Potential Linkage Between Cerebrovascular Diseases and Metabolic Syndrome.

PubMed

Jabir, Nasimudeen R; Firoz, Chelapram Kandy; Khan, Mohd Shahnawaz; Zaidi, Syed Kashif; Ashraf, Ghulam Md; Shakil, Shazi; Kamal, Mohammad Amjad; Tabrez, Shams

2017-01-01

Cerebrovascular disease (CD) and metabolic syndrome (MetS) are two devastating health dilemma that continues to be a potential contributor to disability and mortality in human population all across the world. Scientific data clearly shows several mechanistic similarities between these two co-existing and interlinked conditions. The linkage exacerbates ongoing patho-physiological condition towards more lethal events. In view of the presence of modifiable risk factors in both CD and MetS, their management holds potential therapeutic value. Hence, developing common treatment strategies for these diseases could involve common molecular agents. In this communication, we have summarized some of the common pathological conditions viz. abdominal obesity, insulin resistance, dyslipidemia, hypertension, and endothelial dysfunction that further deteriorate existing homeostasis in CD and MetS. Based on our article, it is advocated that substantial improvements in novel multi-targeted drug discovery could provide the effective treatment methods in order to avoid the fatal complications related with CD and MetS. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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

Irrigated sugarbeet sucrose content in relation to growing season climatic conditions in the northwest U.S.

USDA-ARS?s Scientific Manuscript database

The potential effects of changing climate on world food production have become a political and scientific focus. This study was conducted to investigate linkages between seasonal climatic conditions and sugarbeet sucrose content in southern Idaho and eastern Oregon. Sucrose content of irrigated suga...

Functional Heterogeneity and Senior Management Team Effectiveness

ERIC Educational Resources Information Center

Benoliel, Pascale; Somech, Anit

2016-01-01

Purpose: There has been an increasing trend toward the creation of senior management teams (SMTs) which are characterized by a high degree of functional heterogeneity. Although such teams may create better linkages to information, along with the benefits of functional heterogeneity comes the potential for conflicts that stem from the value…

Towards Principles-Based Approaches to Governance of Health-related Research using Personal Data

PubMed Central

Laurie, Graeme; Sethi, Nayha

2013-01-01

Technological advances in the quality, availability and linkage potential of health data for research make the need to develop robust and effective information governance mechanisms more pressing than ever before; they also lead us to question the utility of governance devices used hitherto such as consent and anonymisation. This article assesses and advocates a principles-based approach, contrasting this with traditional rule-based approaches, and proposes a model of principled proportionate governance. It is suggested that the approach not only serves as the basis for good governance in contemporary data linkage but also that it provides a platform to assess legal reforms such as the draft Data Protection Regulation. PMID:24416087

Towards Principles-Based Approaches to Governance of Health-related Research using Personal Data.

PubMed

Laurie, Graeme; Sethi, Nayha

2013-01-01

Technological advances in the quality, availability and linkage potential of health data for research make the need to develop robust and effective information governance mechanisms more pressing than ever before; they also lead us to question the utility of governance devices used hitherto such as consent and anonymisation. This article assesses and advocates a principles-based approach, contrasting this with traditional rule-based approaches, and proposes a model of principled proportionate governance . It is suggested that the approach not only serves as the basis for good governance in contemporary data linkage but also that it provides a platform to assess legal reforms such as the draft Data Protection Regulation.

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

Climate Change in the US: Potential Consequences for Human Health

NASA Technical Reports Server (NTRS)

Maynard, Nancy G.

2001-01-01

The U.S. National Assessment identified five major areas of consequences of climate change in the United States: temperature-related illnesses and deaths, health effects related to extreme weather events, air pollution-related health effects, water- and food-borne diseases, and insect-, tick-, and rodent-borne diseases. The U.S. National Assessment final conclusions about these potential health effects will be described. In addition, a summary of some of the new tools for studying human health aspects of climate change as well as environment-health linkages through remotely sensed data and observations will be provided.

Perspectives on Evaluation, Linkage and Program Improvement.

ERIC Educational Resources Information Center

Bank, Adrianne; And Others

Actual and potential relationships between evaluators and linkers--curriculum or management specialists who disseminate the products of evaluation to school districts--were explored. Evaluation and linkage evolved as distinct educational occupations, stimulated by federal involvement in research, development, and school improvement since the early…

Accommodating Chromosome Inversions in Linkage Analysis

PubMed Central

Chen, Gary K.; Slaten, Erin; Ophoff, Roel A.; Lange, Kenneth

2006-01-01

This work develops a population-genetics model for polymorphic chromosome inversions. The model precisely describes how an inversion changes the nature of and approach to linkage equilibrium. The work also describes algorithms and software for allele-frequency estimation and linkage analysis in the presence of an inversion. The linkage algorithms implemented in the software package Mendel estimate recombination parameters and calculate the posterior probability that each pedigree member carries the inversion. Application of Mendel to eight Centre d'Étude du Polymorphisme Humain pedigrees in a region containing a common inversion on 8p23 illustrates its potential for providing more-precise estimates of the location of an unmapped marker or trait gene. Our expanded cytogenetic analysis of these families further identifies inversion carriers and increases the evidence of linkage. PMID:16826515

The linkage between Churg-Strauss syndrome and leukotriene receptor antagonists: fact or fiction?

PubMed Central

McDanel, Deanna L; Muller, Barbara A

2005-01-01

Epidemiologic evidence has shown that the worldwide prevalence of asthma is increasing. The leukotriene receptor antagonists (LTRAs) represent a new class of therapy for asthma. They have been developed in the last decade and play a pivotal steroid-sparing role in treating the inflammatory component of asthma. Consequently, reports of Churg-Strauss syndrome (CSS), a rare form of systemic vasculitis, have been recognized as a potential side effect in individuals with moderate to severe asthma on LTRA therapy. The serious nature of this disorder is worthy of prompt recognition by clinicians and aggressive therapy to avoid the subsequent longstanding effects of vasculitis. To validate the postulated linkage between the LTRAs and CSS, this review comprehensively evaluates reported cases in the literature and supports a pathophysiological relationship between the LTRAs and the development of CSS. PMID:18360552

Minnesota Computer Aided Library System (MCALS); University of Minnesota Subsystem Cost/Benefits Analysis.

ERIC Educational Resources Information Center

Lourey, Eugene D., Comp.

The Minnesota Computer Aided Library System (MCALS) provides a basis of unification for library service program development in Minnesota for eventual linkage to the national information network. A prototype plan for communications functions is illustrated. A cost/benefits analysis was made to show the cost/effectiveness potential for MCALS. System…

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.

