable to those of urbanized Kampala and the central region. This could be due to the linkages of culture, insecurity and HIV. We explored community perceptions of HIV and AIDS as a problem and its inter-linkage with culture and insecurity in Pader District. A cross sectional qualitative study was conducted in four sub-counties of Pader District, Uganda between May and June 2008. Data for the study were collected through 12 focus group discussions (FGDs) held separately; 2 FGDs with men, 6 FGDs with women, and 4 FGDs with the youth (2 for each sex). In addition we conducted 15 key informant interviews with; 3 health workers, 4 community leaders at village and parish levels, 3 persons living with HIV and 5 district officials. Data were analysed using the content thematic approach. This process involved identification of the study themes and sub-themes following multiple reading of interview and discussion transcripts. Relevant quotations per thematic area were identified and have been used in the presentation of study findings. The struggles to meet the basic and survival needs by individuals and households overshadowed HIV as a major community problem. Conflict and risky sexual related cultural practices were perceived by communities as major drivers of HIV and AIDS in the district. Insecurity had led to congestion in the camps leading to moral decadence, rape and defilement, prostitution and poverty which increased vulnerability to HIV infection. The cultural drivers of HIV and AIDS were; widow inheritance, polygamy, early marriages, family expectations, silence about sex and alcoholism. Development partners including civil society organisations, central government, district administration, religious and cultural leaders as well as other stakeholders should mainstream HIV in all community development and livelihood interventions in the post conflict Pader district to curtail the likely escalation of the HIV epidemic. A comprehensive behaviour change communication strategy is urgently needed to address the negative cultural practices. Real progress in the region lies in advocacy and negotiation to realise lasting peace.

Risk of neurological diseases among survivors of electric shocks: a nationwide cohort study, Denmark, 1968-2008.

PubMed

Grell, Kathrine; Meersohn, Andrea; Schüz, Joachim; Johansen, Christoffer

2012-09-01

Several studies suggest a link between electric injuries and neurological diseases, where electric shocks may explain elevated risks for neuronal degeneration and, subsequently, neurological diseases. We conducted a retrospective cohort study on the risk of neurological diseases among people in Denmark who had survived an electric accident in 1968-2008. The cohort included 3,133 people and occurrences of neurological diseases were determined by linkage to the nationwide population-based Danish National Register of Patients. The numbers of cases observed at first hospital contact in the cohort were compared with the respective rates of first hospital contacts for neurological diseases in the general population. We observed significantly increased risks for peripheral nerve diseases (standardized hospitalization ratio (SHR), 1.66; 95% confidence interval (CI), 1.22-2.22), for migraine (SHR, 1.80; 95% CI, 1.23-2.54), for vertigo (SHR, 1.60; 95% CI, 1.22-2.05), and for epilepsy (SHR, 1.45; 95% CI, 1.11-1.85). Only small numbers of cases of other neurological diseases were found, making the risk estimates unstable. These findings suggest an association between a single electric shock and increased risks for peripheral nerve diseases, migraines, vertigo, and epilepsy, but confirmation of these observations is needed. Copyright © 2012 Wiley Periodicals, Inc.

Population-Specific Patterns of Linkage Disequilibrium and SNP Variation in Spring and Winter Polyploid Wheat

USDA-ARS?s Scientific Manuscript database

Single nucleotide polymorphisms (SNPs) are ideally suited for the construction of high-resolution genetic maps, studying population evolutionary history and performing genome-wide association mapping experiments. Here we used a genome-wide set of 1536 SNPs to study linkage disequilibrium (LD) and po...

Analysis of sulfidic linkages formed in natural rubber latex medical gloves by using X-ray absorption near edge structure

NASA Astrophysics Data System (ADS)

Chankrachang, M.; Limphirat, W.; Yongyingsakthavorn, P.; Nontakaew, U.; Tohsan, A.

2017-09-01

A study of sulfidic linkages formed in natural rubber (NR) latex medical gloves by using X-ray Absorption Near Edge Structure (XANES) is presented in this paper. The NR latex compound was prepared by using prevulcanization method, that is, it was prevulcanized at room temperature for 24 hrs before utilization. After the 24 hrs of prevulcanization, the latex film samples were obtained by dipping process. The dipped films were subjected to vulcanize at 110°C for 5 to 25 min. It was observed that after the compound was prevulcanized for 24 hrs, polysulfidic linkages were mainly formed in the sample. It was however found that after curing at 110°C for 5-25 min, the polysulfidic linkages are tended to change into disulfide linkages. Especially, in the case of 25 minutes cured sample, disulfide linkages are found to be the main linkages. In term of tensile strength, it was observed that when cure time increased from 5 - 10 min, tensile strengths were also increased. But when the cure time of the film is 25 minutes, tensile strength was slightly dropped. The dropped of tensile strength when cure time is longer than 10 minutes can be ascribed to a degradation of polysulfidic and disulfidic linkages during curing. Therefore, by using XANES analysis, it was found to be very useful to understand the cure characteristic, thus it can be very helpful to optimize cure time and tensile properties of the product.

Neuropsychological Endophenotype Approach to Genome-wide Linkage Analysis Identifies Susceptibility Loci for ADHD on 2q21.1 and 13q12.11

PubMed Central

Rommelse, Nanda N.J.; Arias-Vásquez, Alejandro; Altink, Marieke E.; Buschgens, Cathelijne J.M.; Fliers, Ellen; Asherson, Philip; Faraone, Stephen V.; Buitelaar, Jan K.; Sergeant, Joseph A.; Oosterlaan, Jaap; Franke, Barbara

2008-01-01

ADHD linkage findings have not all been consistently replicated, suggesting that other approaches to linkage analysis in ADHD might be necessary, such as the use of (quantitative) endophenotypes (heritable traits associated with an increased risk for ADHD). Genome-wide linkage analyses were performed in the Dutch subsample of the International Multi-Center ADHD Genetics (IMAGE) study comprising 238 DSM-IV combined-type ADHD probands and their 112 affected and 195 nonaffected siblings. Eight candidate neuropsychological ADHD endophenotypes with heritabilities > 0.2 were used as quantitative traits. In addition, an overall component score of neuropsychological functioning was used. A total of 5407 autosomal single-nucleotide polymorphisms (SNPs) were used to run multipoint regression-based linkage analyses. Two significant genome-wide linkage signals were found, one for Motor Timing on chromosome 2q21.1 (LOD score: 3.944) and one for Digit Span on 13q12.11 (LOD score: 3.959). Ten suggestive linkage signals were found (LOD scores ≥ 2) on chromosomes 2p, 2q, 3p, 4q, 8q, 12p, 12q, 14q, and 17q. The suggestive linkage signal for the component score that was found at 2q14.3 (LOD score: 2.878) overlapped with the region significantly linked to Motor Timing. Endophenotype approaches may increase power to detect susceptibility loci in ADHD and possibly in other complex disorders. PMID:18599010

Incidence and mortality of acute and chronic pancreatitis in the Netherlands: a nationwide record-linked cohort study for the years 1995-2005.

PubMed

Spanier, B W Marcel; Bruno, Marco J; Dijkgraaf, Marcel G W

2013-05-28

To analyze trends in incidence and mortality of acute pancreatitis (AP) and chronic pancreatitis (CP) in the Netherlands and for international standard populations. A nationwide cohort is identified through record linkage of hospital data for AP and CP, accumulated from three nationwide Dutch registries: the hospital discharge register, the population register, and the death certificate register. Sex- and age-group specific incidence rates of AP and CP are defined for the period 2000-2005 and mortality rates of AP and CP for the period 1995-2005. Additionally, incidence and mortality rates over time are reported for Dutch and international (European and World Health Organization) standard populations. Incidence of AP per 100000 persons per year increased between 2000 and 2005 from 13.2 (95%CI: 12.6-13.8) to 14.7 (95%CI: 14.1-15.3). Incidence of AP for males increased from 13.8 (95%CI: 12.9-14.7) to 15.2 (95%CI: 14.3-16.1), for females from 12.7 (95%CI: 11.9-13.5) to 14.2 (95%CI: 13.4-15.1). Irregular patterns over time emerged for CP. Overall mean incidence per 100000 persons per year was 1.77, for males 2.16, and for females 1.4. Mortality for AP fluctuated during 1995-2005 between 6.9 and 11.7 per million persons per year and was almost similar for males and females. Concerning CP, mortality for males fluctuated between 1.1 (95%CI: 0.6-2.3) and 4.0 (95%CI: 2.8-5.8), for females between 0.7 (95%CI: 0.3-1.6) and 2.0 (95%CI: 1.2-3.2). Incidence and mortality of AP and CP increased markedly with age. Standardized rates were lowest for World Health Organization standard population. Incidence of AP steadily increased while incidence of CP fluctuated. Mortality for both AP and CP remained fairly stable. Patient burden and health care costs probably will increase because of an ageing Dutch population.

Linkage of the Canadian Study of Health and Aging to provincial administrative health care databases in Nova Scotia.

PubMed

Yip, A M; Kephart, G; Rockwood, K

2001-01-01

The Canadian Study of Health and Aging (CSHA) was a cohort study that included 528 Nova Scotian community-dwelling participants. Linkage of CSHA and provincial Medical Services Insurance (MSI) data enabled examination of health care utilization in this subsample. This article discusses methodological and ethical issues of database linkage and explores variation in the use of health services by demographic variables and health status. Utilization over 24 months following baseline was extracted from MSI's physician claims, hospital discharge abstracts, and Pharmacare claims databases. Twenty-nine subjects refused consent for access to their MSI file; health card numbers for three others could not be retrieved. A significant difference in healthcare use by age and self-rated health was revealed. Linkage of population-based data with provincial administrative health care databases has the potential to guide health care planning and resource allocation. This process must include steps to ensure protection of confidentiality. Standard practices for linkage consent and routine follow-up should be adopted. The Canadian Study of Health and Aging (CSHA) began in 1991-92 to explore dementia, frailty, and adverse health outcomes (Canadian Study of Health and Aging Working Group, 1994). The original CSHA proposal included linkage to provincial administrative health care databases by the individual CSHA study centers to enhance information on health care utilization and outcomes of study participants. In Nova Scotia, the Medical Services Insurance (MSI) administration, which drew the sampling frame for the original CSHA, did not retain the list of corresponding health card numbers. Furthermore, consent for this access was not asked of participants at the time of the first interview. The objectives of this study reported here were to examine the feasibility and ethical considerations of linking data from the CSHA to MSI utilization data, and to explore variation in health services use by demographic and health status characteristics in the Nova Scotia community cohort.

Guess LOD approach: sufficient conditions for robustness.

PubMed

Williamson, J A; Amos, C I

1995-01-01

Analysis of genetic linkage between a disease and a marker locus requires specifying a genetic model describing both the inheritance pattern and the gene frequencies of the marker and trait loci. Misspecification of the genetic model is likely for etiologically complex diseases. In previous work we have shown through analytic studies that misspecifying the genetic model for disease inheritance does not lead to excess false-positive evidence for genetic linkage provided the genetic marker alleles of all pedigree members are known, or can be inferred without bias from the data. Here, under various selection or ascertainment schemes we extend these previous results to situations in which the genetic model for the marker locus may be incorrect. We provide sufficient conditions for the asymptotic unbiased estimation of the recombination fraction under the null hypothesis of no linkage, and also conditions for the limiting distribution of the likelihood ratio test for no linkage to be chi-squared. Through simulation studies we document some situations under which asymptotic bias can result when the genetic model is misspecified. Among those situations under which an excess of false-positive evidence for genetic linkage can be generated, the most common is failure to provide accurate estimates of the marker allele frequencies. We show that in most cases false-positive evidence for genetic linkage is unlikely to result solely from the misspecification of the genetic model for disease or trait inheritance.

Facilitators and Barriers to Linkage to HIV Care among Female Sex Workers Receiving HIV Testing Services at a Community-Based Organization in Periurban Uganda: A Qualitative Study

PubMed Central

Kintu, Betty N.

2016-01-01

Introduction. While four in ten female sex workers (FSWs) in sub-Saharan Africa are infected with HIV, only a small proportion is enrolled in HIV care. We explored facilitators and barriers to linkage to HIV care among FSWs receiving HIV testing services at a community-based organization in periurban Uganda. Methods. The cross-sectional qualitative study was conducted among 28 HIV positive FSWs from May to July 2014. Key informant interviews were conducted with five project staff and eleven peer educators. Data were collected on facilitators for and barriers to linkage to HIV care and manually analyzed following a thematic framework approach. Results. Facilitators for linkage to HIV care included the perceived good quality of health services with same-day results and immediate initiation of treatment, community peer support systems, individual's need to remain healthy, and having alternative sources of income. Linkage barriers included perceived stigma, fear to be seen at outreach HIV clinics, fear and myths about antiretroviral therapy, lack of time to attend clinic, and financial constraints. Conclusion. Linkage to HIV care among FSWs is influenced by good quality friendly services and peer support. HIV service delivery programs for FSWs should focus on enhancing these and dealing with barriers stemming from stigma and misinformation. PMID:27493826

Evaluation of the impact of genetic linkage in forensic identity and relationship testing for expanded DNA marker sets.

PubMed

Tillmar, Andreas O; Phillips, Chris

2017-01-01

Advances in massively parallel sequencing technology have enabled the combination of a much-expanded number of DNA markers (notably STRs and SNPs in one or combined multiplexes), with the aim of increasing the weight of evidence in forensic casework. However, when data from multiple loci on the same chromosome are used, genetic linkage can affect the final likelihood calculation. In order to study the effect of linkage for different sets of markers we developed the biostatistical tool ILIR, (Impact of Linkage on forensic markers for Identity and Relationship tests). The ILIR tool can be used to study the overall impact of genetic linkage for an arbitrary set of markers used in forensic testing. Application of ILIR can be useful during marker selection and design of new marker panels, as well as being highly relevant for existing marker sets as a way to properly evaluate the effects of linkage on a case-by-case basis. ILIR, implemented via the open source platform R, includes variation and genomic position reference data for over 40 STRs and 140 SNPs, combined with the ability to include additional forensic markers of interest. The use of the software is demonstrated with examples from several different established marker sets (such as the expanded CODIS core loci) including a review of the interpretation of linked genetic data. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

A ddRAD Based Linkage Map of the Cultivated Strawberry, Fragaria xananassa

PubMed Central

Davik, Jahn; Sargent, Daniel James; Brurberg, May Bente; Lien, Sigbjørn; Kent, Matthew; Alsheikh, Muath

2015-01-01

The cultivated strawberry (Fragaria ×ananassa Duch.) is an allo-octoploid considered difficult to disentangle genetically due to its four relatively similar sub-genomic chromosome sets. This has been alleviated by the recent release of the strawberry IStraw90 whole genome genotyping array. However, array resolution relies on the genotypes used in the array construction and may be of limited general use. SNP detection based on reduced genomic sequencing approaches has the potential of providing better coverage in cases where the studied genotypes are only distantly related from the SNP array’s construction foundation. Here we have used double digest restriction-associated DNA sequencing (ddRAD) to identify SNPs in a 145 seedling F1 hybrid population raised from the cross between the cultivars Sonata (♀) and Babette (♂). A linkage map containing 907 markers which spanned 1,581.5 cM across 31 linkage groups representing the 28 chromosomes of the species. Comparing the physical span of the SNP markers with the F. vesca genome sequence, the linkage groups resolved covered 79% of the estimated 830 Mb of the F. ×ananassa genome. Here, we have developed the first linkage map for F. ×ananassa using ddRAD and show that this technique and other related techniques are useful tools for linkage map development and downstream genetic studies in the octoploid strawberry. PMID:26398886

Combined genome-wide linkage and targeted association analysis of head circumference in autism spectrum disorder families.

PubMed

Woodbury-Smith, M; Bilder, D A; Morgan, J; Jerominski, L; Darlington, T; Dyer, T; Paterson, A D; Coon, H

2017-01-01

It has long been recognized that there is an association between enlarged head circumference (HC) and autism spectrum disorder (ASD), but the genetics of HC in ASD is not well understood. In order to investigate the genetic underpinning of HC in ASD, we undertook a genome-wide linkage study of HC followed by linkage signal targeted association among a sample of 67 extended pedigrees with ASD. HC measurements on members of 67 multiplex ASD extended pedigrees were used as a quantitative trait in a genome-wide linkage analysis. The Illumina 6K SNP linkage panel was used, and analyses were carried out using the SOLAR implemented variance components model. Loci identified in this way formed the target for subsequent association analysis using the Illumina OmniExpress chip and imputed genotypes. A modification of the qTDT was used as implemented in SOLAR. We identified a linkage signal spanning 6p21.31 to 6p22.2 (maximum LOD = 3.4). Although targeted association did not find evidence of association with any SNP overall, in one family with the strongest evidence of linkage, there was evidence for association (rs17586672, p  = 1.72E-07). Although this region does not overlap with ASD linkage signals in these same samples, it has been associated with other psychiatric risk, including ADHD, developmental dyslexia, schizophrenia, specific language impairment, and juvenile bipolar disorder. The genome-wide significant linkage signal represents the first reported observation of a potential quantitative trait locus for HC in ASD and may be relevant in the context of complex multivariate risk likely leading to ASD.

Endometriosis, assisted reproduction technology, and risk of adverse pregnancy outcome.

PubMed

Stephansson, Olof; Kieler, Helle; Granath, Fredrik; Falconer, Henrik

2009-09-01

Endometriosis, a common gynaecological disease, is characterized by local and systemic inflammation, which may cause infertility and consequently, increased utilization of assisted reproduction technology (ART). We aimed to estimate the risk for preterm birth, small-for-gestational-age (SGA) birth, stillbirth, Caesarean section, pre-eclampsia and antepartal haemorrhage among women with a previous diagnosis of endometriosis compared with women with no previous diagnosis of endometriosis. In a nationwide Swedish study including 1,442,675 singleton births we assessed the association between adverse pregnancy outcome, ART and a previous diagnosis of endometriosis. Information was obtained by linkage of data between 1992 and 2006 in the Medical Birth Register with the Patient Register between 1964 and 2006. There were 13,090 singleton births among 8922 women diagnosed with endometriosis. Compared with women without endometriosis, women with endometriosis had higher risks of preterm birth [adjusted odds ratio 1.33, 95% confidence interval (CI), 1.23-1.44]. Among women with endometriosis 11.9% conceived after ART compared with 1.4% of women without endometriosis. The risk of preterm birth associated with endometriosis among women with ART was 1.24 (95% CI, 0.99-1.57), and among women without ART 1.37 (95% CI, 1.25-1.50). Women with endometriosis had higher risks of antepartal bleeding/placental complications, pre-eclampsia and Caesarean section. There was no association between endometriosis and risk of SGA-birth or stillbirth. Endometriosis appears to be a risk factor for preterm birth, irrespective of ART. Women with endometriosis may be more likely to be delivered by Caesarean section and to suffer from antepartal haemorrhage/placental complications and pre-eclampsia.

Pupils with special educational needs in basic education schools and teachers' sickness absences--a register-linkage study.

PubMed

Ervasti, Jenni; Kivimäki, Mika; Kawachi, Ichiro; Subramanian, S V; Pentti, Jaana; Ahola, Kirsi; Oksanen, Tuula; Pohjonen, Tiina; Vahtera, Jussi; Virtanen, Marianna

2012-05-01

We examined whether having a high percentage of pupils with special educational needs (SEN) in basic education schools increases the risk of sickness absence among teachers and whether this risk is dependent on the pupil-teacher ratio (PTR), an indicator of teacher resources at school. We obtained register data on 8089 teachers working in 404 schools in 10 municipalities in Finland during the school year 2004-2005. We used multilevel multinomial regression models to examine the risk of teachers' short- and long-term sickness absence in relation to the percentage of SEN pupils and the PTR at school. We tested the equality of trends in groups with high and low PTR using PTR × SEN interaction term. After adjustment for teacher and school characteristics, the risk for long-term absences was higher among teachers at schools with a high percentage of SEN pupils than among teachers at schools with a low percentage of SEN pupils [odds ratio (OR) 1.5, 95% confidence interval (95% CI) 1.2-1.8). This was also the case for short-term absences (OR 1.4, 95% CI 1.2-1.7). In analyses stratified by the PTR levels, the association between the percentage of SEN pupils and long-term absences was 15% higher among teachers with a high PTR than among those with a low PTR (P for interaction=0.10). Teachers' sickness absenteeism seems to increase with a higher percentage of SEN pupils, especially when the PTR is high. Teacher resources at schools that have a high percentage of SEN pupils should be well maintained to ensure the health of teachers.

Individual and combined effects of maternal anemia and prenatal infection on risk for schizophrenia in offspring.

PubMed

Nielsen, Philip R; Meyer, Urs; Mortensen, Preben B

2016-04-01

Maternal iron deficiency and infection during pregnancy have individually been associated with increased risk of schizophrenia in the offspring, but possible interactions between the two remain unidentified thus far. Therefore, we determined the individual and combined effects of maternal infection during pregnancy and prepartum anemia on schizophrenia risk in the offspring. We conducted a population-based study with individual record linkage of the Danish Civil Registration System, the Danish Hospital Register, and the Central Danish Psychiatric Register. In a cohort of Danish singleton births 1,403,183 born between 1977 and 2002, 6729 developed schizophrenia between 1987 and 2012. Cohort members were considered as having a maternal history of anemia if the mother had received a diagnosis of anemia at any time during the pregnancy. Maternal infection was defined based on infections requiring hospital admission during pregnancy. Maternal anemia and infection were both associated with increased risk of schizophrenia in unadjusted analyses (1.45-fold increase for anemia, 95% CI: 1.14-1.82; 1.32-fold increase for infection, 95% CI: 1.17-1.48). The effect of maternal infection remained significant (1.16-fold increase, 95% CI: 1.03-1.31) after adjustment for possible confounding factors. Combined exposure to anemia and an infection increased the effect size to a 2.49-fold increased schizophrenia risk (95% CI: 1.29-4.27). The interaction analysis, however, failed to provide evidence for multiplicative interactions between the two factors. Our findings indicate that maternal anemia and infection have additive but not interactive effects, and therefore, they may represent two independent risk factors of schizophrenia. Copyright © 2016 Elsevier B.V. All rights reserved.

Sequential strategy to identify a susceptibility gene for schizophrenia: Report of potential linkage on chromosome 22q12-q13.1: Part 1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pulver, A.E.; Wolyniec, P.S.; Lasseter, V.K.

To identify genes responsible for the susceptibility for schizophrenia, and to test the hypothesis that schizophrenia is etiologically heterogeneous, we have studied 39 multiplex families from a systematic sample of schizophrenic patients. Using a complex autosomal dominant model, which considers only those with a diagnosis of schizophrenia or schizoaffective disorder as affected, a random search of the genome for detection of linkage was undertaken. Pairwise linkage analyses suggest a potential linkage (LRH = 34.7 or maximum lod score = 1.54) for one region (22q12-q13.1). Reanalyses, varying parameters in the dominant model, maximized the LRH at 660.7 (maximum lod score 2.82).more » This finding is of sufficient interest to warrant further investigation through collaborative studies. 72 refs., 5 tabs.« less

Some methods for blindfolded record linkage.

PubMed

Churches, Tim; Christen, Peter

2004-06-28

The linkage of records which refer to the same entity in separate data collections is a common requirement in public health and biomedical research. Traditionally, record linkage techniques have required that all the identifying data in which links are sought be revealed to at least one party, often a third party. This necessarily invades personal privacy and requires complete trust in the intentions of that party and their ability to maintain security and confidentiality. Dusserre, Quantin, Bouzelat and colleagues have demonstrated that it is possible to use secure one-way hash transformations to carry out follow-up epidemiological studies without any party having to reveal identifying information about any of the subjects - a technique which we refer to as "blindfolded record linkage". A limitation of their method is that only exact comparisons of values are possible, although phonetic encoding of names and other strings can be used to allow for some types of typographical variation and data errors. A method is described which permits the calculation of a general similarity measure, the n-gram score, without having to reveal the data being compared, albeit at some cost in computation and data communication. This method can be combined with public key cryptography and automatic estimation of linkage model parameters to create an overall system for blindfolded record linkage. The system described offers good protection against misdeeds or security failures by any one party, but remains vulnerable to collusion between or simultaneous compromise of two or more parties involved in the linkage operation. In order to reduce the likelihood of this, the use of last-minute allocation of tasks to substitutable servers is proposed. Proof-of-concept computer programmes written in the Python programming language are provided to illustrate the similarity comparison protocol. Although the protocols described in this paper are not unconditionally secure, they do suggest the feasibility, with the aid of modern cryptographic techniques and high speed communication networks, of a general purpose probabilistic record linkage system which permits record linkage studies to be carried out with negligible risk of invasion of personal privacy.

Some methods for blindfolded record linkage

PubMed Central

Churches, Tim; Christen, Peter

2004-01-01

Background The linkage of records which refer to the same entity in separate data collections is a common requirement in public health and biomedical research. Traditionally, record linkage techniques have required that all the identifying data in which links are sought be revealed to at least one party, often a third party. This necessarily invades personal privacy and requires complete trust in the intentions of that party and their ability to maintain security and confidentiality. Dusserre, Quantin, Bouzelat and colleagues have demonstrated that it is possible to use secure one-way hash transformations to carry out follow-up epidemiological studies without any party having to reveal identifying information about any of the subjects – a technique which we refer to as "blindfolded record linkage". A limitation of their method is that only exact comparisons of values are possible, although phonetic encoding of names and other strings can be used to allow for some types of typographical variation and data errors. Methods A method is described which permits the calculation of a general similarity measure, the n-gram score, without having to reveal the data being compared, albeit at some cost in computation and data communication. This method can be combined with public key cryptography and automatic estimation of linkage model parameters to create an overall system for blindfolded record linkage. Results The system described offers good protection against misdeeds or security failures by any one party, but remains vulnerable to collusion between or simultaneous compromise of two or more parties involved in the linkage operation. In order to reduce the likelihood of this, the use of last-minute allocation of tasks to substitutable servers is proposed. Proof-of-concept computer programmes written in the Python programming language are provided to illustrate the similarity comparison protocol. Conclusion Although the protocols described in this paper are not unconditionally secure, they do suggest the feasibility, with the aid of modern cryptographic techniques and high speed communication networks, of a general purpose probabilistic record linkage system which permits record linkage studies to be carried out with negligible risk of invasion of personal privacy. PMID:15222890

A combined genome-wide linkage and association approach to find susceptibility loci for platelet function phenotypes in European American and African American families with coronary artery disease

PubMed Central

2010-01-01

Background The inability of aspirin (ASA) to adequately suppress platelet aggregation is associated with future risk of coronary artery disease (CAD). Heritability studies of agonist-induced platelet function phenotypes suggest that genetic variation may be responsible for ASA responsiveness. In this study, we leverage independent information from genome-wide linkage and association data to determine loci controlling platelet phenotypes before and after treatment with ASA. Methods Clinical data on 37 agonist-induced platelet function phenotypes were evaluated before and after a 2-week trial of ASA (81 mg/day) in 1231 European American and 846 African American healthy subjects with a family history of premature CAD. Principal component analysis was performed to minimize the number of independent factors underlying the covariance of these various phenotypes. Multi-point sib-pair based linkage analysis was performed using a microsatellite marker set, and single-SNP association tests were performed using markers from the Illumina 1 M genotyping chip from deCODE Genetics, Inc. All analyses were performed separately within each ethnic group. Results Several genomic regions appear to be linked to ASA response factors: a 10 cM region in African Americans on chromosome 5q11.2 had several STRs with suggestive (p-value < 7 × 10-4) and significant (p-value < 2 × 10-5) linkage to post aspirin platelet response to ADP, and ten additional factors had suggestive evidence for linkage (p-value < 7 × 10-4) to thirteen genomic regions. All but one of these factors were aspirin response variables. While the strength of genome-wide SNP association signals for factors showing evidence for linkage is limited, especially at the strict thresholds of genome-wide criteria (N = 9 SNPs for 11 factors), more signals were considered significant when the association signal was weighted by evidence for linkage (N = 30 SNPs). Conclusions Our study supports the hypothesis that platelet phenotypes in response to ASA likely have genetic control and the combined approach of linkage and association offers an alternative approach to prioritizing regions of interest for subsequent follow-up. PMID:20529293

Confirmation of Single-Locus Sex Determination and Female Heterogamety in Willow Based on Linkage Analysis.

PubMed

Chen, Yingnan; Wang, Tiantian; Fang, Lecheng; Li, Xiaoping; Yin, Tongming

2016-01-01

In this study, we constructed high-density genetic maps of Salix suchowensis and mapped the gender locus with an F1 pedigree. Genetic maps were separately constructed for the maternal and paternal parents by using amplified fragment length polymorphism (AFLP) markers and the pseudo-testcross strategy. The maternal map consisted of 20 linkage groups that spanned a genetic distance of 2333.3 cM; whereas the paternal map contained 21 linkage groups that covered 2260 cM. Based on the established genetic maps, it was found that the gender of willow was determined by a single locus on linkage group LG_03, and the female was the heterogametic gender. Aligned with mapped SSR markers, linkage group LG_03 was found to be associated with chromosome XV in willow. It is noteworthy that marker density in the vicinity of the gender locus was significantly higher than that expected by chance alone, which indicates severe recombination suppression around the gender locus. In conclusion, this study confirmed the findings on the single-locus sex determination and female heterogamety in willow. It also provided additional evidence that validated the previous studies, which found that different autosomes evolved into sex chromosomes between the sister genera of Salix (willow) and Populus (poplar).

Confirmation of Single-Locus Sex Determination and Female Heterogamety in Willow Based on Linkage Analysis

PubMed Central

Fang, Lecheng; Li, Xiaoping; Yin, Tongming

2016-01-01

In this study, we constructed high-density genetic maps of Salix suchowensis and mapped the gender locus with an F1 pedigree. Genetic maps were separately constructed for the maternal and paternal parents by using amplified fragment length polymorphism (AFLP) markers and the pseudo-testcross strategy. The maternal map consisted of 20 linkage groups that spanned a genetic distance of 2333.3 cM; whereas the paternal map contained 21 linkage groups that covered 2260 cM. Based on the established genetic maps, it was found that the gender of willow was determined by a single locus on linkage group LG_03, and the female was the heterogametic gender. Aligned with mapped SSR markers, linkage group LG_03 was found to be associated with chromosome XV in willow. It is noteworthy that marker density in the vicinity of the gender locus was significantly higher than that expected by chance alone, which indicates severe recombination suppression around the gender locus. In conclusion, this study confirmed the findings on the single-locus sex determination and female heterogamety in willow. It also provided additional evidence that validated the previous studies, which found that different autosomes evolved into sex chromosomes between the sister genera of Salix (willow) and Populus (poplar). PMID:26828940

Meta-analysis of genome-wide scans for blood pressure in African American and Nigerian samples. The National Heart, Lung, and Blood Institute GeneLink Project.

PubMed

Rice, Treva; Cooper, Richard S; Wu, Xiaodong; Bouchard, Claude; Rankinen, Tuomo; Rao, D C; Jaquish, Cashell E; Fabsitz, Richard R; Province, Michael A

2006-03-01

In many genetic studies of complex traits, sample sizes are often too small to detect linkages of low-to-moderate effects. However, the combined linkage evidence across several studies can be synthesized using meta-analysis with the aim of providing more definitive support of linkage. In the current study using the National Heart, Lung, and Blood Institute (NHLBI) GeneLink Project, a meta-analysis based on a modification of Fisher's method of pooling P values was used to investigate linkage for systolic blood pressure (SBP) and diastolic blood pressure (DBP) values across three studies involving African American and Nigerian families (HyperGEN, Health, Risk Factors, Exercise Training and Genetics [HERITAGE], and Genetics of Hypertension in Blacks). The meta results suggest two regions (2p and 7p) provide enhanced linkage evidence compared with the individual study results. The maximal meta Lod score of 2.9 on 2p14-p13.1 (64-78 cM) represented approximately 1-Lod unit increase over the respective individual study scores. This general region has been implicated previously involving primarily families of white ethnicity and provides confirmatory evidence that this QTL is common across ethnic groups. The second finding at 7p21.3-p15.3 (8-25 cM) provided a meta Lod of 3.5. Although region was implicated primarily in the Nigerian subjects the low-level but consistent support involving the African American families (individual Lod score of 1.0) suggests a novel QTL with respect to BP variation in individuals of black ethnicity. Follow-up studies involving positional cloning efforts of the combined families showing linkage evidence in these regions (particularly 2p) may be warranted to verify these findings and identify the genes and causative variants.

Caucasian Families Exhibit Significant Linkage of Myopia to Chromosome 11p.

PubMed

Musolf, Anthony M; Simpson, Claire L; Moiz, Bilal A; Long, Kyle A; Portas, Laura; Murgia, Federico; Ciner, Elise B; Stambolian, Dwight; Bailey-Wilson, Joan E

2017-07-01

Myopia is a common visual disorder caused by eye overgrowth, resulting in blurry vision. It affects one in four Americans, and its prevalence is increasing. The genetic mechanisms that underpin myopia are not completely understood. Here, we use genotype data and linkage analyses to identify high-risk genetic loci that are significantly linked to myopia. Individuals from 56 Caucasian families with a history of myopia were genotyped on an exome-based array, and the single nucleotide polymorphism (SNP) data were merged with microsatellite genotype data. Refractive error measures on the samples were converted into binary phenotypes consisting of affected, unaffected, or unknown myopia status. Parametric linkage analyses assuming an autosomal dominant model with 90% penetrance and 10% phenocopy rate were performed. Single variant two-point analyses yielded three significantly linked SNPs at 11p14.1 and 11p11.2; a further 45 SNPs at 11p were found to be suggestive. No other chromosome had any significant SNPs or more than seven suggestive linkages. Two of the significant SNPs were located in BBOX1-AS1 and one in the intergenic region between ORA47 and TRIM49B. Collapsed haplotype pattern two-point analysis and multipoint analyses also yielded multiple suggestively linked genes at 11p. Multipoint analysis also identified suggestive evidence of linkage on 20q13. We identified three genome-wide significant linked variants on 11p for myopia in Caucasians. Although the novel specific signals still need to be replicated, 11p is a promising region that has been identified by other linkage studies with a number of potentially interesting candidate genes. We hope that the identification of these regions on 11p as potential causal regions for myopia will lead to more focus on these regions and maybe possible replication of our specific linkage peaks in other studies. We further plan targeted sequencing on 11p for our most highly linked families to more clearly understand the source of the linkage in this region.

Intra-facility linkage of HIV-positive mothers and HIV-exposed babies into HIV chronic care: rural and urban experience in a resource limited setting.

PubMed

Mugasha, Christine; Kigozi, Joanita; Kiragga, Agnes; Muganzi, Alex; Sewankambo, Nelson; Coutinho, Alex; Nakanjako, Damalie

2014-01-01

Linkage of HIV-infected pregnant women to HIV care remains critical for improvement of maternal and child outcomes through prevention of maternal-to-child transmission of HIV (PMTCT) and subsequent chronic HIV care. This study determined proportions and factors associated with intra-facility linkage to HIV care and Early Infant Diagnosis care (EID) to inform strategic scale up of PMTCT programs. A cross-sectional review of records was done at 2 urban and 3 rural public health care facilities supported by the Infectious Diseases Institute (IDI). HIV-infected pregnant mothers, identified through routine antenatal care (ANC) and HIV-exposed babies were evaluated for enrollment in HIV clinics by 6 weeks post-delivery. Overall, 1,025 HIV-infected pregnant mothers were identified during ANC between January and June, 2012; 267/1,025 (26%) in rural and 743/1,025 (74%) in urban facilities. Of these 375/1,025 (37%) were linked to HIV clinics [67/267(25%) rural and 308/758(41%) urban]. Of 636 HIV-exposed babies, 193 (30%) were linked to EID. Linkage of mother-baby pairs to HIV chronic care and EID was 16% (101/636); 8/179 (4.5%)] in rural and 93/457(20.3%) in urban health facilities. Within rural facilities, ANC registration <28 weeks-of-gestation was associated with mothers' linkage to HIV chronic care [AoR, 2.0 95% CI, 1.1-3.7, p = 0.019] and mothers' multi-parity was associated with baby's linkage to EID; AoR 4.4 (1.3-15.1), p = 0.023. Stigma, long distance to health facilities and vertical PMTCT services affected linkage in rural facilities, while peer mothers, infant feeding services, long patient queues and limited privacy hindered linkage to HIV care in urban settings. Post-natal linkage of HIV-infected mothers to chronic HIV care and HIV-exposed babies to EID programs was low. Barriers to linkage to HIV care vary in urban and rural settings. We recommend targeted interventions to rapidly improve linkage to antiretroviral therapy for elimination of MTCT.