A Potential Novel Spontaneous Preterm Birth Gene, AR, Identified by Linkage and Association Analysis of X Chromosomal Markers

PubMed Central

Karjalainen, Minna K.; Huusko, Johanna M.; Ulvila, Johanna; Sotkasiira, Jenni; Luukkonen, Aino; Teramo, Kari; Plunkett, Jevon; Anttila, Verneri; Palotie, Aarno; Haataja, Ritva; Muglia, Louis J.; Hallman, Mikko

2012-01-01

Preterm birth is the major cause of neonatal mortality and morbidity. In many cases, it has severe life-long consequences for the health and neurological development of the newborn child. More than 50% of all preterm births are spontaneous, and currently there is no effective prevention. Several studies suggest that genetic factors play a role in spontaneous preterm birth (SPTB). However, its genetic background is insufficiently characterized. The aim of the present study was to perform a linkage analysis of X chromosomal markers in SPTB in large northern Finnish families with recurrent SPTBs. We found a significant linkage signal (HLOD  = 3.72) on chromosome locus Xq13.1 when the studied phenotype was being born preterm. There were no significant linkage signals when the studied phenotype was giving preterm deliveries. Two functional candidate genes, those encoding the androgen receptor (AR) and the interleukin-2 receptor gamma subunit (IL2RG), located near this locus were analyzed as candidates for SPTB in subsequent case-control association analyses. Nine single-nucleotide polymorphisms (SNPs) within these genes and an AR exon-1 CAG repeat, which was previously demonstrated to be functionally significant, were analyzed in mothers with preterm delivery (n = 272) and their offspring (n = 269), and in mothers with exclusively term deliveries (n = 201) and their offspring (n = 199), all originating from northern Finland. A replication study population consisting of individuals born preterm (n = 111) and term (n = 197) from southern Finland was also analyzed. Long AR CAG repeats (≥26) were overrepresented and short repeats (≤19) underrepresented in individuals born preterm compared to those born at term. Thus, our linkage and association results emphasize the role of the fetal genome in genetic predisposition to SPTB and implicate AR as a potential novel fetal susceptibility gene for SPTB. PMID:23227263

Effects of Demographic History on the Detection of Recombination Hotspots from Linkage Disequilibrium

PubMed Central

Dapper, Amy L; Payseur, Bret A

2018-01-01

Abstract In some species, meiotic recombination is concentrated in small genomic regions. These “recombination hotspots” leave signatures in fine-scale patterns of linkage disequilibrium, raising the prospect that the genomic landscape of hotspots can be characterized from sequence variation. This approach has led to the inference that hotspots evolve rapidly in some species, but are conserved in others. Historic demographic events, such as population bottlenecks, are known to affect patterns of linkage disequilibrium across the genome, violating population genetic assumptions of this approach. Although such events are prevalent, demographic history is generally ignored when making inferences about the evolution of recombination hotspots. To determine the effect of demography on the detection of recombination hotspots, we use the coalescent to simulate haplotypes with a known recombination landscape. We measure the ability of popular linkage disequilibrium-based programs to detect hotspots across a range of demographic histories, including population bottlenecks, hidden population structure, population expansions, and population contractions. We find that demographic events have the potential to greatly reduce the power and increase the false positive rate of hotspot discovery. Neither the power nor the false positive rate of hotspot detection can be predicted without also knowing the demographic history of the sample. Our results suggest that ignoring demographic history likely overestimates the power to detect hotspots and therefore underestimates the degree of hotspot sharing between species. We suggest strategies for incorporating demographic history into population genetic inferences about recombination hotspots. PMID:29045724

The Québec BCG Vaccination Registry (1956-1992): assessing data quality and linkage with administrative health databases.

PubMed

Rousseau, Marie-Claude; Conus, Florence; Li, Jun; Parent, Marie-Élise; El-Zein, Mariam

2014-01-09

Vaccination registries have undoubtedly proven useful for estimating vaccination coverage as well as examining vaccine safety and effectiveness. However, their use for population health research is often limited. The Bacillus Calmette-Guérin (BCG) Vaccination Registry for the Canadian province of Québec comprises some 4 million vaccination records (1926-1992). This registry represents a unique opportunity to study potential associations between BCG vaccination and various health outcomes. So far, such studies have been hampered by the absence of a computerized version of the registry. We determined the completeness and accuracy of the recently computerized BCG Vaccination Registry, as well as examined its linkability with demographic and administrative medical databases. Two systematically selected verification samples, each representing ~0.1% of the registry, were used to ascertain accuracy and completeness of the electronic BCG Vaccination Registry. Agreement between the paper [listings (n = 4,987 records) and vaccination certificates (n = 4,709 records)] and electronic formats was determined along several nominal and BCG-related variables. Linkage feasibility with the Birth Registry (probabilistic approach) and provincial Healthcare Registration File (deterministic approach) was examined using nominal identifiers for a random sample of 3,500 individuals born from 1961 to 1974 and BCG vaccinated between 1970 and 1974. Exact agreement was observed for 99.6% and 81.5% of records upon comparing, respectively, the paper listings and vaccination certificates to their corresponding computerized records. The proportion of successful linkage was 77% with the Birth Registry, 70% with the Healthcare Registration File, 57% with both, and varied by birth year. Computerization of this Registry yielded excellent results. The registry was complete and accurate, and linkage with administrative databases was highly feasible. This study represents the first step towards assembling large scale population-based epidemiological studies which will enable filling important knowledge gaps on the potential health effects of early life non-specific stimulation of the immune function, as resulting from BCG vaccination.

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.

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.

Genetic dissection of seed oil and protein content and identification of networks associated with oil content in Brassica napus.

PubMed

Chao, Hongbo; Wang, Hao; Wang, Xiaodong; Guo, Liangxing; Gu, Jianwei; Zhao, Weiguo; Li, Baojun; Chen, Dengyan; Raboanatahiry, Nadia; Li, Maoteng

2017-04-10

High-density linkage maps can improve the precision of QTL localization. A high-density SNP-based linkage map containing 3207 markers covering 3072.7 cM of the Brassica napus genome was constructed in the KenC-8 × N53-2 (KNDH) population. A total of 67 and 38 QTLs for seed oil and protein content were identified with an average confidence interval of 5.26 and 4.38 cM, which could explain up to 22.24% and 27.48% of the phenotypic variation, respectively. Thirty-eight associated genomic regions from BSA overlapped with and/or narrowed the SOC-QTLs, further confirming the QTL mapping results based on the high-density linkage map. Potential candidates related to acyl-lipid and seed storage underlying SOC and SPC, respectively, were identified and analyzed, among which six were checked and showed expression differences between the two parents during different embryonic developmental periods. A large primary carbohydrate pathway based on potential candidates underlying SOC- and SPC-QTLs, and interaction networks based on potential candidates underlying SOC-QTLs, was constructed to dissect the complex mechanism based on metabolic and gene regulatory features, respectively. Accurate QTL mapping and potential candidates identified based on high-density linkage map and BSA analyses provide new insights into the complex genetic mechanism of oil and protein accumulation in the seeds of rapeseed.

Issues in the Linkage and Integration of Treatment and Rehabilitation Services for Chronically Mentally Ill Persons.

ERIC Educational Resources Information Center

Woy, J. Richard; Dellario, Donald J.

1985-01-01

Compares and contrasts characteristics of the mental health system and the Vocational Rehabilitation (VR) service system; examines environmental, intraorganizational, and interorganizational variables as they pertain to potential for linkages between mental health and VR providers; and discusses implications for improved integration of treatment…

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

Accuracy of Probabilistic Linkage Using the Enhanced Matching System for Public Health and Epidemiological Studies.