Intra-Facility Linkage of HIV-Positive Mothers and HIV-Exposed Babies into HIV Chronic Care: Rural and Urban Experience in a Resource Limited Setting

PubMed Central

Mugasha, Christine; Kigozi, Joanita; Kiragga, Agnes; Muganzi, Alex; Sewankambo, Nelson; Coutinho, Alex; Nakanjako, Damalie

2014-01-01

Introduction Linkage of HIV-infected pregnant women to HIV care remains critical for improvement of maternal and child outcomes through prevention of maternal-to-child transmission of HIV (PMTCT) and subsequent chronic HIV care. This study determined proportions and factors associated with intra-facility linkage to HIV care and Early Infant Diagnosis care (EID) to inform strategic scale up of PMTCT programs. Methods A cross-sectional review of records was done at 2 urban and 3 rural public health care facilities supported by the Infectious Diseases Institute (IDI). HIV-infected pregnant mothers, identified through routine antenatal care (ANC) and HIV-exposed babies were evaluated for enrollment in HIV clinics by 6 weeks post-delivery. Results Overall, 1,025 HIV-infected pregnant mothers were identified during ANC between January and June, 2012; 267/1,025 (26%) in rural and 743/1,025 (74%) in urban facilities. Of these 375/1,025 (37%) were linked to HIV clinics [67/267(25%) rural and 308/758(41%) urban]. Of 636 HIV-exposed babies, 193 (30%) were linked to EID. Linkage of mother-baby pairs to HIV chronic care and EID was 16% (101/636); 8/179 (4.5%)] in rural and 93/457(20.3%) in urban health facilities. Within rural facilities, ANC registration <28 weeks-of-gestation was associated with mothers' linkage to HIV chronic care [AoR, 2.0 95% CI, 1.1–3.7, p = 0.019] and mothers' multi-parity was associated with baby's linkage to EID; AoR 4.4 (1.3–15.1), p = 0.023. Stigma, long distance to health facilities and vertical PMTCT services affected linkage in rural facilities, while peer mothers, infant feeding services, long patient queues and limited privacy hindered linkage to HIV care in urban settings. Conclusion Post-natal linkage of HIV-infected mothers to chronic HIV care and HIV-exposed babies to EID programs was low. Barriers to linkage to HIV care vary in urban and rural settings. We recommend targeted interventions to rapidly improve linkage to antiretroviral therapy for elimination of MTCT. PMID:25546453

Linked health data for pharmacovigilance in children: perceived legal and ethical issues for stakeholders and data guardians.

PubMed

Hopf, Yvonne Marina; Bond, Christine B; Francis, Jill J; Haughney, John; Helms, Peter J

2014-02-12

The inclusion of the Community Health Index in the recording of National Health Service (NHS) contacts in Scotland facilitates national linkage of data such as prescribing and healthcare utilisation. This linkage could be the basis for identification of adverse drug reactions. The aim of this article is to report the views of healthcare professionals on data sharing, ownership and the legal and other applicable frameworks relevant to linkage of routinely collected paediatric healthcare data. Qualitative study using semistructured face-to-face interviews addressing the study aims. Purposive sample of professional stakeholders (n=25) including experts on ethics, data protection, pharmacovigilance, data linkage, legal issues and prescribing. Interviews were audio-recorded, transcribed and thematically analysed using a framework approach. Participants identified existing data sharing systems in the UK. Access to healthcare data should be approved by the data owners. The definition of data ownership and associated legal responsibilities for linked healthcare data were seen as important factors to ensure accountability for the use of linked data. Yet data owners were seen as facilitators of the proposed data linkage. Twelve frameworks (legal, regulatory and governance) applicable to the linkage of healthcare data were identified. A large number of potentially relevant legal and regulatory frameworks were identified. Ownership of the linked data was seen as an extension of responsibility for, or guardianship of, the source datasets. The consensus emerging from the present study was that clarity is required on the definition of data sharing, data ownership and responsibilities of data owners.

A study comparing precision of the maximum multipoint heterogeneity LOD statistic to three model-free multipoint linkage methods.

PubMed

Finch, S J; Chen, C H; Gordon, D; Mendell, N R

2001-12-01

This study compared the performance of the maximum lod (MLOD), maximum heterogeneity lod (MHLOD), maximum non-parametric linkage score (MNPL), maximum Kong and Cox linear extension (MKC(lin)) of NPL, and maximum Kong and Cox exponential extension (MKC(exp)) of NPL as calculated in Genehunter 1.2 and Genehunter-Plus. Our performance measure was the distance between the marker with maximum value for each linkage statistic and the trait locus. We performed a simulation study considering: 1) four modes of transmission, 2) 100 replicates for each model, 3) 58 pedigrees (with 592 subjects) per replicate, 4) three linked marker loci each having three equally frequent alleles, and 5) either 0% unlinked families (linkage homogeneity) or 50% unlinked families (linkage heterogeneity). For each replicate, we obtained the Haldane map position of the location at which each of the five statistics is maximized. The MLOD and MHLOD were obtained by maximizing over penetrances, phenocopy rate, and risk-allele frequencies. For the models simulated, MHLOD appeared to be the best statistic both in terms of identifying a marker locus having the smallest mean distance from the trait locus and in terms of the strongest negative correlation between maximum linkage statistic and distance of the identified position and the trait locus. The marker loci with maximum value of the Kong and Cox extensions of the NPL statistic also were closer to the trait locus than the marker locus with maximum value of the NPL statistic. Copyright 2001 Wiley-Liss, Inc.

Privacy preserving interactive record linkage (PPIRL).

PubMed

Kum, Hye-Chung; Krishnamurthy, Ashok; Machanavajjhala, Ashwin; Reiter, Michael K; Ahalt, Stanley

2014-01-01

Record linkage to integrate uncoordinated databases is critical in biomedical research using Big Data. Balancing privacy protection against the need for high quality record linkage requires a human-machine hybrid system to safely manage uncertainty in the ever changing streams of chaotic Big Data. In the computer science literature, private record linkage is the most published area. It investigates how to apply a known linkage function safely when linking two tables. However, in practice, the linkage function is rarely known. Thus, there are many data linkage centers whose main role is to be the trusted third party to determine the linkage function manually and link data for research via a master population list for a designated region. Recently, a more flexible computerized third-party linkage platform, Secure Decoupled Linkage (SDLink), has been proposed based on: (1) decoupling data via encryption, (2) obfuscation via chaffing (adding fake data) and universe manipulation; and (3) minimum information disclosure via recoding. We synthesize this literature to formalize a new framework for privacy preserving interactive record linkage (PPIRL) with tractable privacy and utility properties and then analyze the literature using this framework. Human-based third-party linkage centers for privacy preserving record linkage are the accepted norm internationally. We find that a computer-based third-party platform that can precisely control the information disclosed at the micro level and allow frequent human interaction during the linkage process, is an effective human-machine hybrid system that significantly improves on the linkage center model both in terms of privacy and utility.

Linkages between Vocational Education and Training Providers and Industry.

ERIC Educational Resources Information Center

Choi, Jihee; Misko, Josie; Kang, Kyeong-Jong; Phan, Oanh

A study described the general and vocational education and training (VET) systems in Korea and Australia, focusing on the role of training providers and industry in the delivery of entry-level vocational education and training in both countries. The study also analyzed the nature of the linkages established between VET institutions in the two…

Education-Work Linkage and Policy: A Cross-National Analysis of Contextual Influences on School to Work Transition.

ERIC Educational Resources Information Center

Wiseman, Alexander W.; Alromi, Naif

A cross-national analysis was conducted to identify contextual influences that shape policies regarding the school-to-work transition and education-work linkages. The study's theoretical framework included principles based on technical-rational perspectives and neo-institutional perspectives. The study tested the following hypotheses: (1) schools…

Genomewide Scan in Families with Schizophrenia from the Founder Population of Afrikaners Reveals Evidence for Linkage and Uniparental Disomy on Chromosome 1

PubMed Central

Abecasis, Gonçalo R.; Burt, Rachel A.; Hall, Diana; Bochum, Sylvia; Doheny, Kimberly F.; Lundy, S. Laura; Torrington, Marie; Roos, J. Louw; Gogos, Joseph A.; Karayiorgou, Maria

2004-01-01

We report on our initial genetic linkage studies of schizophrenia in the genetically isolated population of the Afrikaners from South Africa. A 10-cM genomewide scan was performed on 143 small families, 34 of which were informative for linkage. Using both nonparametric and parametric linkage analyses, we obtained evidence for a small number of disease loci on chromosomes 1, 9, and 13. These results suggest that few genes of substantial effect exist for schizophrenia in the Afrikaner population, consistent with our previous genealogical tracing studies. The locus on chromosome 1 reached genomewide significance levels (nonparametric LOD score of 3.30 at marker D1S1612, corresponding to an empirical P value of .012) and represents a novel susceptibility locus for schizophrenia. In addition to providing evidence for linkage for chromosome 1, we also identified a proband with a uniparental disomy (UPD) of the entire chromosome 1. This is the first time a UPD has been described in a patient with schizophrenia, lending further support to involvement of chromosome 1 in schizophrenia susceptibility in the Afrikaners. PMID:14750073

Construction of an ultrahigh-density genetic linkage map for Jatropha curcas L. and identification of QTL for fruit yield.

PubMed

Xia, Zhiqiang; Zhang, Shengkui; Wen, Mingfu; Lu, Cheng; Sun, Yufang; Zou, Meiling; Wang, Wenquan

2018-01-01

As an important biofuel plant, the demand for higher yield Jatropha curcas L. is rapidly increasing. However, genetic analysis of Jatropha and molecular breeding for higher yield have been hampered by the limited number of molecular markers available. An ultrahigh-density linkage map for a Jatropha mapping population of 153 individuals was constructed and covered 1380.58 cM of the Jatropha genome, with average marker density of 0.403 cM. The genetic linkage map consisted of 3422 SNP and indel markers, which clustered into 11 linkage groups. With this map, 13 repeatable QTLs (reQTLs) for fruit yield traits were identified. Ten reQTLs, qNF - 1 , qNF - 2a , qNF - 2b , qNF - 2c , qNF - 3 , qNF - 4 , qNF - 6 , qNF - 7a , qNF - 7b and qNF - 8, that control the number of fruits (NF) mapped to LGs 1, 2, 3, 4, 6, 7 and 8, whereas three reQTLs, qTWF - 1 , qTWF - 2 and qTWF - 3, that control the total weight of fruits (TWF) mapped to LGs 1, 2 and 3, respectively. It is interesting that there are two candidate critical genes, which may regulate Jatropha fruit yield. We also identified three pleiotropic reQTL pairs associated with both the NF and TWF traits. This study is the first to report an ultrahigh-density Jatropha genetic linkage map construction, and the markers used in this study showed great potential for QTL mapping. Thirteen fruit-yield reQTLs and two important candidate genes were identified based on this linkage map. This genetic linkage map will be a useful tool for the localization of other economically important QTLs and candidate genes for Jatropha .

Comparison of linkage analysis methods for genome-wide scanning of extended pedigrees, with application to the TG/HDL-C ratio in the Framingham Heart Study

PubMed Central

Horne, Benjamin D; Malhotra, Alka; Camp, Nicola J

2003-01-01

Background High triglycerides (TG) and low high-density lipoprotein cholesterol (HDL-C) jointly increase coronary disease risk. We performed linkage analysis for TG/HDL-C ratio in the Framingham Heart Study data as a quantitative trait, using methods implemented in LINKAGE, GENEHUNTER (GH), MCLINK, and SOLAR. Results were compared to each other and to those from a previous evaluation using SOLAR for TG/HDL-C ratio on this sample. We also investigated linked pedigrees in each region using by-pedigree analysis. Results Fourteen regions with at least suggestive linkage evidence were identified, including some that may increase and some that may decrease coronary risk. Ten of the 14 regions were identified by more than one analysis, and several of these regions were not previously detected. The best regions identified for each method were on chromosomes 2 (LOD = 2.29, MCLINK), 5 (LOD = 2.65, GH), 7 (LOD = 2.67, SOLAR), and 22 (LOD = 3.37, LINKAGE). By-pedigree multi-point LOD values in MCLINK showed linked pedigrees for all five regions, ranging from 3 linked pedigrees (chromosome 5) to 14 linked pedigrees (chromosome 7), and suggested localizations of between 9 cM and 27 cM in size. Conclusion Reasonable concordance was found across analysis methods. No single method identified all regions, either by full sample LOD or with by-pedigree analysis. Concordance across methods appeared better at the pedigree level, with many regions showing by-pedigree support in MCLINK when no evidence was observed in the full sample. Thus, investigating by-pedigree linkage evidence may provide a useful tool for evaluating linkage regions. PMID:14975161

Comparison of linkage analysis methods for genome-wide scanning of extended pedigrees, with application to the TG/HDL-C ratio in the Framingham Heart Study.

PubMed

Horne, Benjamin D; Malhotra, Alka; Camp, Nicola J

2003-12-31

High triglycerides (TG) and low high-density lipoprotein cholesterol (HDL-C) jointly increase coronary disease risk. We performed linkage analysis for TG/HDL-C ratio in the Framingham Heart Study data as a quantitative trait, using methods implemented in LINKAGE, GENEHUNTER (GH), MCLINK, and SOLAR. Results were compared to each other and to those from a previous evaluation using SOLAR for TG/HDL-C ratio on this sample. We also investigated linked pedigrees in each region using by-pedigree analysis. Fourteen regions with at least suggestive linkage evidence were identified, including some that may increase and some that may decrease coronary risk. Ten of the 14 regions were identified by more than one analysis, and several of these regions were not previously detected. The best regions identified for each method were on chromosomes 2 (LOD = 2.29, MCLINK), 5 (LOD = 2.65, GH), 7 (LOD = 2.67, SOLAR), and 22 (LOD = 3.37, LINKAGE). By-pedigree multi-point LOD values in MCLINK showed linked pedigrees for all five regions, ranging from 3 linked pedigrees (chromosome 5) to 14 linked pedigrees (chromosome 7), and suggested localizations of between 9 cM and 27 cM in size. Reasonable concordance was found across analysis methods. No single method identified all regions, either by full sample LOD or with by-pedigree analysis. Concordance across methods appeared better at the pedigree level, with many regions showing by-pedigree support in MCLINK when no evidence was observed in the full sample. Thus, investigating by-pedigree linkage evidence may provide a useful tool for evaluating linkage regions.

Motor sequencing deficit as an endophenotype of speech sound disorder: a genome-wide linkage analysis in a multigenerational family.

PubMed

Peter, Beate; Matsushita, Mark; Raskind, Wendy H

2012-10-01

The aim of this pilot study was to investigate a measure of motor sequencing deficit as a potential endophenotype of speech sound disorder (SSD) in a multigenerational family with evidence of familial SSD. In a multigenerational family with evidence of a familial motor-based SSD, affectation status and a measure of motor sequencing during oral motor testing were obtained. To further investigate the role of motor sequencing as an endophenotype for genetic studies, parametric and nonparametric linkage analyses were carried out using a genome-wide panel of 404 microsatellites. In seven of the 10 family members with available data, SSD affectation status and motor sequencing status coincided. Linkage analysis revealed four regions of interest, 6p21, 7q32, 7q36, and 8q24, primarily identified with the measure of motor sequencing ability. The 6p21 region overlaps with a locus implicated in rapid alternating naming in a recent genome-wide dyslexia linkage study. The 7q32 locus contains a locus implicated in dyslexia. The 7q36 locus borders on a gene known to affect the component traits of language impairment. The results are consistent with a motor-based endophenotype of SSD that would be informative for genetic studies. The linkage results in this first genome-wide study in a multigenerational family with SSD warrant follow-up in additional families and with fine mapping or next-generation approaches to gene identification.

Motor sequencing deficit as an endophenotype of speech sound disorder: A genome-wide linkage analysis in a multigenerational family

PubMed Central

Peter, Beate; Matsushita, Mark; Raskind, Wendy H.

2012-01-01

Objectives The purpose of this pilot study was to investigate a measure of motor sequencing deficit as a potential endophenotype of speech sound disorder (SSD) in a multigenerational family with evidence of familial SSD. Methods In a multigenerational family with evidence of a familial motor-based SSD, affectation status and a measure of motor sequencing during oral motor testing were obtained. To further investigate the role of motor sequencing as an endophenotype for genetic studies, parametric and nonparametric linkage analyses were conducted using a genome-wide panel of 404 microsatellites. Results In seven of the ten family members with available data, SSD affectation status and motor sequencing status coincided. Linkage analysis revealed four regions of interest, 6p21, 7q32, 7q36, and 8q24, primarily identified with the measure of motor sequencing ability. The 6p21 region overlaps with a locus implicated in rapid alternating naming in a recent genome-wide dyslexia linkage study. The 7q32 locus contains a locus implicated in dyslexia. The 7q36 locus borders on a gene known to affect component traits of language impairment. Conclusions Results are consistent with a motor-based endophenotype of SSD that would be informative for genetic studies. The linkage results in this first genome-wide study in a multigenerational family with SSD warrant follow-up in additional families and with fine mapping or next-generation approaches to gene identification. PMID:22517379

Linking HIV-Negative Youth to Prevention Services in 12 U.S. Cities: Barriers and Facilitators to Implementing the HIV Prevention Continuum.

PubMed

Doll, Mimi; Fortenberry, J Dennis; Roseland, Denise; McAuliff, Kathleen; Wilson, Craig M; Boyer, Cherrie B

2018-04-01

Linkage of HIV-negative youth to prevention services is increasingly important with the development of effective pre-exposure prophylaxis that complements behavioral and other prevention-focused interventions. However, effective infrastructure for delivery of prevention services does not exist, leaving many programs to address HIV prevention without data to guide program development/implementation. The objective of this study was to provide a qualitative description of barriers and facilitators of linkage to prevention services among high-risk, HIV-negative youth. Thematic analysis of structured interviews with staff implementing linkage to prevention services programs for youth aged 12-24 years. Twelve adolescent medicine HIV primary care programs as part of larger testing research program focused on young sexual minority men of color. The study included staff implementing linkage to prevention services programs along with community-based HIV testing programs. The main outcomes of the study were key barriers/facilitators to linkage to prevention services. Eight themes summarized perspectives on linkage to prevention services: (1) relationships with community partners, (2) trust between providers and youth, (3) youth capacity to navigate prevention services, (4) pre-exposure prophylaxis specific issues, (5) privacy issues, (6) gaps in health records preventing tailored services, (7) confidentiality of care for youth accessing services through parents'/caretakers' insurance, and (8) need for health-care institutions to keep pace with models that prioritize HIV prevention among at-risk youth. Themes are discussed in the context of factors that facilitated/challenged linkage to prevention services. Several evidence-based HIV prevention tools are available; infrastructures for coordinated service delivery to high-risk youth have not been developed. Implementation of such infrastructures requires attention to community-, provider-, and youth-related issues. Copyright © 2017 The Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

HIV-1 transmission linkage in an HIV-1 prevention clinical trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Leitner, Thomas; Campbell, Mary S; Mullins, James I

2009-01-01

HIV-1 sequencing has been used extensively in epidemiologic and forensic studies to investigate patterns of HIV-1 transmission. However, the criteria for establishing genetic linkage between HIV-1 strains in HIV-1 prevention trials have not been formalized. The Partners in Prevention HSV/HIV Transmission Study (ClinicaITrials.gov NCT00194519) enrolled 3408 HIV-1 serodiscordant heterosexual African couples to determine the efficacy of genital herpes suppression with acyclovir in reducing HIV-1 transmission. The trial analysis required laboratory confirmation of HIV-1 linkage between enrolled partners in couples in which seroconversion occurred. Here we describe the process and results from HIV-1 sequencing studies used to perform transmission linkage determinationmore » in this clinical trial. Consensus Sanger sequencing of env (C2-V3-C3) and gag (p17-p24) genes was performed on plasma HIV-1 RNA from both partners within 3 months of seroconversion; env single molecule or pyrosequencing was also performed in some cases. For linkage, we required monophyletic clustering between HIV-1 sequences in the transmitting and seroconverting partners, and developed a Bayesian algorithm using genetic distances to evaluate the posterior probability of linkage of participants sequences. Adjudicators classified transmissions as linked, unlinked, or indeterminate. Among 151 seroconversion events, we found 108 (71.5%) linked, 40 (26.5%) unlinked, and 3 (2.0%) to have indeterminate transmissions. Nine (8.3%) were linked by consensus gag sequencing only and 8 (7.4%) required deep sequencing of env. In this first use of HIV-1 sequencing to establish endpoints in a large clinical trial, more than one-fourth of transmissions were unlinked to the enrolled partner, illustrating the relevance of these methods in the design of future HIV-1 prevention trials in serodiscordant couples. A hierarchy of sequencing techniques, analysis methods, and expert adjudication contributed to the linkage determination process.« less

Genome Scan Meta-Analysis of Schizophrenia and Bipolar Disorder, Part II: Schizophrenia

PubMed Central

Lewis, Cathryn M.; Levinson, Douglas F.; Wise, Lesley H.; DeLisi, Lynn E.; Straub, Richard E.; Hovatta, Iiris; Williams, Nigel M.; Schwab, Sibylle G.; Pulver, Ann E.; Faraone, Stephen V.; Brzustowicz, Linda M.; Kaufmann, Charles A.; Garver, David L.; Gurling, Hugh M. D.; Lindholm, Eva; Coon, Hilary; Moises, Hans W.; Byerley, William; Shaw, Sarah H.; Mesen, Andrea; Sherrington, Robin; O’Neill, F. Anthony; Walsh, Dermot; Kendler, Kenneth S.; Ekelund, Jesper; Paunio, Tiina; Lönnqvist, Jouko; Peltonen, Leena; O’Donovan, Michael C.; Owen, Michael J.; Wildenauer, Dieter B.; Maier, Wolfgang; Nestadt, Gerald; Blouin, Jean-Louis; Antonarakis, Stylianos E.; Mowry, Bryan J.; Silverman, Jeremy M.; Crowe, Raymond R.; Cloninger, C. Robert; Tsuang, Ming T.; Malaspina, Dolores; Harkavy-Friedman, Jill M.; Svrakic, Dragan M.; Bassett, Anne S.; Holcomb, Jennifer; Kalsi, Gursharan; McQuillin, Andrew; Brynjolfson, Jon; Sigmundsson, Thordur; Petursson, Hannes; Jazin, Elena; Zoëga, Tomas; Helgason, Tomas

2003-01-01

Schizophrenia is a common disorder with high heritability and a 10-fold increase in risk to siblings of probands. Replication has been inconsistent for reports of significant genetic linkage. To assess evidence for linkage across studies, rank-based genome scan meta-analysis (GSMA) was applied to data from 20 schizophrenia genome scans. Each marker for each scan was assigned to 1 of 120 30-cM bins, with the bins ranked by linkage scores (1 = most significant) and the ranks averaged across studies (Ravg) and then weighted for sample size (\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} \\begin{equation*}\\sqrt{N[affected cases]}\\end{equation*}\\end{document}). A permutation test was used to compute the probability of observing, by chance, each bin’s average rank (PAvgRnk) or of observing it for a bin with the same place (first, second, etc.) in the order of average ranks in each permutation (Pord). The GSMA produced significant genomewide evidence for linkage on chromosome 2q (PAvgRnk<.000417). Two aggregate criteria for linkage were also met (clusters of nominally significant P values that did not occur in 1,000 replicates of the entire data set with no linkage present): 12 consecutive bins with both PAvgRnk and Pord<.05, including regions of chromosomes 5q, 3p, 11q, 6p, 1q, 22q, 8p, 20q, and 14p, and 19 consecutive bins with Pord<.05, additionally including regions of chromosomes 16q, 18q, 10p, 15q, 6q, and 17q. There is greater consistency of linkage results across studies than has been previously recognized. The results suggest that some or all of these regions contain loci that increase susceptibility to schizophrenia in diverse populations. PMID:12802786

Evaluating Health Outcomes of Criminal Justice Populations Using Record Linkage: The Importance of Aliases

ERIC Educational Resources Information Center

Larney, Sarah; Burns, Lucy

2011-01-01

Individuals in contact with the criminal justice system are a key population of concern to public health. Record linkage studies can be useful for studying health outcomes for this group, but the use of aliases complicates the process of linking records across databases. This study was undertaken to determine the impact of aliases on sensitivity…

Dynamic analysis of six-bar mechanical press for deep drawing

NASA Astrophysics Data System (ADS)

Mitsi, S.; Tsiafis, I.; Bouzakis, K. D.

2017-02-01

This paper analyzes the dynamical behavior of a six-bar linkage used in mechanical presses for metal forming such as deep drawing. In the under study mechanism, a four-bar linkage is connected to a slider through an articulated binary link. The motion of the six-bar linkage is studied by kinematic analysis developing an analytical method. Furthermore, using an iterative method and d’ Alembert’s principle, the joint forces and drive moment are evaluated considering joint frictions. The simulation results obtained with a MATLAB program are validated by comparing the theoretical values of the input moment with the ones obtained from the conservation of energy law.

Modifier gene study of meconium ileus in cystic fibrosis: statistical considerations and gene mapping results

PubMed Central

Dorfman, Ruslan; Li, Weili; Sun, Lei; Lin, Fan; Wang, Yongqian; Sandford, Andrew; Paré, Peter D.; McKay, Karen; Kayserova, Hana; Piskackova, Tereza; Macek, Milan; Czerska, Kamila; Sands, Dorota; Tiddens, Harm; Margarit, Sonia; Repetto, Gabriela; Sontag, Marci K.; Accurso, Frank J.; Blackman, Scott; Cutting, Garry R.; Tsui, Lap-Chee; Corey, Mary; Durie, Peter; Zielenski, Julian; Strug, Lisa J.

2010-01-01

Cystic fibrosis (CF) is a monogenic disease due to mutations in the CFTR gene. Yet, variability in CF disease presentation is presumed to be affected by modifier genes, such as those recently demonstrated for the pulmonary aspect. Here, we conduct a modifier gene study for meconium ileus (MI), an intestinal obstruction that occurs in 16–20% of CF newborns, providing linkage and association results from large family and case–control samples. Linkage analysis of modifier traits is different than linkage analysis of primary traits on which a sample was ascertained. Here, we articulate a source of confounding unique to modifier gene studies and provide an example of how one might overcome the confounding in the context of linkage studies. Our linkage analysis provided evidence of a MI locus on chromosome 12p13.3, which was segregating in up to 80% of MI families with at least one affected offspring (HLOD = 2.9). Fine mapping of the 12p13.3 region in a large case–control sample of pancreatic insufficient Canadian CF patients with and without MI pointed to the involvement of ADIPOR2 in MI (p = 0.002). This marker was substantially out of Hardy–Weinberg equilibrium in the cases only, and provided evidence of a cohort effect. The association with rs9300298 in the ADIPOR2 gene at the 12p13.3 locus was replicated in an independent sample of CF families. A protective locus, using the phenotype of no-MI, mapped to 4q13.3 (HLOD = 3.19), with substantial heterogeneity. A candidate gene in the region, SLC4A4, provided preliminary evidence of association (p = 0.002), warranting further follow-up studies. Our linkage approach was used to direct our fine-mapping studies, which uncovered two potential modifier genes worthy of follow-up. PMID:19662435

A Targeted Capture Linkage Map Anchors the Genome of the Schistosomiasis Vector Snail, Biomphalaria glabrata.

PubMed

Tennessen, Jacob A; Bollmann, Stephanie R; Blouin, Michael S

2017-07-05

The aquatic planorbid snail Biomphalaria glabrata is one of the most intensively-studied mollusks due to its role in the transmission of schistosomiasis. Its 916 Mb genome has recently been sequenced and annotated, but it remains poorly assembled. Here, we used targeted capture markers to map over 10,000 B. glabrata scaffolds in a linkage cross of 94 F1 offspring, generating 24 linkage groups (LGs). We added additional scaffolds to these LGs based on linkage disequilibrium (LD) analysis of targeted capture and whole-genome sequences of 96 unrelated snails. Our final linkage map consists of 18,613 scaffolds comprising 515 Mb, representing 56% of the genome and 75% of genic and nonrepetitive regions. There are 18 large (> 10 Mb) LGs, likely representing the expected 18 haploid chromosomes, and > 50% of the genome has been assigned to LGs of at least 17 Mb. Comparisons with other gastropod genomes reveal patterns of synteny and chromosomal rearrangements. Linkage relationships of key immune-relevant genes may help clarify snail-schistosome interactions. By focusing on linkage among genic and nonrepetitive regions, we have generated a useful resource for associating snail phenotypes with causal genes, even in the absence of a complete genome assembly. A similar approach could potentially improve numerous poorly-assembled genomes in other taxa. This map will facilitate future work on this host of a serious human parasite. Copyright © 2017 Tennessen et al.

Linkage of A-to-I RNA Editing in Metazoans and the Impact on Genome Evolution.

PubMed

Duan, Yuange; Dou, Shengqian; Zhang, Hong; Wu, Changcheng; Wu, Mingming; Lu, Jian

2018-01-01

The adenosine-to-inosine (A-to-I) RNA editomes have been systematically characterized in various metazoan species, and many editing sites were found in clusters. However, it remains unclear whether the clustered editing sites tend to be linked in the same RNA molecules or not. By adopting a method originally designed to detect linkage disequilibrium of DNA mutations, we examined the editomes of ten metazoan species and detected extensive linkage of editing in Drosophila and cephalopods. The prevalent linkages of editing in these two clades, many of which are conserved between closely related species and might be associated with the adaptive proteomic recoding, are maintained by natural selection at the cost of genome evolution. Nevertheless, in worms and humans, we only detected modest proportions of linked editing events, the majority of which were not conserved. Furthermore, the linkage of editing in coding regions of worms and humans might be overall deleterious, which drives the evolution of DNA sites to escape promiscuous editing. Altogether, our results suggest that the linkage landscape of A-to-I editing has evolved during metazoan evolution. This present study also suggests that linkage of editing should be considered in elucidating the functional consequences of RNA editing. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

SNP Discovery and Linkage Map Construction in Cultivated Tomato

PubMed Central

Shirasawa, Kenta; Isobe, Sachiko; Hirakawa, Hideki; Asamizu, Erika; Fukuoka, Hiroyuki; Just, Daniel; Rothan, Christophe; Sasamoto, Shigemi; Fujishiro, Tsunakazu; Kishida, Yoshie; Kohara, Mitsuyo; Tsuruoka, Hisano; Wada, Tsuyuko; Nakamura, Yasukazu; Sato, Shusei; Tabata, Satoshi

2010-01-01

Few intraspecific genetic linkage maps have been reported for cultivated tomato, mainly because genetic diversity within Solanum lycopersicum is much less than that between tomato species. Single nucleotide polymorphisms (SNPs), the most abundant source of genomic variation, are the most promising source of polymorphisms for the construction of linkage maps for closely related intraspecific lines. In this study, we developed SNP markers based on expressed sequence tags for the construction of intraspecific linkage maps in tomato. Out of the 5607 SNP positions detected through in silico analysis, 1536 were selected for high-throughput genotyping of two mapping populations derived from crosses between ‘Micro-Tom’ and either ‘Ailsa Craig’ or ‘M82’. A total of 1137 markers, including 793 out of the 1338 successfully genotyped SNPs, along with 344 simple sequence repeat and intronic polymorphism markers, were mapped onto two linkage maps, which covered 1467.8 and 1422.7 cM, respectively. The SNP markers developed were then screened against cultivated tomato lines in order to estimate the transferability of these SNPs to other breeding materials. The molecular markers and linkage maps represent a milestone in the genomics and genetics, and are the first step toward molecular breeding of cultivated tomato. Information on the DNA markers, linkage maps, and SNP genotypes for these tomato lines is available at http://www.kazusa.or.jp/tomato/. PMID:21044984

High-Density Genetic Linkage Map Construction and Quantitative Trait Locus Mapping for Hawthorn (Crataegus pinnatifida Bunge).

PubMed

Zhao, Yuhui; Su, Kai; Wang, Gang; Zhang, Liping; Zhang, Jijun; Li, Junpeng; Guo, Yinshan

2017-07-14

Genetic linkage maps are an important tool in genetic and genomic research. In this study, two hawthorn cultivars, Qiujinxing and Damianqiu, and 107 progenies from a cross between them were used for constructing a high-density genetic linkage map using the 2b-restriction site-associated DNA (2b-RAD) sequencing method, as well as for mapping quantitative trait loci (QTL) for flavonoid content. In total, 206,411,693 single-end reads were obtained, with an average sequencing depth of 57× in the parents and 23× in the progeny. After quality trimming, 117,896 high-quality 2b-RAD tags were retained, of which 42,279 were polymorphic; of these, 12,951 markers were used for constructing the genetic linkage map. The map contained 17 linkage groups and 3,894 markers, with a total map length of 1,551.97 cM and an average marker interval of 0.40 cM. QTL mapping identified 21 QTLs associated with flavonoid content in 10 linkage groups, which explained 16.30-59.00% of the variance. This is the first high-density linkage map for hawthorn, which will serve as a basis for fine-scale QTL mapping and marker-assisted selection of important traits in hawthorn germplasm and will facilitate chromosome assignment for hawthorn whole-genome assemblies in the future.

Genetic linkage map of the interspecific grape rootstock cross Ramsey (Vitis champinii) x Riparia Gloire (Vitis riparia).

PubMed

Lowe, K M; Walker, M A

2006-05-01

The first genetic linkage map of grape derived from rootstock parents was constructed using 188 progeny from a cross of Ramsey (Vitis champinii) x Riparia Gloire (V. riparia). Of 354 simple sequence repeat markers tested, 205 were polymorphic for at least one parent, and 57.6% were fully informative. Maps of Ramsey, Riparia Gloire, and the F1 population were created using JoinMap software, following a pseudotestcross strategy. The set of 205 SSRs allowed for the identification of all 19 Vitis linkage groups (2n=38), with a total combined map length of 1,304.7 cM, averaging 6.8 cM between markers. The maternal map consists of 172 markers aligned into 19 linkage groups (1,244.9 cM) while 126 markers on the paternal map cover 18 linkage groups (1,095.5 cM). The expected genome coverage is over 92%. Segregation distortion occurred in the Ramsey, Riparia Gloire, and consensus maps for 10, 13, and 16% of the markers, respectively. These distorted markers clustered primarily on the linkage groups 3, 5, 14 and 17. No genome-wide difference in recombination rate was observed between Ramsey and Riparia Gloire based on 315 common marker intervals. Fifty-four new Vitis-EST-derived SSR markers were mapped, and were distributed evenly across the genome on 16 of the 19 linkage groups. These dense linkage maps of two phenotypically diverse North American Vitis species are valuable tools for studying the genetics of many rootstock traits including nematode resistance, lime and salt tolerance, and ability to induce vigor.

Salmonid Chromosome Evolution as Revealed by a Novel Method for Comparing RADseq Linkage Maps

PubMed Central

Gosselin, Thierry; Normandeau, Eric; Lamothe, Manuel; Isabel, Nathalie; Audet, Céline; Bernatchez, Louis

2016-01-01

Whole genome duplication (WGD) can provide material for evolutionary innovation. Family Salmonidae is ideal for studying the effects of WGD as the ancestral salmonid underwent WGD relatively recently, ∼65 Ma, then rediploidized and diversified. Extensive synteny between homologous chromosome arms occurs in extant salmonids, but each species has both conserved and unique chromosome arm fusions and fissions. Assembly of large, outbred eukaryotic genomes can be difficult, but structural rearrangements within such taxa can be investigated using linkage maps. RAD sequencing provides unprecedented ability to generate high-density linkage maps for nonmodel species, but can result in low numbers of homologous markers between species due to phylogenetic distance or differences in library preparation. Here, we generate a high-density linkage map (3,826 markers) for the Salvelinus genera (Brook Charr S. fontinalis), and then identify corresponding chromosome arms among the other available salmonid high-density linkage maps, including six species of Oncorhynchus, and one species for each of Salmo, Coregonus, and the nonduplicated sister group for the salmonids, Northern Pike Esox lucius for identifying post-duplicated homeologs. To facilitate this process, we developed MapComp to identify identical and proximate (i.e. nearby) markers between linkage maps using a reference genome of a related species as an intermediate, increasing the number of comparable markers between linkage maps by 5-fold. This enabled a characterization of the most likely history of retained chromosomal rearrangements post-WGD, and several conserved chromosomal inversions. Analyses of RADseq-based linkage maps from other taxa will also benefit from MapComp, available at: https://github.com/enormandeau/mapcomp/ PMID:28173098

A Linkage Map of the Asian Tiger Mosquito (Aedes albopictus) Based on cDNA Markers

PubMed Central

Sutherland, Ian W.; Mori, Akio; Montgomery, John; Fleming, Karen L.; Anderson, Jennifer M.; Valenzuela, Jesus G.; Severson, David W.

2011-01-01

The Asian tiger mosquito, Aedes (Stegomyia) albopictus (Skuse), is an important vector of a number of arboviruses, and populations exhibit extreme variation in adaptive traits such as egg diapause, cold hardiness, and autogeny (ability to mature a batch of eggs without blood feeding). The genetic basis of some of these traits has been established, but lack of a high-resolution linkage map has prevented in-depth genetic analyses of the genes underlying these complex traits. We report here on the breeding of 4 F1 intercross mapping families and the use of these to locate 35 cDNA markers to the A. albopictus linkage map. The present study increases the number of markers on the A. albopictus cDNA linkage map from 38 to 73 and the density of markers from 1 marker/5.7 cM to 1 marker/2.9 cM and adds 9, 16, and 10 markers to the 3 linkage groups, respectively. The overall lengths of the 3 linkage groups are 64.5, 76.5, and 71.6 cM, respectively, for a combined length of 212.6 cM. Despite conservation in the order of most genes among the 4 families and a previous mapping family, we found substantial heterogeneity in the amount of recombination among markers. This was most marked in linkage group I, which varied between 16.7 and 69.3 cM. A map integrating the results from these 4 families with an earlier cDNA linkage map is presented. PMID:21148282

Serum uric acid and the risk of mortality during 23 years follow-up in the Scottish Heart Health Extended Cohort Study.