PubMed

Aldridge, Robert W; Shaji, Kunju; Hayward, Andrew C; Abubakar, Ibrahim

2015-01-01

The Enhanced Matching System (EMS) is a probabilistic record linkage program developed by the tuberculosis section at Public Health England to match data for individuals across two datasets. This paper outlines how EMS works and investigates its accuracy for linkage across public health datasets. EMS is a configurable Microsoft SQL Server database program. To examine the accuracy of EMS, two public health databases were matched using National Health Service (NHS) numbers as a gold standard unique identifier. Probabilistic linkage was then performed on the same two datasets without inclusion of NHS number. Sensitivity analyses were carried out to examine the effect of varying matching process parameters. Exact matching using NHS number between two datasets (containing 5931 and 1759 records) identified 1071 matched pairs. EMS probabilistic linkage identified 1068 record pairs. The sensitivity of probabilistic linkage was calculated as 99.5% (95%CI: 98.9, 99.8), specificity 100.0% (95%CI: 99.9, 100.0), positive predictive value 99.8% (95%CI: 99.3, 100.0), and negative predictive value 99.9% (95%CI: 99.8, 100.0). Probabilistic matching was most accurate when including address variables and using the automatically generated threshold for determining links with manual review. With the establishment of national electronic datasets across health and social care, EMS enables previously unanswerable research questions to be tackled with confidence in the accuracy of the linkage process. In scenarios where a small sample is being matched into a very large database (such as national records of hospital attendance) then, compared to results presented in this analysis, the positive predictive value or sensitivity may drop according to the prevalence of matches between databases. Despite this possible limitation, probabilistic linkage has great potential to be used where exact matching using a common identifier is not possible, including in low-income settings, and for vulnerable groups such as homeless populations, where the absence of unique identifiers and lower data quality has historically hindered the ability to identify individuals across datasets.

Quantitative trait loci controlling cyanogenic glucoside and dry matter content in cassava (Manihot esculenta Crantz) roots.

PubMed

Balyejusa Kizito, Elizabeth; Rönnberg-Wästljung, Ann-Christin; Egwang, Thomas; Gullberg, Urban; Fregene, Martin; Westerbergh, Anna

2007-09-01

Cassava (Manihot esculenta Crantz) is a starchy root crop grown in the tropics mainly by small-scale farmers even though agro-industrial processing is rapidly increasing. For this processing market improved varieties with high dry matter root content (DMC) is required. Potentially toxic cyanogenic glucosides are synthesized in the leaves and translocated to the roots. Selection for varieties with low cyanogenic glucoside potential (CNP) and high DMC is among the principal objectives in cassava breeding programs. However, these traits are highly influenced by the environmental conditions and the genetic control of these traits is not well understood. An S(1) population derived from a cross between two bred cassava varieties (MCOL 1684 and Rayong 1) that differ in CNP and DMC was used to study the heritability and genetic basis of these traits. A broad-sense heritability of 0.43 and 0.42 was found for CNP and DMC, respectively. The moderate heritabilities for DMC and CNP indicate that the phenotypic variation of these traits is explained by a genetic component. We found two quantitative trait loci (QTL) on two different linkage groups controlling CNP and six QTL on four different linkage groups controlling DMC. One QTL for CNP and one QTL for DMC mapped near each other, suggesting pleiotrophy and/or linkage of QTL. The two QTL for CNP showed additive effects while the six QTL for DMC showed additive effect, dominance or overdominance. This study is a first step towards developing molecular marker tools for efficient breeding of CNP and DMC in cassava.

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

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.

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

Assessment of in Vitro Digestibility of Dietary Carbohydrates Using Rat Small Intestinal Extract.

PubMed

Ferreira-Lazarte, Alvaro; Olano, Agustín; Villamiel, Mar; Moreno, F Javier

2017-09-13

There are few studies on the assessment of digestibility of nondigestible carbohydrates, despite their increasingly important role in human health. In vitro digestibility of a range of dietary carbohydrates classified as digestible (maltose, sucrose, and lactose), well-recognized (lactulose, fructooligosaccharides (FOS), and two types of galactooligosaccharides (GOS) differing in the predominant glycosidic linkage), and potential (lactosucrose and GOS from lactulose, OsLu) prebiotics using a rat small intestinal extract (RSIE) under physiological conditions of temperature and pH is described. Recognized and potential prebiotics were highly resistant to RSIE digestion although partial hydrolysis at different extents was observed. FOS and lactulose were the most resistant to digestion, followed closely by OsLu and more distantly by both types of GOS and lactosucrose. In GOS, β(1 → 6) linkages were more resistant to digestion than β(1 → 4) bonds. The reported in vitro digestion model is a useful, simple, and cost-effective tool to evaluate the digestibility of dietary oligosaccharides.

Use of graph theory measures to identify errors in record linkage.

PubMed

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

2014-07-01

Ensuring high linkage quality is important in many record linkage applications. Current methods for ensuring quality are manual and resource intensive. This paper seeks to determine the effectiveness of graph theory techniques in identifying record linkage errors. A range of graph theory techniques was applied to two linked datasets, with known truth sets. The ability of graph theory techniques to identify groups containing errors was compared to a widely used threshold setting technique. This methodology shows promise; however, further investigations into graph theory techniques are required. The development of more efficient and effective methods of improving linkage quality will result in higher quality datasets that can be delivered to researchers in shorter timeframes. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

The centrality of laboratory services in the HIV treatment and prevention cascade: The need for effective linkages and referrals in resource-limited settings.

PubMed

Alemnji, George; Fonjungo, Peter; Van Der Pol, Barbara; Peter, Trevor; Kantor, Rami; Nkengasong, John

2014-05-01

Strong laboratory services and systems are critical for delivering timely and quality health services that are vital to reduce patient attrition in the HIV treatment and prevention cascade. However, challenges exist in ensuring effective laboratory health systems strengthening and linkages. In particular, linkages and referrals between laboratory testing and other services need to be considered in the context of an integrated health system that includes prevention, treatment, and strategic information. Key components of laboratory health systems that are essential for effective linkages include an adequate workforce, appropriate point-of-care (POC) technology, available financing, supply chain management systems, and quality systems improvement, including accreditation. In this review, we highlight weaknesses of and gaps between laboratory testing and other program services. We propose a model for strengthening these systems to ensure effective linkages of laboratory services for improved access and retention in care of HIV/AIDS patients, particularly in low- and middle-income countries.

Linkages and Interactions Analysis of Major Effect Drought Grain Yield QTLs in Rice.

PubMed

Vikram, Prashant; Swamy, B P Mallikarjuna; Dixit, Shalabh; Trinidad, Jennylyn; Sta Cruz, Ma Teresa; Maturan, Paul C; Amante, Modesto; Kumar, Arvind

2016-01-01

Quantitative trait loci conferring high grain yield under drought in rice are important genomic resources for climate resilient breeding. Major and consistent drought grain yield QTLs usually co-locate with flowering and/or plant height QTLs, which could be due to either linkage or pleiotropy. Five mapping populations used for the identification of major and consistent drought grain yield QTLs underwent multiple-trait, multiple-interval mapping test (MT-MIM) to estimate the significance of pleiotropy effects. Results indicated towards possible linkages between the drought grain yield QTLs with co-locating flowering and/or plant height QTLs. Linkages of days to flowering and plant height were eliminated through a marker-assisted breeding approach. Drought grain yield QTLs also showed interaction effects with flowering QTLs. Drought responsiveness of the flowering locus on chromosome 3 (qDTY3.2) has been revealed through allelic analysis. Considering linkage and interaction effects associated with drought QTLs, a comprehensive marker-assisted breeding strategy was followed to develop rice genotypes with improved grain yield under drought stress.

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

Health services research and data linkages: issues, methods, and directions for the future.

PubMed

Bradley, Cathy J; Penberthy, Lynne; Devers, Kelly J; Holden, Debra J

2010-10-01

Research on pressing health services and policy issues requires access to complete, accurate, and timely patient and organizational data. This paper describes how administrative and health records (including electronic medical records) can be linked for comparative effectiveness and health services research. We categorize the major agents (i.e., who owns and controls data and who carries out the data linkage) into three areas: (1) individual investigators; (2) government sponsored linked data bases; and (3) public-private partnerships that facilitate linkage of data owned by private organizations. We describe challenges that may be encountered in the linkage process, and the benefits of combining secondary databases with primary qualitative and quantitative sources. We use cancer care research to illustrate our points. To fill the gaps in the existing data infrastructure, additional steps are required to foster collaboration among institutions, researchers, and public and private components of the health care sector. Without such effort, independent researchers, governmental agencies, and nonprofit organizations are likely to continue building upon a fragmented and costly system with limited access. Discussion. Without the development and support for emerging information technologies across multiple health care settings, the potential for data collected for clinical and transactional purposes to benefit the research community and, ultimately, the patient population may go unrealized. The current environment is characterized by budget and technical challenges, but investments in data infrastructure are arguably cost-effective given the need to reform our health care system and to monitor the impact of health reform initiatives. © Health Research and Educational Trust.

Effects of Demographic History on the Detection of Recombination Hotspots from Linkage Disequilibrium.

PubMed

Dapper, Amy L; Payseur, Bret A

2018-02-01

In some species, meiotic recombination is concentrated in small genomic regions. These "recombination hotspots" leave signatures in fine-scale patterns of linkage disequilibrium, raising the prospect that the genomic landscape of hotspots can be characterized from sequence variation. This approach has led to the inference that hotspots evolve rapidly in some species, but are conserved in others. Historic demographic events, such as population bottlenecks, are known to affect patterns of linkage disequilibrium across the genome, violating population genetic assumptions of this approach. Although such events are prevalent, demographic history is generally ignored when making inferences about the evolution of recombination hotspots. To determine the effect of demography on the detection of recombination hotspots, we use the coalescent to simulate haplotypes with a known recombination landscape. We measure the ability of popular linkage disequilibrium-based programs to detect hotspots across a range of demographic histories, including population bottlenecks, hidden population structure, population expansions, and population contractions. We find that demographic events have the potential to greatly reduce the power and increase the false positive rate of hotspot discovery. Neither the power nor the false positive rate of hotspot detection can be predicted without also knowing the demographic history of the sample. Our results suggest that ignoring demographic history likely overestimates the power to detect hotspots and therefore underestimates the degree of hotspot sharing between species. We suggest strategies for incorporating demographic history into population genetic inferences about recombination hotspots. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Poly-Cross-Linked PEI Through Aromatically Conjugated Imine Linkages as a New Class of pH-Responsive Nucleic Acids Packing Cationic Polymers

PubMed Central

Chen, Shun; Jin, Tuo

2016-01-01

Cationic polyimines polymerized through aromatically conjugated bis-imine linkages and intra-molecular cross-linking were found to be a new class of effective transfection materials for their flexibility in structural optimization, responsiveness to intracellular environment, the ability to facilitate endosome escape and cytosol release of the nucleic acids, as well as self-metabolism. When three phthalaldehydes of different substitution positions were used to polymerize highly branched low-molecular weight polyethylenimine (PEI 1.8K), the product through ortho-phthalimines (named PPOP) showed significantly higher transfection activity than its two tere- and iso-analogs (named PPTP and PPIP). Physicochemical characterization confirmed the similarity of three polyimines in pH-responded degradability, buffer capacity, as well as the size and Zeta potential of the polyplexes formed from the polymers. A mechanistic speculation may be that the ortho-positioned bis-imine linkage of PPOP may only lead to the straight trans-configuration due to steric hindrance, resulting in larger loops of intra-polymer cross-linking and more flexible backbone. PMID:26869931

Structural Characterization and Disulfide Assignment of Spider Peptide Phα1β by Mass Spectrometry

NASA Astrophysics Data System (ADS)

Wormwood, Kelly L.; Ngounou Wetie, Armand Gatien; Gomez, Marcus Vinicius; Ju, Yue; Kowalski, Paul; Mihasan, Marius; Darie, Costel C.

2018-05-01

Native Phα1β is a peptide purified from the venom of the armed spider Phoneutria nigriventer that has been shown to have an extensive analgesic effect with fewer side effects than ω-conotoxin MVIIA. Recombinant Phα1β mimics the effects of the native Phα1β. Because of this, it has been suggested that Phα1β may have potential to be used as a therapeutic for controlling persistent pathological pain. The amino acid sequence of Phα1β is known; however, the exact structure and disulfide arrangement has yet to be determined. Determination of the disulfide linkages and exact structure could greatly assist in pharmacological analysis and determination of why this peptide is such an effective analgesic. Here, we used biochemical and mass spectrometry approaches to determine the disulfide linkages present in the recombinant Phα1β peptide. Using a combination of MALDI-MS, direct infusion ESI-MS, and nanoLC-MS/MS analysis of the undigested recombinant Phα1β peptide and digested with AspN, trypsin, or AspN/trypsin, we were able to identify and confirm all six disulfide linkages present in the peptide as Cys1-2, Cys3-4, Cys5-6, Cys7-8, Cys9-10, and Cys11-12. These results were also partially confirmed in the native Phα1β peptide. These experiments provide essential structural information about Phα1β and may assist in providing insight into the peptide's analgesic effect with very low side effects. [Figure not available: see fulltext.

Structural Characterization and Disulfide Assignment of Spider Peptide Phα1β by Mass Spectrometry.

PubMed

Wormwood, Kelly L; Ngounou Wetie, Armand Gatien; Gomez, Marcus Vinicius; Ju, Yue; Kowalski, Paul; Mihasan, Marius; Darie, Costel C

2018-05-01

Native Phα1β is a peptide purified from the venom of the armed spider Phoneutria nigriventer that has been shown to have an extensive analgesic effect with fewer side effects than ω-conotoxin MVIIA. Recombinant Phα1β mimics the effects of the native Phα1β. Because of this, it has been suggested that Phα1β may have potential to be used as a therapeutic for controlling persistent pathological pain. The amino acid sequence of Phα1β is known; however, the exact structure and disulfide arrangement has yet to be determined. Determination of the disulfide linkages and exact structure could greatly assist in pharmacological analysis and determination of why this peptide is such an effective analgesic. Here, we used biochemical and mass spectrometry approaches to determine the disulfide linkages present in the recombinant Phα1β peptide. Using a combination of MALDI-MS, direct infusion ESI-MS, and nanoLC-MS/MS analysis of the undigested recombinant Phα1β peptide and digested with AspN, trypsin, or AspN/trypsin, we were able to identify and confirm all six disulfide linkages present in the peptide as Cys1-2, Cys3-4, Cys5-6, Cys7-8, Cys9-10, and Cys11-12. These results were also partially confirmed in the native Phα1β peptide. These experiments provide essential structural information about Phα1β and may assist in providing insight into the peptide's analgesic effect with very low side effects. Graphical Abstract ᅟ.

Structural Characterization and Disulfide Assignment of Spider Peptide Phα1β by Mass Spectrometry

NASA Astrophysics Data System (ADS)

Wormwood, Kelly L.; Ngounou Wetie, Armand Gatien; Gomez, Marcus Vinicius; Ju, Yue; Kowalski, Paul; Mihasan, Marius; Darie, Costel C.