PubMed

Juraschek, Stephen P; Tunstall-Pedoe, Hugh; Woodward, Mark

2014-04-01

Elevated uric acid is a prevalent condition with controversial health consequences. Observational studies disagree with regard to the relationship of uric acid with mortality, and with factors modifying this relationship. We examined the association of serum uric acid with mortality in 15,083 participants in the Scottish Heart Health Extended Cohort (SHHEC) Study. Serum uric acid was measured at study enrollment. Death was ascertained using both the Scottish death register and record linkage. During a median follow-up of 23 years, there were 3980 deaths. In Cox proportional hazards models with sexes combined, those in the highest fifth of uric acid had significantly greater mortality (HR 1.18, 95% CI: 1.06, 1.31) compared with the second fifth, after adjustment for traditional cardiovascular risk factors. This relationship was modified by sex (P-interaction=0.002) with adjusted HRs of 1.69 (95% CI: 1.40, 2.04) and 0.99 (95% CI: 0.86, 1.14) in women and men, respectively. Compared with the second fifth, the highest fifth of uric acid was most associated with kidney-related death (HR: 2.08, 95% CI: 1.31, 3.32). Elevated uric acid is associated with earlier mortality, especially in women. Future studies should evaluate mechanisms for these interactions and explore the strong association with renal-related mortality. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Serum Uric Acid and the Risk of Mortality During 23 Years Follow-up in the Scottish Heart Health Extended Cohort Study

PubMed Central

Juraschek, Stephen P.; Tunstall-Pedoe, Hugh; Woodward, Mark

2017-01-01

Background Elevated uric acid is a prevalent condition with controversial health consequences. Observational studies disagree with regard to the relationship of uric acid with mortality, and with factors modifying this relationship. Objective We examined the association of serum uric acid with mortality in 15,083 participants in the Scottish Heart Health Extended Cohort (SHHEC) Study. Methods Serum uric acid measured at study enrollment. Death was ascertained using both the Scottish death register and record linkage. Results During a median follow-up of 23 years, there were 3,980 deaths. In Cox proportional hazards models with sexes combined, those in the highest fifth of uric acid had significantly greater mortality (HR 1.18, 95% CI: 1.06, 1.31) compared with the second fifth, after adjustment for traditional cardiovascular risk factors. This relationship was modified by sex (P-interaction = 0.002) with adjusted HRs of 1.69 (95% CI: 1.40, 2.04) and 0.99 (95% CI: 0.86, 1.14) in women and men, respectively. Compared with the second fifth, the highest fifth of uric acid was most associated with kidney-related death (HR: 2.08, 95% CI: 1.31, 3.32). Conclusion Elevated uric acid is associated with earlier mortality, especially in women. Future studies should evaluate mechanisms for these interactions and explore the strong association with renal-related mortality. PMID:24534458

Association of higher parental and grandparental education and higher school grades with risk of hospitalization for eating disorders in females: the Uppsala birth cohort multigenerational study.

PubMed

Ahrén-Moonga, Jennie; Silverwood, Richard; Klinteberg, Britt Af; Koupil, Ilona

2009-09-01

Eating disorders are a leading cause of disease burden among young women. This study investigated associations of social characteristics of parents and grandparents, sibling position, and school performance with incidence of eating disorders. The authors studied Swedish females born in 1952-1989 (n = 13,376), third-generation descendants of a cohort born in Uppsala in 1915-1929. Data on grandparental and parental social characteristics, sibling position, school grades, hospitalizations, emigrations, and deaths were obtained by register linkages. Associations with incidence of hospitalization for eating disorders were studied with multivariable Cox regression, adjusted for age and study period. Overall incidence of hospitalization for eating disorders was 32.0/100,000 person-years. Women with more highly educated parents and maternal grandparents were at higher risk (hazard ratio for maternal grandmother with higher education relative to elementary education = 6.5, 95% confidence interval: 2.2, 19.3, adjusted for parental education). Independent of family social characteristics, women with the highest school grades had a higher risk of eating disorders (hazard ratio = 7.7, 95% confidence interval: 2.5, 24.1 for high compared with low grades in Swedish, adjusted for parental education). Thus, higher parental and grandparental education and higher school grades may increase risk of hospitalization for eating disorders in female offspring, possibly because of high internal and external demands.

Establishing a process for conducting cross-jurisdictional record linkage in Australia.

PubMed

Moore, Hannah C; Guiver, Tenniel; Woollacott, Anthony; de Klerk, Nicholas; Gidding, Heather F

2016-04-01

To describe the realities of conducting a cross-jurisdictional data linkage project involving state and Australian Government-based data collections to inform future national data linkage programs of work. We outline the processes involved in conducting a Proof of Concept data linkage project including the implementation of national data integration principles, data custodian and ethical approval requirements, and establishment of data flows. The approval process involved nine approval and regulatory bodies and took more than two years. Data will be linked across 12 datasets involving three data linkage centres. A framework was established to allow data to flow between these centres while maintaining the separation principle that serves to protect the privacy of the individual. This will be the first project to link child immunisation records from an Australian Government dataset to other administrative health datasets for a population cohort covering 2 million births in two Australian states. Although the project experienced some delays, positive outcomes were realised, primarily the development of strong collaborations across key stakeholder groups including community engagement. We have identified several recommendations and enhancements to this now established framework to further streamline the process for data linkage studies involving Australian Government data. © 2015 Public Health Association of Australia.

Privacy preserving interactive record linkage (PPIRL)

PubMed Central

Kum, Hye-Chung; Krishnamurthy, Ashok; Machanavajjhala, Ashwin; Reiter, Michael K; Ahalt, Stanley

2014-01-01

Objective Record linkage to integrate uncoordinated databases is critical in biomedical research using Big Data. Balancing privacy protection against the need for high quality record linkage requires a human–machine hybrid system to safely manage uncertainty in the ever changing streams of chaotic Big Data. Methods In the computer science literature, private record linkage is the most published area. It investigates how to apply a known linkage function safely when linking two tables. However, in practice, the linkage function is rarely known. Thus, there are many data linkage centers whose main role is to be the trusted third party to determine the linkage function manually and link data for research via a master population list for a designated region. Recently, a more flexible computerized third-party linkage platform, Secure Decoupled Linkage (SDLink), has been proposed based on: (1) decoupling data via encryption, (2) obfuscation via chaffing (adding fake data) and universe manipulation; and (3) minimum information disclosure via recoding. Results We synthesize this literature to formalize a new framework for privacy preserving interactive record linkage (PPIRL) with tractable privacy and utility properties and then analyze the literature using this framework. Conclusions Human-based third-party linkage centers for privacy preserving record linkage are the accepted norm internationally. We find that a computer-based third-party platform that can precisely control the information disclosed at the micro level and allow frequent human interaction during the linkage process, is an effective human–machine hybrid system that significantly improves on the linkage center model both in terms of privacy and utility. PMID:24201028

Key practices for implementing geospatial technologies for a planning and environment linkages (PEL) approach

DOT National Transportation Integrated Search

2008-07-01

This report presents three case studies that illustrate how geographic information systems (GIS) have been used to implement the Federal Highway Administrations (FHWA) Planning and Environment Linkages (PEL) approach. The PEL approach provides inf...

School environment and mental health in early adolescence - a longitudinal study in Sweden (KUPOL).

PubMed

Galanti, Maria Rosaria; Hultin, Hanna; Dalman, Christina; Engström, Karin; Ferrer-Wreder, Laura; Forsell, Yvonne; Karlberg, Martin; Lavebratt, Catharina; Magnusson, Cecilia; Sundell, Knut; Zhou, Jia; Almroth, Melody; Raffetti, Elena

2016-07-16

Longitudinal studies indicate strong associations between school proficiency and indicators of mental health throughout adulthood, but the mechanisms of such associations are not fully elucidated. The Kupol study is a prospective cohort study in Sweden set up in order to: (i) describe the association of school pedagogic and social environment and its specific dimensions with the risk of mental ill-health and psychiatric disorders in adolescence; (ii) evaluate the direct effects of school pedagogic and social environment on mental health and the effects mediated by the individual's academic achievements; and (iii) assess if school pedagogic and social environment are associated with mental ill-health through epigenetic mechanisms, in particular those involving genes regulating the response to stress. The Kupol cohort at baseline consists of 3959 children attending the 7th grade of compulsory school (13-14 years old) in 8 regions of central Sweden in the school years 2013-2014 or 2014-2015. Three follow-up surveys in subsequent years are planned. Teachers' and students' perceptions of the culture, climate and ethos of their schools, and students' mental ill-health are assessed at the whole school level by annual questionnaire surveys. In order to conduct epigenetic analyses saliva specimens are collected from a nested sample of students at inception and two years later. Further, class-, family- and child-level information is collected at baseline and during each year of follow-up. Self-reported information is being complemented with register data via record-linkages to national and regional health and administrative registers. The topic being investigated is new, and the sample constitutes the largest adolescent cohort in Sweden involved in an ad hoc study. Epigenetic analyses centered on environmental cues to stress response are a thoroughly new approach. Finally a notable feature is the multi-informant and multi-method data collection, with surveys at the school, class, family, and student level. Collaboration and data access: interested investigators should contact the coordinating centre. Additional information is available on the study's website, http://kupolstudien.se/ .

Linkage analysis in a Dutch family with X-linked recessive congenital stationary night blindness (XL-CSNB).

PubMed

Berger, W; van Duijnhoven, G; Pinckers, A; Smits, A; Ropers, H H; Cremers, F

1995-01-01

Linkage analysis has been performed in a large Dutch pedigree with X-linked recessive congenital stationary night blindness (CSNB) by utilizing 16 DNA markers from the proximal short arm of the human X chromosome (Xp21.1-11.2). Thirteen polymorphic markers are at least partially informative and have enabled pairwise and multipoint linkage analysis. For three loci, i.e. DXS228, the monoamine oxidase B gene and the Norrie disease gene (NDG), multipoint linkage studies have yielded maximum lod scores of > 3.0 at a recombination fraction of zero. Analysis of recombination events has enabled us to rule out the possibility that the underlying defect in this family is allelic to RP3; the gene defect could also be excluded from the proximal part of the region known to carry RP2. Linkage data are consistent with a possible involvement of the NDG but mutations in the open reading frame of this gene have not been found.

High-frequency stock linkage and multi-dimensional stationary processes

NASA Astrophysics Data System (ADS)

Wang, Xi; Bao, Si; Chen, Jingchao

2017-02-01

In recent years, China's stock market has experienced dramatic fluctuations; in particular, in the second half of 2014 and 2015, the market rose sharply and fell quickly. Many classical financial phenomena, such as stock plate linkage, appeared repeatedly during this period. In general, these phenomena have usually been studied using daily-level data or minute-level data. Our paper focuses on the linkage phenomenon in Chinese stock 5-second-level data during this extremely volatile period. The method used to select the linkage points and the arbitrage strategy are both based on multi-dimensional stationary processes. A new program method for testing the multi-dimensional stationary process is proposed in our paper, and the detailed program is presented in the paper's appendix. Because of the existence of the stationary process, the strategy's logarithmic cumulative average return will converge under the condition of the strong ergodic theorem, and this ensures the effectiveness of the stocks' linkage points and the more stable statistical arbitrage strategy.

Construction of integrated linkage map of a recombinant inbred line population of white lupin (Lupinus albus L.)

PubMed Central

Vipin, Cina Ann; Luckett, David J.; Harper, John D.I.; Ash, Gavin J.; Kilian, Andrzej; Ellwood, Simon R.; Phan, Huyen T.T.; Raman, Harsh

2013-01-01

We report the development of a Diversity Arrays Technology (DArT) marker panel and its utilisation in the development of an integrated genetic linkage map of white lupin (Lupinus albus L.) using an F8 recombinant inbred line population derived from Kiev Mutant/P27174. One hundred and thirty-six DArT markers were merged into the first genetic linkage map composed of 220 amplified fragment length polymorphisms (AFLPs) and 105 genic markers. The integrated map consists of 38 linkage groups of 441 markers and spans a total length of 2,169 cM, with an average interval size of 4.6 cM. The DArT markers exhibited good genome coverage and were associated with previously identified genic and AFLP markers linked with quantitative trait loci for anthracnose resistance, flowering time and alkaloid content. The improved genetic linkage map of white lupin will aid in the identification of markers for traits of interest and future syntenic studies. PMID:24273424

Linkages: Effective Keys to Success.

ERIC Educational Resources Information Center

Tindall, Lloyd W.

1986-01-01

Discusses various elements of linkages: informal agreements; formal written agreements; making agreements work; the non-financial agreement; how linkages work at the elementary, secondary, and postsecondary levels in Wisconsin; mandated linkages; and the importance of linkages in the vocational education and training arena. (CT)

Understanding high diastereomeric discrimination in formation of oligoribonucleotide phosphorothioate linkages: the first study of pKa-dependent activation in solid-supported coupling of 2'-O-substituted ribonucleoside phosphoramidites.

PubMed

Ravikumar, Vasulinga T; Cole, Douglas L

2003-01-01

Activation of 2'-O-substituted ribonucleoside phosphoramidites with various activators during solid-supported synthesis of phosphorothioate oligonucleotides was studied. The Rp:Sp diastereomeric composition of resulting phosphorothioate linkage dependent on pKa of activator utilized for coupling.

The Human Lexinome: Genes of Language and Reading

ERIC Educational Resources Information Center

Gibson, Christopher J.; Gruen, Jeffrey R.

2008-01-01

Within the human genome, genetic mapping studies have identified 10 regions of different chromosomes, known as DYX loci, in genetic linkage with dyslexia, and two, known as SLI loci, in genetic linkage with Specific Language Impairment (SLI). Further genetic studies have identified four dyslexia genes within the DYX loci: "DYX1C1" on 15q,…

Genomewide Linkage Disequilibrium Mapping of Severe Bipolar Disorder in a Population Isolate

PubMed Central

Ophoff, Roel A.; Escamilla, Michael A.; Service, Susan K.; Spesny, Mitzi; Meshi, Dar B.; Poon, Wingman; Molina, Julio; Fournier, Eduardo; Gallegos, Alvaro; Mathews, Carol; Neylan, Thomas; Batki, Steven L.; Roche, Erin; Ramirez, Margarita; Silva, Sandra; De Mille, Melissa C.; Dong, Penny; Leon, Pedro E.; Reus, Victor I.; Sandkuijl, Lodewijk A.; Freimer, Nelson B.

2002-01-01

Genomewide association studies may offer the best promise for genetic mapping of complex traits. Such studies in outbred populations require very densely spaced single-nucleotide polymorphisms. In recently founded population isolates, however, extensive linkage disequilibrium (LD) may make these studies feasible with currently available sets of short tandem repeat markers, spaced at intervals as large as a few centimorgans. We report the results of a genomewide association study of severe bipolar disorder (BP-I), using patients from the isolated population of the central valley of Costa Rica. We observed LD with BP-I on several chromosomes; the most striking results were in proximal 8p, a region that has previously shown linkage to schizophrenia. This region could be important for severe psychiatric disorders, rather than for a specific phenotype. PMID:12119601

Hierarchic Agglomerative Clustering Methods for Automatic Document Classification.

ERIC Educational Resources Information Center

Griffiths, Alan; And Others

1984-01-01

Considers classifications produced by application of single linkage, complete linkage, group average, and word clustering methods to Keen and Cranfield document test collections, and studies structure of hierarchies produced, extent to which methods distort input similarity matrices during classification generation, and retrieval effectiveness…

Job task-competency linkages for FAA first-level supervisors.

DOT National Transportation Integrated Search

1991-04-01

A study was conducted to determine the linkages between the job tasks and competencies of first level supervisors in the FAA. A sample was drawn from each of nine job groups: Flight Service, Terminal, En Route, Regional Office/Headquarters Air Traffi...

X Linkage of AP3A, a Homolog of the Y-Linked MADS-Box Gene AP3Y in Silene latifolia and S. dioica

PubMed Central

Penny, Rebecca H.; Montgomery, Benjamin R.; Delph, Lynda F.

2011-01-01

Background The duplication of autosomal genes onto the Y chromosome may be an important element in the evolution of sexual dimorphism.A previous cytological study reported on a putative example of such a duplication event in a dioecious tribe of Silene (Caryophyllaceae): it was inferred that the Y-linked MADS-box gene AP3Y originated from a duplication of the reportedly autosomal orthologAP3A. However, a recent study, also using cytological methods, indicated that AP3A is X-linked in Silenelatifolia. Methodology/Principal Findings In this study, we hybridized S. latifolia and S. dioicato investigate whether the pattern of X linkage is consistent among distinct populations, occurs in both species, and is robust to genetic methods. We found inheritance patterns indicative of X linkage of AP3A in widely distributed populations of both species. Conclusions/Significance X linkage ofAP3A and Y linkage of AP3Yin both species indicates that the genes' ancestral progenitor resided on the autosomes that gave rise to the sex chromosomesand that neither gene has moved between chromosomes since species divergence.Consequently, our results do not support the contention that inter-chromosomal gene transfer occurred in the evolution of SlAP3Y from SlAP3A. PMID:21533056

Evidence for bivariate linkage of obesity and HDL-C levels in the Framingham Heart Study.

PubMed

Arya, Rector; Lehman, Donna; Hunt, Kelly J; Schneider, Jennifer; Almasy, Laura; Blangero, John; Stern, Michael P; Duggirala, Ravindranath

2003-12-31

Epidemiological studies have indicated that obesity and low high-density lipoprotein (HDL) levels are strong cardiovascular risk factors, and that these traits are inversely correlated. Despite the belief that these traits are correlated in part due to pleiotropy, knowledge on specific genes commonly affecting obesity and dyslipidemia is very limited. To address this issue, we first conducted univariate multipoint linkage analysis for body mass index (BMI) and HDL-C to identify loci influencing variation in these phenotypes using Framingham Heart Study data relating to 1702 subjects distributed across 330 pedigrees. Subsequently, we performed bivariate multipoint linkage analysis to detect common loci influencing covariation between these two traits. We scanned the genome and identified a major locus near marker D6S1009 influencing variation in BMI (LOD = 3.9) using the program SOLAR. We also identified a major locus for HDL-C near marker D2S1334 on chromosome 2 (LOD = 3.5) and another region near marker D6S1009 on chromosome 6 with suggestive evidence for linkage (LOD = 2.7). Since these two phenotypes have been independently mapped to the same region on chromosome 6q, we used the bivariate multipoint linkage approach using SOLAR. The bivariate linkage analysis of BMI and HDL-C implicated the genetic region near marker D6S1009 as harboring a major gene commonly influencing these phenotypes (bivariate LOD = 6.2; LODeq = 5.5) and appears to improve power to map the correlated traits to a region, precisely. We found substantial evidence for a quantitative trait locus with pleiotropic effects, which appears to influence both BMI and HDL-C phenotypes in the Framingham data.

Optimizing linkage to care and initiation and retention on treatment of adolescents with newly diagnosed HIV infection

PubMed Central

Ruria, Eva Caroline; Masaba, Rose; Kose, Judith; Woelk, Godfrey; Mwangi, Eliud; Matu, Lucy; Ng’eno, Hillary; Bikeri, Beatrice; Rakhmanina, Natella

2017-01-01

Objective: Unsuccessful linkage to care and treatment increases adolescent HIV-related morbidity and mortality. This study evaluated the effect of a novel adolescent and youth Red Carpet Program (RCP) on the timing and outcomes of linkage to care. Design: A prepost implementation evaluation of the pilot RCP program. Settings: Healthcare facilities (HCFs) and schools in Homa Bay County, Kenya. Study participants: HIV-infected adolescents (15–19 years) and youth (20–21 years). Interventions: RCP provided fast-track peer-navigated services, peer counseling, and psychosocial support at HCFs and schools in six Homa Bay subcounties in 2016. RCP training and sensitization was implemented in 50 HCFs and 25 boarding schools. Main outcome measures: New adolescent and youth HIV diagnosis, linkage to and retention in care and treatment. Results: Within 6 months of program rollout, 559 adolescents and youths (481 women; 78 men) were newly diagnosed with HIV (15–19 years n = 277; 20–21 years, n = 282). The majority (n = 544; 97.3%) were linked to care, compared to 56.5% at preimplementation (P < 0.001). All (100.0%; n = 559) adolescents and youths received peer counseling and psychosocial support, and the majority (n = 430; 79.0%) were initiated on treatment. Compared to preimplementation, the proportion of adolescents and youths who were retained on treatment increased from 66.0 to 90.0% at 3 months (P < 0.001), and from 54.4 to 98.6% at 6 months (P < 0.001). Conclusion: Implementation of RCP was associated with significant improvement in linkage to and early retention in care among adolescent and youth. The ongoing study will fully assess the efficacy of this linkage-to-care approach. PMID:28665883

Using linked educational attainment data to reduce bias due to missing outcome data in estimates of the association between the duration of breastfeeding and IQ at 15 years.

PubMed

Cornish, Rosie P; Tilling, Kate; Boyd, Andy; Davies, Amy; Macleod, John

2015-06-01

Most epidemiological studies have missing information, leading to reduced power and potential bias. Estimates of exposure-outcome associations will generally be biased if the outcome variable is missing not at random (MNAR). Linkage to administrative data containing a proxy for the missing study outcome allows assessment of whether this outcome is MNAR and the evaluation of bias. We examined this in relation to the association between infant breastfeeding and IQ at 15 years, where a proxy for IQ was available through linkage to school attainment data. Subjects were those who enrolled in the Avon Longitudinal Study of Parents and Children in 1990-91 (n = 13 795), of whom 5023 had IQ measured at age 15. For those with missing IQ, 7030 (79%) had information on educational attainment at age 16 obtained through linkage to the National Pupil Database. The association between duration of breastfeeding and IQ was estimated using a complete case analysis, multiple imputation and inverse probability-of-missingness weighting; these estimates were then compared with those derived from analyses informed by the linkage. IQ at 15 was MNAR-individuals with higher attainment were less likely to have missing IQ data, even after adjusting for socio-demographic factors. All the approaches underestimated the association between breastfeeding and IQ compared with analyses informed by linkage. Linkage to administrative data containing a proxy for the outcome variable allows the MNAR assumption to be tested and more efficient analyses to be performed. Under certain circumstances, this may produce unbiased results. © The Author 2015. Published by Oxford University Press on behalf of the International Epidemiological Association.

Fine mapping of the chromosome 10q11-q21 linkage region in Alzheimer's disease cases and controls.

PubMed

Fallin, Margaret Daniele; Szymanski, Megan; Wang, Ruihua; Gherman, Adrian; Bassett, Susan S; Avramopoulos, Dimitrios

2010-07-01

We have previously reported strong linkage on chromosome 10q in pedigrees transmitting Alzheimer's disease through the mother, overlapping with many significant linkage reports including the largest reported study. Here, we report the most comprehensive fine mapping of this region to date. In a sample of 638 late-onset Alzheimer's disease (LOAD) cases and controls including 104 maternal LOAD cases, we genotyped 3,884 single nucleotide polymorphisms (SNPs) covering 15.2 Mb. We then used imputations and publicly available data to generate an extended dataset including 4,329 SNPs for 1,209 AD cases and 839 controls in the same region. Further, we screened eight genes in this region for rare alleles in 283 individuals by nucleotide sequencing, and we tested for possible monoallelic expression as it might underlie our maternal parent of origin linkage. We excluded the possibility of multiple rare coding risk variants for these genes and monoallelic expression when we could test for it. One SNP, rs10824310 in the PRKG1 gene, showed study-wide significant association without a parent of origin effect, but the effect size estimate is not of sufficient magnitude to explain the linkage, and no association is observed in an independent genome-wide association studies (GWAS) report. Further, no causative variants were identified though sequencing. Analysis of cases with maternal disease origin pointed to a few regions of interest that included the genes PRKG1 and PCDH15 and an intergenic interval of 200 Kb. It is likely that non-transcribed rare variants or other mechanisms involving these genomic regions underlie the observed linkage and parent of origin effect. Acquiring additional support and clarifying the mechanisms of such involvement is important for AD and other complex disorder genetics research.

Increased psychiatric morbidity before and after the diagnosis of hypothyroidism: a nationwide register study.

PubMed

Thvilum, Marianne; Brandt, Frans; Almind, Dorthe; Christensen, Kaare; Brix, Thomas Heiberg; Hegedüs, Laszlo

2014-05-01

Thyroid hormones are necessary for fetal brain development, and hypothyroidism in adults has been associated with mood symptoms and reduced quality of life. Nevertheless, our knowledge regarding the association and temporal relation between hypothyroidism and mental disorders is ambiguous. Our objective was to investigate, at a nationwide level, whether a diagnosis of hypothyroidism is associated with psychiatric morbidity. This is an observational cohort study. On the basis of record linkage between different Danish health registers, 2822 hypothyroid singletons each matched with 4 nonhypothyroid controls were identified and followed over a mean period of 6 years (range 1-13). Additionally, we included 385 same-sex twin pairs discordant for hypothyroidism. Diagnoses of psychiatric disorders as well as treatment with antidepressants, antipsychotics, and anxiolytics were recorded. Logistic and cox regression models were used to assess the risk of psychiatric morbidity before and after the diagnosis of hypothyroidism, respectively. Before the diagnosis of hypothyroidism, such individuals had an increased prevalence of diagnoses with psychiatric disorders (odds ratio, OR, 1.51; 95% confidence interval [CI 1.12-2.04]) and increased prevalence of treatment with antipsychotics (OR 1.49 [CI 1.29-1.73]), antidepressants (OR 1.50 [CI 1.35-1.67]), and anxiolytics (OR 1.28 [CI 1.16-1.41]). After the diagnosis of hypothyroidism, patients had a higher risk of being diagnosed with a psychiatric disorder (hazard ratio, HR, 2.40 [CI 1.81-3.18]), and an increased risk of being treated with antidepressants (HR 1.30 [CI 1.15-1.47]) and anxiolytics (HR 1.27 [CI 1.10-1.47]), but not antipsychotics (HR 1.13 [CI 0.91-1.41]). On the basis of the twin data, we could not demonstrate genetic confounding. Subjects with hypothyroidism have an increased risk of being diagnosed with a psychiatric disorder as well as being treated with antidepressants, antipsychotics, and anxiolytics both before and after the diagnosis of hypothyroidism.

Joint association of physical activity and overweight with subsequent psychotropic medication: a register-linked follow-up study among employees.

PubMed

Loponen, Tiina; Lallukka, Tea; Holstila, Ansku; Lahti, Jouni

2015-10-03

Physical activity level and overweight have shown associations with mental health problems but it is not known whether the risk of mental health problems due to overweight varies by physical activity. We examined joint association of physical activity and overweight with subsequent psychotropic medication among 40-60-year-old employees. The questionnaire survey data were derived from Helsinki Health Study baseline postal questionnaires in 2000-02 among employees of the City of Helsinki aged 40-60 years (n = 8960, response rate 67%). Baseline survey data were linked with prospective register data on prescribed psychotropic medication (ATC-codes N05 and N06, except N06D) among those with written consent (74%) for such linkage. The analyses included 6169 responders (78% women, corresponding to the target population). We divided participants into six groups according to their baseline self-reported body mass index and leisure-time physical activity using physically highly active normal-weight participants as a reference group. We used Cox regression analysis adjusted for age, gender, psychotropic medication prior to baseline, and socioeconomic position, marital status, working conditions, limiting long-standing illness, alcohol use, and smoking. At baseline, 49% were overweight and 23% were physically inactive. After adjusting for age and gender, inactive normal-weight (hazard ratio (HR) 1.3, 95% CI 1.1-1.5), moderately active overweight (HR 1.3, 95% CI 1.1-1.5) and inactive overweight (HR 1.4, 95% CI 1.2-1.6) had higher risk for any psychotropic medication compared with group of highly active normal-weight. After adjusting for prior medication, only the inactive overweight group had higher risk (HR 1.4, 95% CI 1.2-1.6). Other covariates made but a minor contribution to the examined associations. For antidepressants the associations were somewhat stronger than for sedatives. Both normal-weight and physical activity help prevent psychotropic medication but physical activity dominates the association over normal-weight.

Chernobyl cleanup workers from Estonia: cohort description and related epidemiological research.

PubMed

Rahu, Kaja; Rahu, Mati; Tekkel, Mare; Veidebaum, Toomas; Hakulinen, Timo; Auvinen, Anssi; Bigbee, William L; Hartshorne, Michael F; Inskip, Peter D; Boice, John D

2015-12-01

The Estonian study of Chernobyl cleanup workers was one of the first investigations to evaluate the possible health consequences of working in the Chernobyl area (the 30 km exclusion zone and/or adjacent territories) after the 1986 reactor accident. The cohort consists of 4831 men who were dispatched in 1986-1991 for tasks involving decontamination, construction of buildings, transport, radiation measurement, guard duty or other activities. By 31 December 2012, the follow-up of the cohort yielded 102 158 person-years of observation. Exposure and health data were collected by postal questionnaires, biodosimetry evaluations, thyroid screenings, and record-linkages with cancer, causes of death and health insurance reimbursement registers and databases. These data cover socio-demographic factors, employment history, aspects of health behaviour, medical history, work and living conditions in the Chernobyl area, biomarkers of exposure, cancer and non-cancer disease occurrence and causes of death. Cancer incidence data were obtained for 1986-2008, mortality data for 1986-2011 and non-cancer morbidity data for 2004-2012. Although the cohort is relatively small, it has been extensively examined and benefited from comprehensive nationwide population and health registers. The major finding was an increased risk of suicide. Thyroid examinations did not reveal an association with thyroid nodular disease and radiation dose, but did indicate the importance of accounting for screening when making comparisons with unscreened populations. No risk of leukaemia was observed and risks higher than 2.5-fold could be excluded with 95% confidence. Biodosimetry included GPA analyses and chromosomal translocation analyses and indicated that the Estonian cleanup workers experienced a relatively low mean exposure of the order of 0.1 Gy. One value of the Estonian study is in the methodologic processes brought to bear in addressing possible health effects from the Chernobyl accident. Twenty-five years of research are summarised and opportunities for the future listed.

Working conditions as risk factors for disability retirement: a longitudinal register linkage study

PubMed Central

2012-01-01

Background Early retirement due to disability is a public health and work environment problem that shortens working careers. Transition to disability retirement is based on ill-health, but working conditions are also of relevance. We examined the contributions of work arrangements, physical working conditions and psychosocial working conditions to subsequent disability retirement. Methods The data were derived from the Helsinki Health Study cohort on employees of the City of Helsinki, Finland. Information on working conditions was obtained from the baseline surveys conducted in 2000, 2001 and 2002. These data were linked with register data on disability retirement and their main diagnoses obtained from the Finnish Centre for Pensions. Follow up by the end of 2008 yielded 525 disability retirement events. The analysed data included 6525 participants and 525 disability retirement events. Hazard ratios (HR) and 95% confidence intervals (95% CI) were calculated from Cox regression analysis. Results Several working conditions showed own associations with disability retirement before adjustment. After adjustment for all working conditions, the primary risk factors for all-cause disability retirement were physical workload among women (HR 2.02, 95% CI 1.57-2.59) and men (HR 2.00, 95% CI 1.18-3.38), and low job control among women (HR 1.60, 95% CI 1.29-1.99). In addition, for disability retirement due to musculoskeletal causes, the risk factors were physical workload and low job control. For disability retirement due to mental causes the risk factors were computer work and low job control. Furthermore, occupational class was a risk factor for disability retirement due to all causes and musculoskeletal diseases. Conclusions Among various working conditions, those that are physically demanding and those that imply low job control are potential risk factors for disability retirement. Improving the physical working environment and enhancing control over one’s job is likely to help prevent early retirement due to disability. PMID:22537302

Linkage analysis of chromosome 22q12-13 in a United Kingdom/Icelandic sample of 23 multiplex schizophrenia families

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kalsi, G.; Read, T.; Butler, R.

A possible linkage to a genetic subtype of schizophrenia and related disorders has been reported on the long arm of chromosome 22 at q12-13. However formal statistical tests in a combined sample could not reject homogeneity and prove that there was linked subgroup of families. We have studied 23 schizophrenia pedigrees to test whether some multiplex schizophrenia families may be linked to the microsatellite markers D22S274 and D22S283 which span the 22q12-13 region. Two point followed by multipoint lod and non-parametric linkage analyses under the assumption of heterogeneity provided no evidence for linkage over the relevant region. 16 refs., 4more » tabs.« less

Factors Associated with Delayed Enrollment in HIV Medical Care among HIV-Positive Individuals in Odessa Region, Ukraine.

PubMed

Neduzhko, Oleksandr; Postnov, Oleksandr; Perehinets, Ihor; DeHovitz, Jack; Joseph, Michael; Odegaard, David; Kaplan, Robert; Kiriazova, Tetiana

In Ukraine, about one-third of identified HIV-positive individuals are not connected to care. We conducted a cross-sectional survey (n = 200) among patients registered at Odessa AIDS centers in October to December 2011. Factors associated with delayed enrollment in HIV care (>3 months since positive HIV test) were evaluated using logistic regression. Among study participants (mean age 35 ± 8.2 years, 47.5% female, 42.5% reported history of injecting drugs), 55% delayed HIV care enrollment. Odds of delayed enrollment were higher for those with lower educational attainment (adjusted odds ratio [aOR]: 2.65, 95% confidence interval [CI]: 1.04-6.76), not feeling ill (aOR: 2.98, 95% CI: 1.50-5.93), or not having time to go to the AIDS center (aOR: 3.89, 95% CI: 1.39-10.89); injection drug use was not associated with delayed enrollment. Programs linking HIV-positive individuals to specialized care should address enrollment barriers and include education on HIV care benefits and case management for direct linkage to care. HIV testing and treatment should be coupled to ensure a continuum of care.

Leg-ulcer care in the community, before and after implementation of an evidence-based service

PubMed Central

Harrison, Margaret B.; Graham, Ian D.; Lorimer, Karen; Friedberg, Elaine; Pierscianowski, Tadeusz; Brandys, Tim

2005-01-01

Background Leg ulcers usually occur in older patients, a growing population for which increasing health care resources are required. Treatment is mainly provided in patients' homes; however, patients often receive poorly integrated services in multiple settings. We report the results of a prospective study of a community-based care strategy for leg ulcers. Methods International practice recommendations and guidelines were adapted to make a new clinical protocol. The new model, for a dedicated service staffed by specially trained registered nurses, established initial and ongoing assessment time frames and provided enhanced linkages to medical specialists. Data were collected for 1 year before and after implementation; outcome measures included 3-month healing rates, quality of life and resource usage. Results Three-month healing rates more than doubled between the year before implementation (23% [18/78]) and the year afterward (56% [100/180]). The number of nursing visits per case declined, from a median of 37 to 25 (p = 0.041); the median supply cost per case was reduced from $1923 to $406 (p = 0.005). Interpretation Reorganization of care for people with leg ulcers was associated with improved healing and a more efficient use of nursing visits. PMID:15911859

Single nucleotide polymorphisms in an intergenic chromosome 2q region associated with tissue factor pathway inhibitor plasma levels and venous thromboembolism.

PubMed

Dennis, J; Truong, V; Aïssi, D; Medina-Rivera, A; Blankenberg, S; Germain, M; Lemire, M; Antounians, L; Civelek, M; Schnabel, R; Wells, P; Wilson, M D; Morange, P-E; Trégouët, D-A; Gagnon, F

2016-10-01

Essentials Tissue factor pathway inhibitor (TFPI) regulates the blood coagulation cascade. We replicated previously reported linkage of TFPI plasma levels to the chromosome 2q region. The putative causal locus, rs62187992, was associated with TFPI plasma levels and thrombosis. rs62187992 was marginally associated with TFPI expression in human aortic endothelial cells. Click to hear Ann Gil's presentation on new insights into thrombin activatable fibrinolysis inhibitor SUMMARY: Background Tissue factor pathway inhibitor (TFPI) regulates fibrin clot formation, and low TFPI plasma levels increase the risk of arterial thromboembolism and venous thromboembolism (VTE). TFPI plasma levels are also heritable, and a previous linkage scan implicated the chromosome 2q region, but no specific genes. Objectives To replicate the finding of the linkage region in an independent sample, and to identify the causal locus. Methods We first performed a linkage analysis of microsatellite markers and TFPI plasma levels in 251 individuals from the F5L Family Study, and replicated the finding of the linkage peak on chromosome 2q (LOD = 3.06). We next defined a follow-up region that included 112 603 single nucleotide polymorphisms (SNPs) under the linkage peak, and meta-analyzed associations between these SNPs and TFPI plasma levels across the F5L Family Study and the Marseille Thrombosis Association (MARTHA) Study, a study of 1033 unrelated VTE patients. SNPs with false discovery rate q-values of < 0.10 were tested for association with TFPI plasma levels in 892 patients with coronary artery disease in the AtheroGene Study. Results and Conclusions One SNP, rs62187992, was associated with TFPI plasma levels in all three samples (β = + 0.14 and P = 4.23 × 10 -6 combined; β = + 0.16 and P = 0.02 in the F5L Family Study; β = + 0.13 and P = 6.3 × 10 -4 in the MARTHA Study; β = + 0.17 and P = 0.03 in the AtheroGene Study), and contributed to the linkage peak in the F5L Family Study. rs62187992 was also associated with clinical VTE (odds ratio 0.90, P = 0.03) in the INVENT Consortium of > 7000 cases and their controls, and was marginally associated with TFPI expression (β = + 0.19, P = 0.08) in human aortic endothelial cells, a primary site of TFPI synthesis. The biological mechanisms underlying these associations remain to be elucidated. © 2016 International Society on Thrombosis and Haemostasis.

Detection of linkage between a quantitative trait and a marker locus by the lod score method: sample size and sampling considerations.

PubMed

Demenais, F; Lathrop, G M; Lalouel, J M

1988-07-01

A simulation study is here conducted to measure the power of the lod score method to detect linkage between a quantitative trait and a marker locus in various situations. The number of families necessary to detect such linkage with 80% power is assessed for different sets of parameters at the trait locus and different values of the recombination fraction. The effects of varying the mode of sampling families and the sibship size are also evaluated.

Familial discoid lupus erythematosus associated with heterozygote C2 deficiency.

PubMed

Belin, D C; Bordwell, B J; Einarson, M E; McLean, R H; Weinstein, A; Yunis, E J; Rothfield, N F

1980-08-01

Two siblings with chronic discoid lupus erythematosus and several family members were found with heterozygous C2 deficiency. An association with histocompatibility markers HLA-B18 and HLA-Dw2 was demonstrated, and the slow allotype of factor B was present. Linkage studies in this family suggested a close linkage between the C2 deficiency gene and genes coding for B18, Dw2, and BfS antigens. One HLA-ACB/DBf recombinant was observed showing closer linkage between HLA-D and Bf than between HLA-B and Bf.

Richness-Productivity Relationships Between Trophic Levels in a Detritus-Based System: Significance of Abundance and Trophic Linkage.

EPA Science Inventory

Most theoretical and empirical studies of productivity–species richness relationships fail to consider linkages among trophic levels. We quantified productivity–richness relationships in detritus-based, water-filled tree-hole communities for two trophic levels: invertebrate consu...

The Search for Autism Disease Genes

ERIC Educational Resources Information Center

Wassink, Thomas H.; Brzustowicz, Linda M.; Bartlett, Christopher W.; Szatmari, Peter

2004-01-01

Autism is a heritable disorder characterized by phenotypic and genetic complexity. This review begins by surveying current linkage, gene association, and cytogenetic studies performed with the goal of identifying autism disease susceptibility variants. Though numerous linkages and associations have been identified, they tend to diminish upon…

A saturated SSR/DArT linkage map of Musa acuminata addressing genome rearrangements among bananas.

PubMed

Hippolyte, Isabelle; Bakry, Frederic; Seguin, Marc; Gardes, Laetitia; Rivallan, Ronan; Risterucci, Ange-Marie; Jenny, Christophe; Perrier, Xavier; Carreel, Françoise; Argout, Xavier; Piffanelli, Pietro; Khan, Imtiaz A; Miller, Robert N G; Pappas, Georgios J; Mbéguié-A-Mbéguié, Didier; Matsumoto, Takashi; De Bernardinis, Veronique; Huttner, Eric; Kilian, Andrzej; Baurens, Franc-Christophe; D'Hont, Angélique; Cote, François; Courtois, Brigitte; Glaszmann, Jean-Christophe

2010-04-13

The genus Musa is a large species complex which includes cultivars at diploid and triploid levels. These sterile and vegetatively propagated cultivars are based on the A genome from Musa acuminata, exclusively for sweet bananas such as Cavendish, or associated with the B genome (Musa balbisiana) in cooking bananas such as Plantain varieties. In M. acuminata cultivars, structural heterozygosity is thought to be one of the main causes of sterility, which is essential for obtaining seedless fruits but hampers breeding. Only partial genetic maps are presently available due to chromosomal rearrangements within the parents of the mapping populations. This causes large segregation distortions inducing pseudo-linkages and difficulties in ordering markers in the linkage groups. The present study aims at producing a saturated linkage map of M. acuminata, taking into account hypotheses on the structural heterozygosity of the parents. An F1 progeny of 180 individuals was obtained from a cross between two genetically distant accessions of M. acuminata, 'Borneo' and 'Pisang Lilin' (P. Lilin). Based on the gametic recombination of each parent, two parental maps composed of SSR and DArT markers were established. A significant proportion of the markers (21.7%) deviated (p < 0.05) from the expected Mendelian ratios. These skewed markers were distributed in different linkage groups for each parent. To solve some complex ordering of the markers on linkage groups, we associated tools such as tree-like graphic representations, recombination frequency statistics and cytogenetical studies to identify structural rearrangements and build parsimonious linkage group order. An illustration of such an approach is given for the P. Lilin parent. We propose a synthetic map with 11 linkage groups containing 489 markers (167 SSRs and 322 DArTs) covering 1197 cM. This first saturated map is proposed as a "reference Musa map" for further analyses. We also propose two complete parental maps with interpretations of structural rearrangements localized on the linkage groups. The structural heterozygosity in P. Lilin is hypothesized to result from a duplication likely accompanied by an inversion on another chromosome. This paper also illustrates a methodological approach, transferable to other species, to investigate the mapping of structural rearrangements and determine their consequences on marker segregation.

A high-density SNP genetic linkage map for the silver-lipped pearl oyster, Pinctada maxima: a valuable resource for gene localisation and marker-assisted selection.

PubMed

Jones, David B; Jerry, Dean R; Khatkar, Mehar S; Raadsma, Herman W; Zenger, Kyall R

2013-11-20

The silver-lipped pearl oyster, Pinctada maxima, is an important tropical aquaculture species extensively farmed for the highly sought "South Sea" pearls. Traditional breeding programs have been initiated for this species in order to select for improved pearl quality, but many economic traits under selection are complex, polygenic and confounded with environmental factors, limiting the accuracy of selection. The incorporation of a marker-assisted selection (MAS) breeding approach would greatly benefit pearl breeding programs by allowing the direct selection of genes responsible for pearl quality. However, before MAS can be incorporated, substantial genomic resources such as genetic linkage maps need to be generated. The construction of a high-density genetic linkage map for P. maxima is not only essential for unravelling the genomic architecture of complex pearl quality traits, but also provides indispensable information on the genome structure of pearl oysters. A total of 1,189 informative genome-wide single nucleotide polymorphisms (SNPs) were incorporated into linkage map construction. The final linkage map consisted of 887 SNPs in 14 linkage groups, spans a total genetic distance of 831.7 centimorgans (cM), and covers an estimated 96% of the P. maxima genome. Assessment of sex-specific recombination across all linkage groups revealed limited overall heterochiasmy between the sexes (i.e. 1.15:1 F/M map length ratio). However, there were pronounced localised differences throughout the linkage groups, whereby male recombination was suppressed near the centromeres compared to female recombination, but inflated towards telomeric regions. Mean values of LD for adjacent SNP pairs suggest that a higher density of markers will be required for powerful genome-wide association studies. Finally, numerous nacre biomineralization genes were localised providing novel positional information for these genes. This high-density SNP genetic map is the first comprehensive linkage map for any pearl oyster species. It provides an essential genomic tool facilitating studies investigating the genomic architecture of complex trait variation and identifying quantitative trait loci for economically important traits useful in genetic selection programs within the P. maxima pearling industry. Furthermore, this map provides a foundation for further research aiming to improve our understanding of the dynamic process of biomineralization, and pearl oyster evolution and synteny.

Towards identification of an epilepsy gene in a large family with idiopathic generalized epilepsy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roussear, M.; Lopes-Cendes, I.; Berkovic, S.F.

1994-09-01

To identify the disease gene in a large, multiplex family segregating an autosomal dominant form of idiopathic generalized epilepsy (IGE). The IGEs have been recognized for several decades as being genetically determined. However, large pedigrees with a clear Mendelian inheritance are not commonly available. This, and the presence of locus heterogeneity have been obstacles to the identification of linkage in several IGE syndromes. We have identified a large IGE kindred with fifty-eight living individuals, including 26 affecteds, showing a clear autosomal dominant inheritance with incomplete penetrance. Forty-fur informative individuals, including 23 affecteds, were selected for the linkage studies. We havemore » chosen 200 polymorphic microsatellite markers, about 20 cM apart, throughout the human autosomes as a genome-search linkage strategy. To date, 47 markers, representing 30% of the human genome, have been excluded for linkage in the Australian kindred. As our study progresses, we will report up-to-date results.« less

Identifying causal linkages between environmental variables and African conflicts

NASA Astrophysics Data System (ADS)

Nguy-Robertson, A. L.; Dartevelle, S.

2017-12-01

Environmental variables that contribute to droughts, flooding, and other natural hazards are often identified as factors contributing to conflict; however, few studies attempt to quantify these causal linkages. Recent research has demonstrated that the environment operates within a dynamical system framework and the influence of variables can be identified from convergent cross mapping (CCM) between shadow manifolds. We propose to use CCM to identify causal linkages between environmental variables and incidences of conflict. This study utilizes time series data from Climate Forecast System ver. 2 and MODIS satellite sensors processed using Google Earth Engine to aggregate country and regional trends. These variables are then compared to Armed Conflict Location & Event Data Project observations at similar scales. Results provide relative rankings of variables and their linkage to conflict. Being able to identify which factors contributed more strongly to a conflict can allow policy makers to prepare solutions to mitigate future crises. Knowledge of the primary environmental factors can lead to the identification of other variables to examine in the causal network influencing conflict.

U.S. Maternally Linked Birth Records May Be Biased for Hispanics and Other Population Groups

PubMed Central

LEISS, JACK K.; GILES, DENISE; SULLIVAN, KRISTIN M.; MATHEWS, RAHEL; SENTELLE, GLENDA; TOMASHEK, KAY M.

2010-01-01

Purpose To advance understanding of linkage error in U.S. maternally linked datasets, and how the error may affect results of studies based on the linked data. Methods North Carolina birth and fetal death records for 1988-1997 were maternally linked (n=1,030,029). The maternal set probability, defined as the probability that all records assigned to the same maternal set do in fact represent events to the same woman, was used to assess differential maternal linkage error across race/ethnic groups. Results Maternal set probabilities were lower for records specifying Asian or Hispanic race/ethnicity, suggesting greater maternal linkage error. The lower probabilities for Hispanics were concentrated in women of Mexican origin who were not born in the United States. Conclusions Differential maternal linkage error may be a source of bias in studies using U.S. maternally linked datasets to make comparisons between Hispanics and other groups or among Hispanic subgroups. Methods to quantify and adjust for this potential bias are needed. PMID:20006273

Linkage studies on 13 biochemical loci and 2 coat color loci in a [(BN x TM) x TM] backcross progeny of the rat (Rattus norvegicus).

PubMed

Yamada, J; Hamada, S; Bender, K; Adams, M

1986-10-01

In a [(BN X TM) X TM] backcross progeny of rats, nine significant linkage associations were found among 105 pairwise combinations of 15 loci. After comparing this with other published data and data of personal communications, we considered that the d gene we tentatively designated may be identical to the gene for pink-eyed dilution (p), and that the associations of Gc-Hbb, RT1-h, and Gc-Fh were due to chance rather than real linkage. The linkages obtained in this study, therefore, were Hbb-p (26.5 +/- 5.5) in LG I, Mup-1-Acon-1 (12.5 +/- 4.1) in LG II, Hao-1-Svp-1 (23.8 +/- 6.6) in LG IV, Es-1-Es-3 (17.2 +/- 4.7) in LG V, h-Gc (10.9 +/- 3.3) in LG VI, and Fh-Pep-3 (32.3 +/- 5.9) in LG X.

Empirical characteristics of family-based linkage to a complex trait: the ADIPOQ region and adiponectin levels.

PubMed

Hellwege, Jacklyn N; Palmer, Nicholette D; Mark Brown, W; Brown, Mark W; Ziegler, Julie T; Sandy An, S; An, Sandy S; Guo, Xiuqing; Ida Chen, Y-D; Chen, Ida Y-D; Taylor, Kent; Hawkins, Gregory A; Ng, Maggie C Y; Speliotes, Elizabeth K; Lorenzo, Carlos; Norris, Jill M; Rotter, Jerome I; Wagenknecht, Lynne E; Langefeld, Carl D; Bowden, Donald W

2015-02-01

We previously identified a low-frequency (1.1 %) coding variant (G45R; rs200573126) in the adiponectin gene (ADIPOQ) which was the basis for a multipoint microsatellite linkage signal (LOD = 8.2) for plasma adiponectin levels in Hispanic families. We have empirically evaluated the ability of data from targeted common variants, exome chip genotyping, and genome-wide association study data to detect linkage and association to adiponectin protein levels at this locus. Simple two-point linkage and association analyses were performed in 88 Hispanic families (1,150 individuals) using 10,958 SNPs on chromosome 3. Approaches were compared for their ability to map the functional variant, G45R, which was strongly linked (two-point LOD = 20.98) and powerfully associated (p value = 8.1 × 10(-50)). Over 450 SNPs within a broad 61 Mb interval around rs200573126 showed nominal evidence of linkage (LOD > 3) but only four other SNPs in this region were associated with p values < 1.0 × 10(-4). When G45R was accounted for, the maximum LOD score across the interval dropped to 4.39 and the best p value was 1.1 × 10(-5). Linked and/or associated variants ranged in frequency (0.0018-0.50) and type (coding, non-coding) and had little detectable linkage disequilibrium with rs200573126 (r (2) < 0.20). In addition, the two-point linkage approach empirically outperformed multipoint microsatellite and multipoint SNP analysis. In the absence of data for rs200573126, family-based linkage analysis using a moderately dense SNP dataset, including both common and low-frequency variants, resulted in stronger evidence for an adiponectin locus than association data alone. Thus, linkage analysis can be a useful tool to facilitate identification of high-impact genetic variants.

Independent genetic control of early and late stages of chemically induced skin tumors in a cross of a Japanese wild-derived inbred mouse strain, MSM/Ms.

PubMed

Okumura, Kazuhiro; Sato, Miho; Saito, Megumi; Miura, Ikuo; Wakana, Shigeharu; Mao, Jian-Hua; Miyasaka, Yuki; Kominami, Ryo; Wakabayashi, Yuichi

2012-11-01

MSM/Ms is an inbred mouse strain derived from a Japanese wild mouse, Mus musculus molossinus. In this study, we showed that MSM/Ms mice exhibit dominant resistance when crossed with susceptible FVB/N mice and subjected to the two-stage skin carcinogenesis protocol using 7,12-dimethylbenz(a)anthracene (DMBA)/ 12-O-tetradecanoylphorbol-13-acetate (TPA). A series of F1 backcross mice were generated by crossing p53(+/+) or p53(+/-) F1 (FVB/N × MSM/Ms) males with FVB/N female mice. These generated 228 backcross animals, approximately half of which were p53(+/-), enabling us to search for p53-dependent skin tumor modifier genes. Highly significant linkage for papilloma multiplicity was found on chromosomes 6 and 7 and suggestive linkage was found on chromosomes 3, 5 and 12. Furthermore, in order to identify stage-dependent linkage loci we classified tumors into three categories (<2mm, 2-6mm and >6mm), and did linkage analysis. The same locus on chromosome 7 showed strong linkage in groups with <2mm or 2-6mm papillomas. No linkage was detected on chromosome 7 to papillomas >6mm, but a different locus on chromosome 4 showed strong linkage both to papillomas >6mm and to carcinomas. This locus, which maps near the Cdkn2a/p19(Arf) gene, was entirely p53-dependent, and was not seen in p53 (+/-) backcross animals. Suggestive linkage conferring susceptibility to carcinoma was also found on chromosome 5. These results clearly suggest distinct loci regulate each stage of tumorigenesis, some of which are p53-dependent.

Pregnancy associated death in record linkage studies relative to delivery, termination of pregnancy, and natural losses: A systematic review with a narrative synthesis and meta-analysis

PubMed Central

Reardon, David C; Thorp, John M

2017-01-01

Objectives: Measures of pregnancy associated deaths provide important guidance for public health initiatives. Record linkage studies have significantly improved identification of deaths associated with childbirth but relatively few have also examined deaths associated with pregnancy loss even though higher rates of maternal death have been associated with the latter. Following PRISMA guidelines we undertook a systematic review of record linkage studies examining the relative mortality risks associated with pregnancy loss to develop a narrative synthesis, a meta-analysis, and to identify research opportunities. Methods: MEDLINE and SCOPUS were searched in July 2015 using combinations of: mortality, maternal death, record linkage, linked records, pregnancy associated mortality, and pregnancy associated death to identify papers using linkage of death certificates to independent records identifying pregnancy outcomes. Additional studies were identified by examining all citations for relevant studies. Results: Of 989 studies, 11 studies from three countries reported mortality rates associated with termination of pregnancy, miscarriage or failed pregnancy. Within a year of their pregnancy outcomes, women experiencing a pregnancy loss are over twice as likely to die compared to women giving birth. The heightened risk is apparent within 180 days and remains elevated for many years. There is a dose effect, with exposure to each pregnancy loss associated with increasing risk of death. Higher rates of death from suicide, accidents, homicide and some natural causes, such as circulatory diseases, may be from elevated stress and risk taking behaviors. Conclusions: Both miscarriage and termination of pregnancy are markers for reduced life expectancy. This association should inform research and new public health initiatives including screening and interventions for patients exhibiting known risk factors. PMID:29163945

Nonsyndromic cleft lip with or without cleft palate: Evidence of linkage to BCL3 in 17 multigenerational families

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stein, J.; Hecht, T.; Stal, S.

1995-08-01

Nonsyndromic cleft lip with or without cleft palate (CL/P) is a common craniofacial developmental defect. Recent segregation analyses have suggested that major genes play a role in the etiology of CL/P. Linkage to 22 candidate genes was tested in 11 multigenerational families with CL/P, and 21 of these candidates were excluded. APOC2, 19q13.1, which is linked to the proto-oncogene BCL3, gave suggestive evidence for linkage to CL/P. The study was expanded to include a total of 39 multigenerational CL/P families. Linkage was tested in all families, using anonymous marker, D19S178, and intragenic markers in BCL3 and APOC2. Linkage was testedmore » under two models, autosomal dominant with reduced penetrance and affecteds-only model. Both models showed evidence of heterogeneity, with 43% of families linked at zero recombination to BCL3 when marker data from BCL3 and APOC2 were included. A maximum multipoint LOD score of 7.00 at BCL3 was found among the 17 families that had posterior probabilities {ge}50% in favor of linkage. The transmission disequilibrium test provided additional evidence for linkage with the 3 allele of BCL3 more often transmitted to affected children. These results suggest that BCL3, or a nearby gene, plays a role in the etiology of CL/P in some families. 39 refs., 8 figs., 4 tabs.« less

A Test of Outreach and Drop-in Linkage Versus Shelter Linkage for Connecting Homeless Youth to Services.

PubMed

Slesnick, Natasha; Feng, Xin; Guo, Xiamei; Brakenhoff, Brittany; Carmona, Jasmin; Murnan, Aaron; Cash, Scottye; McRee, Annie-Laurie

2016-05-01

Outreach and service linkage are key for engaging marginalized populations, such as homeless youth, in services. Research to date has focused primarily on engaging individuals already receiving some services through emergency shelters, clinics, or other programs. Less is known about those who are not connected to services and, thus, likely the most vulnerable and in need of assistance. The current study sought to engage non-service-connected homeless youth (N = 79) into a strengths-based outreach and advocacy intervention. Youth were randomly assigned to receive 6 months of advocacy that focused on linking youth to a drop-in center (n = 40) or to a crisis shelter (n = 39). All youth were assessed at baseline and 3, 6, and 9 months post-baseline. Findings indicated that youth prefer drop-in center services to the shelter. Also, the drop-in center linkage condition was associated with more service linkage overall (B = 0.34, SE = 0.04, p < 0.01) and better alcohol-l [B = -0.39, SE = 0.09, t(75) = -4.48, p < 0.001] and HIV-related outcomes [B = 0.62, SE = 0.10, t(78) = 6.34, p < 0.001] compared to the shelter linkage condition. Findings highlight the importance of outreach and service linkage for reconnecting service-marginalized youth, and drop-in centers as a primary service option for homeless youth.

A Dense Brown Trout (Salmo trutta) Linkage Map Reveals Recent Chromosomal Rearrangements in the Salmo Genus and the Impact of Selection on Linked Neutral Diversity

PubMed Central

Leitwein, Maeva; Guinand, Bruno; Pouzadoux, Juliette; Desmarais, Erick; Berrebi, Patrick; Gagnaire, Pierre-Alexandre

2017-01-01

High-density linkage maps are valuable tools for conservation and eco-evolutionary issues. In salmonids, a complex rediploidization process consecutive to an ancient whole genome duplication event makes linkage maps of prime importance for investigating the evolutionary history of chromosome rearrangements. Here, we developed a high-density consensus linkage map for the brown trout (Salmo trutta), a socioeconomically important species heavily impacted by human activities. A total of 3977 ddRAD markers were mapped and ordered in 40 linkage groups using sex- and lineage-averaged recombination distances obtained from two family crosses. Performing map comparison between S. trutta and its sister species, S. salar, revealed extensive chromosomal rearrangements. Strikingly, all of the fusion and fission events that occurred after the S. salar/S. trutta speciation happened in the Atlantic salmon branch, whereas the brown trout remained closer to the ancestral chromosome structure. Using the strongly conserved synteny within chromosome arms, we aligned the brown trout linkage map to the Atlantic salmon genome sequence to estimate the local recombination rate in S. trutta at 3721 loci. A significant positive correlation between recombination rate and within-population nucleotide diversity (π) was found, indicating that selection constrains variation at linked neutral sites in brown trout. This new high-density linkage map provides a useful genomic resource for future aquaculture, conservation, and eco-evolutionary studies in brown trout. PMID:28235829

Convergent linkage evidence from two Latin-American population isolates supports the presence of a susceptibility locus for bipolar disorder in 5q31-34.

PubMed

Herzberg, Ibi; Jasinska, Anna; García, Jenny; Jawaheer, Damini; Service, Susan; Kremeyer, Barbara; Duque, Constanza; Parra, María V; Vega, Jorge; Ortiz, Daniel; Carvajal, Luis; Polanco, Guadalupe; Restrepo, Gabriel J; López, Carlos; Palacio, Carlos; Levinson, Matthew; Aldana, Ileana; Mathews, Carol; Davanzo, Pablo; Molina, Julio; Fournier, Eduardo; Bejarano, Julio; Ramírez, Magui; Ortiz, Carmen Araya; Araya, Xinia; Sabatti, Chiara; Reus, Victor; Macaya, Gabriel; Bedoya, Gabriel; Ospina, Jorge; Freimer, Nelson; Ruiz-Linares, Andrés

2006-11-01

We performed a whole genome microsatellite marker scan in six multiplex families with bipolar (BP) mood disorder ascertained in Antioquia, a historically isolated population from North West Colombia. These families were characterized clinically using the approach employed in independent ongoing studies of BP in the closely related population of the Central Valley of Costa Rica. The most consistent linkage results from parametric and non-parametric analyses of the Colombian scan involved markers on 5q31-33, a region implicated by the previous studies of BP in Costa Rica. Because of these concordant results, a follow-up study with additional markers was undertaken in an expanded set of Colombian and Costa Rican families; this provided a genome-wide significant evidence of linkage of BPI to a candidate region of approximately 10 cM in 5q31-33 (maximum non-parametric linkage score=4.395, P<0.00004). Interestingly, this region has been implicated in several previous genetic studies of schizophrenia and psychosis, including disease association with variants of the enthoprotin and gamma-aminobutyric acid receptor genes.

How home HIV testing and counselling with follow-up support achieves high testing coverage and linkage to treatment and prevention: a qualitative analysis from Uganda.

PubMed

Ware, Norma C; Wyatt, Monique A; Asiimwe, Stephen; Turyamureeba, Bosco; Tumwesigye, Elioda; van Rooyen, Heidi; Barnabas, Ruanne V; Celum, Connie L

2016-01-01

The successes of HIV treatment scale-up and the availability of new prevention tools have raised hopes that the epidemic can finally be controlled and ended. Reduction in HIV incidence and control of the epidemic requires high testing rates at population levels, followed by linkage to treatment or prevention. As effective linkage strategies are identified, it becomes important to understand how these strategies work. We use qualitative data from The Linkages Study, a recent community intervention trial of community-based testing with linkage interventions in sub-Saharan Africa, to show how lay counsellor home HIV testing and counselling (home HTC) with follow-up support leads to linkage to clinic-based HIV treatment and medical male circumcision services. We conducted 99 semi-structured individual interviews with study participants and three focus groups with 16 lay counsellors in Kabwohe, Sheema District, Uganda. The participant sample included both HIV+ men and women (N=47) and HIV-uncircumcised men (N=52). Interview and focus group audio-recordings were translated and transcribed. Each transcript was summarized. The summaries were analyzed inductively to identify emergent themes. Thematic concepts were grouped to develop general constructs and framing propositional statements. Trial participants expressed interest in linking to clinic-based services at testing, but faced obstacles that eroded their initial enthusiasm. Follow-up support by lay counsellors intervened to restore interest and inspire action. Together, home HTC and follow-up support improved morale, created a desire to reciprocate, and provided reassurance that services were trustworthy. In different ways, these functions built links to the health service system. They worked to strengthen individuals' general sense of capability, while making the idea of accessing services more manageable and familiar, thus reducing linkage barriers. Home HTC with follow-up support leads to linkage by building "social bridges," interpersonal connections established and developed through repeated face-to-face contact between counsellors and prospective users of HIV treatment and male circumcision services. Social bridges link communities to the service system, inspiring individuals to overcome obstacles and access care.

First High-Density Linkage Map and Single Nucleotide Polymorphisms Significantly Associated With Traits of Economic Importance in Yellowtail Kingfish Seriola lalandi.

PubMed

Nguyen, Nguyen H; Rastas, Pasi M A; Premachandra, H K A; Knibb, Wayne

2018-01-01

The genetic resources available for the commercially important fish species Yellowtail kingfish (YTK) ( Seriola lalandi) are relative sparse. To overcome this, we aimed (1) to develop a linkage map for this species, and (2) to identify markers/variants associated with economically important traits in kingfish (with an emphasis on body weight). Genetic and genomic analyses were conducted using 13,898 single nucleotide polymorphisms (SNPs) generated from a new high-throughput genotyping by sequencing platform, Diversity Arrays Technology (DArTseq TM ) in a pedigreed population comprising 752 animals. The linkage analysis enabled to map about 4,000 markers to 24 linkage groups (LGs), with an average density of 3.4 SNPs per cM. The linkage map was integrated into a genome-wide association study (GWAS) and identified six variants/SNPs associated with body weight ( P < 5e -8 ) when a multi-locus mixed model was used. Two out of the six significant markers were mapped to LGs 17 and 23, and collectively they explained 5.8% of the total genetic variance. It is concluded that the newly developed linkage map and the significantly associated markers with body weight provide fundamental information to characterize genetic architecture of growth-related traits in this population of YTK S. lalandi .

African American church-based HIV testing and linkage to care: assets, challenges and needs.

PubMed

Stewart, Jennifer M; Thompson, Keitra; Rogers, Christopher

2016-01-01

The US National HIV AIDS strategy promotes the use of faith communities to lessen the burden of HIV in African American communities. One specific strategy presented is the use of these non-traditional venues for HIV testing and co-location of services. African American churches can be at the forefront of this endeavour through the provision of HIV testing and linkage to care. However, there are few interventions to promote the churches' involvement in both HIV testing and linkage to care. We conducted 4 focus groups (n = 39 participants), 4 interviews and 116 surveys in a mixed-methods study to examine the feasibility of a church-based HIV testing and linkage to care intervention in Philadelphia, PA, USA. Our objectives were to examine: (1) available assets, (2) challenges and barriers and (3) needs associated with church-based HIV testing and linkage to care. Analyses revealed several factors of importance, including the role of the church as an access point for testing in low-income neighbourhoods, challenges in openly discussing the relationship between sexuality and HIV, and buy-in among church leadership. These findings can support intervention development and necessitate situating African American church-based HIV testing and linkage to care interventions within a multi-level framework.

Autosomal Dominant Nonsyndromic Cleft Lip and Palate: Significant Evidence of Linkage at 18q21.1

PubMed Central

Beiraghi, Soraya ; Nath, Swapan K. ; Gaines, Matthew ; Mandhyan, Desh D. ; Hutchings, David ; Ratnamala, Uppala ; McElreavey, Ken ; Bartoloni, Lucia ; Antonarakis, Gregory S. ; Antonarakis, Stylianos E. ; Radhakrishna, Uppala 

2007-01-01

Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is one of the most common congenital facial defects, with an incidence of 1 in 700–1,000 live births among individuals of European descent. Several linkage and association studies of NSCL/P have suggested numerous candidate genes and genomic regions. A genomewide linkage analysis of a large multigenerational family (UR410) with NSCL/P was performed using a single-nucleotide–polymorphism array. Nonparametric linkage (NPL) analysis provided significant evidence of linkage for marker rs728683 on chromosome 18q21.1 (NPL=43.33 and P=.000061; nonparametric LOD=3.97 and P=.00001). Parametric linkage analysis with a dominant mode of inheritance and reduced penetrance resulted in a maximum LOD score of 3.61 at position 47.4 Mb on chromosome 18q21.1. Haplotype analysis with informative crossovers defined a 5.7-Mb genomic region spanned by proximal marker rs1824683 (42,403,918 bp) and distal marker rs768206 (48,132,862 bp). Thus, a novel genomic region on 18q21.1 was identified that most likely harbors a high-risk variant for NSCL/P in this family; we propose to name this locus “OFC11” (orofacial cleft 11). PMID:17564975

Analysis of quantitative lipid traits in the genetics of NIDDM (GENNID) study.

PubMed

Malhotra, Alka; Wolford, Johanna K

2005-10-01

Coronary heart disease (CHD) is the leading cause of death among individuals with type 2 diabetes. Dyslipidemia contributes significantly to CHD in diabetic patients, in whom lipid abnormalities include hypertriglyceridemia, low HDL cholesterol, and increased levels of small, dense LDL particles. To identify genes for lipid-related traits, we performed genome-wide linkage analyses for levels of triglycerides and HDL, LDL, and total cholesterol in Caucasian, Hispanic, and African-American families from the Genetics of NIDDM (GENNID) study. Most lipid traits showed significant estimates of heritability (P < 0.001) with the exception of triglycerides and the triglyceride/HDL ratio in African Americans. Variance components analysis identified linkage on chromosome 3p12.1-3q13.31 for the triglyceride/HDL ratio (logarithm of odds [LOD] = 3.36) and triglyceride (LOD = 3.27) in Caucasian families. Statistically significant evidence for linkage was identified for the triglyceride/HDL ratio (LOD = 2.45) on 11p in Hispanic families in a region that showed suggestive evidence for linkage (LOD = 2.26) for triglycerides in this population. In African Americans, the strongest evidence for linkage (LOD = 2.26) was found on 19p13.2-19q13.42 for total cholesterol. Our findings provide strong support for previous reports of linkage for lipid-related traits, suggesting the presence of genes on 3p12.1-3q13.31, 11p15.4-11p11.3, and 19p13.2-19q13.42 that may influence traits underlying lipid abnormalities associated with type 2 diabetes.

Genetic counseling in Usher syndrome: linkage and mutational analysis of 10 Colombian families.

PubMed

Tamayo, M L; Lopez, G; Gelvez, N; Medina, D; Kimberling, W J; Rodríguez, V; Tamayo, G E; Bernal, J E

2008-01-01

Usher Syndrome (US), an autosomal recessive disease, is characterized by retinitis pigmentosa (RP), vestibular dysfunction, and congenital sensorineural deafness. There are three recognized clinical types of the disorder. In order to improve genetic counseling for affected families, we conducted linkage analysis and DNA sequencing in 10 Colombian families with confirmed diagnosis of US (4 type I and 6 type II). Seventy-five percent of the US1 families showed linkage to locus USH1B, while the remaining 25% showed linkage to loci USH1B and USH1C. Among families showing linkage to USH1B we found two different mutations in the MYO7A gene: IVS42-26insTTGAG in exon 43 (heterozygous state) and R634X (CGA-TGA) in exon 16 (homozygous state). All six US2 families showed linkage to locus USH2A. Of them, 4 had c.2299delG mutation (1 homozygote state and 3 heterozygous); in the remaining 2 we did not identify any pathologic DNA variant. USH2A individuals with a 2299delG mutation presented a typical and homogeneous retinal phenotype with bilateral severe hearing loss, except for one individual with a heterozygous 2299delG mutation, whose hearing loss was asymmetric, but more profound than in the other cases. The study of these families adds to the genotype-phenotype characterization of the different types and subtypes of US and facilitates genetic counseling in these families. We would like to emphasize the need to perform DNA studies as a prerequisite for genetic counseling in affected families.

New South Wales Child Development Study (NSW-CDS): an Australian multiagency, multigenerational, longitudinal record linkage study

PubMed Central

Carr, Vaughan J; Harris, Felicity; Raudino, Alessandra; Luo, Luming; Kariuki, Maina; Liu, Enwu; Tzoumakis, Stacy; Smith, Maxwell; Holbrook, Allyson; Bore, Miles; Brinkman, Sally; Lenroot, Rhoshel; Dix, Katherine; Dean, Kimberlie; Laurens, Kristin R; Green, Melissa J

2016-01-01

Purpose The initial aim of this multiagency, multigenerational record linkage study is to identify childhood profiles of developmental vulnerability and resilience, and to identify the determinants of these profiles. The eventual aim is to identify risk and protective factors for later childhood-onset and adolescent-onset mental health problems, and other adverse social outcomes, using subsequent waves of record linkage. The research will assist in informing the development of public policy and intervention guidelines to help prevent or mitigate adverse long-term health and social outcomes. Participants The study comprises a population cohort of 87 026 children in the Australian State of New South Wales (NSW). The cohort was defined by entry into the first year of full-time schooling in NSW in 2009, at which time class teachers completed the Australian Early Development Census (AEDC) on each child (with 99.7% coverage in NSW). The AEDC data have been linked to the children's birth, health, school and child protection records for the period from birth to school entry, and to the health and criminal records of their parents, as well as mortality databases. Findings to date Descriptive data summarising sex, geographic and socioeconomic distributions, and linkage rates for the various administrative databases are presented. Child data are summarised, and the mental health and criminal records data of the children's parents are provided. Future plans In 2015, at age 11 years, a self-report mental health survey was administered to the cohort in collaboration with government, independent and Catholic primary school sectors. A second record linkage, spanning birth to age 11 years, will be undertaken to link this survey data with the aforementioned administrative databases. This will enable a further identification of putative risk and protective factors for adverse mental health and other outcomes in adolescence, which can then be tested in subsequent record linkages. PMID:26868941

A strabismus susceptibility locus on chromosome 7p

PubMed Central

Parikh, Vaishali; Shugart, Yin Yao; Doheny, Kimberly F.; Zhang, Jie; Li, Lan; Williams, John; Hayden, David; Craig, Brian; Capo, Hilda; Chamblee, Denise; Chen, Cathy; Collins, Mary; Dankner, Stuart; Fiergang, Dean; Guyton, David; Hunter, David; Hutcheon, Marcia; Keys, Marshall; Morrison, Nancy; Munoz, Michelle; Parks, Marshall; Plotsky, David; Protzko, Eugene; Repka, Michael X.; Sarubbi, Maria; Schnall, Bruce; Siatkowski, R. Michael; Traboulsi, Elias; Waeltermann, Joanne; Nathans, Jeremy

2003-01-01

Strabismus has been known to have a significant genetic component, but the mode of inheritance and the identity of the relevant genes have been enigmatic. This paper reports linkage analysis of nonsyndromic strabismus. The principal results of this study are: (i) the demonstrated feasibility of identifying and recruiting large families in which multiple members have (or had) strabismus; (ii) the linkage in one large family of a presumptive strabismus susceptibility locus to 7p22.1 with a multipoint logarithm of odds score of 4.51 under a model of recessive inheritance; and (iii) the failure to observe significant linkage to 7p in six other multiplex families, consistent with genetic heterogeneity among families. These findings suggest that it will be possible to localize and ultimately identify strabismus susceptibility genes by linkage analysis and mutation screening of candidate genes. PMID:14519848

A SSR-based genetic linkage map of cultivated peanut (Arachis hypogaea L.)

USDA-ARS?s Scientific Manuscript database

The objective of this study was to construct a molecular linkage map of cultivated tetraploid peanut using simple sequence repeat (SSR) markers derived primarily from peanut genomic sequences, expressed sequence tags (ESTs), and by "data mining" sequences released in GenBank. Three recombinant inbre...

Linkages over Time between Adolescents' Relationships with Parents and Friends

ERIC Educational Resources Information Center

De Goede, Irene H. A.; Branje, Susan J. T.; Delsing, Marc J. M. H.; Meeus, Wim H. J.