2018-04-01

Native Phα1β is a peptide purified from the venom of the armed spider Phoneutria nigriventer that has been shown to have an extensive analgesic effect with fewer side effects than ω-conotoxin MVIIA. Recombinant Phα1β mimics the effects of the native Phα1β. Because of this, it has been suggested that Phα1β may have potential to be used as a therapeutic for controlling persistent pathological pain. The amino acid sequence of Phα1β is known; however, the exact structure and disulfide arrangement has yet to be determined. Determination of the disulfide linkages and exact structure could greatly assist in pharmacological analysis and determination of why this peptide is such an effective analgesic. Here, we used biochemical and mass spectrometry approaches to determine the disulfide linkages present in the recombinant Phα1β peptide. Using a combination of MALDI-MS, direct infusion ESI-MS, and nanoLC-MS/MS analysis of the undigested recombinant Phα1β peptide and digested with AspN, trypsin, or AspN/trypsin, we were able to identify and confirm all six disulfide linkages present in the peptide as Cys1-2, Cys3-4, Cys5-6, Cys7-8, Cys9-10, and Cys11-12. These results were also partially confirmed in the native Phα1β peptide. These experiments provide essential structural information about Phα1β and may assist in providing insight into the peptide's analgesic effect with very low side effects. [Figure not available: see fulltext.

Sex-dependent selection differentially shapes genetic variation on and off the guppy Y chromosome.

PubMed

Postma, Erik; Spyrou, Nicolle; Rollins, Lee Ann; Brooks, Robert C

2011-08-01

Because selection is often sex-dependent, alleles can have positive effects on fitness in one sex and negative effects in the other, resulting in intralocus sexual conflict. Evolutionary theory predicts that intralocus sexual conflict can drive the evolution of sex limitation, sex-linkage, and sex chromosome differentiation. However, evidence that sex-dependent selection results in sex-linkage is limited. Here, we formally partition the contribution of Y-linked and non-Y-linked quantitative genetic variation in coloration, tail, and body size of male guppies (Poecilia reticulata)-traits previously implicated as sexually antagonistic. We show that these traits are strongly genetically correlated, both on and off the Y chromosome, but that these correlations differ in sign and magnitude between both parts of the genome. As predicted, variation in attractiveness was found to be associated with the Y-linked, rather than with the non-Y-linked component of genetic variation in male ornamentation. These findings show how the evolution of Y-linkage may be able to resolve sexual conflict. More generally, they provide unique insight into how sex-specific selection has the potential to differentially shape the genetic architecture of fitness traits across different parts of the genome. © 2011 The Author(s). Evolution© 2011 The Society for the Study of Evolution.

Improving Information on Maternal Medication Use by Linking Prescription Data to Congenital Anomaly Registers: A EUROmediCAT Study.

PubMed

de Jonge, Linda; Garne, Ester; Gini, Rosa; Jordan, Susan E; Klungsoyr, Kari; Loane, Maria; Neville, Amanda J; Pierini, Anna; Puccini, Aurora; Thayer, Daniel S; Tucker, David; Vinkel Hansen, Anne; Bakker, Marian K

2015-11-01

Research on associations between medication use during pregnancy and congenital anomalies is significative for assessing the safe use of a medicine in pregnancy. Congenital anomaly (CA) registries do not have optimal information on medicine exposure, in contrast to prescription databases. Linkage of prescription databases to the CA registries is a potentially effective method of obtaining accurate information on medicine use in pregnancies and the risk of congenital anomalies. We linked data from primary care and prescription databases to five European Surveillance of Congenital Anomalies (EUROCAT) CA registries. The linkage was evaluated by looking at linkage rate, characteristics of linked and non-linked cases, first trimester exposure rates for six groups of medicines according to the prescription data and information on medication use registered in the CA databases, and agreement of exposure. Of the 52,619 cases registered in the CA databases, 26,552 could be linked. The linkage rate varied between registries over time and by type of birth. The first trimester exposure rates and the agreements between the databases varied for the different medicine groups. Information on anti-epileptic drugs and insulins and analogue medicine use recorded by CA registries was of good quality. For selective serotonin reuptake inhibitors, anti-asthmatics, antibacterials for systemic use, and gonadotropins and other ovulation stimulants, the recorded information was less complete. Linkage of primary care or prescription databases to CA registries improved the quality of information on maternal use of medicines in pregnancy, especially for medicine groups that are less fully registered in CA registries.

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

The Fire and Fuels Extension to the Forest Vegetation Simulator

Treesearch

Elizabeth Reinhardt; Nicholas L. Crookston

2003-01-01

The Fire and Fuels Extension (FFE) to the Forest Vegetation Simulator (FVS) simulates fuel dynamics and potential fire behaviour over time, in the context of stand development and management. Existing models of fire behavior and fire effects were added to FVS to form this extension. New submodels representing snag and fuel dynamics were created to complete the linkages...

Genetic dissection of seed oil and protein content and identification of networks associated with oil content in Brassica napus

PubMed Central

Chao, Hongbo; Wang, Hao; Wang, Xiaodong; Guo, Liangxing; Gu, Jianwei; Zhao, Weiguo; Li, Baojun; Chen, Dengyan; Raboanatahiry, Nadia; Li, Maoteng

2017-01-01

High-density linkage maps can improve the precision of QTL localization. A high-density SNP-based linkage map containing 3207 markers covering 3072.7 cM of the Brassica napus genome was constructed in the KenC-8 × N53-2 (KNDH) population. A total of 67 and 38 QTLs for seed oil and protein content were identified with an average confidence interval of 5.26 and 4.38 cM, which could explain up to 22.24% and 27.48% of the phenotypic variation, respectively. Thirty-eight associated genomic regions from BSA overlapped with and/or narrowed the SOC-QTLs, further confirming the QTL mapping results based on the high-density linkage map. Potential candidates related to acyl-lipid and seed storage underlying SOC and SPC, respectively, were identified and analyzed, among which six were checked and showed expression differences between the two parents during different embryonic developmental periods. A large primary carbohydrate pathway based on potential candidates underlying SOC- and SPC-QTLs, and interaction networks based on potential candidates underlying SOC-QTLs, was constructed to dissect the complex mechanism based on metabolic and gene regulatory features, respectively. Accurate QTL mapping and potential candidates identified based on high-density linkage map and BSA analyses provide new insights into the complex genetic mechanism of oil and protein accumulation in the seeds of rapeseed. PMID:28393910

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.

Potential linkage disequilibrium between schizophrenia and locus D22S278 on the long arm of chromosome 22

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

Moises, H.W.; Yang, L.; Havsteen, B.

Locus D22S278 at 22q12 has been implicated in schizophrenia by sib-pair analysis. In order to replicate these results, we performed the transmission test for linkage disequilibrium (TDT) in 113 unrelated schizophrenic patients and their 226 parents. Evidence for potential linkage disequilibrium was obtained between schizophrenia and allele 243 of the marker AFM 182xd12 at the locus D22S278 (P = 0.02). The results of our study suggest a detectable oligogenic gene in a multigene system for schizophrenia closely linked to D22S278 on the long arm of chromosome 22. If confirmed by others, this finding could lead to the identification of amore » schizophrenia susceptibility gene. 12 refs., 1 tab.« less

Linking Canadian Population Health Data: Maximizing the Potential of Cohort and Administrative Data

PubMed Central

Doiron, Dany; Raina, Parminder; Fortier, Isabel

2013-01-01

Linkage of data collected by large Canadian cohort studies with provincially managed administrative health databases can offer very interesting avenues for multidisciplinary and cost-effective health research in Canada. Successfully co-analyzing cohort data and administrative health data (AHD) can lead to research results capable of improving the health and well-being of Canadians and enhancing the delivery of health care services. However, such an endeavour will require strong coordination and long-term commitment between all stakeholders involved. The challenges and opportunities of a pan-Canadian cohort-to-AHD data linkage program have been considered by cohort study investigators and data custodians from each Canadian province. Stakeholders acknowledge the important public health benefits of establishing such a program and have established an action plan to move forward. PMID:23823892

Linking Canadian population health data: maximizing the potential of cohort and administrative data.

PubMed

Doiron, Dany; Raina, Parminder; Fortier, Isabel

2013-03-06

Linkage of data collected by large Canadian cohort studies with provincially managed administrative health databases can offer very interesting avenues for multidisciplinary and cost-effective health research in Canada. Successfully co-analyzing cohort data and administrative health data (AHD) can lead to research results capable of improving the health and well-being of Canadians and enhancing the delivery of health care services. However, such an endeavour will require strong coordination and long-term commitment between all stakeholders involved. The challenges and opportunities of a pan-Canadian cohort-to-AHD data linkage program have been considered by cohort study investigators and data custodians from each Canadian province. Stakeholders acknowledge the important public health benefits of establishing such a program and have established an action plan to move forward.

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.

Conclusion of LOD-score analysis for family data generated under two-locus models.

PubMed

Dizier, M H; Babron, M C; Clerget-Darpoux, F

1996-06-01

The power to detect linkage by the LOD-score method is investigated here for diseases that depend on the effects of two genes. The classical strategy is, first, to detect a major-gene (MG) effect by segregation analysis and, second, to seek for linkage with genetic markers by the LOD-score method using the MG parameters. We already showed that segregation analysis can lead to evidence for a MG effect for many two-locus models, with the estimates of the MG parameters being very different from those of the two genes involved in the disease. We show here that use of these MG parameter estimates in the LOD-score analysis may lead to a failure to detect linkage for some two-locus models. For these models, use of the sib-pair method gives a non-negligible increase of power to detect linkage. The linkage-homogeneity test among subsamples differing for the familial disease distribution provides evidence of parameter misspecification, when the MG parameters are used. Moreover, for most of the models, use of the MG parameters in LOD-score analysis leads to a large bias in estimation of the recombination fraction and sometimes also to a rejection of linkage for the true recombination fraction. A final important point is that a strong evidence of an MG effect, obtained by segregation analysis, does not necessarily imply that linkage will be detected for at least one of the two genes, even with the true parameters and with a close informative marker.

Effective Linkages of Continuum of Care for Improving Neonatal, Perinatal, and Maternal Mortality: A Systematic Review and Meta-Analysis

PubMed Central

Kikuchi, Kimiyo; Enuameh, Yeetey; Yasuoka, Junko; Nanishi, Keiko; Shibanuma, Akira; Gyapong, Margaret; Owusu-Agyei, Seth; Oduro, Abraham Rexford; Asare, Gloria Quansah; Hodgson, Abraham; Jimba, Masamine

2015-01-01

Background Continuum of care has the potential to improve maternal, newborn, and child health (MNCH) by ensuring care for mothers and children. Continuum of care in MNCH is widely accepted as comprising sequential time (from pre-pregnancy to motherhood and childhood) and space dimensions (from community-family care to clinical care). However, it is unclear which linkages of care could have a greater effect on MNCH outcomes. The objective of the present study is to assess the effectiveness of different continuum of care linkages for reducing neonatal, perinatal, and maternal mortality in low- and middle-income countries. Methods We searched for randomized and quasi-randomized controlled trials that addressed two or more linkages of continuum of care and attempted to increase mothers’ uptake of antenatal care, skilled birth attendance, and postnatal care. The outcome variables were neonatal, perinatal, and maternal mortality. Results Out of the 7,142 retrieved articles, we selected 19 as eligible for the final analysis. Of these studies, 13 used packages of intervention that linked antenatal care, skilled birth attendance, and postnatal care. One study each used packages that linked antenatal care and skilled birth attendance or skilled birth attendance and postnatal care. Four studies used an intervention package that linked antenatal care and postnatal care. Among the packages that linked antenatal care, skilled birth attendance, and postnatal care, a significant reduction was observed in combined neonatal, perinatal, and maternal mortality risks (RR 0.83; 95% CI 0.77 to 0.89, I2 79%). Furthermore, this linkage reduced combined neonatal, perinatal, and maternal mortality when integrating the continuum of care space dimension (RR 0.85; 95% CI 0.77 to 0.93, I2 81%). Conclusions Our review suggests that continuous uptake of antenatal care, skilled birth attendance, and postnatal care is necessary to improve MNCH outcomes in low- and middle-income countries. The review was conclusive for the reduction of neonatal and perinatal deaths. Although maternal deaths were not significantly reduced, composite measures of all mortality were. Thus, the evidence is sufficient to scale up this intervention package for the improvement of MNCH outcomes. PMID:26422685

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.

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.

Amides are excellent mimics of phosphate internucleoside linkages and are well tolerated in short interfering RNAs

PubMed Central

Mutisya, Daniel; Selvam, Chelliah; Lunstad, Benjamin D.; Pallan, Pradeep S.; Haas, Amanda; Leake, Devin; Egli, Martin; Rozners, Eriks

2014-01-01

RNA interference (RNAi) has become an important tool in functional genomics and has an intriguing therapeutic potential. However, the current design of short interfering RNAs (siRNAs) is not optimal for in vivo applications. Non-ionic phosphate backbone modifications may have the potential to improve the properties of siRNAs, but are little explored in RNAi technologies. Using X-ray crystallography and RNAi activity assays, the present study demonstrates that 3′-CH2-CO-NH-5′ amides are excellent replacements for phosphodiester internucleoside linkages in RNA. The crystal structure shows that amide-modified RNA forms a typical A-form duplex. The amide carbonyl group points into the major groove and assumes an orientation that is similar to the P–OP2 bond in the phosphate linkage. Amide linkages are well hydrated by tandem waters linking the carbonyl group and adjacent phosphate oxygens. Amides are tolerated at internal positions of both the guide and passenger strand of siRNAs and may increase the silencing activity when placed near the 5′-end of the passenger strand. As a result, an siRNA containing eight amide linkages is more active than the unmodified control. The results suggest that RNAi may tolerate even more extensive amide modification, which may be useful for optimization of siRNAs for in vivo applications. PMID:24813446

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.

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.

The Québec BCG Vaccination Registry (1956–1992): assessing data quality and linkage with administrative health databases

PubMed Central

2014-01-01

Background Vaccination registries have undoubtedly proven useful for estimating vaccination coverage as well as examining vaccine safety and effectiveness. However, their use for population health research is often limited. The Bacillus Calmette-Guérin (BCG) Vaccination Registry for the Canadian province of Québec comprises some 4 million vaccination records (1926-1992). This registry represents a unique opportunity to study potential associations between BCG vaccination and various health outcomes. So far, such studies have been hampered by the absence of a computerized version of the registry. We determined the completeness and accuracy of the recently computerized BCG Vaccination Registry, as well as examined its linkability with demographic and administrative medical databases. Methods Two systematically selected verification samples, each representing ~0.1% of the registry, were used to ascertain accuracy and completeness of the electronic BCG Vaccination Registry. Agreement between the paper [listings (n = 4,987 records) and vaccination certificates (n = 4,709 records)] and electronic formats was determined along several nominal and BCG-related variables. Linkage feasibility with the Birth Registry (probabilistic approach) and provincial Healthcare Registration File (deterministic approach) was examined using nominal identifiers for a random sample of 3,500 individuals born from 1961 to 1974 and BCG vaccinated between 1970 and 1974. Results Exact agreement was observed for 99.6% and 81.5% of records upon comparing, respectively, the paper listings and vaccination certificates to their corresponding computerized records. The proportion of successful linkage was 77% with the Birth Registry, 70% with the Healthcare Registration File, 57% with both, and varied by birth year. Conclusions Computerization of this Registry yielded excellent results. The registry was complete and accurate, and linkage with administrative databases was highly feasible. This study represents the first step towards assembling large scale population-based epidemiological studies which will enable filling important knowledge gaps on the potential health effects of early life non-specific stimulation of the immune function, as resulting from BCG vaccination. PMID:24400924