2009-01-01

This 5-wave longitudinal study examines linkages over time between adolescents' perceptions of relationships with parents and friends with respect to support, negative interaction, and power. A total of 575 early adolescents (54.1% boys) and 337 middle adolescents (43.3% boys) participated. Path analyses mainly showed bidirectional associations…

Joint QTL linkage mapping for multiple-cross mating design sharing one common parent

USDA-ARS?s Scientific Manuscript database

Nested association mapping (NAM) is a novel genetic mating design that combines the advantages of linkage analysis and association mapping. This design provides opportunities to study the inheritance of complex traits, but also requires more advanced statistical methods. In this paper, we present th...

Developing Industry Linkages: Learning from Practice.

ERIC Educational Resources Information Center

Misko, Josie

Linkages between Australia's vocational education and training (VET) and technical and further education (TAFE) sectors and industry were examined through 13 case studies involving a variety of industrial sectors in South Australia, New South Wales, and Victoria. Special attention was paid to the processes established by school clusters to develop…

Siblings versus Parents and Friends: Longitudinal Linkages to Adolescent Externalizing Problems

ERIC Educational Resources Information Center

Defoe, Ivy N.; Keijsers, Loes; Hawk, Skyler T.; Branje, Susan; Dubas, Judith Semon; Buist, Kirsten; Frijns, Tom; van Aken, Marcel A. G.; Koot, Hans M.; van Lier, Pol A. C.; Meeus, Wim

2013-01-01

Background: It is well documented that friends' externalizing problems and negative parent-child interactions predict externalizing problems in adolescence, but relatively little is known about the role of siblings. This four-wave, multi-informant study investigated linkages of siblings' externalizing problems and sibling-adolescent negative…

A first insight into population structure and linkage disequilibrium in the US peanut minicore collection

USDA-ARS?s Scientific Manuscript database

Knowledge of genetic diversity, population structure, and degree of linkage disequilibrium (LD) in target association mapping populations is of great importance and is a prerequisite for LD-based mapping. In the present study, 96 genotypes comprising 92 accessions of the US peanut minicore collectio...

Construction of high-quality recombination maps with low-coverage genomic sequencing for joint linkage analysis in maize

USDA-ARS?s Scientific Manuscript database

A genome-wide association study (GWAS) is the foremost strategy used for finding genes that control human diseases and agriculturally important traits, but it often reports false positives. In contrast, its complementary method, linkage analysis, provides direct genetic confirmation, but with limite...

Quantifying landscape linkages among giant panda subpopulations in regional scale conservation.

PubMed

Qi, Dunwu; Hu, Yibo; Gu, Xiaodong; Yang, Xuyi; Yang, Guang; Wei, Fuwen

2012-06-01

Understanding habitat requirements and identifying landscape linkages are essential for the survival of isolated populations of endangered species. Currently, some of the giant panda populations are isolated, which threatens their long-term survival, particularly in the Xiaoxiangling mountains. In the present study, we quantified niche requirements and then identified potential linkages of giant panda subpopulations in the most isolated region, using ecological niche factor analysis and a least-cost path model. Giant pandas preferred habitat with conifer forest and gentle slopes (>20 to ≤30°). Based on spatial distribution of suitable habitat, linkages were identified for the Yele subpopulation to 4 other subpopulations (Liziping, Matou, Xinmin and Wanba). Their lengths ranged from 15 to 54 km. The accumulated cost ranged from 693 to 3166 and conifer forest covered over 31%. However, a variety of features (e.g. major roads, human settlements and large unforested areas) might act as barriers along the linkages for giant panda dispersal. Our analysis quantified giant panda subpopulation connectivity to ensure long-term survival. © 2012 ISZS, Blackwell Publishing and IOZ/CAS.

An Interaction Landscape of Ubiquitin Signaling.

PubMed

Zhang, Xiaofei; Smits, Arne H; van Tilburg, Gabrielle B A; Jansen, Pascal W T C; Makowski, Matthew M; Ovaa, Huib; Vermeulen, Michiel

2017-03-02

Intracellular signaling via the covalent attachment of different ubiquitin linkages to protein substrates is fundamental to many cellular processes. Although linkage-selective ubiquitin interactors have been studied on a case-by-case basis, proteome-wide analyses have not been conducted yet. Here, we present ubiquitin interactor affinity enrichment-mass spectrometry (UbIA-MS), a quantitative interaction proteomics method that makes use of chemically synthesized diubiquitin to enrich and identify ubiquitin linkage interactors from crude cell lysates. UbIA-MS reveals linkage-selective diubiquitin interactions in multiple cell types. For example, we identify TAB2 and TAB3 as novel K6 diubiquitin interactors and characterize UCHL3 as a K27-linkage selective interactor that regulates K27 polyubiquitin chain formation in cells. Additionally, we show a class of monoubiquitin and K6 diubiquitin interactors whose binding is induced by DNA damage. We expect that our proteome-wide diubiquitin interaction landscape and established workflows will have broad applications in the ongoing efforts to decipher the complex language of ubiquitin signaling. Copyright © 2017 Elsevier Inc. All rights reserved.

Linkage localization of X-linked Charcot-Marie-Tooth disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bergoffen, J.; Trofatter, J.; Haines, J.L.

1993-02-01

Charcot-Marie-Tooth disease (CMT), also known as hereditary motor and sensory neuropathy, is a heterogeneous group of slowly progressive, degenerative disorders of peripheral nerve. X-linked CMT (CMTX) (McKusick 302800), a subdivision of type I, or demyelinating, CMT is an X-linked dominant condition with variable penetrance. Previous linkage analysis using RFLPs demonstrated linkage to markers on the proximal long and short arms of the X chromosome, with the more likely localization on the proximal long arm of the X chromosome. Available variable simple-sequence repeats (VSSRs) broaden the possibilities for linkage analysis. This paper presents new linkage data and recombination analysis derived frommore » work with four VSSR markers - AR, PGKP1, DXS453, and DXYS1X - in addition to analysis using RFLP markers described elsewhere. These studies localize the CMTX gene to the proximal Xq segment between PGKP1 (Xq11.2-12) and DXS72 (Xq21.1), with a combined maximum multipoint lod score of 15.3 at DXS453 ([theta] = 0). 32 refs., 3 figs., 2 tabs.« less

First genetic linkage map of Taraxacum koksaghyz Rodin based on AFLP, SSR, COS and EST-SSR markers.

PubMed

Arias, Marina; Hernandez, Monica; Remondegui, Naroa; Huvenaars, Koen; van Dijk, Peter; Ritter, Enrique

2016-08-04

Taraxacum koksaghyz Rodin (TKS) has been studied in many occasions as a possible alternative source for natural rubber production of good quality and for inulin production. Some tire companies are already testing TKS tire prototypes. There are also many investigations on the production of bio-fuels from inulin and inulin applications for health improvement and in the food industry. A limited amount of genomic resources exist for TKS and particularly no genetic linkage map is available in this species. We have constructed the first TKS genetic linkage map based on AFLP, COS, SSR and EST-SSR markers. The integrated linkage map with eight linkage groups (LG), representing the eight chromosomes of Russian dandelion, has 185 individual AFLP markers from parent 1, 188 individual AFLP markers from parent 2, 75 common AFLP markers and 6 COS, 1 SSR and 63 EST-SSR loci. Blasting the EST-SSR sequences against known sequences from lettuce allowed a partial alignment of our TKS map with a lettuce map. Blast searches against plant gene databases revealed some homologies with useful genes for downstream applications in the future.

An Expressed Sequence Tag (EST)-enriched genetic map of turbot (Scophthalmus maximus): a useful framework for comparative genomics across model and farmed teleosts

PubMed Central

2012-01-01

Background The turbot (Scophthalmus maximus) is a relevant species in European aquaculture. The small turbot genome provides a source for genomics strategies to use in order to understand the genetic basis of productive traits, particularly those related to sex, growth and pathogen resistance. Genetic maps represent essential genomic screening tools allowing to localize quantitative trait loci (QTL) and to identify candidate genes through comparative mapping. This information is the backbone to develop marker-assisted selection (MAS) programs in aquaculture. Expressed sequenced tag (EST) resources have largely increased in turbot, thus supplying numerous type I markers suitable for extending the previous linkage map, which was mostly based on anonymous loci. The aim of this study was to construct a higher-resolution turbot genetic map using EST-linked markers, which will turn out to be useful for comparative mapping studies. Results A consensus gene-enriched genetic map of the turbot was constructed using 463 SNP and microsatellite markers in nine reference families. This map contains 438 markers, 180 EST-linked, clustered at 24 linkage groups. Linkage and comparative genomics evidences suggested additional linkage group fusions toward the consolidation of turbot map according to karyotype information. The linkage map showed a total length of 1402.7 cM with low average intermarker distance (3.7 cM; ~2 Mb). A global 1.6:1 female-to-male recombination frequency (RF) ratio was observed, although largely variable among linkage groups and chromosome regions. Comparative sequence analysis revealed large macrosyntenic patterns against model teleost genomes, significant hits decreasing from stickleback (54%) to zebrafish (20%). Comparative mapping supported particular chromosome rearrangements within Acanthopterygii and aided to assign unallocated markers to specific turbot linkage groups. Conclusions The new gene-enriched high-resolution turbot map represents a useful genomic tool for QTL identification, positional cloning strategies, and future genome assembling. This map showed large synteny conservation against model teleost genomes. Comparative genomics and data mining from landmarks will provide straightforward access to candidate genes, which will be the basis for genetic breeding programs and evolutionary studies in this species. PMID:22747677

Exploiting genotyping by sequencing to characterize the genomic structure of the American cranberry through high-density linkage mapping.

PubMed

Covarrubias-Pazaran, Giovanny; Diaz-Garcia, Luis; Schlautman, Brandon; Deutsch, Joseph; Salazar, Walter; Hernandez-Ochoa, Miguel; Grygleski, Edward; Steffan, Shawn; Iorizzo, Massimo; Polashock, James; Vorsa, Nicholi; Zalapa, Juan

2016-06-13

The application of genotyping by sequencing (GBS) approaches, combined with data imputation methodologies, is narrowing the genetic knowledge gap between major and understudied, minor crops. GBS is an excellent tool to characterize the genomic structure of recently domesticated (~200 years) and understudied species, such as cranberry (Vaccinium macrocarpon Ait.), by generating large numbers of markers for genomic studies such as genetic mapping. We identified 10842 potentially mappable single nucleotide polymorphisms (SNPs) in a cranberry pseudo-testcross population wherein 5477 SNPs and 211 short sequence repeats (SSRs) were used to construct a high density linkage map in cranberry of which a total of 4849 markers were mapped. Recombination frequency, linkage disequilibrium (LD), and segregation distortion at the genomic level in the parental and integrated linkage maps were characterized for first time in cranberry. SSR markers, used as the backbone in the map, revealed high collinearity with previously published linkage maps. The 4849 point map consisted of twelve linkage groups spanning 1112 cM, which anchored 2381 nuclear scaffolds accounting for ~13 Mb of the estimated 470 Mb cranberry genome. Bin mapping identified 592 and 672 unique bins in the parentals and a total of 1676 unique marker positions in the integrated map. Synteny analyses comparing the order of anchored cranberry scaffolds to their homologous positions in kiwifruit, grape, and coffee genomes provided initial evidence of homology between cranberry and closely related species. GBS data was used to rapidly saturate the cranberry genome with markers in a pseudo-testcross population. Collinearity between the present saturated genetic map and previous cranberry SSR maps suggests that the SNP locations represent accurate marker order and chromosome structure of the cranberry genome. SNPs greatly improved current marker genome coverage, which allowed for genome-wide structure investigations such as segregation distortion, recombination, linkage disequilibrium, and synteny analyses. In the future, GBS can be used to accelerate cranberry molecular breeding through QTL mapping and genome-wide association studies (GWAS).

Genome-Wide Linkage and Regional Association Study of Blood Pressure Response to the Cold Pressor Test in Han Chinese: The GenSalt Study

PubMed Central

Yang, Xueli; Gu, Dongfeng; He, Jiang; Hixson, James E.; Rao, Dabeeru C.; Lu, Fanghong; Mu, Jianjun; Jaquish, Cashell E.; Chen, Jing; Huang, Jianfeng; Shimmin, Lawrence C.; Rice, Treva K.; Chen, Jichun; Wu, Xigui; Liu, Depei; Kelly, Tanika N.

2014-01-01

Background Blood pressure (BP) response to cold pressor test (CPT) is associated with increased risk of cardiovascular disease. We performed a genome-wide linkage scan and regional association analysis to identify genetic determinants of BP response to CPT. Methods and Results A total of 1,961 Chinese participants completed the CPT. Multipoint quantitative trait linkage analysis was performed, followed by single-marker and gene-based analyses of variants in promising linkage regions (logarithm of odds, LOD ≥ 2). A suggestive linkage signal was identified for systolic BP (SBP) response to CPT at 20p13-20p12.3, with a maximum multipoint LOD score of 2.37. Based on regional association analysis with 1,351 SNPs in the linkage region, we found that marker rs2326373 at 20p13 was significantly associated with mean arterial pressure (MAP) responses to CPT (P = 8.8×10−6) after FDR adjustment for multiple comparisons. A similar trend was also observed for SBP response (P = 0.03) and DBP response (P = 4.6×10−5). Results of gene-based analyses showed that variants in genes MCM8 and SLC23A2 were associated with SBP response to CPT (P = 4.0×10−5 and 2.7×10−4, respectively), and variants in genes MCM8 and STK35 were associated with MAP response to CPT (P = 1.5×10−5 and 5.0×10−5, respectively). Conclusions Within a suggestive linkage region on chromosome 20, we identified a novel variant associated with BP responses to CPT. We also found gene-based associations of MCM8, SLC23A2 and STK35 in this region. Further work is warranted to confirm these findings. Clinical Trial Registration URL: http://www.clinicaltrials.gov; Unique identifier: NCT00721721. PMID:25028485

Climate fluctuations during the Holocene in NW Iberia: High and low latitude linkages

NASA Astrophysics Data System (ADS)

Pena, L. D.; Francés, G.; Diz, P.; Esparza, M.; Grimalt, J. O.; Nombela, M. A.; Alejo, I.

2010-07-01

High resolution benthic foraminiferal stable isotopes (δ 18O, δ 13C) and molecular biomarkers in the sediments are used here to infer rapid climatic changes for the last 8200 years in the Ría de Muros (NW Iberian Margin). Benthic foraminiferal δ 18O and δ 13C potentially register migrations in the position of the hydrographic front formed between two different intermediate water masses: Eastern North Atlantic Central Water of subpolar origin (ENACW sp) and subtropical origin (ENACW st). The molecular biomarkers in the sediment show a strong coupling between continental organic matter inputs and negative δ 13C values in benthic foraminifera. The rapid centennial and millennial events registered in these records have been compared with two well known North Atlantic Holocene records from the subtropical Atlantic sea surface temperatures (SST) anomalies off Cape Blanc, NW Africa and the subpolar Atlantic (Hematite Stained Grains percentage, subpolar North Atlantic). Comparison supports a strong link between high- and low-latitude climatic perturbations at centennial-millennial time scales during the Holocene. Spectral analyses also points to a pole-to-equator propagation of the so-called 1500 yr cycles. Our results demonstrate that during the Holocene, the NW Iberian Margin has undergone a series of rapid events which are likely triggered at high latitudes in the North Atlantic and are rapidly propagated towards lower latitudes. Conceivably, the propagation of these rapid climatic changes involves a shift in atmospheric and oceanic circulatory systems.

The Danish Cardiac Rehabilitation Database.

PubMed

Zwisler, Ann-Dorthe; Rossau, Henriette Knold; Nakano, Anne; Foghmar, Sussie; Eichhorst, Regina; Prescott, Eva; Cerqueira, Charlotte; Soja, Anne Merete Boas; Gislason, Gunnar H; Larsen, Mogens Lytken; Andersen, Ulla Overgaard; Gustafsson, Ida; Thomsen, Kristian K; Boye Hansen, Lene; Hammer, Signe; Viggers, Lone; Christensen, Bo; Kvist, Birgitte; Lindström Egholm, Cecilie; May, Ole

2016-01-01

The Danish Cardiac Rehabilitation Database (DHRD) aims to improve the quality of cardiac rehabilitation (CR) to the benefit of patients with coronary heart disease (CHD). Hospitalized patients with CHD with stenosis on coronary angiography treated with percutaneous coronary intervention, coronary artery bypass grafting, or medication alone. Reporting is mandatory for all hospitals in Denmark delivering CR. The database was initially implemented in 2013 and was fully running from August 14, 2015, thus comprising data at a patient level from the latter date onward. Patient-level data are registered by clinicians at the time of entry to CR directly into an online system with simultaneous linkage to other central patient registers. Follow-up data are entered after 6 months. The main variables collected are related to key outcome and performance indicators of CR: referral and adherence, lifestyle, patient-related outcome measures, risk factor control, and medication. Program-level online data are collected every third year. Based on administrative data, approximately 14,000 patients with CHD are hospitalized at 35 hospitals annually, with 75% receiving one or more outpatient rehabilitation services by 2015. The database has not yet been running for a full year, which explains the use of approximations. The DHRD is an online, national quality improvement database on CR, aimed at patients with CHD. Mandatory registration of data at both patient level as well as program level is done on the database. DHRD aims to systematically monitor the quality of CR over time, in order to improve the quality of CR throughout Denmark to benefit patients.

Obesity and psychotropic medication: a prospective register linkage study among midlife women and men.

PubMed

Svärd, Anna; Lahti, Jouni; Rahkonen, Ossi; Lahelma, Eero; Lallukka, Tea

2016-06-06

Both obesity and mental health are major public health issues. This study aimed to examine whether overweight and obesity among midlife employees are associated with subsequent psychotropic medication. A further aim was to examine the potential effect of key covariates on the association. The Helsinki Health Study baseline survey was conducted in 2000-2002 among 40-60-year-old employees of the City of Helsinki, Finland (n = 8960). The participants were classified as of normal weight (18.5-24.9 kg/m(2)), overweight (25-29.9 kg/m(2)), obese (30-34.9 kg/m(2)) or severely obese (≥35 kg/m(2)) based on self-reported body mass index. Data on psychotropic medication purchases from baseline to 2009 were derived from registers of the Social Insurance Institution of Finland. The final analysis included 4760 women and 1338 men. Antidepressants and sedatives were examined separately. Covariates included socio-demographic factors, workload, health behaviours, physical functioning, somatic ill-health and psychotropic medication prior to baseline. Hazard ratios (HR) for the first psychotropic medication purchase were calculated using Cox regression analysis. Third of women and quarter of men made at least one psychotropic medication purchase during the follow-up. Adjusting for age, obese (HR = 1.57; 95 % CI = 1.10-2.24) and severely obese (HR = 2.15; 95 % CI = 1.29-3.56) men were at risk of having psychotropic medication compared to men of normal weight. These associations disappeared after further adjustment. Severe obesity remained associated with subsequent sedative medication among the men even after full adjustment (HR = 2.12; 95 % CI = 1.17-3.84). No associations were found among the women. Obese and severely obese men, but not women, were at risk of psychotropic medication. Further studies are needed to deepen understanding of the relationship between obesity and mental ill-health, and the possible protecting effects of age, employment, and living environment.

Exploring the Association Between Rosacea and Parkinson Disease: A Danish Nationwide Cohort Study.

PubMed

Egeberg, Alexander; Hansen, Peter Riis; Gislason, Gunnar H; Thyssen, Jacob P

2016-05-01

The pathogenesis of rosacea is unclear, but increased matrix metalloproteinase target tissue activity appears to play an important role. Parkinson disease and other neurodegenerative disorders also display increased matrix metalloproteinase activity that contribute to neuronal loss. To investigate the risk of incident (new-onset) Parkinson disease in patients with rosacea. A nationwide cohort study of the Danish population was conducted using individual-level linkage of administrative registers. All Danish citizens 18 years or older from January 1, 1997, to December 31, 2011 (N = 5 472 745), were included. Data analysis was conducted from June 26 to July 27, 2015. The main outcome was a diagnosis of Parkinson disease. Incidence rates (IRs) per 10 000 person-years were calculated, and incidence rate ratios (IRRs) adjusted for age, sex, socioeconomic status, smoking, alcohol abuse, medication, and comorbidity were estimated by Poisson regression models. A total of 5 404 692 individuals were included in the reference population; of these, 22 387 individuals (9812 [43.8%] women; mean [SD] age at diagnosis, 75.9 [10.2] years) received a diagnosis of Parkinson disease during the study period and 68 053 individuals (45 712 [67.2%] women; mean age, 42.2 [16.5] years) were registered as having rosacea. The IRs of Parkinson disease per 10 000 person-years were 3.54 (95% CI, 3.49-3.59) in the reference population and 7.62 (95% CI, 6.78-8.57) in patients with rosacea. The adjusted IRR of Parkinson disease was 1.71 (95%, CI 1.52-1.92) in patients with rosacea compared with the reference population. There was a 2-fold increased risk of Parkinson disease in patients classified as having ocular rosacea (adjusted IRR, 2.03 [95% CI, 1.67-2.48]), and tetracycline therapy appeared to reduce the risk of Parkinson disease (adjusted IRR, 0.98 [95% CI, 0.97-0.99]). Rosacea constitutes an independent risk factor for Parkinson disease. This association could be due to shared pathogenic mechanisms involving elevated matrix metalloproteinase activity. The clinical consequences of this association require further study.

(67/68)Ga-labeling agent that liberates (67/68)Ga-NOTA-methionine by lysosomal proteolysis of parental low molecular weight polypeptides to reduce renal radioactivity levels.

PubMed

Uehara, Tomoya; Rokugawa, Takemi; Kinoshita, Mai; Nemoto, Souki; Fransisco Lazaro, Guerra Gomez; Hanaoka, Hirofumi; Arano, Yasushi

2014-11-19

The renal localization of gallium-67 or gallium-68 ((67/68)Ga)-labeled low molecular weight (LMW) probes such as peptides and antibody fragments constitutes a problem in targeted imaging. Wu et al. previously showed that (67)Ga-labeled S-2-(4-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (SCN-Bz-NOTA)-conjugated methionine ((67)Ga-NOTA-Met) was rapidly excreted from the kidney in urine following lysosomal proteolysis of the parental (67)Ga-NOTA-Bz-SCN-disulfide-stabilized Fv fragment (Bioconjugate Chem., (1997) 8, 365-369). In the present study, a new (67/68)Ga-labeling reagent for LMW probes that liberates (67/68)Ga-NOTA-Met was designed, synthesized, and evaluated using longer-lived (67)Ga in order to reduce renal radioactivity levels. We employed a methionine-isoleucine (MI) dipeptide bond as the cleavable linkage. The amine residue of MI was coupled with SCN-Bz-NOTA for (67)Ga-labeling, while the carboxylic acid residue of MI was derivatized to maleimide for antibody conjugation in order to synthesize NOTA-MI-Mal. A Fab fragment of the anti-Her2 antibody was thiolated with iminothiolane, and NOTA-MI-Mal was conjugated with the antibody fragment by maleimide-thiol chemistry. The Fab fragment was also conjugated with SCN-Bz-NOTA (NOTA-Fab) for comparison. (67)Ga-NOTA-MI-Fab was obtained at radiochemical yields of over 95% and was stable in murine serum for 24 h. In the biodistribution study using normal mice, (67)Ga-NOTA-MI-Fab registered significantly lower renal radioactivity levels from 1 to 6 h postinjection than those of (67)Ga-NOTA-Fab. An analysis of urine samples obtained 6 h after the injection of (67)Ga-NOTA-MI-Fab showed that the majority of radioactivity was excreted as (67)Ga-NOTA-Met. In the biodistribution study using tumor-bearing mice, the tumor to kidney ratios of (67)Ga-NOTA-MI-Fab were 4 times higher (6 h postinjection) than those of (67)Ga-NOTA-Fab. Although further studies including the structure of radiometabolites and/or cleavable linkages are required, the results of the present study indicate that the current chemical design is applicable to the development of (67)Ga-labeled Fabs for low renal radioactivity levels.

Meat, fish, poultry and egg consumption in relation to risk of pancreatic cancer: a prospective study.

PubMed

Larsson, Susanna C; Håkanson, Niclas; Permert, Johan; Wolk, Alicja

2006-06-01

High meat consumption has been associated with increased risk of pancreatic cancer in several, although not all, case-control studies. However, prospective data on this relationship are sparse, and the results have been inconsistent. We prospectively evaluated meat, fish, poultry, and egg consumption in relation to pancreatic cancer incidence in a population-based cohort of 61,433 Swedish women. Diet was assessed with a food-frequency questionnaire at baseline (1987-1990) and again in 1997. Pancreatic cancers were ascertained through linkage to the Swedish Cancer Register. Cox proportional hazards models were used to estimate multivariate hazard ratios with 95% confidence intervals (CI). During the 941,218 person-years of follow-up, from 1987 through 2004, 172 incident cases of pancreatic cancer were diagnosed. Long-term red meat consumption (using data from both dietary questionnaires) was positively associated with risk of pancreatic cancer (p-trend = 0.01), whereas long-term poultry consumption was inversely (p-trend = 0.04) associated with risk. The multivariate hazard ratios for the highest versus the lowest category of consumption were 1.73 (95% CI = 0.99-2.98) for red meat and 0.44 (95% CI = 0.20-0.97) for poultry. There were no significant associations with processed meat, fish or egg consumption. Findings from this prospective study suggest that substituting poultry for red meat might reduce the risk of pancreatic cancer.

Parity and risk of stomach cancer by sub-site: a national Swedish study.

PubMed

Bahmanyar, S; Lambe, M; Zendehdel, K; Nyrén, O; Boffetta, P; Ye, W

2008-04-08

We investigated stomach cancer risk by anatomic sub-site in relation to parity, as a marker for higher exposure to sex hormones, in a case-control study, nested within a cohort of 2,406,439 Swedish women born in 1925 or later and followed from 1970 or age 30 until emigration, death, any cancer diagnosis, or through 2004, whichever occurred first. We identified 286 cardia and 2498 non-cardia stomach cancer cases with five matched controls for each case. Cross-linkage with the Multi-Generation Register provided information about reproductive history. Using conditional logistic regression models for estimating odds ratios (ORs) and corresponding 95% confidence intervals (CIs), adjusted for education level and occupation, we found no association between any aspect of parity and non-cardia stomach cancer (OR=1.01, 95% CI 0.89-1.15, comparing parous with nulliparous women). However, a 30% risk reduction for postmenopausal cardia cancer (OR=0.7, 95% CI 0.4-1.0) was noted among parous relative to nulliparous women and the risk for premenopausal cardia cancer fell with increasing number of children (P for trend=0.04). Our results indicate that exposure to female sex hormones does not protect against non-cardia stomach cancer and does not explain male predominance. The observed moderate inverse relationship between parity and cardia cancer may be mediated by non-hormonal factors and warrants further study.

Mapping Flagellar Genes in Chlamydomonas Using Restriction Fragment Length Polymorphisms

PubMed Central

Ranum, LPW.; Thompson, M. D.; Schloss, J. A.; Lefebvre, P. A.; Silflow, C. D.

1988-01-01

To correlate cloned nuclear DNA sequences with previously characterized mutations in Chlamydomonas and, to gain insight into the organization of its nuclear genome, we have begun to map molecular markers using restriction fragment length polymorphisms (RFLPs). A Chlamydomonas reinhardtii strain (CC-29) containing phenotypic markers on nine of the 19 linkage groups was crossed to the interfertile species Chlamydomonas smithii. DNA from each member of 22 randomly selected tetrads was analyzed for the segregation of RFLPs associated with cloned genes detected by hybridization with radioactive DNA probes. The current set of markers allows the detection of linkage to new molecular markers over approximately 54% of the existing genetic map. This study focused on mapping cloned flagellar genes and genes whose transcripts accumulate after deflagellation. Twelve different molecular clones have been assigned to seven linkage groups. The α-1 tubulin gene maps to linkage group III and is linked to the genomic sequence homologous to pcf6-100, a cDNA clone whose corresponding transcript accumulates after deflagellation. The α-2 tubulin gene maps to linkage group IV. The two β-tubulin genes are linked, with the β-1 gene being approximately 12 cM more distal from the centromere than the β-2 gene. A clone corresponding to a 73-kD dynein protein maps to the opposite arm of the same linkage group. The gene corresponding to the cDNA clone pcf6-187, whose mRNA accumulates after deflagellation, maps very close to the tightly linked pf-26 and pf-1 mutations on linkage group V. PMID:2906025

Effective interventions to improve young adults' linkage to HIV care in Sub-Saharan Africa: a systematic review.

PubMed

Mavegam, Bertille Octavie; Pharr, Jennifer R; Cruz, Patricia; Ezeanolue, Echezona E

2017-10-01

HIV/AIDS remains a major public health problem despite the efforts to prevent and decrease its spread. Sub-Saharan Africa (SSA) represents 70% of the global number of people living with HIV and 73% of all HIV/AIDS-related deaths. Young adults age 15-24 years are disproportionately impacted by HIV/AIDS in SSA with 34% of people living with HIV (PLWHIV) and 37% of newly diagnosed individuals being in this age group. It is important that PLWHIV be linked to care to facilitate antiretroviral therapy (ART) initiation and limit the spread of infection. We conducted a systematic literature review to identify effective interventions designed to improve linkage to care among HIV-infected young adults in SSA. One hundred and forty-six titles and abstracts were screened, 28 full-texts were reviewed, and 6 articles met the inclusion and exclusion criteria. Home-based HIV counseling and testing, home-based HIV self-testing, and mobile HIV counseling and testing followed by proper referral of HIV-positive patients to HIV care were effective for improving linkage of young adults to care. Other factors such as referral forms, transportation allowance, home initiation of HIV care, and volunteer escort to the HIV treatment clinic were effective in reducing time to linkage to care. There is a vast need for research and interventions that target HIV-positive young adults in SSA which aim to improve their linkage and access to HIV care. The results of this study illustrate effective interventions in improving linkage to care and reducing time to linkage to care of young adults in SSA.

[Implementation and (cost-)effectiveness of case management for people with dementia and their informal caregivers: results of the COMPAS study].

PubMed

van Mierlo, Lisa D; MacNeil-Vroomen, Janet; Meiland, Franka J M; Joling, Karlijn J; Bosmans, Judith E; Dröes, Rose Marie; Moll van Charante, Eric P; de Rooij, Sophia E J A; van Hout, Hein P J

2016-12-01

Different forms of case management for dementia have emerged over the past few years. In the COMPAS study (Collaborative dementia care for patients and caregivers study), two prominent Dutch case management forms were studied: the linkage and the integrated care form. Evaluation of the (cost)effectiveness of two dementia case management forms compared to usual care as well as factors that facilitated or impeded their implementation. A mixed methods design with a) a prospective, observational controlled cohort study with 2 years follow-up among 521 dyads of people with dementia and their primary informal caregiver with and without case management; b) interviews with 22 stakeholders on facilitating and impeding factors of the implementation and continuity of the two case management models. Outcome measures were severity and frequency of behavioural problems (NPI) for the person with dementia and mental health complaints (GHQ-12) for the informal caregiver, total met and unmet care needs (CANE) and quality adjusted life years (QALYs). Outcomes showed a better quality of life of informal caregivers in the integrated model compared to the linkage model. Caregivers in the control group reported more care needs than those in both case management groups. The independence of the case management provider in the integrated model facilitated the implementation, while the rivalry between multiple providers in the linkage model impeded the implementation. The costs of care were lower in the linkage model (minus 22 %) and integrated care model (minus 33 %) compared to the control group. The integrated care form was (very) cost-effective in comparison with the linkage form or no case management. The integrated care form is easy to implement.

Chocolate consumption and risk of atrial fibrillation: Two cohort studies and a meta-analysis.

PubMed

Larsson, Susanna C; Drca, Nikola; Jensen-Urstad, Mats; Wolk, Alicja

2018-01-01

Chocolate consumption has been inconsistently associated with risk of atrial fibrillation (AF). We investigated the association between chocolate consumption and risk of AF in Swedish adults from two cohort studies and conducted a meta-analysis to summarize available evidence from cohort studies on this topic. Our study population comprised 40,009 men from the Cohort of Swedish Men and 32,486 women from the Swedish Mammography Cohort. Incident AF cases were ascertained through linkage with the Swedish National Patient Register. Published cohort studies of chocolate consumption in relation to risk of AF were identified by a PubMed search through September 14, 2017. During a mean follow-up of 14.6 years, AF was diagnosed in 9978 Swedish men and women. Compared with non-consumers, the multivariable hazard ratio of AF for those in the highest category of chocolate consumption (≥3-4 servings/week) was 0.96 (95% CI 0.88-1.04). In a random-effects meta-analysis of 5 cohort studies, including 180,454 participants and 16,356 AF cases, the hazard ratios of AF were 0.97 (95% CI 0.94-1.01) per 2 servings/week increase in chocolate consumption and 0.96 (95% CI 0.90-1.03) for the highest versus lowest category of chocolate consumption. Available data provide no evidence of an association of chocolate consumption with risk of AF. Copyright © 2017 Elsevier Inc. All rights reserved.

Limited privacy protection and poor sensitivity: Is it time to move on from the statistical linkage key-581?

PubMed

Randall, Sean M; Ferrante, Anna M; Boyd, James H; Brown, Adrian P; Semmens, James B

2016-08-01

The statistical linkage key (SLK-581) is a common tool for record linkage in Australia, due to its ability to provide some privacy protection. However, newer privacy-preserving approaches may provide greater privacy protection, while allowing high-quality linkage. To evaluate the standard SLK-581, encrypted SLK-581 and a newer privacy-preserving approach using Bloom filters, in terms of both privacy and linkage quality. Linkage quality was compared by conducting linkages on Australian health datasets using these three techniques and examining results. Privacy was compared qualitatively in relation to a series of scenarios where privacy breaches may occur. The Bloom filter technique offered greater privacy protection and linkage quality compared to the SLK-based method commonly used in Australia. The adoption of new privacy-preserving methods would allow both greater confidence in research results, while significantly improving privacy protection. © The Author(s) 2016.

High-Throughput Sequencing and Linkage Mapping of a Clownfish Genome Provide Insights on the Distribution of Molecular Players Involved in Sex Change.

PubMed

Casas, Laura; Saenz-Agudelo, Pablo; Irigoien, Xabier

2018-03-06

Clownfishes are an excellent model system for investigating the genetic mechanism governing hermaphroditism and socially-controlled sex change in their natural environment because they are broadly distributed and strongly site-attached. Genomic tools, such as genetic linkage maps, allow fine-mapping of loci involved in molecular pathways underlying these reproductive processes. In this study, a high-density genetic map of Amphiprion bicinctus was constructed with 3146 RAD markers in a full-sib family organized in 24 robust linkage groups which correspond to the haploid chromosome number of the species. The length of the map was 4294.71 cM, with an average marker interval of 1.38 cM. The clownfish linkage map showed various levels of conserved synteny and collinearity with the genomes of Asian and European seabass, Nile tilapia and stickleback. The map provided a platform to investigate the genomic position of genes with differential expression during sex change in A. bicinctus. This study aims to bridge the gap of genome-scale information for this iconic group of species to facilitate the study of the main gene regulatory networks governing social sex change and gonadal restructuring in protandrous hermaphrodites.

Genome-wide association and linkage identify modifier loci of lung disease severity in cystic fibrosis at 11p13 and 20q13.2

PubMed Central

Wright, Fred A.; Strug, Lisa J.; Doshi, Vishal K.; Commander, Clayton W.; Blackman, Scott M.; Sun, Lei; Berthiaume, Yves; Cutler, David; Cojocaru, Andreea; Collaco, J. Michael; Corey, Mary; Dorfman, Ruslan; Goddard, Katrina; Green, Deanna; Kent, Jack W.; Lange, Ethan M.; Lee, Seunggeun; Li, Weili; Luo, Jingchun; Mayhew, Gregory M.; Naughton, Kathleen M.; Pace, Rhonda G.; Paré, Peter; Rommens, Johanna M.; Sandford, Andrew; Stonebraker, Jaclyn R.; Sun, Wei; Taylor, Chelsea; Vanscoy, Lori L.; Zou, Fei; Blangero, John; Zielenski, Julian; O’Neal, Wanda K.; Drumm, Mitchell L.; Durie, Peter R.; Knowles, Michael R.; Cutting, Garry R.

2012-01-01

A combined genome-wide association and linkage study was used to identify loci causing variation in CF lung disease severity. A significant association (P=3. 34 × 10-8) near EHF and APIP (chr11p13) was identified in F508del homozygotes (n=1,978). The association replicated in F508del homozygotes (P=0.006) from a separate family-based study (n=557), with P=1.49 × 10-9 for the three-study joint meta-analysis. Linkage analysis of 486 sibling pairs from the family-based study identified a significant QTL on chromosome 20q13.2 (LOD=5.03). Our findings provide insight into the causes of variation in lung disease severity in CF and suggest new therapeutic targets for this life-limiting disorder. PMID:21602797

Facilitating mental health research for patients, clinicians and researchers: a mixed-method study.