Can Network Linkage Effects Determine Return? Evidence from Chinese Stock Market

PubMed Central

Qiao, Haishu; Xia, Yue; Li, Ying

2016-01-01

This study used the dynamic conditional correlations (DCC) method to identify the linkage effects of Chinese stock market, and further detected the influence of network linkage effects on magnitude of security returns across different industries. Applying two physics-derived techniques, the minimum spanning tree and the hierarchical tree, we analyzed the stock interdependence within the network of the China Securities Index (CSI) industry index basket. We observed that that obvious linkage effects existed among stock networks. CII and CCE, CAG and ITH as well as COU, CHA and REI were confirmed as the core nodes in the three different networks respectively. We also investigated the stability of linkage effects by estimating the mean correlations and mean distances, as well as the normalized tree length of these indices. In addition, using the GMM model approach, we found inter-node influence within the stock network had a pronounced effect on stock returns. Our results generally suggested that there appeared to be greater clustering effect among the indexes belonging to related industrial sectors than those of diverse sectors, and network comovement was significantly affected by impactive financial events in the reality. Besides, stocks that were more central within the network of stock market usually had higher returns for compensation because they endured greater exposure to correlation risk. PMID:27257816

Can Network Linkage Effects Determine Return? Evidence from Chinese Stock Market.

PubMed

Qiao, Haishu; Xia, Yue; Li, Ying

2016-01-01

This study used the dynamic conditional correlations (DCC) method to identify the linkage effects of Chinese stock market, and further detected the influence of network linkage effects on magnitude of security returns across different industries. Applying two physics-derived techniques, the minimum spanning tree and the hierarchical tree, we analyzed the stock interdependence within the network of the China Securities Index (CSI) industry index basket. We observed that that obvious linkage effects existed among stock networks. CII and CCE, CAG and ITH as well as COU, CHA and REI were confirmed as the core nodes in the three different networks respectively. We also investigated the stability of linkage effects by estimating the mean correlations and mean distances, as well as the normalized tree length of these indices. In addition, using the GMM model approach, we found inter-node influence within the stock network had a pronounced effect on stock returns. Our results generally suggested that there appeared to be greater clustering effect among the indexes belonging to related industrial sectors than those of diverse sectors, and network comovement was significantly affected by impactive financial events in the reality. Besides, stocks that were more central within the network of stock market usually had higher returns for compensation because they endured greater exposure to correlation risk.

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

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

Introgression of Aegilops speltoides segments in Triticum aestivum and the effect of the gametocidal genes.

PubMed

King, Julie; Grewal, Surbhi; Yang, Cai-Yun; Hubbart Edwards, Stella; Scholefield, Duncan; Ashling, Stephen; Harper, John A; Allen, Alexandra M; Edwards, Keith J; Burridge, Amanda J; King, Ian P

2018-02-12

Bread wheat (Triticum aestivum) has been through a severe genetic bottleneck as a result of its evolution and domestication. It is therefore essential that new sources of genetic variation are generated and utilized. This study aimed to generate genome-wide introgressed segments from Aegilops speltoides. Introgressions generated from this research will be made available for phenotypic analysis. Aegilops speltoides was crossed as the male parent to T. aestivum 'Paragon'. The interspecific hybrids were then backcrossed to Paragon. Introgressions were detected and characterized using the Affymetrix Axiom Array and genomic in situ hybridization (GISH). Recombination in the gametes of the F1 hybrids was at a level where it was possible to generate a genetic linkage map of Ae. speltoides. This was used to identify 294 wheat/Ae. speltoides introgressions. Introgressions from all seven linkage groups of Ae. speltoides were found, including both large and small segments. Comparative analysis showed that overall macro-synteny is conserved between Ae. speltoides and T. aestivum, but that Ae. speltoides does not contain the 4A/5A/7B translocations present in wheat. Aegilops speltoides has been reported to carry gametocidal genes, i.e. genes that ensure their transmission through the gametes to the next generation. Transmission rates of the seven Ae. speltoides linkage groups introgressed into wheat varied. A 100 % transmission rate of linkage group 2 demonstrates the presence of the gametocidal genes on this chromosome. A high level of recombination occurs between the chromosomes of wheat and Ae. speltoides, leading to the generation of large numbers of introgressions with the potential for exploitation in breeding programmes. Due to the gametocidal genes, all germplasm developed will always contain a segment from Ae. speltoides linkage group 2S, in addition to an introgression from any other linkage group. © The Authors 2017. Published by Oxford University Press on behalf of the Annals of Botany Company.

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

Bivariate Linkage Scan for Reading Disability and Attention-Deficit/Hyperactivity Disorder Localizes Pleiotropic Loci

ERIC Educational Resources Information Center

Gayan, J.; Willcutt, E. G.; Fisher, S. E.; Francks, C.; Cardon, L. R.; Olson, R. K.; Pennington, B. F.; Smith, S. D.; Monaco, A. P.; DeFries, J. C.

2005-01-01

Background: There is a growing interest in the study of the genetic origins of comorbidity, a direct consequence of the recent findings of genetic loci that are seemingly linked to more than one disorder. There are several potential causes for these shared regions of linkage, but one possibility is that these loci may harbor genes with manifold…

Water quality and coral bleaching thresholds: formalising the linkage for the inshore reefs of the Great Barrier Reef, Australia.

PubMed

Wooldridge, Scott A

2009-05-01

The threats of wide-scale coral bleaching and reef demise associated with anthropogenic climate change are widely known. Here, the additional role of poor water quality in lowering the thermal tolerance (i.e. bleaching 'resistance') of symbiotic reef corals is considered. In particular, a quantitative linkage is established between terrestrially-sourced dissolved inorganic nitrogen (DIN) loading and the upper thermal bleaching thresholds of inshore reefs on the Great Barrier Reef, Australia. Significantly, this biophysical linkage provides concrete evidence for the oft-expressed belief that improved coral reef management will increase the regional-scale survival prospects of corals reefs to global climate change. Indeed, for inshore reef areas with a high runoff exposure risk, it is shown that the potential benefit of this 'local' management imperative is equivalent to approximately 2.0-2.5 degrees C in relation to the upper thermal bleaching limit; though in this case, a potentially cost-prohibitive reduction in end-of-river DIN of >50-80% would be required. An integrated socio-economic modelling framework is outlined that will assist future efforts to understand (optimise) the alternate tradeoffs that the water quality/coral bleaching linkage presents.

Conclusion of LOD-score analysis for family data generated under two-locus models.

PubMed Central

Dizier, M. H.; Babron, M. C.; Clerget-Darpoux, F.