PubMed

Robotham, D; Waterman, S; Oduola, S; Papoulias, C; Craig, T; Wykes, T

2016-08-08

Research registers using Consent for Contact (C4C) can facilitate recruitment into mental health research studies, allowing investigators to contact patients based on clinical records information. We investigated whether such a register was useful for mental health research, seeking the perspectives of patients and research investigators. In 2012, a C4C register was developed in a large secondary mental health provider within the UK; almost 9000 patients have joined. This mixed-method study audited the effectiveness of the register. A 'mystery shopper' exercise was conducted, and patients (n=21) were recruited to ask clinicians about the availability of research opportunities. Structured interviews were conducted with patients (n=52) about their experiences of being on the register. Similar interviews were conducted with 18 investigators from 19 studies, who had attempted to use the register to recruit participants. The impact of C4C on study recruitment, and whether it helped patients learn about research. So far, the register has provided 928 individuals with 1085 research opportunities (in 60% of cases, the individual agreed to participate in the study). Clinicians were willing to link patients to research opportunities, but often lacked information about studies. For patients, the register provided opportunities which they may not otherwise have; 27 of 52 had participated in studies since joining the register (18 participating for the first time). Most investigators used the register to supplement recruitment to their studies, but described problems in prescreening potential participants from a clinical record for complex studies. Although the register helped investigators recruit for studies, and provided patients with research opportunities, clinicians' input is still useful for identifying suitable participants. C4C registers should be adapted to provide clinicians with automatically updated information on local studies allowing them to match patients on their caseload with active studies. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Facilitating mental health research for patients, clinicians and researchers: a mixed-method study

PubMed Central

Robotham, D; Waterman, S; Oduola, S; Papoulias, C; Craig, T; Wykes, T

2016-01-01

Objectives Research registers using Consent for Contact (C4C) can facilitate recruitment into mental health research studies, allowing investigators to contact patients based on clinical records information. We investigated whether such a register was useful for mental health research, seeking the perspectives of patients and research investigators. Setting and design In 2012, a C4C register was developed in a large secondary mental health provider within the UK; almost 9000 patients have joined. This mixed-method study audited the effectiveness of the register. Participants A ‘mystery shopper’ exercise was conducted, and patients (n=21) were recruited to ask clinicians about the availability of research opportunities. Structured interviews were conducted with patients (n=52) about their experiences of being on the register. Similar interviews were conducted with 18 investigators from 19 studies, who had attempted to use the register to recruit participants. Outcome measures The impact of C4C on study recruitment, and whether it helped patients learn about research. Results So far, the register has provided 928 individuals with 1085 research opportunities (in 60% of cases, the individual agreed to participate in the study). Clinicians were willing to link patients to research opportunities, but often lacked information about studies. For patients, the register provided opportunities which they may not otherwise have; 27 of 52 had participated in studies since joining the register (18 participating for the first time). Most investigators used the register to supplement recruitment to their studies, but described problems in prescreening potential participants from a clinical record for complex studies. Conclusions Although the register helped investigators recruit for studies, and provided patients with research opportunities, clinicians' input is still useful for identifying suitable participants. C4C registers should be adapted to provide clinicians with automatically updated information on local studies allowing them to match patients on their caseload with active studies. PMID:27503859

Genetic linkage study of bipolar disorder and the serotonin transporter

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kelsoe, J.R.; Morison, M.; Mroczkowski-Parker, Z.

1996-04-09

The serotonin transporter (HTT) is an important candidate gene for the genetic transmission of bipolar disorder. It is the site of action of many antidepressants, and plays a key role in the regulation of serotonin neurotransmission. Many studies of affectively ill patients have found abnormalities in serotonin metabolism, and dysregulation of the transporter itself. The human serotonin transporter has been recently cloned and mapped to chromosome 17. We have identified a PstI RFLP at the HTT locus, and here report our examination of this polymorphism for possible linkage to bipolar disorder. Eighteen families were examined from three populations: the Oldmore » Order Amish, Iceland, and the general North American population. In addition to HTT, three other microsatellite markers were examined, which span an interval known to contain HTT. Linkage analyses were conducted under both dominant and recessive models, as well as both narrow (bipolar only) and broad (bipolar + recurrent unipolar) diagnostic models. Linkage could be excluded to HTT under all models examined. Linkage to the interval spanned by the microsatellites was similarly excluded under the dominant models. In two individual families, maximum lod scores of 1.02 and 0.84 were obtained at D17S798 and HTT, respectively. However, these data overall do not support the presence of a susceptibility locus for bipolar disorder near the serotonin transporter. 20 refs., 2 tabs.« less

Haplotype analysis and a novel allele-sharing method refines a chromosome 4p locus linked to bipolar affective disorder.

PubMed

Le Hellard, Stephanie; Lee, Andrew J; Underwood, Sarah; Thomson, Pippa A; Morris, Stewart W; Torrance, Helen S; Anderson, Susan M; Adams, Richard R; Navarro, Pau; Christoforou, Andrea; Houlihan, Lorna M; Detera-Wadleigh, Sevilla; Owen, Michael J; Asherson, Philip; Muir, Walter J; Blackwood, Douglas H R; Wray, Naomi R; Porteous, David J; Evans, Kathryn L

2007-03-15

Bipolar affective disorder (BPAD) and schizophrenia (SCZ) are common conditions. Their causes are unknown, but they include a substantial genetic component. Previously, we described significant linkage of BPAD to a chromosome 4p locus within a large pedigree (F22). Others subsequently have found evidence for linkage of BPAD and SCZ to this region. We constructed high-resolution haplotypes for four linked families, calculated logarithm of the odds (LOD) scores, and developed a novel method to assess the extent of allele sharing within genes between the families. We describe an increase in the F22 LOD score for this region. Definition and comparison of the linked haplotypes allowed us to prioritize two subregions of 3.8 and 4.4 Mb. Analysis of the extent of allele sharing within these subregions identified 200 kb that shows increased allele sharing between families. Linkage of BPAD to chromosome 4p has been strengthened. Haplotype analysis in the additional linked families refined the 20-Mb linkage region. Development of a novel allele-sharing method allowed us to bridge the gap between conventional linkage and association studies. Description of a 200-kb region of increased allele sharing prioritizes this region, which contains two functional candidate genes for BPAD, SLC2A9, and WDR1, for subsequent studies.

The ties that bind: interorganizational linkages and physician-system alignment.

PubMed

Alexander, J A; Waters, T M; Burns, L R; Shortell, S M; Gillies, R R; Budetti, P P; Zuckerman, H S

2001-07-01

To examine the association between the degree of alignment between physicians and health care systems, and interorganizational linkages between physician groups and health care systems. The study used a cross sectional, comparative analysis using a sample of 1,279 physicians practicing in loosely affiliated arrangements and 1,781 physicians in 61 groups closely affiliated with 14 vertically integrated health systems. Measures of physician alignment were based on multiitem scales validated in previous studies and derived from surveys sent to individual physicians. Measures of interorganizational linkages were specified at the institutional, administrative, and technical core levels of the physician group and were developed from surveys sent to the administrator of each of the 61 physician groups in the sample. Two stage Heckman models with fixed effects adjustments in the second stage were used to correct for sample selection and clustering respectively. After accounting for sample selection, fixed effects, and group and individual controls, physicians in groups with more valued practice service linkages display consistently higher alignment with systems than physicians in groups that have fewer such linkages. Results also suggest that centralized administrative control lowers physician-system alignment for selected measures of alignment. Governance interlocks exhibited only weak associations with alignment. Our findings suggest that alignment generally follows resource exchanges that promote value-added contributions to physicians and physician groups while preserving control and authority within the group.

Identification of stable QTLs for seed oil content by combined linkage and association mapping in Brassica napus.

PubMed

Sun, Fengming; Liu, Jing; Hua, Wei; Sun, Xingchao; Wang, Xinfa; Wang, Hanzhong

2016-11-01

Seed oil content is an important agricultural trait in rapeseed breeding. Although numerous quantitative trait locus (QTL) have been identified, most of them cannot be applied in practical breeding mainly due to environmental instability or large confidence intervals. The purpose of this study was to identify and validate high quality and more stable QTLs by combining linkage mapping and genome-wide association study (GWAS). For linkage mapping, we constructed two F 2 populations from crosses of high-oil content (∼50%) lines 6F313 and 61616 with a low-oil content (∼40%) line 51070. Two high density linkage maps spanned 1987cM (1659 bins) and 1856cM (1746 bins), respectively. For GWAS, we developed more than 34,000 high-quality SNP markers based on 227 accessions. Finally, 40 QTLs and 29 associations were established by linkage and association mapping in different environments. After merging the results, 32 consensus QTLs were obtained and 7 of them were identified by both mapping methods. Seven overlapping QTLs covered an average confidence interval of 183kb and explained the phenotypic variation of 10.23 to 24.45%. We further developed allele-specific PCR primers to identify each of the seven QTLs. These stable QTLs should be useful in gene cloning and practical breeding application. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Report from the Maryland epidemiology schizophrenia linkage study: No evidence for linkage between schizophrenia and a number of candidate and other genomic regions using a complex dominant model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Karayiorgou, M.; Hwang, J.; Elango, R.

Our collaborative group has undertaken a linkage study of schizophrenia, using a systematic sample of patients admitted to Maryland hospitals. An initial sample of 39 families, each having two or more affecteds, was available for genotyping candidate genes, candidate regions, and highly polymorphic markers randomly distributed throughout the genome. We used a single complex dominant model (with a disease gene frequency of 0.005 and age-dependent penetrance for affected phenotype: for under 35, penetrance = .45; for 35 and older, penetrance = .85). We report here 130 markers which met the exclusion criteria of LOD score < -2.00 at theta >more » 0.01 in at least 10 informative families, and no evidence for heterogeneity. We also report here markers that were tested as candidates for linkage to the schizophrenic phenotype. They were selected based on the following criteria: (a) proximity to reported chromosomal rearrangements (both 5q and 11q), (b) suggestions of linkage from other families (5q), or (c) presence of a candidate gene (5q, 11q, 3q: dopamine receptors 1, 2, and 3, respectively). We also tested for mutations of codon 717 in exon 17 of the amyloid precursor protein (APP) gene and were unable to detect the C to T substitution in our schizophrenic group. 48 refs., 2 tabs.« less

Autosomal dominant cerebellar ataxia with retinal degeneration (ADCA II): clinical and neuropathological findings in two pedigrees and genetic linkage to 3p12-p21.1.

PubMed

Jöbsis, G J; Weber, J W; Barth, P G; Keizers, H; Baas, F; van Schooneveld, M J; van Hilten, J J; Troost, D; Geesink, H H; Bolhuis, P A

1997-04-01

To investigate relations between clinical and neuropathological features and age of onset, presence of anticipation, and genetic linkage in autosomal dominant cerebellar ataxia type II (ADCA II). The natural history of ADCA II was studied on the basis of clinical and neuropathological findings in two pedigrees and genetic linkage studies were carried out with polymorphic DNA markers in the largest, four generation, pedigree. Ataxia was constant in all age groups. Retinal degeneration with early extinction of the electroretinogram constituted an important component in juvenile and early adult (< 25 years) onset but was variable in late adult presentation. Neuromuscular involvement due to spinal anterior horn disease was an important contributing factor to illness in juvenile cases. Postmortem findings in four patients confirm the general neurodegenerative nature of the disease, which includes prominent spinal anterior horn involvement and widespread involvement of grey and white matter. Genetic linkage was found with markers to chromosome 3p12-p21.1 (maximum pairwise lod score 4.42 at D3S1285). The sequence of clinical involvement seems related to age at onset. Retinal degeneration is variable in late onset patients and neuromuscular features are important in patients with early onset. Strong anticipation was found in subsequent generations. Linkage of ADCA II to chromosome 3p12-p21.1 is confirmed.

Variation in GIGYF2 is not associated with Parkinson disease.

PubMed

Nichols, W C; Kissell, D K; Pankratz, N; Pauciulo, M W; Elsaesser, V E; Clark, K A; Halter, C A; Rudolph, A; Wojcieszek, J; Pfeiffer, R F; Foroud, T

2009-06-02

A recent study reported that mutations in a gene on chromosome 2q36-37, GIGYF2, result in Parkinson disease (PD). We have previously reported linkage to this chromosomal region in a sample of multiplex PD families, with the strongest evidence of linkage obtained using the subset of the sample having the strongest family history of disease and meeting the strictest diagnostic criteria. We have tested whether mutations in GIGYF2 may account for the previously observed linkage finding. We sequenced the GIGYF2 coding region in 96 unrelated patients with PD used in our original study that contributed to the chromosome 2q36-37 linkage signal. Subsequently, we genotyped the entire sample of 566 multiplex PD kindreds as well as 1,447 controls to test whether variants in GIGYF2 are causative or increase susceptibility for PD. We detected three novel variants as well as one of the previously reported seven variants in a total of five multiple PD families; however, there was no consistent evidence that these variants segregated with PD in these families. We also did not find a significant increase in risk for PD among those inheriting variants in GIGYF2 (p = 0.28). We believe that variation in a gene other than GIGYF2 accounts for the previously reported linkage finding on chromosome 2q36-37.

Linkage and association studies identify a novel locus for Alzheimer disease at 7q36 in a Dutch population-based sample.

PubMed

Rademakers, Rosa; Cruts, Marc; Sleegers, Kristel; Dermaut, Bart; Theuns, Jessie; Aulchenko, Yurii; Weckx, Stefan; De Pooter, Tim; Van den Broeck, Marleen; Corsmit, Ellen; De Rijk, Peter; Del-Favero, Jurgen; van Swieten, John; van Duijn, Cornelia M; Van Broeckhoven, Christine

2005-10-01

We obtained conclusive linkage of Alzheimer disease (AD) with a candidate region of 19.7 cM at 7q36 in an extended multiplex family, family 1270, ascertained in a population-based study of early-onset AD in the northern Netherlands. Single-nucleotide polymorphism and haplotype association analyses of a Dutch patient-control sample further supported the linkage at 7q36. In addition, we identified a shared haplotype at 7q36 between family 1270 and three of six multiplex AD-affected families from the same geographical region, which is indicative of a founder effect and defines a priority region of 9.3 cM. Mutation analysis of coding exons of 29 candidate genes identified one linked synonymous mutation, g.38030G-->C in exon 10, that affected codon 626 of the PAX transactivation domain interacting protein gene (PAXIP1). It remains to be determined whether PAXIP1 has a functional role in the expression of AD in family 1270 or whether another mutation at this locus explains the observed linkage and sharing. Together, our linkage data from the informative family 1270 and the association data in the population-based early-onset AD patient-control sample strongly support the identification of a novel AD locus at 7q36 and re-emphasize the genetic heterogeneity of AD.

Data linkage capabilities in Australia: practical issues identified by a Population Health Research Network 'Proof of Concept project'.

PubMed

Mitchell, Rebecca J; Cameron, Cate M; McClure, Rod J; Williamson, Ann M

2015-08-01

To describe the practical issues that need to be overcome to conduct national data linkage projects in Australia and propose recommendations to improve efficiency. Review of the processes, documentation and applications required to conduct national data linkage in Australia. The establishment of state and national data linkage centres in Australia has placed Australia at the forefront of research linking health-related administrative data collections. However, improvements are needed to reduce the clerical burden on researchers, simplify the process of obtaining ethics approval, improve data accessibility, and thus improve the efficiency of data linkage research. While a sound state and national data linkage infrastructure is in place, the current complexity, duplication and lack of cohesion undermines any attempts to conduct research involving national record linkage in a timely manner. Data linkage applications and Human Research Ethics Committee approval processes need to be streamlined and duplication removed, in order to reduce the administrative and financial burden on researchers if national data linkage research is to be viable. © 2015 Public Health Association of Australia.

Postadoption and Guardianship: An Evaluation of the Adoption Preservation, Assessment, and Linkage Program

ERIC Educational Resources Information Center

Liao, Minli; Testa, Mark

2016-01-01

Objectives: This study evaluated the effects of the Adoption Preservation, Assessment, and Linkage (APAL) postpermanency program. Method: A quasi-experimental, posttest-only design was used to estimate the program's effects on youth discharged from foster care to adoption or legal guardianship. A random sample was surveyed (female = 44.7%; African…

Linkages among Adolescent Girls' Romantic Relationships, Best Friendships, and Peer Networks

ERIC Educational Resources Information Center

Kuttler, Ami Flam; La Greca, Annette M.

2004-01-01

This study examined the linkages among girls' best friendships and romantic relationships and accounted for the level of dating involvement as a moderating variable. Social exchange and Sullivan's socioemotional theories served as guides in this process. Questionnaires were administered to 446 girls aged 15-19 years. Results showed that: (a)…

Nested association mapping for dissecting complex traits using Peanut 58K SNP array

USDA-ARS?s Scientific Manuscript database

Genome-wide association studies (GWAS) and linkage mapping have been the two most predominant strategies to dissect complex traits, but are limited by the occurrence of false positives reported for GWAS, and low resolution in the case of linkage analysis. This has led to the development of a joint a...

Construction of a high-density high-resolution genetic map and its integration with BAC-based physical map in channel catfish

USDA-ARS?s Scientific Manuscript database

Construction of genetic linkage map is essential for genetic and genomic studies. Recent advances in sequencing and genotyping technologies made it possible to generate high-density and high-resolution genetic linkage maps, especially for the organisms lacking extensive genomic resources. In the pre...

Examining Linkages between Psychological Health Problems, Socio-Demographic Characteristics and Workplace Stressors in Pakistan's Academia

ERIC Educational Resources Information Center

Khan, Anwar; Yusoff, Rosman Bin Md; Isa, Khairunesa Binti

2016-01-01

Scholarly work and research are globally known as stressful and challenging. Teachers may develop different psychological health problems once they are exposed to workplace stressors. Considering it as a serious issue of education sector, this study has examined the linkages between prevalent workplace stressors and psychological health problems…

The Interplay of Graph and Text in the Acquisition of Historical Constructs

ERIC Educational Resources Information Center

Shand, Kristen

2009-01-01

Graphs are often conjoined with text passages in history textbooks to help students comprehend complex constructs. Four linkages connect text and graphs: appropriate elements, fitting patterns, suitable labels and causal markers. Graphs in current textbooks contain few such linkages and seldom mirror the construct under study. An experiment…

Work Values and Job Satisfaction of Family Physicians

ERIC Educational Resources Information Center

Bouwkamp-Memmer, Jennifer C.; Whiston, Susan C.; Hartung, Paul J.

2013-01-01

Theory and prior research suggest linkages between work values and job satisfaction. The present study examined such linkages in a group of workers in a professional occupation. Family physicians (134 women, 206 men, 88% Caucasian) responded to context-specific measures of work values and job satisfaction. ANOVA results indicated a work values…

Potential linkage for schizophrenia on chromosome 22q12-q13: A replication study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schwab, S.G.; Bondy, B.; Wildenauer, D.B.

1995-10-09

In an attempt to replicate a potential linkage on chromosome 22q12-q13.1 reported by Pulver et al., we have analyzed 4 microsatellite markers which span this chromosomal region, including the IL2RB locus, for linkage with schizophrenia in 30 families from Israel and Germany. Linkage analysis by pairwise lod score analysis as well as by multipoint analysis did not provide evidence for a single major gene locus. However, a lod score of Z{sub max} = 0.612 was obtained for a dominant model of inheritance with the marker D22S304 at recombination fraction 0.2 by pairwise analysis. In addition, using a nonparametric method, sibmore » pair analysis, a P value of 0.068 corresponding to a lod score of 0.48 was obtained for this marker. This finding, together with those of Pulver et al., is suggestive of a genetic factor in this region, predisposing for schizophrenia in a subset of families. Further studies using nonparametric methods should be conducted in order to clarify this point. 32 refs., 1 fig., 4 tabs.« less

Reactivity of phosphorus mononitride and interstellar formation of molecules containing phospazo linkage: A computational study on the reaction between HSi (X2Γ) and PN (X1Σ+)

NASA Astrophysics Data System (ADS)

Bhasi, Priya; Nhlabatsi, Zanele P.; Sitha, Sanyasi

2017-12-01

Phosphorus mononitride (PN) shows some interesting chemistry due to its low dissociation energy (compared to N2) and small dipole moment (zero dipole moment for N2). In this work, a reaction between HSi (X2Γ) and PN (X1Σ+) has been studied using various computational methods. Analysis of the doublet surface of the HSi+PN reaction indicates that the reaction is exothermic in nature leading to the formation of various products. In view of the barrierless association of the reactants and exothermic nature for the product formation, it is suggested that species like HPNSi, cyclic-SiN(H)P (these two most stable isomers have phosphazo linkage) and HSiNP (third most stable isomer has phosphdiazo linkage) can possibly be detected in the interstellar medium. In view of the potential applications of phosphazo compounds in amide synthesis and pervasive nature of amide linkages in the nature, possible interstellar prebiotic applications can be advocated for these compounds.

Introductory guide to the statistics of molecular genetics.

PubMed

Eley, Thalia C; Rijsdijk, Frühling

2005-10-01

This introductory guide presents the main two analytical approaches used by molecular geneticists: linkage and association. Traditional linkage and association methods are described, along with more recent advances in methodologies such as those using a variance components approach. New methods are being developed all the time but the core principles of linkage and association remain the same. The basis of linkage is the transmission of a marker along with a disease within families, whereas association is based on the comparison of marker frequencies in case and control groups. It is becoming increasingly clear that effect sizes of individual markers on diseases and traits are likely to be very small. As such, much greater power is needed, and correspondingly greater sample sizes. Although non-replication is still a problem, molecular genetic studies in some areas such as attention deficit/hyperactivity disorder (ADHD) are starting to show greater convergence. Epidemiologists and other researchers with large well-characterized samples will be well placed to use these methods. Inter-disciplinary studies can then ask far more interesting questions such as those relating to developmental, multivariate and gene-environment interaction hypotheses.

Rapid genotyping with DNA micro-arrays for high-density linkage mapping and QTL mapping in common buckwheat (Fagopyrum esculentum Moench)

PubMed Central

Yabe, Shiori; Hara, Takashi; Ueno, Mariko; Enoki, Hiroyuki; Kimura, Tatsuro; Nishimura, Satoru; Yasui, Yasuo; Ohsawa, Ryo; Iwata, Hiroyoshi

2014-01-01

For genetic studies and genomics-assisted breeding, particularly of minor crops, a genotyping system that does not require a priori genomic information is preferable. Here, we demonstrated the potential of a novel array-based genotyping system for the rapid construction of high-density linkage map and quantitative trait loci (QTL) mapping. By using the system, we successfully constructed an accurate, high-density linkage map for common buckwheat (Fagopyrum esculentum Moench); the map was composed of 756 loci and included 8,884 markers. The number of linkage groups converged to eight, which is the basic number of chromosomes in common buckwheat. The sizes of the linkage groups of the P1 and P2 maps were 773.8 and 800.4 cM, respectively. The average interval between adjacent loci was 2.13 cM. The linkage map constructed here will be useful for the analysis of other common buckwheat populations. We also performed QTL mapping for main stem length and detected four QTL. It took 37 days to process 178 samples from DNA extraction to genotyping, indicating the system enables genotyping of genome-wide markers for a few hundred buckwheat plants before the plants mature. The novel system will be useful for genomics-assisted breeding in minor crops without a priori genomic information. PMID:25914583

SNP Identification from RNA Sequencing and Linkage Map Construction of Rubber Tree for Anchoring the Draft Genome

PubMed Central

Shearman, Jeremy R.; Sangsrakru, Duangjai; Jomchai, Nukoon; Ruang-areerate, Panthita; Sonthirod, Chutima; Naktang, Chaiwat; Theerawattanasuk, Kanikar; Tragoonrung, Somvong; Tangphatsornruang, Sithichoke

2015-01-01

Hevea brasiliensis, or rubber tree, is an important crop species that accounts for the majority of natural latex production. The rubber tree nuclear genome consists of 18 chromosomes and is roughly 2.15 Gb. The current rubber tree reference genome assembly consists of 1,150,326 scaffolds ranging from 200 to 531,465 bp and totalling 1.1 Gb. Only 143 scaffolds, totalling 7.6 Mb, have been placed into linkage groups. We have performed RNA-seq on 6 varieties of rubber tree to identify SNPs and InDels and used this information to perform target sequence enrichment and high throughput sequencing to genotype a set of SNPs in 149 rubber tree offspring from a cross between RRIM 600 and RRII 105 rubber tree varieties. We used this information to generate a linkage map allowing for the anchoring of 24,424 contigs from 3,009 scaffolds, totalling 115 Mb or 10.4% of the published sequence, into 18 linkage groups. Each linkage group contains between 319 and 1367 SNPs, or 60 to 194 non-redundant marker positions, and ranges from 156 to 336 cM in length. This linkage map includes 20,143 of the 69,300 predicted genes from rubber tree and will be useful for mapping studies and improving the reference genome assembly. PMID:25831195

SNP identification from RNA sequencing and linkage map construction of rubber tree for anchoring the draft genome.

PubMed

Shearman, Jeremy R; Sangsrakru, Duangjai; Jomchai, Nukoon; Ruang-Areerate, Panthita; Sonthirod, Chutima; Naktang, Chaiwat; Theerawattanasuk, Kanikar; Tragoonrung, Somvong; Tangphatsornruang, Sithichoke

2015-01-01

Hevea brasiliensis, or rubber tree, is an important crop species that accounts for the majority of natural latex production. The rubber tree nuclear genome consists of 18 chromosomes and is roughly 2.15 Gb. The current rubber tree reference genome assembly consists of 1,150,326 scaffolds ranging from 200 to 531,465 bp and totalling 1.1 Gb. Only 143 scaffolds, totalling 7.6 Mb, have been placed into linkage groups. We have performed RNA-seq on 6 varieties of rubber tree to identify SNPs and InDels and used this information to perform target sequence enrichment and high throughput sequencing to genotype a set of SNPs in 149 rubber tree offspring from a cross between RRIM 600 and RRII 105 rubber tree varieties. We used this information to generate a linkage map allowing for the anchoring of 24,424 contigs from 3,009 scaffolds, totalling 115 Mb or 10.4% of the published sequence, into 18 linkage groups. Each linkage group contains between 319 and 1367 SNPs, or 60 to 194 non-redundant marker positions, and ranges from 156 to 336 cM in length. This linkage map includes 20,143 of the 69,300 predicted genes from rubber tree and will be useful for mapping studies and improving the reference genome assembly.

Construction of a reference molecular linkage map of globe artichoke (Cynara cardunculus var. scolymus).

PubMed

Portis, E; Mauromicale, G; Mauro, R; Acquadro, A; Scaglione, D; Lanteri, S

2009-12-01

The genome organization of globe artichoke (Cynara cardunculus var. scolymus), unlike other species belonging to Asteraceae (=Compositae) family (i.e. sunflower, lettuce and chicory), remains largely unexplored. The species is highly heterozygous and suffers marked inbreeding depression when forced to self-fertilize. Thus a two-way pseudo-testcross represents the optimal strategy for linkage analysis. Here, we report linkage maps based on the progeny of a cross between globe artichoke (C. cardunculus var. scolymus) and cultivated cardoon (C. cardunculus var. altilis). The population was genotyped using a variety of PCR-based marker platforms, resulting in the identification of 708 testcross markers suitable for map construction. The male map consisted of 177 loci arranged in 17 major linkage groups, spanning 1,015.5 cM, while female map was built with 326 loci arranged into 20 major linkage groups, spanning 1,486.8 cM. The presence of 84 loci shared between these maps and those previously developed from a cross within globe artichoke allowed for map alignment and the definition of 17 homologous linkage groups, corresponding to the haploid number of the species. This will provide a favourable property for QTL scanning; furthermore, as 25 mapped markers (8%) correspond to coding regions, it has an additional value as functional map and might represent an important genetic tool for candidate gene studies in globe artichoke.

Rapid genotyping with DNA micro-arrays for high-density linkage mapping and QTL mapping in common buckwheat (Fagopyrum esculentum Moench).

PubMed

Yabe, Shiori; Hara, Takashi; Ueno, Mariko; Enoki, Hiroyuki; Kimura, Tatsuro; Nishimura, Satoru; Yasui, Yasuo; Ohsawa, Ryo; Iwata, Hiroyoshi

2014-12-01

For genetic studies and genomics-assisted breeding, particularly of minor crops, a genotyping system that does not require a priori genomic information is preferable. Here, we demonstrated the potential of a novel array-based genotyping system for the rapid construction of high-density linkage map and quantitative trait loci (QTL) mapping. By using the system, we successfully constructed an accurate, high-density linkage map for common buckwheat (Fagopyrum esculentum Moench); the map was composed of 756 loci and included 8,884 markers. The number of linkage groups converged to eight, which is the basic number of chromosomes in common buckwheat. The sizes of the linkage groups of the P1 and P2 maps were 773.8 and 800.4 cM, respectively. The average interval between adjacent loci was 2.13 cM. The linkage map constructed here will be useful for the analysis of other common buckwheat populations. We also performed QTL mapping for main stem length and detected four QTL. It took 37 days to process 178 samples from DNA extraction to genotyping, indicating the system enables genotyping of genome-wide markers for a few hundred buckwheat plants before the plants mature. The novel system will be useful for genomics-assisted breeding in minor crops without a priori genomic information.

Transcriptome Sequencing of Hevea brasiliensis for Development of Microsatellite Markers and Construction of a Genetic Linkage Map

PubMed Central

Triwitayakorn, Kanokporn; Chatkulkawin, Pornsupa; Kanjanawattanawong, Supanath; Sraphet, Supajit; Yoocha, Thippawan; Sangsrakru, Duangjai; Chanprasert, Juntima; Ngamphiw, Chumpol; Jomchai, Nukoon; Therawattanasuk, Kanikar; Tangphatsornruang, Sithichoke

2011-01-01

To obtain more information on the Hevea brasiliensis genome, we sequenced the transcriptome from the vegetative shoot apex yielding 2 311 497 reads. Clustering and assembly of the reads produced a total of 113 313 unique sequences, comprising 28 387 isotigs and 84 926 singletons. Also, 17 819 expressed sequence tag (EST)-simple sequence repeats (SSRs) were identified from the data set. To demonstrate the use of this EST resource for marker development, primers were designed for 430 of the EST-SSRs. Three hundred and twenty-three primer pairs were amplifiable in H. brasiliensis clones. Polymorphic information content values of selected 47 SSRs among 20 H. brasiliensis clones ranged from 0.13 to 0.71, with an average of 0.51. A dendrogram of genetic similarities between the 20 H. brasiliensis clones using these 47 EST-SSRs suggested two distinct groups that correlated well with clone pedigree. These novel EST-SSRs together with the published SSRs were used for the construction of an integrated parental linkage map of H. brasiliensis based on 81 lines of an F1 mapping population. The map consisted of 97 loci, consisting of 37 novel EST-SSRs and 60 published SSRs, distributed on 23 linkage groups and covered 842.9 cM with a mean interval of 11.9 cM and ∼4 loci per linkage group. Although the numbers of linkage groups exceed the haploid number (18), but with several common markers between homologous linkage groups with the previous map indicated that the F1 map in this study is appropriate for further study in marker-assisted selection. PMID:22086998

Hepatitis C Virus Testing and Linkage to Care in North Carolina and South Carolina Jails, 2012–2014

PubMed Central

Smith, Bryce D.; Seña, Arlene C.; Hilton, Alison; Bachman, Sallie; Lunda, Mulamba; Spaulding, Anne C.

2016-01-01

Objective We evaluated a hepatitis C virus (HCV) testing and linkage-to-care post-release program among detainees of small- to medium-sized jails in North Carolina and South Carolina as part of the Hepatitis Testing and Linkage to Care initiative. Methods An HCV testing and linkage-to-care program was implemented in selected jails in North Carolina and South Carolina from December 2012 to March 2014. Health-care workers not affiliated with the jails conducted HCV antibody (anti-HCV) and HCV ribonucleic acid (RNA) testing and linkage-to-care activities. The North Carolina jail provided universal opt-out testing for HCV; South Carolina jails initially targeted high-risk individuals before expanding to routine testing. Results Of 669 detainees tested for HCV in North Carolina, 88 (13.2%) tested anti-HCV positive, of whom 81 (92.0%) received an HCV RNA test, 66 (81.5%) of whom tested HCV RNA positive (i.e., currently infected). Of the 66 detainees with current HCV infection, 18 were referred to HCV medical care post-release and 10 attended their first appointment. Of 224 detainees tested for HCV in South Carolina, 18 (8.0%) tested anti-HCV positive, of whom 13 received an HCV RNA test. Nine of 13 detainees tested HCV RNA positive, seven detainees were referred to post-release medical care, and two detainees attended their first appointment. Overall, 106 of 893 (11.9%) detainees were anti-HCV positive. Conclusion This study demonstrated that HCV testing, identification of infection, and linkage to care are feasible among jail populations. The rate of anti-HCV positivity was lower than that found in national studies of incarcerated populations, suggesting that HCV infection prevalence in jails may vary across U.S. states or regions. PMID:27168668

Barriers and facilitators of linkage to HIV care among HIV-infected young Chinese men who have sex with men: a qualitative study.

PubMed

Li, Haochu; Wei, Chongyi; Tucker, Joseph; Kang, Dianmin; Liao, Meizhen; Holroyd, Eleanor; Zheng, Jietao; Qi, Qian; Ma, Wei

2017-03-16

The Four Free and One Care Policy (HIV/AIDS-related free services) has been in place in China since 2004. However, linkage to human immunodeficiency virus (HIV) care is not yet achieved very well among people living with HIV. We conducted a qualitative study to explore individual and contextual factors that may influence a linkage to HIV care from the perspective of young HIV-infected men who have sex with men (MSM) in a highly centralized HIV care context of China. Purposive sampling was used to recruit 21 HIV-infected MSM in Shandong Province, with in-depth interviews conducted between March and July 2015. Thematic content analysis was subsequently used for data analysis. Key barriers and facilitators related to a linkage to HIV care emerged from participants' narratives. The barriers included perceived healthy status, low health literacy, and stigma associated with receiving HIV care. The facilitators included an awareness of responsibility, knowledge associated with health literacy, social support, and trusting and relying on services provided by the Center for Disease Control and Prevention (CDC) and the government. These were related to the quality of current HIV counselling and testing, service promotion, and the cost and placement of these HIV services. In order to improve the MSM linkage to HIV care in China, it is imperative to improve the quality of the current on-going counselling and testing. Further critical linkage support includes increasing supportive services among local CDC systems, designated hospitals and community-based organizations (CBOs), and more financial support for HIV/AIDS related testing, medical checkups and treatments.

Genetic linkage map construction and QTL mapping of salt tolerance traits in Zoysiagrass (Zoysia japonica).

PubMed

Guo, Hailin; Ding, Wanwen; Chen, Jingbo; Chen, Xuan; Zheng, Yiqi; Wang, Zhiyong; Liu, Jianxiu

2014-01-01

Zoysiagrass (Zoysia Willd.) is an important warm season turfgrass that is grown in many parts of the world. Salt tolerance is an important trait in zoysiagrass breeding programs. In this study, a genetic linkage map was constructed using sequence-related amplified polymorphism markers and random amplified polymorphic DNA markers based on an F1 population comprising 120 progeny derived from a cross between Zoysia japonica Z105 (salt-tolerant accession) and Z061 (salt-sensitive accession). The linkage map covered 1211 cM with an average marker distance of 5.0 cM and contained 24 linkage groups with 242 marker loci (217 sequence-related amplified polymorphism markers and 25 random amplified polymorphic DNA markers). Quantitative trait loci affecting the salt tolerance of zoysiagrass were identified using the constructed genetic linkage map. Two significant quantitative trait loci (qLF-1 and qLF-2) for leaf firing percentage were detected; qLF-1 at 36.3 cM on linkage group LG4 with a logarithm of odds value of 3.27, which explained 13.1% of the total variation of leaf firing and qLF-2 at 42.3 cM on LG5 with a logarithm of odds value of 2.88, which explained 29.7% of the total variation of leaf firing. A significant quantitative trait locus (qSCW-1) for reduced percentage of dry shoot clipping weight was detected at 44.1 cM on LG5 with a logarithm of odds value of 4.0, which explained 65.6% of the total variation. This study provides important information for further functional analysis of salt-tolerance genes in zoysiagrass. Molecular markers linked with quantitative trait loci for salt tolerance will be useful in zoysiagrass breeding programs using marker-assisted selection.

Refining genome-wide linkage intervals using a meta-analysis of genome-wide association studies identifies loci influencing personality dimensions

PubMed Central

Amin, Najaf; Hottenga, Jouke-Jan; Hansell, Narelle K; Janssens, A Cecile JW; de Moor, Marleen HM; Madden, Pamela AF; Zorkoltseva, Irina V; Penninx, Brenda W; Terracciano, Antonio; Uda, Manuela; Tanaka, Toshiko; Esko, Tonu; Realo, Anu; Ferrucci, Luigi; Luciano, Michelle; Davies, Gail; Metspalu, Andres; Abecasis, Goncalo R; Deary, Ian J; Raikkonen, Katri; Bierut, Laura J; Costa, Paul T; Saviouk, Viatcheslav; Zhu, Gu; Kirichenko, Anatoly V; Isaacs, Aaron; Aulchenko, Yurii S; Willemsen, Gonneke; Heath, Andrew C; Pergadia, Michele L; Medland, Sarah E; Axenovich, Tatiana I; de Geus, Eco; Montgomery, Grant W; Wright, Margaret J; Oostra, Ben A; Martin, Nicholas G; Boomsma, Dorret I; van Duijn, Cornelia M

2013-01-01

Personality traits are complex phenotypes related to psychosomatic health. Individually, various gene finding methods have not achieved much success in finding genetic variants associated with personality traits. We performed a meta-analysis of four genome-wide linkage scans (N=6149 subjects) of five basic personality traits assessed with the NEO Five-Factor Inventory. We compared the significant regions from the meta-analysis of linkage scans with the results of a meta-analysis of genome-wide association studies (GWAS) (N∼17 000). We found significant evidence of linkage of neuroticism to chromosome 3p14 (rs1490265, LOD=4.67) and to chromosome 19q13 (rs628604, LOD=3.55); of extraversion to 14q32 (ATGG002, LOD=3.3); and of agreeableness to 3p25 (rs709160, LOD=3.67) and to two adjacent regions on chromosome 15, including 15q13 (rs970408, LOD=4.07) and 15q14 (rs1055356, LOD=3.52) in the individual scans. In the meta-analysis, we found strong evidence of linkage of extraversion to 4q34, 9q34, 10q24 and 11q22, openness to 2p25, 3q26, 9p21, 11q24, 15q26 and 19q13 and agreeableness to 4q34 and 19p13. Significant evidence of association in the GWAS was detected between openness and rs677035 at 11q24 (P-value=2.6 × 10−06, KCNJ1). The findings of our linkage meta-analysis and those of the GWAS suggest that 11q24 is a susceptible locus for openness, with KCNJ1 as the possible candidate gene. PMID:23211697

A basis for translational cancer research on aetiology, pathogenesis and prognosis: Guideline for standardised and population-based linkages of biobanks to cancer registries.

PubMed

Dillner, Joakim

2015-06-01

Population-based cancer research is paramount for controlling cancer. Cancer research is increasingly dependent on access to biospecimens from subjects that have been followed-up for future health outcomes. This is achieved using longitudinal follow-up of cohorts and biobanks using cancer registry linkages. All over the world, more and more large population-based cohorts and advanced biobanking facilities are established. International standardisation and networking in the linkage of cohorts and biobanks to cancer registries is required in order to enable international cancer research and comparability of research results. An international operating procedure and standard minimum dataset for linkages of biobanks, cohorts and cancer registries is proposed. An internationally comparable provision of well characterised study bases for molecular cancer research will be an essential prerequisite for the success of translational medicine. Copyright © 2013 Elsevier Ltd. All rights reserved.

Use of tangential visual symbols to increase the long-term learning process: applications of linkage in teaching pharmacological principles of addiction.

PubMed

Giannini, A J; Giannini, J N; Condon, M

2000-07-01

Medieval and Renaissance teaching techniques using linkage between course content and tangentially related visual symbols were applied to the teaching of the pharmacological principles of addiction. Forty medical students randomly divided into two blinded groups viewed a lecture. One lecture was supplemented by symbolic slides, and the second was not. Students who viewed symbolic slides had significantly higher scores in a written 15-question multiple-choice test 30 days after the lecture. These results were consistent with learning and semiotic models. These models hypothesize a linkage between conceptual content and perception of visual symbols that thereby increases conceptual retention. Recent neurochemical research supports the existence of a linkage between two chemically distinct memory systems. Simultaneous stimulation of both chemical systems by teaching formats similar to those employed in the study can augment neurochemical signaling in the neocortex.

Evaluation of the Efficiency of the Nursing Care Plan Applied Using NANDA, NOC, and NIC Linkages to Elderly Women with Incontinence Living in a Nursing Home: A Randomized Controlled Study.

PubMed

Gencbas, Dercan; Bebis, Hatice; Cicek, Hatice

2017-05-30

Evaluate the efficiency of the nursing care plan, applied with the use of NANDA-I, NOC, and NIC (NNN) linkages, for elderly women with incontinence who live in nursing homes. A randomized controlled experimental design was applied. NNN linkages were prepared and applied for 12 weeks in an experimental group. NOC scales were evaluated again for two groups. A 0.5 NOC point change targeted in all elderly in the experimental group were provided between pretest-posttest scores. The experimental group had higher life quality and lower incontinence severity/symptoms than the control group. It is important that NNN linkages effective for solving the problems are used in different groups and with larger samples to create further evidence linking NNN. © 2017 NANDA International, Inc.

Record linkage for pharmacoepidemiological studies in cancer patients.

PubMed

Herk-Sukel, Myrthe P P van; Lemmens, Valery E P P; Poll-Franse, Lonneke V van de; Herings, Ron M C; Coebergh, Jan Willem W

2012-01-01

An increasing need has developed for the post-approval surveillance of (new) anti-cancer drugs by means of pharmacoepidemiology and outcomes research in the area of oncology. To create an overview that makes researchers aware of the available database linkages in Northern America and Europe which facilitate pharmacoepidemiology and outcomes research in cancer patients. In addition to our own database, i.e. the Eindhoven Cancer Registry (ECR) linked to the PHARMO Record Linkage System, we considered database linkages between a population-based cancer registry and an administrative healthcare database that at least contains information on drug use and offers a longitudinal perspective on healthcare utilization. Eligible database linkages were limited to those that had been used in multiple published articles in English language included in Pubmed. The HMO Cancer Research Network (CRN) in the US was excluded from this review, as an overview of the linked databases participating in the CRN is already provided elsewhere. Researchers who had worked with the data resources included in our review were contacted for additional information and verification of the data presented in the overview. The following database linkages were included: the Surveillance, Epidemiology, and End-Results-Medicare; cancer registry data linked to Medicaid; Canadian cancer registries linked to population-based drug databases; the Scottish cancer registry linked to the Tayside drug dispensing data; linked databases in the Nordic Countries of Europe: Norway, Sweden, Finland and Denmark; and the ECR-PHARMO linkage in the Netherlands. Descriptives of the included database linkages comprise population size, generalizability of the population, year of first data availability, contents of the cancer registry, contents of the administrative healthcare database, the possibility to select a cancer-free control cohort, and linkage to other healthcare databases. The linked databases offer a longitudinal perspective, allowing for observations of health care utilization before, during, and after cancer diagnosis. They create new powerful data resources for the monitoring of post-approval drug utilization, as well as a framework to explore the (cost-)effectiveness of new, often expensive, anti-cancer drugs as used in everyday practice. Copyright © 2011 John Wiley & Sons, Ltd.

Does probabilistic modelling of linkage disequilibrium evolution improve the accuracy of QTL location in animal pedigree?

PubMed

Cierco-Ayrolles, Christine; Dejean, Sébastien; Legarra, Andrés; Gilbert, Hélène; Druet, Tom; Ytournel, Florence; Estivals, Delphine; Oumouhou, Naïma; Mangin, Brigitte

2010-10-22

Since 2001, the use of more and more dense maps has made researchers aware that combining linkage and linkage disequilibrium enhances the feasibility of fine-mapping genes of interest. So, various method types have been derived to include concepts of population genetics in the analyses. One major drawback of many of these methods is their computational cost, which is very significant when many markers are considered. Recent advances in technology, such as SNP genotyping, have made it possible to deal with huge amount of data. Thus the challenge that remains is to find accurate and efficient methods that are not too time consuming. The study reported here specifically focuses on the half-sib family animal design. Our objective was to determine whether modelling of linkage disequilibrium evolution improved the mapping accuracy of a quantitative trait locus of agricultural interest in these populations. We compared two methods of fine-mapping. The first one was an association analysis. In this method, we did not model linkage disequilibrium evolution. Therefore, the modelling of the evolution of linkage disequilibrium was a deterministic process; it was complete at time 0 and remained complete during the following generations. In the second method, the modelling of the evolution of population allele frequencies was derived from a Wright-Fisher model. We simulated a wide range of scenarios adapted to animal populations and compared these two methods for each scenario. Our results indicated that the improvement produced by probabilistic modelling of linkage disequilibrium evolution was not significant. Both methods led to similar results concerning the location accuracy of quantitative trait loci which appeared to be mainly improved by using four flanking markers instead of two. Therefore, in animal half-sib designs, modelling linkage disequilibrium evolution using a Wright-Fisher model does not significantly improve the accuracy of the QTL location when compared to a simpler method assuming complete and constant linkage between the QTL and the marker alleles. Finally, given the high marker density available nowadays, the simpler method should be preferred as it gives accurate results in a reasonable computing time.

Building an Entrepreneurial University in Brazil: The Role and Potential of University-Industry Linkages in Promoting Regional Economic Development

ERIC Educational Resources Information Center

Amaral, Marcelo; Ferreira, Andre; Teodoro, Pitias

2011-01-01

This study is part of a broader research project, conducted by the Triple Helix Research Group--Brazil, focusing on university-industry-government linkages in the state of Rio de Janeiro. The case study reported here is that of the Regional University of Volta Redonda: the aim was to develop an understanding of how a regional university can be…

Adaptive Behavior in Childhood as an Antecedent of Psychological Functioning in Early Middle Age: Linkage via Career Orientation

ERIC Educational Resources Information Center

Pulkkinen, Lea; Feldt, Taru; Kokko, Katja

2006-01-01

The main aim of the study was to investigate the link between child and adolescent adaptive behavior and adult psychological functioning, and the role of career orientation in this linkage. This was based on a Finnish longitudinal study, where data at ages 8, 14, and 42 were available for 118 females and 115 males. Adaptive behavior, indicated by…

Linkage analyses of cannabis dependence, craving, and withdrawal in the San Francisco family study.

PubMed

Ehlers, Cindy L; Gizer, Ian R; Vieten, Cassandra; Wilhelmsen, Kirk C

2010-04-05

Cannabis is the most widely used illicit drug in the United States. There is ample evidence that cannabis use has a heritable component, yet the genes underlying cannabis use disorders are yet to be completely identified. This study's aims were to map susceptibility loci for cannabis use and dependence and two narrower cannabis-related phenotypes of "craving" and "withdrawal" using a family study design. Participants were 2,524 adults participating in the University of California San Francisco (UCSF) Family Alcoholism Study. DSM-IV diagnoses of cannabis dependence, as well as indices of cannabis craving and withdrawal, were obtained using a modified version of the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA). Genotypes were determined for a panel of 791 microsatellite polymorphisms. Multipoint variance component LOD scores were obtained using SOLAR. Genome-wide significance for linkage (LOD > 3.0) was not found for the DSM-IV cannabis dependence diagnosis; however, linkage analyses of cannabis "craving" and the cannabis withdrawal symptom of "nervous, tense, restless, or irritable" revealed five sites with LOD scores over 3.0 on chromosomes 1, 3, 6, 7, and 9. These results identify new regions of the genome associated with cannabis use phenotypes as well as corroborate the importance of several chromosome regions highlighted in previous linkage analyses for other substance dependence phenotypes.

Structural synthesis of linkages for quadruped bio-robot legs

NASA Astrophysics Data System (ADS)

Antonescu, O.; Robu, C.; Antonescu, P.

2016-08-01

The paper presents a few kinematic schemes of planar mechanisms with bars (linkages) used as part of the quadruped robot legs. The Dunshee linkage having only four elements as crank-rocker mechanism is analyzed. Further, the Klann linkage, which is accomplished by amplifying the crank-rocker mechanism with a dyadic kinematic chain, is also presented. More than that, the Jansen linkage, which is obtained by extending and amplifying the crank-rocker mechanism with two dyadic kinematic chains, is also analyzed. At the end of the paper, the authors present a novel linkage application consisting of a quadric kinematic chain.

Polygenic sex determination in the cichlid fish Astatotilapia burtoni.

PubMed

Roberts, Natalie B; Juntti, Scott A; Coyle, Kaitlin P; Dumont, Bethany L; Stanley, M Kaitlyn; Ryan, Allyson Q; Fernald, Russell D; Roberts, Reade B

2016-10-26

The East African riverine cichlid species Astatotilapia burtoni serves as an important laboratory model for sexually dimorphic physiology and behavior, and also serves as an outgroup species for the explosive adaptive radiations of cichlid species in Lake Malawi and Lake Victoria. An astounding diversity of genetic sex determination systems have been revealed within the adaptive radiation of East African cichlids thus far, including polygenic sex determination systems involving the epistatic interaction of multiple, independently segregating sex determination alleles. However, sex determination has remained unmapped in A. burtoni. Here we present mapping results supporting the presence of multiple, novel sex determination alleles, and thus the presence of polygenic sex determination in A. burtoni. Using mapping in small families in conjunction with restriction-site associated DNA sequencing strategies, we identify associations with sex at loci on linkage group 13 and linkage group 5-14. Inheritance patterns support an XY sex determination system on linkage group 5-14 (a chromosome fusion relative to other cichlids studied), and an XYW system on linkage group 13, and these associations are replicated in multiple families. Additionally, combining our genetic data with comparative genomic analysis identifies another fusion that is unassociated with sex, with linkage group 8-24 and linkage group 16-21 fused in A. burtoni relative to other East African cichlid species. We identify genetic signals supporting the presence of three previously unidentified sex determination alleles at two loci in the species A. burtoni, strongly supporting the presence of polygenic sex determination system in the species. These results provide a foundation for future mapping of multiple sex determination genes and their interactions. A better understanding of sex determination in A. burtoni provides important context for their use in behavioral studies, as well as studies of the evolution of genetic sex determination and sexual conflicts in East African cichlids.

A two-state comparative implementation of peer-support intervention to link veterans to health-related services after incarceration: a study protocol.

PubMed

Simmons, Molly M; Fincke, Benjamin G; Drainoni, Mari-Lynn; Kim, Bo; Byrne, Tom; Smelson, David; Casey, Kevin; Ellison, Marsha L; Visher, Christy; Blue-Howells, Jessica; McInnes, D Keith

2017-09-12

Approximately 600,000 persons are released from prison annually in the United States. Relatively few receive sufficient re-entry services and are at risk for unemployment, homelessness, poverty, substance abuse relapse and recidivism. Persons leaving prison who have a mental illness and/or a substance use disorder are particularly challenged. This project aims to create a peer mentor program to extend the reach and effectiveness of reentry services provided by the Department of Veterans' Affairs (VA). We will implement a peer support for reentry veterans sequentially in two states. Our outcome measures are 1) fidelity of the intervention, 2) linkage to VA health care and, 3) continued engagement in health care. The aims for this project are as follows: (1) Conduct contextual analysis to identify VA and community reentry resources, and describe how reentry veterans use them. (2) Implement peer-support, in one state, to link reentry veterans to Veterans' Health Administration (VHA) primary care, mental health, and SUD services. (3) Port the peer-support intervention to another, geographically, and contextually different state. This intervention involves a 2-state sequential implementation study (Massachusetts, followed by Pennsylvania) using a Facilitation Implementation strategy. We will conduct formative and summative analyses, including assessment of fidelity, and a matched comparison group to evaluate the intervention's outcomes of veteran linkage and engagement in VHA health care (using health care utilization measures). The study proceeds in 3 phases. We anticipate that a peer support program will be effective at improving the reentry process for veterans, particularly in linking them to health, mental health, and SUD services and helping them to stay engaged in those services. It will fill a gap by providing veterans with access to a trusted individual, who understands their experience as a veteran and who has experienced justice involvement. The outputs from this project, including training materials, peer guidebooks, and implementation strategies can be adapted by other states and regions that wish to enhance services for veterans (or other populations) leaving incarceration. A larger cluster-randomized implementation-effectiveness study is planned. This protocol is registered with clinicaltrials.gov on November 4, 2016 and was assigned the number NCT02964897 .

Kazusa Marker DataBase: a database for genomics, genetics, and molecular breeding in plants.

PubMed

Shirasawa, Kenta; Isobe, Sachiko; Tabata, Satoshi; Hirakawa, Hideki

2014-09-01

In order to provide useful genomic information for agronomical plants, we have established a database, the Kazusa Marker DataBase (http://marker.kazusa.or.jp). This database includes information on DNA markers, e.g., SSR and SNP markers, genetic linkage maps, and physical maps, that were developed at the Kazusa DNA Research Institute. Keyword searches for the markers, sequence data used for marker development, and experimental conditions are also available through this database. Currently, 10 plant species have been targeted: tomato (Solanum lycopersicum), pepper (Capsicum annuum), strawberry (Fragaria × ananassa), radish (Raphanus sativus), Lotus japonicus, soybean (Glycine max), peanut (Arachis hypogaea), red clover (Trifolium pratense), white clover (Trifolium repens), and eucalyptus (Eucalyptus camaldulensis). In addition, the number of plant species registered in this database will be increased as our research progresses. The Kazusa Marker DataBase will be a useful tool for both basic and applied sciences, such as genomics, genetics, and molecular breeding in crops.

[The Willingness to Consent to the Linkage of Primary and Secondary Data: An Analysis Based on a Survey of Patients with Primary Breast Cancer in Northrhine Westfalia].

PubMed

Scholten, N; Pfaff, H; Raabe, N; Kowalski, C

2017-03-01

Introduction: By linking data it is possible to merge, for example, survey data with routine data from statutory health insurance (GKV), to gain benefit from the advantages of both. As personal data is involved, it is necessary to obtain consent. Previous studies show that willingness to release this kind of data for scientific research is limited. This fact restricts the number of participants and can cause selection bias. The aim of our study was to analyze willingness to consent to the linkage of survey data with statutory health insurance data in patients with primary breast cancer. Associations between approval and socio-demographic characteristics were explored. Method: In the annual survey of patients with primary breast cancer in certified breast centers in North Rhine-Westphalia, all included patients were questioned concerning their willingness to consent to data linkage. We distinguished between patients insured by AOK Rhineland/Hamburg and all other patients: based on cooperation with AOK Rhineland/Hamburg, we obtained consent to actually link the data for all patients insured there. All other patients were questioned in terms of their insurance and their willingness to consent in general. Results: A total of 2,387 questionnaires were returned, giving a return rate of 49.3%. For the AOK Rhineland/Hamburg-insured patients, the consent rate was at 89.6%. At 75.7%, positive attitudes towards data linkage turned out to be a bit lower for patients with other insurers. Under the assumption that all non-responders disapprove data linkage, still 38.1% of patients showed a positive attitude towards data linkage. As a result of the multivariable model, insurance status (private vs. statutory) and first language turned out to be the only significant factors influencing the response. The consent of patients insured by AOK Rhineland/Hamburg is not significantly influenced by any of the measured socio-demographic factors. Conclusion: Currently, there is not much knowledge on the acceptance of data linkage in patients suffering from an acute illness. Although our results are restricted to breast cancer patients, they are able to uncover problems and chances concerning data linkage. © Georg Thieme Verlag KG Stuttgart · New York.

The role of the GABRA2 polymorphism in multiplex alcohol dependence families with minimal comorbidity: within-family association and linkage analyses.

PubMed

Matthews, Abigail G; Hoffman, Eric K; Zezza, Nicholas; Stiffler, Scott; Hill, Shirley Y

2007-09-01

The genes encoding the gamma-aminobutyric acid(A) (GABA(A)) receptor have been the focus of several recent studies investigating the genetic etiology of alcohol dependence. Analyses of multiplex families found a particular gene, GABRA2, to be highly associated with alcohol dependence, using within-family association tests and other methods. Results were confirmed in three case-control studies. The objective of this study was to investigate the GABRA2 gene in another collection of multiplex families. Analyses were based on phenotypic and genotypic data available for 330 individuals from 65 bigenerational pedigrees with a total of 232 alcohol-dependent subjects. A proband pair of same-sex siblings meeting Diagnostic and Statistical Manual of Mental Disorders, Third Edition, criteria for alcohol dependence was required for entry of a family into the study. One member of the proband pair was identified while in treatment for alcohol dependence. Linkage and association of GABRA2 and alcohol dependence were evaluated using SIBPAL (a nonparametric linkage package) and both the Pedigree Disequilibrium Test and the Family-Based Association Test, respectively. We find no evidence of a relationship between GABRA2 and alcohol dependence. Linkage analyses exhibited no linkage using affected/affected, affected/unaffected, and unaffected/unaffected sib pairs (all p's < .13). There was no evidence of a within-family association (all p's > .39). Comorbidity may explain why our results differ from those in the literature. The presence of primary drug dependence and/or other psychiatric disorders is minimal in our pedigrees, although several of the other previously published multiplex family analyses exhibit a greater degree of comorbidity.

Genome-wide linkage scan for submaximal exercise heart rate in the HERITAGE family study.

PubMed

Spielmann, Nadine; Leon, Arthur S; Rao, D C; Rice, Treva; Skinner, James S; Rankinen, Tuomo; Bouchard, Claude

2007-12-01

The purpose of this study was to identify regions of the human genome linked to submaximal exercise heart rates in the sedentary state and in response to a standardized 20-wk endurance training program in blacks and whites of the HERITAGE Family Study. A total of 701 polymorphic markers covering the 22 autosomes were used in the genome-wide linkage scan, with 328 sibling pairs from 99 white nuclear families and 102 pairs from 115 black family units. Steady-state heart rates were measured at the relative intensity of 60% maximal oxygen uptake (HR60) and at the absolute intensity of 50 W (HR50). Baseline phenotypes were adjusted for age, sex, and baseline body mass index (BMI) and training responses (posttraining minus baseline, Delta) were adjusted for age, sex, baseline BMI, and baseline value of the phenotype. Two analytic strategies were used, a multipoint variance components and a regression-based multipoint linkage analysis. In whites, promising linkages (LOD > 1.75) were identified on 18q21-q22 for baseline HR50 (LOD = 2.64; P = 0.0002) and DeltaHR60 (LOD = 2.10; P = 0.0009) and on chromosome 2q33.3 for DeltaHR50 (LOD = 2.13; P = 0.0009). In blacks, evidence of promising linkage for baseline HR50 was detected with several markers within the chromosomal region 10q24-q25.3 (peak LOD = 2.43, P = 0.0004 with D10S597). The most promising regions for fine mapping in the HERITAGE Family Study were found on 2q33 for HR50 training response in whites, on 10q25-26 for baseline HR60 in blacks, and on 18q21-22 for both baseline HR50 and DeltaHR60 in whites.

Incidence rates of Guillain Barré (GBS), chronic fatigue/systemic exertion intolerance disease (CFS/SEID) and postural orthostatic tachycardia syndrome (POTS) prior to introduction of human papilloma virus (HPV) vaccination among adolescent girls in Finland, 2002-2012.

PubMed

Skufca, J; Ollgren, J; Ruokokoski, E; Lyytikäinen, O; Nohynek, H

2017-06-01

In Finland a vaccination programme against human papillomavirus (HPV) was introduced in November 2013 for girls aged 11-12 years with a catchup for girls 13-15 years. Allegations that HPV vaccine is causing Guillain Barré syndrome (GBS) and non-specific diagnostic entities, such as chronic fatigue syndrome/systemic exertion intolerance disease (CFS/SEID) and postural orthostatic tachycardia syndrome (POTS), continue to surface. We examined population register-based incidence rates of CFS/SEID, GBS and POTS to provide baseline data for future HPV vaccine safety evaluations. First diagnosis of CFS/SEID, GBS and POTS in girls aged 11-15 years were obtained from the National Hospital Discharge Register during 2002-2012. We considered the following ICD-10 codes: G93.3 for CFS; G61.0 for GBS and G90.9, G90.8, G93.3, I49.8 for POTS. We calculated incidence rates per 100,000 person-years with 95% confidence intervals (CI). In total, 9 CFS/SEID, 19 GBS and 72 POTS cases were identified. The overall incidence rate was 0.53/100,000 (95% CI; 0.27-1.01) for CFS/SEID, 1.11 (95% CI; 0.71-1.74) for GBS and 4.21 (95%CI; 3.34-5.30) for POTS. Significant relative increase in annual incidence rate with a peak in 2012 was observed in CFS/SEID (33% (95% CI; 3.0-70.3: p=0.029) and POTS (16.5% (95% CI; 7.8-25.9: p<0.05), but not in GBS (5.4% (95% CI; -8.4-21.3: p=0.460). Our findings provide baseline estimates of CFS/SEID, GBS and POTS incidences in Finland. However, rates based on register data should be interpreted with caution, especially for non-specific diagnostic entities for which internationally and even nationally agreed criteria are still being discussed. To assess the associations with HPV vaccine, methods using register linkage for cohort and self-controlled case series should be explored in addition to factors contributing to patients seeking care, treating physicians setting the diagnoses, and their preference of using of codes for these clinical entities. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

PRKCA: A Positional Candidate Gene for Body Mass Index and Asthma

PubMed Central

Murphy, Amy; Tantisira, Kelan G.; Soto-Quirós, Manuel E.; Avila, Lydiana; Klanderman, Barbara J.; Lake, Stephen; Weiss, Scott T.; Celedón, Juan C.

2009-01-01

Asthma incidence and prevalence are higher in obese individuals. A potential mechanistic basis for this relationship is pleiotropy. We hypothesized that significant linkage and candidate-gene association would be found for body mass index (BMI) in a population ascertained on asthma affection status. Linkage analysis for BMI was performed on 657 subjects in eight Costa Rican families enrolled in a study of asthma. Family-based association studies were conducted for BMI with SNPs within a positional candidate gene, PRKCA. SNPs within PRKCA were also tested for association with asthma. Association studies were conducted in 415 Costa Rican parent-child trios and 493 trios participating in the Childhood Asthma Management Program (CAMP). Although only modest evidence of linkage for BMI was obtained for the whole cohort, significant linkage was noted for BMI in females on chromosome 17q (peak LOD = 3.39). Four SNPs in a candidate gene in this region (PRKCA) had unadjusted association p values < 0.05 for BMI in both cohorts, with the joint p value for two SNPs remaining significant after adjustment for multiple comparisons (rs228883 and rs1005651, joint p values = 9.5 × 10−5 and 5.6 × 10−5). Similarly, eight SNPs had unadjusted association p values < 0.05 for asthma in both populations, with one SNP remaining significant after adjustment for multiple comparisons (rs11079657, joint p value = 2.6 × 10−5). PRKCA is a pleiotropic locus that is associated with both BMI and asthma and that has been identified via linkage analysis of BMI in a population ascertained on asthma. PMID:19576566

Methodological developments in searching for studies for systematic reviews: past, present and future?

PubMed

Lefebvre, Carol; Glanville, Julie; Wieland, L Susan; Coles, Bernadette; Weightman, Alison L

2013-09-25

The Cochrane Collaboration was established in 1993, following the opening of the UK Cochrane Centre in 1992, at a time when searching for studies for inclusion in systematic reviews was not well-developed. Review authors largely conducted their own searches or depended on medical librarians, who often possessed limited awareness and experience of systematic reviews. Guidance on the conduct and reporting of searches was limited. When work began to identify reports of randomized controlled trials (RCTs) for inclusion in Cochrane Reviews in 1992, there were only approximately 20,000 reports indexed as RCTs in MEDLINE and none indexed as RCTs in Embase. No search filters had been developed with the aim of identifying all RCTs in MEDLINE or other major databases. This presented The Cochrane Collaboration with a considerable challenge in identifying relevant studies.Over time, the number of studies indexed as RCTs in the major databases has grown considerably and the Cochrane Central Register of Controlled Trials (CENTRAL) has become the best single source of published controlled trials, with approximately 700,000 records, including records identified by the Collaboration from Embase and MEDLINE. Search filters for various study types, including systematic reviews and the Cochrane Highly Sensitive Search Strategies for RCTs, have been developed. There have been considerable advances in the evidence base for methodological aspects of information retrieval. The Cochrane Handbook for Systematic Reviews of Interventions now provides detailed guidance on the conduct and reporting of searches. Initiatives across The Cochrane Collaboration to improve the quality inter alia of information retrieval include: the recently introduced Methodological Expectations for Cochrane Intervention Reviews (MECIR) programme, which stipulates 'mandatory' and 'highly desirable' standards for various aspects of review conduct and reporting including searching, the development of Standard Training Materials for Cochrane Reviews and work on peer review of electronic search strategies. Almost all Cochrane Review Groups and some Cochrane Centres and Fields now have a Trials Search Co-ordinator responsible for study identification and medical librarians and other information specialists are increasingly experienced in searching for studies for systematic reviews.Prospective registration of clinical trials is increasing and searching trials registers is now mandatory for Cochrane Reviews, where relevant. Portals such as the WHO International Clinical Trials Registry Platform (ICTRP) are likely to become increasingly attractive, given concerns about the number of trials which may not be registered and/or published. The importance of access to information from regulatory and reimbursement agencies is likely to increase. Cross-database searching, gateways or portals and improved access to full-text databases will impact on how searches are conducted and reported, as will services such as Google Scholar, Scopus and Web of Science. Technologies such as textual analysis, semantic analysis, text mining and data linkage will have a major impact on the search process but efficient and effective updating of reviews may remain a challenge.In twenty years' time, we envisage that the impact of universal social networking, as well as national and international legislation, will mean that all trials involving humans will be registered at inception and detailed trial results will be routinely available to all. Challenges will remain, however, to ensure the discoverability of relevant information in diverse and often complex sources and the availability of metadata to provide the most efficient access to information. We envisage an ongoing role for information professionals as experts in identifying new resources, researching efficient ways to link or mine them for relevant data and managing their content for the efficient production of systematic reviews.

Methodological developments in searching for studies for systematic reviews: past, present and future?

PubMed Central

2013-01-01

The Cochrane Collaboration was established in 1993, following the opening of the UK Cochrane Centre in 1992, at a time when searching for studies for inclusion in systematic reviews was not well-developed. Review authors largely conducted their own searches or depended on medical librarians, who often possessed limited awareness and experience of systematic reviews. Guidance on the conduct and reporting of searches was limited. When work began to identify reports of randomized controlled trials (RCTs) for inclusion in Cochrane Reviews in 1992, there were only approximately 20,000 reports indexed as RCTs in MEDLINE and none indexed as RCTs in Embase. No search filters had been developed with the aim of identifying all RCTs in MEDLINE or other major databases. This presented The Cochrane Collaboration with a considerable challenge in identifying relevant studies. Over time, the number of studies indexed as RCTs in the major databases has grown considerably and the Cochrane Central Register of Controlled Trials (CENTRAL) has become the best single source of published controlled trials, with approximately 700,000 records, including records identified by the Collaboration from Embase and MEDLINE. Search filters for various study types, including systematic reviews and the Cochrane Highly Sensitive Search Strategies for RCTs, have been developed. There have been considerable advances in the evidence base for methodological aspects of information retrieval. The Cochrane Handbook for Systematic Reviews of Interventions now provides detailed guidance on the conduct and reporting of searches. Initiatives across The Cochrane Collaboration to improve the quality inter alia of information retrieval include: the recently introduced Methodological Expectations for Cochrane Intervention Reviews (MECIR) programme, which stipulates 'mandatory’ and 'highly desirable’ standards for various aspects of review conduct and reporting including searching, the development of Standard Training Materials for Cochrane Reviews and work on peer review of electronic search strategies. Almost all Cochrane Review Groups and some Cochrane Centres and Fields now have a Trials Search Co-ordinator responsible for study identification and medical librarians and other information specialists are increasingly experienced in searching for studies for systematic reviews. Prospective registration of clinical trials is increasing and searching trials registers is now mandatory for Cochrane Reviews, where relevant. Portals such as the WHO International Clinical Trials Registry Platform (ICTRP) are likely to become increasingly attractive, given concerns about the number of trials which may not be registered and/or published. The importance of access to information from regulatory and reimbursement agencies is likely to increase. Cross-database searching, gateways or portals and improved access to full-text databases will impact on how searches are conducted and reported, as will services such as Google Scholar, Scopus and Web of Science. Technologies such as textual analysis, semantic analysis, text mining and data linkage will have a major impact on the search process but efficient and effective updating of reviews may remain a challenge. In twenty years’ time, we envisage that the impact of universal social networking, as well as national and international legislation, will mean that all trials involving humans will be registered at inception and detailed trial results will be routinely available to all. Challenges will remain, however, to ensure the discoverability of relevant information in diverse and often complex sources and the availability of metadata to provide the most efficient access to information. We envisage an ongoing role for information professionals as experts in identifying new resources, researching efficient ways to link or mine them for relevant data and managing their content for the efficient production of systematic reviews. PMID:24066664

ReaxFF Study of the Oxidation of Softwood Lignin in View of Carbon Fiber Production

DOE PAGES

Beste, Ariana

2014-10-06

We investigate the oxidative, thermal conversion of softwood lignin by performing molecular dynamics simulations based on a reactive force field (ReaxFF). The lignin samples are constructed from coniferyl alcohol units, which are connected through linkages that are randomly selected from a natural distribution of linkages in softwood. The goal of this work is to simulate the oxidative stabilization step during carbon fiber production from lignin precursor. We find that at simulation conditions where stabilization reactions occur, the lignin fragments have already undergone extensive degradation. The 5-5 linkage shows the highest reactivity towards cyclization and dehydrogenation.

Linkage localization of the thoraco-abdominal syndrome (TAS) gene to Xq25-26.

PubMed

Parvari, R; Weinstein, Y; Ehrlich, S; Steinitz, M; Carmi, R

1994-02-15

The thoraco-abdominal syndrome (TAS) presents a closure defect confined to the ventral midline, manifested as ventral hernia of various degrees in all affected individuals and antero-lateral diaphragmatic defect manifested almost exclusively in affected males. The syndrome is inherited as an X-linked dominant trait affecting blastogenesis (XLB mutation). We studied 27 members of the TAS family for linkage on the X chromosome. The best lod score of 5.5 at theta 0.04 was found for the HPRT locus on Xq26.1. A multilocus lod score of 12.4 was observed when the linkage analysis utilized additional markers in Xq25-26.

Mapping autism risk loci using genetic linkage and chromosomal rearrangements

PubMed Central

Szatmari, Peter; Paterson, Andrew; Zwaigenbaum, Lonnie; Roberts, Wendy; Brian, Jessica; Liu, Xiao-Qing; Vincent, John; Skaug, Jennifer; Thompson, Ann; Senman, Lili; Feuk, Lars; Qian, Cheng; Bryson, Susan; Jones, Marshall; Marshall, Christian; Scherer, Stephen; Vieland, Veronica; Bartlett, Christopher; Mangin, La Vonne; Goedken, Rhinda; Segre, Alberto; Pericak-Vance, Margaret; Cuccaro, Michael; Gilbert, John; Wright, Harry; Abramson, Ruth; Betancur, Catalina; Bourgeron, Thomas; Gillberg, Christopher; Leboyer, Marion; Buxbaum, Joseph; Davis, Kenneth; Hollander, Eric; Silverman, Jeremy; Hallmayer, Joachim; Lotspeich, Linda; Sutcliffe, James; Haines, Jonathan; Folstein, Susan; Piven, Joseph; Wassink, Thomas; Sheffield, Val; Geschwind, Daniel; Bucan, Maja; Brown, Ted; Cantor, Rita; Constantino, John; Gilliam, Conrad; Herbert, Martha; Lajonchere, Clara; Ledbetter, David; Lese-Martin, Christa; Miller, Janet; Nelson, Stan; Samango-Sprouse, Carol; Spence, Sarah; State, Matthew; Tanzi, Rudolph; Coon, Hilary; Dawson, Geraldine; Devlin, Bernie; Estes, Annette; Flodman, Pamela; Klei, Lambertus; Mcmahon, William; Minshew, Nancy; Munson, Jeff; Korvatska, Elena; Rodier, Patricia; Schellenberg, Gerard; Smith, Moyra; Spence, Anne; Stodgell, Chris; Tepper, Ping Guo; Wijsman, Ellen; Yu, Chang-En; Rogé, Bernadette; Mantoulan, Carine; Wittemeyer, Kerstin; Poustka, Annemarie; Felder, Bärbel; Klauck, Sabine; Schuster, Claudia; Poustka, Fritz; Bölte, Sven; Feineis-Matthews, Sabine; Herbrecht, Evelyn; Schmötzer, Gabi; Tsiantis, John; Papanikolaou, Katerina; Maestrini, Elena; Bacchelli, Elena; Blasi, Francesca; Carone, Simona; Toma, Claudio; Van Engeland, Herman; De Jonge, Maretha; Kemner, Chantal; Koop, Frederieke; Langemeijer, Marjolein; Hijmans, Channa; Staal, Wouter; Baird, Gillian; Bolton, Patrick; Rutter, Michael; Weisblatt, Emma; Green, Jonathan; Aldred, Catherine; Wilkinson, Julie-Anne; Pickles, Andrew; Le Couteur, Ann; Berney, Tom; Mcconachie, Helen; Bailey, Anthony; Francis, Kostas; Honeyman, Gemma; Hutchinson, Aislinn; Parr, Jeremy; Wallace, Simon; Monaco, Anthony; Barnby, Gabrielle; Kobayashi, Kazuhiro; Lamb, Janine; Sousa, Ines; Sykes, Nuala; Cook, Edwin; Guter, Stephen; Leventhal, Bennett; Salt, Jeff; Lord, Catherine; Corsello, Christina; Hus, Vanessa; Weeks, Daniel; Volkmar, Fred; Tauber, Maïté; Fombonne, Eric; Shih, Andy; Meyer, Kacie

2007-01-01

Autism spectrum disorders (ASD) are common, heritable neurodevelopmental conditions. The genetic architecture of ASD is complex, requiring large samples to overcome heterogeneity. Here we broaden coverage and sample size relative to other studies of ASD by using Affymetrix 10K single nucleotide polymorphism (SNP) arrays and 1168 families with ≥ 2 affected individuals to perform the largest linkage scan to date, while also analyzing copy number variation (CNV) in these families. Linkage and CNV analyses implicate chromosome 11p12-p13 and neurexins, respectively, amongst other candidate loci. Neurexins team with previously-implicated neuroligins for glutamatergic synaptogenesis, highlighting glutamate-related genes as promising candidates for ASD. PMID:17322880

First genetic linkage map of Taraxacum koksaghyz Rodin based on AFLP, SSR, COS and EST-SSR markers

PubMed Central

Arias, Marina; Hernandez, Monica; Remondegui, Naroa; Huvenaars, Koen; van Dijk, Peter; Ritter, Enrique

2016-01-01

Taraxacum koksaghyz Rodin (TKS) has been studied in many occasions as a possible alternative source for natural rubber production of good quality and for inulin production. Some tire companies are already testing TKS tire prototypes. There are also many investigations on the production of bio-fuels from inulin and inulin applications for health improvement and in the food industry. A limited amount of genomic resources exist for TKS and particularly no genetic linkage map is available in this species. We have constructed the first TKS genetic linkage map based on AFLP, COS, SSR and EST-SSR markers. The integrated linkage map with eight linkage groups (LG), representing the eight chromosomes of Russian dandelion, has 185 individual AFLP markers from parent 1, 188 individual AFLP markers from parent 2, 75 common AFLP markers and 6 COS, 1 SSR and 63 EST-SSR loci. Blasting the EST-SSR sequences against known sequences from lettuce allowed a partial alignment of our TKS map with a lettuce map. Blast searches against plant gene databases revealed some homologies with useful genes for downstream applications in the future. PMID:27488242

Conditional Tests for Localizing Trait Genes

PubMed Central

Di, Yanming; Thompson, Elizabeth A.

2009-01-01

Background/Aims With pedigree data, genetic linkage can be detected using inheritance vector tests, which explore the discrepancy between the posterior distribution of the inheritance vectors given observed trait values and the prior distribution of the inheritance vectors. In this paper, we propose conditional inheritance vector tests for linkage localization. These conditional tests can also be used to detect additional linkage signals in the presence of previously detected causal genes. Methods For linkage localization, we propose to perform inheritance vector tests conditioning on the inheritance vectors at two positions bounding a test region. We can detect additional linkage signals by conducting a further conditional test in a region with no previously detected genes. We use randomized p values to extend the marginal and conditional tests when the inheritance vectors cannot be completely determined from genetic marker data. Results We conduct simulation studies to compare and contrast the marginal and the conditional tests and to demonstrate that randomized p values can capture both the significance and the uncertainty in the test results. Conclusions The simulation results demonstrate that the proposed conditional tests provide useful localization information, and with informative marker data, the uncertainty in randomized marginal and conditional test results is small. PMID:19439976

Genomewide scan for gout in taiwanese aborigines reveals linkage to chromosome 4q25.

PubMed

Cheng, Li Shu-Chuan; Chiang, Shang-Lun; Tu, Hung-Pin; Chang, Shun-Jen; Wang, Tsu-Nai; Ko, Allen Min-Jen; Chakraborty, Ranajit; Ko, Ying-Chin

2004-09-01

Gout is a disorder of uric-acid metabolism. The Pacific Austronesian population, including Taiwanese aborigines, has a remarkably high prevalence of hyperuricemia and gout, which suggests a founder effect across the Pacific region. We report here a genomewide linkage study of 21 multiplex pedigrees with gout from an aboriginal tribe in Taiwan. From observations of familial clustering, early onset of gout, and clinically severe manifestations, we hypothesized that a major gene plays a role in this trait. Using 382 random polymorphic markers spread across 22 autosomes, we demonstrated a highly significant linkage for gout at marker D4S2623 on chromosome 4q25 (P=.0002 by nonparametric linkage [the NPL(all) statistic]; empirical P=.0006; LOD=4.3, P=4.4x10-6 by logistic regression). When alcohol consumption was included as a covariate in the model, the LOD score increased to 5.66 (P=1.3x10-6). Quantitative traits, including serum uric acid and creatinine, also showed a moderate linkage to this region. To our knowledge, this is the first genome-scan report to identify a genetic locus harboring a gout-susceptibility gene.

Polarization-induced interference within electromagnetically induced transparency for atoms of double-V linkage

NASA Astrophysics Data System (ADS)

Sun, Yuan; Liu, Chang; Chen, Ping-Xing; Liu, Liang

2018-02-01

People have been paying attention to the role of atoms' complex internal level structures in the research of electromagnetically induced transparency (EIT) for a long time, where the various degenerate Zeeman levels usually generate complex linkage patterns for the atomic transitions. It turns out, with special choices of the atomic states and the atomic transitions' linkage structure, clear signatures of quantum interference induced by the probe and coupling light's polarizations can emerge from a typical EIT phenomena. We propose to study a four-state system with double-V linkage pattern for the transitions and analyze the polarization-induced interference under the EIT condition. We show that such interference arises naturally under mild conditions on the optical field and atom manipulation techniques. Moreover, we construct a variation form of double-M linkage pattern where the polarization-induced interference enables polarization-dependent cross modulation between incident weak lights that can be effective even at the few-photon level. The theme is to gain more insight into the essential question: how can we build a nontrivial optical medium where incident lights experience polarization-dependent nonlinear optical interactions, valid for a wide range of incidence intensities down to the few-photon level?

Rapid genotyping by low-coverage resequencing to construct genetic linkage maps of fungi: a case study in Lentinula edodes

PubMed Central

2013-01-01

Background Genetic linkage maps are important tools in breeding programmes and quantitative trait analyses. Traditional molecular markers used for genotyping are limited in throughput and efficiency. The advent of next-generation sequencing technologies has facilitated progeny genotyping and genetic linkage map construction in the major grains. However, the applicability of the approach remains untested in the fungal system. Findings Shiitake mushroom, Lentinula edodes, is a basidiomycetous fungus that represents one of the most popular cultivated edible mushrooms. Here, we developed a rapid genotyping method based on low-coverage (~0.5 to 1.5-fold) whole-genome resequencing. We used the approach to genotype 20 single-spore isolates derived from L. edodes strain L54 and constructed the first high-density sequence-based genetic linkage map of L. edodes. The accuracy of the proposed genotyping method was verified experimentally with results from mating compatibility tests and PCR-single-strand conformation polymorphism on a few known genes. The linkage map spanned a total genetic distance of 637.1 cM and contained 13 linkage groups. Two hundred sequence-based markers were placed on the map, with an average marker spacing of 3.4 cM. The accuracy of the map was confirmed by comparing with previous maps the locations of known genes such as matA and matB. Conclusions We used the shiitake mushroom as an example to provide a proof-of-principle that low-coverage resequencing could allow rapid genotyping of basidiospore-derived progenies, which could in turn facilitate the construction of high-density genetic linkage maps of basidiomycetous fungi for quantitative trait analyses and improvement of genome assembly. PMID:23915543

Impact of a low intensity and broadly inclusive ED care coordination intervention on linkage to primary care and ED utilization.

PubMed

Foster, Sean D; Hart, Kim; Lindsell, Christopher J; Miller, Christopher N; Lyons, Michael S

2018-04-05

We aim to evaluate the effectiveness of a broadly inclusive, comparatively low intensity intervention linking ED patients to a primary care home. This retrospective cohort study evaluated ED patients referred for primary care linkage in a large, urban, academic ED. A care coordination specialist performed a brief interview to gauge access barriers and provide a clinic referral with optional scheduling assistance. Data were abstracted from program records and the electronic medical record. The primary outcome was the proportion of referred individuals who attended at least one primary care appointment. Secondary outcomes included return ED encounters within one year, and factors associated with linkage outcomes. There were 2142 referrals made for 2064 patients; 1688/2142 accepted assistance. Linkage was successful for 1059/1688 (63%, CI95 60% to 65%). Among patients accepting assistance, those without successful linkage were younger (41 vs 45years, difference 3years, CI95 2 to 3), more often male (62% vs 55%,difference 7%, CI95 2% to 12%), and less likely to have a chronic medical condition (37% vs 45%, difference 8%; CI95 3% to 12%) or to have had an appointment scheduled within two weeks (26% vs 33%, difference 7%, CI95 2% to 12%). Insurance status and self-reported barriers to care were not associated with linkage success. Patterns of subsequent ED use were similar, regardless of referral status or linkage outcome. Low intensity, broadly inclusive, ED care coordination linked nearly 50% of patients referred for intervention, and two-thirds of willing participants, with a primary care home. Copyright © 2018 Elsevier Inc. All rights reserved.

Genetic heterogeneity in Finnish hereditary prostate cancer using ordered subset analysis

PubMed Central

Simpson, Claire L; Cropp, Cheryl D; Wahlfors, Tiina; George, Asha; Jones, MaryPat S; Harper, Ursula; Ponciano-Jackson, Damaris; Tammela, Teuvo; Schleutker, Johanna; Bailey-Wilson, Joan E

2013-01-01

Prostate cancer (PrCa) is the most common male cancer in developed countries and the second most common cause of cancer death after lung cancer. We recently reported a genome-wide linkage scan in 69 Finnish hereditary PrCa (HPC) families, which replicated the HPC9 locus on 17q21-q22 and identified a locus on 2q37. The aim of this study was to identify and to detect other loci linked to HPC. Here we used ordered subset analysis (OSA), conditioned on nonparametric linkage to these loci to detect other loci linked to HPC in subsets of families, but not the overall sample. We analyzed the families based on their evidence for linkage to chromosome 2, chromosome 17 and a maximum score using the strongest evidence of linkage from either of the two loci. Significant linkage to a 5-cM linkage interval with a peak OSA nonparametric allele-sharing LOD score of 4.876 on Xq26.3-q27 (ΔLOD=3.193, empirical P=0.009) was observed in a subset of 41 families weakly linked to 2q37, overlapping the HPCX1 locus. Two peaks that were novel to the analysis combining linkage evidence from both primary loci were identified; 18q12.1-q12.2 (OSA LOD=2.541, ΔLOD=1.651, P=0.03) and 22q11.1-q11.21 (OSA LOD=2.395, ΔLOD=2.36, P=0.006), which is close to HPC6. Using OSA allows us to find additional loci linked to HPC in subsets of families, and underlines the complex genetic heterogeneity of HPC even in highly aggregated families. PMID:22948022

A systematic review and meta-analysis of community and facility-based approaches to address gaps in HIV testing and linkage in sub-Saharan Africa

PubMed Central

Sharma, Monisha; Ying, Roger; Tarr, Gillian; Barnabas, Ruanne

2016-01-01

HIV testing and counselling is the first crucial step for linkage to HIV treatment and prevention. However, despite high HIV burden in sub-Saharan Africa, testing coverage is low, particularly among young adults and men. Community-based HIV testing and counselling (testing outside of health facilities) has the potential to reduce coverage gaps, but the relative impact of different modalities is not well assessed. We conducted a systematic review of HIV testing and counselling modalities, characterizing facility and community (home, mobile, index, key populations, campaign, workplace and self-testing) approaches by population reached, HIV-positivity, CD4 count at diagnosis and linkage. Of 2,520 abstracts screened, 126 met eligibility criteria. Community HIV testing had high coverage and uptake and identified HIV-positive individuals at higher CD4 counts than facility testing. Mobile HIV testing reached the highest proportion of men of all modalities examined (50%, 95% CI = 47–54%) and home with self-testing reached the highest proportion of young adults (66%, 95% CI = 65–67%). Few studies evaluated HIV testing and counselling for key populations (commercial sex workers and men who have sex with men), but these interventions yielded high HIV positivity (38%, 95% CI = 19–62%) combined with the highest proportion of first-time testers (78%, 95% CI = 63–88%), indicating service gaps. Facilitated linkage (for example, counsellor follow-up to support linkage) achieved high linkage to care (95%, 95% CI = 87–98%) and ART initiation (75%, 95% CI = 68–82%). Expanding mobile HIV testing, self-testing and outreach to key populations with facilitated linkage can increase the proportion of men, young adults and high-risk individuals linked to HIV treatment and prevention. PMID:26633769

Discrimination of candidate subgenome-specific loci by linkage map construction with an S1 population of octoploid strawberry (Fragaria × ananassa).

PubMed

Nagano, Soichiro; Shirasawa, Kenta; Hirakawa, Hideki; Maeda, Fumi; Ishikawa, Masami; Isobe, Sachiko N

2017-05-12

The strawberry, Fragaria × ananassa, is an allo-octoploid (2n = 8x = 56) and outcrossing species. Although it is the most widely consumed berry crop in the world, its complex genome structure has hindered its genetic and genomic analysis, and thus discrimination of subgenome-specific loci among the homoeologous chromosomes is needed. In the present study, we identified candidate subgenome-specific single nucleotide polymorphism (SNP) and simple sequence repeat (SSR) loci, and constructed a linkage map using an S 1 mapping population of the cultivar 'Reikou' with an IStraw90 Axiom® SNP array and previously published SSR markers. The 'Reikou' linkage map consisted of 11,574 loci (11,002 SNPs and 572 SSR loci) spanning 2816.5 cM of 31 linkage groups. The 11,574 loci were located on 4738 unique positions (bin) on the linkage map. Of the mapped loci, 8999 (8588 SNPs and 411 SSR loci) showed a 1:2:1 segregation ratio of AA:AB:BB allele, which suggested the possibility of deriving loci from candidate subgenome-specific sequences. In addition, 2575 loci (2414 SNPs and 161 SSR loci) showed a 3:1 segregation of AB:BB allele, indicating they were derived from homoeologous genomic sequences. Comparative analysis of the homoeologous linkage groups revealed differences in genome structure among the subgenomes. Our results suggest that candidate subgenome-specific loci are randomly located across the genomes, and that there are small- to large-scale structural variations among the subgenomes. The mapped SNPs and SSR loci on the linkage map are expected to be seed points for the construction of pseudomolecules in the octoploid strawberry.

Linking product-elicited emotional associations and sensory perceptions through a circumplex model based on valence and arousal: Five consumer studies.

PubMed

Jaeger, Sara R; Spinelli, Sara; Ares, Gastón; Monteleone, Erminio

2018-07-01

Sensory product characterisation by consumers is increasingly supplemented by measurement of emotional associations. However, studies that link products' sensory perception and emotional associations are still scarce. Five consumer studies were conducted using cashew nuts, peanuts, chocolate, fruit and processed tomatoes as the product categories. Consumers (n = 685) completed check-all-that-apply (CATA) questions to obtain sensory product perceptions and associations with emotion words. The latter were conceptualised and interpreted through a circumplex emotion model spanned by the dimensions of valence (pleasure to displeasure) and arousal (activation to deactivation). Through regression analysis, sensory terms were mapped to the circumplex model to represent statistical linkages with emotion words. Within a were interpretable. The most notable finding was the highly study-specific nature of the linkages, which was mainly attributed to the influence of product category. Methodological choices may also have been partly responsible for the differences. Three studies used a general emotion vocabulary (EsSense Profile®) and an identical number of sensory terms (n = 39). The less complete coverage of the emotional circumplex and the presence of synonymous sensory terms could have diminished the ability to interpret the results. Conversely, two studies used fewer emotion words and sensory terms and these, furthermore, were purposefully selected for the focal sets of samples. The linkages in these latter studies were more interpretable and this could suggest that customised vocabularies of modest length may be desirable when seeking to establish linkages between emotional associations and sensory characteristics of food/beverage stimuli. Purposeful inclusion of emotion words that fully span the circumplex emotion model may also be desirable. Overall, the research represents a new method for establishing linkages between the sensory properties and emotional association to food and beverage products. Copyright © 2018 Elsevier Ltd. All rights reserved.

Romantic Relationship Commitment and Its Linkages with Commitment to Parents and Friends during Adolescence

ERIC Educational Resources Information Center

De Goede, Irene H. A.; Branje, Susan; van Duin, Jet; VanderValk, Inge E.; Meeus, Wim

2012-01-01

This five-wave longitudinal study examines linkages between adolescents' perceptions of romantic relationship commitment and the development of adolescents' perceptions of commitment to parents and friends. A total of 218 early-to-middle adolescents (39.0 percent boys) and 185 middle-to-late adolescents (30.8 percent boys) participated.…

Isozyme variation and linkage in six conifer species

Treesearch

M. Thompson Conkle

1981-01-01

Isozymes of female gametophyte tissue were analyzed for allelic variation in knobcone, lodgepole, loblolly, Jeffrey, and sugar pines and in Douglas-fir. Linkage was studied in the five pines. The average number of alleles and average herozygosity per enzyme locus were estimated. Knobcone pine ranked lowest among the six species in number of alleles and average...

Human Capital Linkages to Labour Productivity: Implications from Thai Manufacturers

ERIC Educational Resources Information Center

Rukumnuaykit, Pungpond; Pholphirul, Piriya

2016-01-01

Human capital investment is a necessary condition for improving labour market outcomes in most countries. Empirical studies to investigate human capital and its linkages on the labour demand side are, however, relatively scarce due to limitations of firm-level data-sets. Using firm-level data from the Thai manufacturing sector, this paper aims to…

Lexical and Clause-Linkage Properties of the Converbal Constructions in Sakha (Yakut)

ERIC Educational Resources Information Center

Petrova, Nyurguyana

2011-01-01

This thesis is a comprehensive study of lexical and clause-linkage properties of converbs in an underdescribed language, Sakha (aka Yakut). Following Haspelmath (1995b) a converb is defined as a non-finite verb form which mainly indicates an adverbial subordination. Converbs are attested in diverse languages of the world, but are used extensively…

Development of Public Immortal Mapping Populations, Molecular Markers and Linkage Maps for Rapid Cycling Brassica rapa and B. oleracea

USDA-ARS?s Scientific Manuscript database

In this study we describe public immortal mapping populations of self-compatible lines, molecular markers, and linkage maps for Brassica rapa and B. oleracea. We propose that these resources are valuable reference tools for the Brassica community. The B. rapa population consists of 150 recombinant...

Linkages between Approaches to Learning, Perceived Stress and Expected and Actual Academic Outcomes among First-Semester Psychology Students

ERIC Educational Resources Information Center

Öhrstedt, Maria; Lindfors, Petra

2018-01-01

Previous research indicates that higher educational students' perceptions of stress are in part related to the teaching and learning context, and influence academic outcomes. This study intends to deepen our understanding of these processes by examining the linkages between approaches to learning, perceived stress and expected and actual academic…

Lightning Discharges, Cosmic Rays and Climate

NASA Astrophysics Data System (ADS)

Kumar, Sanjay; Siingh, Devendraa; Singh, R. P.; Singh, A. K.; Kamra, A. K.

2018-03-01

The entirety of the Earth's climate system is continuously bombarded by cosmic rays and exhibits about 2000 thunderstorms active at any time of the day all over the globe. Any linkage among these vast systems should have global consequences. Numerous studies done in the past deal with partial links between some selected aspects of this grand linkage. Results of these studies vary from weakly to strongly significant and are not yet complete enough to justify the physical mechanism proposed to explain such links. This review is aimed at presenting the current understanding, based on the past studies on the link between cosmic ray, lightning and climate. The deficiencies in some proposed links are pointed out. Impacts of cosmic rays on engineering systems and the possible effects of cosmic rays on human health are also briefly discussed. Also enumerated are some problems for future work which may help in developing the grand linkage among these three vast systems.

Terminal sialic acid linkages determine different cell infectivities of human parainfluenza virus type 1 and type 3.

PubMed

Fukushima, Keijo; Takahashi, Tadanobu; Ito, Seigo; Takaguchi, Masahiro; Takano, Maiko; Kurebayashi, Yuuki; Oishi, Kenta; Minami, Akira; Kato, Tatsuya; Park, Enoch Y; Nishimura, Hidekazu; Takimoto, Toru; Suzuki, Takashi

2014-09-01

Human parainfluenza virus type 1 (hPIV1) and type 3 (hPIV3) initiate infection by sialic acid binding. Here, we investigated sialic acid linkage specificities for binding and infection of hPIV1 and hPIV3 by using sialic acid linkage-modified cells treated with sialidases or sialyltransferases. The hPIV1 is bound to only α2,3-linked sialic acid residues, whereas hPIV3 is bound to α2,6-linked sialic acid residues in addition to α2,3-linked sialic acid residues in human red blood cells. α2,3 linkage-specific sialidase treatment of LLC-MK2 cells and A549 cells decreased the infectivity of hPIV1 but not that of hPIV3. Treatment of A549 cells with α2,3 linkage-specific sialyltransferase increased infectivities of both hPIV1 and hPIV3, whereas α2,6 linkage-specific sialyltransferase treatment increased only hPIV3 infectivity. Clinical isolates also showed similar sialic acid linkage specificities. We concluded that hPIV1 utilizes only α2,3 sialic acid linkages and that hPIV3 makes use of α2,6 sialic acid linkages in addition to α2,3 sialic acid linkages as viral receptors. Copyright © 2014. Published by Elsevier Inc.

What If? Conditionals in Educational Registers

ERIC Educational Resources Information Center

Louwerse, Max M.; Crossley, Scott A.; Jeuniaux, Patrick

2008-01-01

Many corpus linguistic studies have investigated classification of texts into genres and registers, but relatively few of these studies have looked at linguistic features in educational registers. From a pedagogical perspective it is important to determine whether certain linguistic features behave differently across registers within particular…

Physiological Linkage in Couples and its Implications for Individual and Interpersonal Functioning: A Literature Review

PubMed Central

Timmons, Adela C.; Margolin, Gayla; Saxbe, Darby E.

2015-01-01

Do partners’ levels of physiological arousal become linked in close relationships? The term “physiological linkage” describes covariation between people in their moment-to-moment physiological states. The current review presents a conceptual framework to guide research on linkage in romantic relationships and discusses the potential implications of being “linked.” Evidence of linkage was found across a broad range of physiological indices and in a variety of contexts, including during laboratory-based conflict and in daily life. Four hypotheses regarding how linkage relates to individual and interpersonal functioning are evaluated: (1) co-activation of the sympathetic nervous system or hypothalamic-pituitary adrenal axis is “bad,” (2) moderate physiological linkage is “just right,” (3) physiological linkage is problematic if the individual or couple is overloaded, and (4) the implications of physiological linkage depend on the emotional context. We found partial support for the first hypothesis and determined that more research is needed to evaluate the remaining hypotheses. Linkage in cortisol was negatively associated with relationship satisfaction; but at the same time, linkage in multiple systems was positively associated with indices of relationship connectedness, such as the amount of time spent together and the ability to identify the emotions of one’s partner. These results suggest that linkage may confer benefits but also may put couples at risk if they become entrenched in patterns of conflict or stress. With research in this area burgeoning in recent years, this review indicates that linkage is a promising construct with applications for interventions targeting individual health and couple functioning. PMID:26147932

Ten-year mortality and cardiovascular morbidity in the Finnish Diabetes Prevention Study--secondary analysis of the randomized trial.

PubMed

Uusitupa, Matti; Peltonen, Markku; Lindström, Jaana; Aunola, Sirkka; Ilanne-Parikka, Pirjo; Keinänen-Kiukaanniemi, Sirkka; Valle, Timo T; Eriksson, Johan G; Tuomilehto, Jaakko

2009-05-21

The Finnish Diabetes Prevention Study (DPS) was a randomized controlled trial, which showed that it is possible to prevent type 2 diabetes by lifestyle changes. The aim of the present study was to examine whether the lifestyle intervention had an effect on the ten-year mortality and cardiovascular morbidity in the DPS participants originally randomized either into an intervention or control group. Furthermore, we compared these results with a population-based cohort comprising individuals of varying glucose tolerance states. Middle-aged, overweight people with IGT (n = 522) were randomized into intensive intervention (including physical activity, weight reduction and dietary counseling), or control "mini-intervention" group. Median length of the intervention period was 4 years and the mean follow-up was 10.6 years. The population-based reference study cohort included 1881 individuals (1570 with normal glucose tolerance, 183 with IGT, 59 with screen-detected type 2 diabetes, 69 with previously known type 2 diabetes) with the mean follow-up of 13.8 years. Mortality and cardiovascular morbidity data were collected from the national Hospital Discharge Register and Causes of Death Register. Among the DPS participants who consented for register linkage (n = 505), total mortality (2.2 vs. 3.8 per 1000 person years, hazard ratio HR = 0.57, 95% CI 0.21-1.58) and cardiovascular morbidity (22.9 vs. 22.0 per 1000 person years, HR = 1.04, 95% CI 0.72-1.51) did not differ significantly between the intervention and control groups. Compared with the population-based cohort with impaired glucose tolerance, adjusted HRs were 0.21 (95% CI 0.09-0.52) and 0.39 (95% CI 0.20-0.79) for total mortality, and 0.89 (95% CI 0.62-1.27) and 0.87 (0.60-1.27) for cardiovascular morbidity in the intervention and control groups of the DPS, respectively. The risk of death in DPS combined cohort was markedly lower than in FINRISK IGT cohort (adjusted HR 0.30, 95% CI 0.17-0.54), but there was no significant difference in the risk of CVD (adjusted HR 0.88, 95% CI 0.64-1.21). Lifestyle intervention among persons with IGT did not decrease cardiovascular morbidity during the first 10 years of follow-up. However, the statistical power may not be sufficient to detect small differences between the intervention and control groups. Low total mortality among participants of the DPS compared with individuals with IGT in the general population could be ascribed to a lower cardiovascular risk profile at baseline and regular follow-up. ClinicalTrials.gov NCT00518167.

New South Wales Child Development Study (NSW-CDS): an Australian multiagency, multigenerational, longitudinal record linkage study.

PubMed

Carr, Vaughan J; Harris, Felicity; Raudino, Alessandra; Luo, Luming; Kariuki, Maina; Liu, Enwu; Tzoumakis, Stacy; Smith, Maxwell; Holbrook, Allyson; Bore, Miles; Brinkman, Sally; Lenroot, Rhoshel; Dix, Katherine; Dean, Kimberlie; Laurens, Kristin R; Green, Melissa J

2016-02-11

The initial aim of this multiagency, multigenerational record linkage study is to identify childhood profiles of developmental vulnerability and resilience, and to identify the determinants of these profiles. The eventual aim is to identify risk and protective factors for later childhood-onset and adolescent-onset mental health problems, and other adverse social outcomes, using subsequent waves of record linkage. The research will assist in informing the development of public policy and intervention guidelines to help prevent or mitigate adverse long-term health and social outcomes. The study comprises a population cohort of 87,026 children in the Australian State of New South Wales (NSW). The cohort was defined by entry into the first year of full-time schooling in NSW in 2009, at which time class teachers completed the Australian Early Development Census (AEDC) on each child (with 99.7% coverage in NSW). The AEDC data have been linked to the children's birth, health, school and child protection records for the period from birth to school entry, and to the health and criminal records of their parents, as well as mortality databases. Descriptive data summarising sex, geographic and socioeconomic distributions, and linkage rates for the various administrative databases are presented. Child data are summarised, and the mental health and criminal records data of the children's parents are provided. In 2015, at age 11 years, a self-report mental health survey was administered to the cohort in collaboration with government, independent and Catholic primary school sectors. A second record linkage, spanning birth to age 11 years, will be undertaken to link this survey data with the aforementioned administrative databases. This will enable a further identification of putative risk and protective factors for adverse mental health and other outcomes in adolescence, which can then be tested in subsequent record linkages. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Effects of naloxone distribution alone or in combination with addiction treatment with or without pre-exposure prophylaxis for HIV prevention in people who inject drugs: a cost-effectiveness modelling study.

PubMed

Uyei, Jennifer; Fiellin, David A; Buchelli, Marianne; Rodriguez-Santana, Ramon; Braithwaite, R Scott

2017-03-01

In the USA, an epidemic of opioid overdose deaths is occurring, many of which are from heroin. Combining naloxone distribution with linkage to addiction treatment or pre-exposure prophylaxis (PrEP) for HIV prevention through syringe service programmes has the potential to save lives and be cost-effective. We estimated the outcomes and cost-effectiveness of five alternative strategies: no additional intervention, naloxone distribution, naloxone distribution plus linkage to addiction treatment, naloxone distribution plus PrEP, and naloxone distribution plus linkage to addiction treatment and PrEP. We developed a decision analytical Markov model to simulate opioid overdose, HIV incidence, overdose-related deaths, and HIV-related deaths in people who inject drugs in Connecticut, USA. Model input parameters were derived from published sources. We compared each strategy with no intervention, as well as simultaneously considering all strategies. Sensitivity analysis was done for all variables. Linkage to addiction treatment was referral to an opioid treatment programme for methadone. Endpoints were survival, life expectancy, quality-adjusted life-years (QALYs), number and percentage of overdose deaths averted, number of HIV-related deaths averted, total costs (in 2015 US$) associated with each strategy, and incremental cost per QALY gained. In the base-case analysis, compared with no additional intervention, the naloxone distribution strategy yielded an incremental cost-effectiveness ratio (ICER) of $323 per QALY, and naloxone distribution plus linkage to addiction treatment was cost saving compared with no additional intervention (greater effectiveness and less expensive). The most efficient strategies (ie, those conferring the greatest health benefit for a particular budget) were naloxone distribution combined with linkage to addiction treatment (cost saving), and naloxone distribution combined with PrEP and linkage to addiction treatment (ICER $95 337 per QALY) at a willingness-to-pay threshold of $100 000. In probabilistic sensitivity analysis, the combination of naloxone distribution, PrEP, and linkage to addiction treatment was the optimal strategy in 37% of iterations and the combination of naloxone distribution and linkage to addiction treatment was the optimal strategy in 34% of iterations. Naloxone distribution through syringe service programmes is cost-effective compared with syringe distribution alone, but when combined with linkage to addiction treatment is cost saving compared with no additional services. A strategy that combines naloxone distribution, PrEP, and linkage to addiction treatment results in greater health benefits in people who inject drugs and is also cost-effective. State of Connecticut Department of Public Health and the National Institute of Mental Health. Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND license. Published by Elsevier Ltd.. All rights reserved.

A High-Density Linkage Map for Astyanax mexicanus Using Genotyping-by-Sequencing Technology

PubMed Central

Carlson, Brian M.; Onusko, Samuel W.; Gross, Joshua B.

2014-01-01

The Mexican tetra, Astyanax mexicanus, is a unique model system consisting of cave-adapted and surface-dwelling morphotypes that diverged >1 million years (My) ago. This remarkable natural experiment has enabled powerful genetic analyses of cave adaptation. Here, we describe the application of next-generation sequencing technology to the creation of a high-density linkage map. Our map comprises more than 2200 markers populating 25 linkage groups constructed from genotypic data generated from a single genotyping-by-sequencing project. We leveraged emergent genomic and transcriptomic resources to anchor hundreds of anonymous Astyanax markers to the genome of the zebrafish (Danio rerio), the most closely related model organism to our study species. This facilitated the identification of 784 distinct connections between our linkage map and the Danio rerio genome, highlighting several regions of conserved genomic architecture between the two species despite ∼150 My of divergence. Using a Mendelian cave-associated trait as a proof-of-principle, we successfully recovered the genomic position of the albinism locus near the gene Oca2. Further, our map successfully informed the positions of unplaced Astyanax genomic scaffolds within particular linkage groups. This ability to identify the relative location, orientation, and linear order of unaligned genomic scaffolds will facilitate ongoing efforts to improve on the current early draft and assemble future versions of the Astyanax physical genome. Moreover, this improved linkage map will enable higher-resolution genetic analyses and catalyze the discovery of the genetic basis for cave-associated phenotypes. PMID:25520037

Genomewide Linkage Scan for Diabetic Renal Failure and Albuminuria: The FIND Study

PubMed Central

Igo, Robert P.; Iyengar, Sudha K.; Nicholas, Susanne B.; Goddard, Katrina A.B.; Langefeld, Carl D.; Hanson, Robert L.; Duggirala, Ravindranath; Divers, Jasmin; Abboud, Hanna; Adler, Sharon G.; Arar, Nedal H.; Horvath, Amanda; Elston, Robert C.; Bowden, Donald W.; Guo, Xiuqing; Ipp, Eli; Kao, W.H. Linda; Kimmel, Paul L.; Knowler, William C.; Meoni, Lucy A.; Molineros, Julio; Nelson, Robert G.; Pahl, Madeline V.; Parekh, Rulan S.; Rasooly, Rebekah S.; Schelling, Jeffrey R.; Shah, Vallabh O.; Smith, Michael W.; Winkler, Cheryl A.; Zager, Philip G.; Sedor, John R.; Freedman, Barry I.

2011-01-01

Background Diabetic nephropathy (DN) is a leading cause of mortality and morbidity in patients with type 1 and type 2 diabetes. The multicenter FIND consortium aims to identify genes for DN and its associated quantitative traits, e.g. the urine albumin:creatinine ratio (ACR). Herein, the results of whole-genome linkage analysis and a sparse association scan for ACR and a dichotomous DN phenotype are reported in diabetic individuals. Methods A genomewide scan comprising more than 5,500 autosomal single nucleotide polymorphism markers (average spacing of 0.6 cM) was performed on 1,235 nuclear and extended pedigrees (3,972 diabetic participants) ascertained for DN from African-American (AA), American-Indian (AI), European-American (EA) and Mexican-American (MA) populations. Results Strong evidence for linkage to DN was detected on chromosome 6p (p = 8.0 × 10−5, LOD = 3.09) in EA families as well as suggestive evidence for linkage to chromosome 7p in AI families. Regions on chromosomes 3p in AA, 7q in EA, 16q in AA and 22q in MA displayed suggestive evidence of linkage for urine ACR. The linkage peak on chromosome 22q overlaps the MYH9/APOL1 gene region, previously implicated in AA diabetic and nondiabetic nephropathies. Conclusion These results strengthen the evidence for previously identified genomic regions and implicate several novel loci potentially involved in the pathogenesis of DN. PMID:21454968

The promise of record linkage for assessing the uptake of health services in resource constrained settings: a pilot study from South Africa.

PubMed

Kabudula, Chodziwadziwa W; Clark, Benjamin D; Gómez-Olivé, Francesc Xavier; Tollman, Stephen; Menken, Jane; Reniers, Georges

2014-05-24

Health and Demographic Surveillance Systems (HDSS) have been instrumental in advancing population and health research in low- and middle- income countries where vital registration systems are often weak. However, the utility of HDSS would be enhanced if their databases could be linked with those of local health facilities. We assess the feasibility of record linkage in rural South Africa using data from the Agincourt HDSS and a local health facility. Using a gold standard dataset of 623 record pairs matched by means of fingerprints, we evaluate twenty record linkage scenarios (involving different identifiers, string comparison techniques and with and without clerical review) based on the Fellegi-Sunter probabilistic record linkage model. Matching rates and quality are measured by their sensitivity and positive predictive value (PPV). Background characteristics of matched and unmatched cases are compared to assess systematic bias in the resulting record-linked dataset. A hybrid approach of deterministic followed by probabilistic record linkage, and scenarios that use an extended set of identifiers including another household member's first name yield the best results. The best fully automated record linkage scenario has a sensitivity of 83.6% and PPV of 95.1%. The sensitivity and PPV increase to 84.3% and 96.9%, respectively, when clerical review is undertaken on 10% of the record pairs. The likelihood of being linked is significantly lower for females, non-South Africans and the elderly. Using records matched by means of fingerprints as the gold standard, we have demonstrated the feasibility of fully automated probabilistic record linkage using identifiers that are routinely collected in health facilities in South Africa. Our study also shows that matching statistics can be improved if other identifiers (e.g., another household member's first name) are added to the set of matching variables, and, to a lesser extent, with clerical review. Matching success is, however, correlated with background characteristics that are indicative of the instability of personal attributes over time (e.g., surname in the case of women) or with misreporting (e.g., age).

The promise of record linkage for assessing the uptake of health services in resource constrained settings: a pilot study from South Africa

PubMed Central

2014-01-01

Background Health and Demographic Surveillance Systems (HDSS) have been instrumental in advancing population and health research in low- and middle- income countries where vital registration systems are often weak. However, the utility of HDSS would be enhanced if their databases could be linked with those of local health facilities. We assess the feasibility of record linkage in rural South Africa using data from the Agincourt HDSS and a local health facility. Methods Using a gold standard dataset of 623 record pairs matched by means of fingerprints, we evaluate twenty record linkage scenarios (involving different identifiers, string comparison techniques and with and without clerical review) based on the Fellegi-Sunter probabilistic record linkage model. Matching rates and quality are measured by their sensitivity and positive predictive value (PPV). Background characteristics of matched and unmatched cases are compared to assess systematic bias in the resulting record-linked dataset. Results A hybrid approach of deterministic followed by probabilistic record linkage, and scenarios that use an extended set of identifiers including another household member’s first name yield the best results. The best fully automated record linkage scenario has a sensitivity of 83.6% and PPV of 95.1%. The sensitivity and PPV increase to 84.3% and 96.9%, respectively, when clerical review is undertaken on 10% of the record pairs. The likelihood of being linked is significantly lower for females, non-South Africans and the elderly. Conclusion Using records matched by means of fingerprints as the gold standard, we have demonstrated the feasibility of fully automated probabilistic record linkage using identifiers that are routinely collected in health facilities in South Africa. Our study also shows that matching statistics can be improved if other identifiers (e.g., another household member’s first name) are added to the set of matching variables, and, to a lesser extent, with clerical review. Matching success is, however, correlated with background characteristics that are indicative of the instability of personal attributes over time (e.g., surname in the case of women) or with misreporting (e.g., age). PMID:24884457