1996-01-01

The power to detect linkage by the LOD-score method is investigated here for diseases that depend on the effects of two genes. The classical strategy is, first, to detect a major-gene (MG) effect by segregation analysis and, second, to seek for linkage with genetic markers by the LOD-score method using the MG parameters. We already showed that segregation analysis can lead to evidence for a MG effect for many two-locus models, with the estimates of the MG parameters being very different from those of the two genes involved in the disease. We show here that use of these MG parameter estimates in the LOD-score analysis may lead to a failure to detect linkage for some two-locus models. For these models, use of the sib-pair method gives a non-negligible increase of power to detect linkage. The linkage-homogeneity test among subsamples differing for the familial disease distribution provides evidence of parameter misspecification, when the MG parameters are used. Moreover, for most of the models, use of the MG parameters in LOD-score analysis leads to a large bias in estimation of the recombination fraction and sometimes also to a rejection of linkage for the true recombination fraction. A final important point is that a strong evidence of an MG effect, obtained by segregation analysis, does not necessarily imply that linkage will be detected for at least one of the two genes, even with the true parameters and with a close informative marker. PMID:8651311

Linking the oceans to public health: current efforts and future directions

PubMed Central

Kite-Powell, Hauke L; Fleming, Lora E; Backer, Lorraine C; Faustman, Elaine M; Hoagland, Porter; Tsuchiya, Ami; Younglove, Lisa R; Wilcox, Bruce A; Gast, Rebecca J

2008-01-01

We review the major linkages between the oceans and public health, focusing on exposures and potential health effects due to anthropogenic and natural factors including: harmful algal blooms, microbes, and chemical pollutants in the oceans; consumption of seafood; and flooding events. We summarize briefly the current state of knowledge about public health effects and their economic consequences; and we discuss priorities for future research. We find that: • There are numerous connections between the oceans, human activities, and human health that result in both positive and negative exposures and health effects (risks and benefits); and the study of these connections comprises a new interdisciplinary area, "oceans and human health." • The state of present knowledge about the linkages between oceans and public health varies. Some risks, such as the acute health effects caused by toxins associated with shellfish poisoning and red tide, are relatively well understood. Other risks, such as those posed by chronic exposure to many anthropogenic chemicals, pathogens, and naturally occurring toxins in coastal waters, are less well quantified. Even where there is a good understanding of the mechanism for health effects, good epidemiological data are often lacking. Solid data on economic and social consequences of these linkages are also lacking in most cases. • The design of management measures to address these risks must take into account the complexities of human response to warnings and other guidance, and the economic tradeoffs among different risks and benefits. Future research in oceans and human health to address public health risks associated with marine pathogens and toxins, and with marine dimensions of global change, should include epidemiological, behavioral, and economic components to ensure that resulting management measures incorporate effective economic and risk/benefit tradeoffs. PMID:19025677

Linking the oceans to public health: current efforts and future directions.

PubMed

Kite-Powell, Hauke L; Fleming, Lora E; Backer, Lorraine C; Faustman, Elaine M; Hoagland, Porter; Tsuchiya, Ami; Younglove, Lisa R; Wilcox, Bruce A; Gast, Rebecca J

2008-11-07

We review the major linkages between the oceans and public health, focusing on exposures and potential health effects due to anthropogenic and natural factors including: harmful algal blooms, microbes, and chemical pollutants in the oceans; consumption of seafood; and flooding events. We summarize briefly the current state of knowledge about public health effects and their economic consequences; and we discuss priorities for future research.We find that:* There are numerous connections between the oceans, human activities, and human health that result in both positive and negative exposures and health effects (risks and benefits); and the study of these connections comprises a new interdisciplinary area, "oceans and human health."* The state of present knowledge about the linkages between oceans and public health varies. Some risks, such as the acute health effects caused by toxins associated with shellfish poisoning and red tide, are relatively well understood. Other risks, such as those posed by chronic exposure to many anthropogenic chemicals, pathogens, and naturally occurring toxins in coastal waters, are less well quantified. Even where there is a good understanding of the mechanism for health effects, good epidemiological data are often lacking. Solid data on economic and social consequences of these linkages are also lacking in most cases.* The design of management measures to address these risks must take into account the complexities of human response to warnings and other guidance, and the economic tradeoffs among different risks and benefits. Future research in oceans and human health to address public health risks associated with marine pathogens and toxins, and with marine dimensions of global change, should include epidemiological, behavioral, and economic components to ensure that resulting management measures incorporate effective economic and risk/benefit tradeoffs.

Physico-chemical properties and cytotoxic effects of sugar-based surfactants: Impact of structural variations.

PubMed

Lu, Biao; Vayssade, Muriel; Miao, Yong; Chagnault, Vincent; Grand, Eric; Wadouachi, Anne; Postel, Denis; Drelich, Audrey; Egles, Christophe; Pezron, Isabelle

2016-09-01

Surfactants derived from the biorefinery process can present interesting surface-active properties, low cytotoxicity, high biocompatibility and biodegradability. They are therefore considered as potential sustainable substitutes to currently used petroleum-based surfactants. To better understand and anticipate their performances, structure-property relationships need to be carefully investigated. For this reason, we applied a multidisciplinary approach to systematically explore the effect of subtle structural variations on both physico-chemical properties and biological effects. Four sugar-based surfactants, each with an eight carbon alkyl chain bound to a glucose or maltose head group by an amide linkage, were synthesized and evaluated together along with two commercially available standard surfactants. Physico-chemical properties including solubility, Krafft point, surface-tension lowering and critical micellar concentration (CMC) in water and biological medium were explored. Cytotoxicity evaluation by measuring proliferation index and metabolic activity against dermal fibroblasts showed that all surfactants studied may induce cell death at low concentrations (below their CMC). Results revealed significant differences in both physico-chemical properties and cytotoxic effects depending on molecule structural features, such as the position of the linkage on the sugar head-group, or the orientation of the amide linkage. Furthermore, the cytotoxic response increased with the reduction of surfactant CMC. This study underscores the relevance of a methodical and multidisciplinary approach that enables the consideration of surfactant solution properties when applied to biological materials. Overall, our results will contribute to a better understanding of the concomitant impact of surfactant structure at physico-chemical and biological levels. Copyright © 2016 Elsevier B.V. All rights reserved.

Amides are excellent mimics of phosphate internucleoside linkages and are well tolerated in short interfering RNAs.

PubMed

Mutisya, Daniel; Selvam, Chelliah; Lunstad, Benjamin D; Pallan, Pradeep S; Haas, Amanda; Leake, Devin; Egli, Martin; Rozners, Eriks

2014-06-01

RNA interference (RNAi) has become an important tool in functional genomics and has an intriguing therapeutic potential. However, the current design of short interfering RNAs (siRNAs) is not optimal for in vivo applications. Non-ionic phosphate backbone modifications may have the potential to improve the properties of siRNAs, but are little explored in RNAi technologies. Using X-ray crystallography and RNAi activity assays, the present study demonstrates that 3'-CH2-CO-NH-5' amides are excellent replacements for phosphodiester internucleoside linkages in RNA. The crystal structure shows that amide-modified RNA forms a typical A-form duplex. The amide carbonyl group points into the major groove and assumes an orientation that is similar to the P-OP2 bond in the phosphate linkage. Amide linkages are well hydrated by tandem waters linking the carbonyl group and adjacent phosphate oxygens. Amides are tolerated at internal positions of both the guide and passenger strand of siRNAs and may increase the silencing activity when placed near the 5'-end of the passenger strand. As a result, an siRNA containing eight amide linkages is more active than the unmodified control. The results suggest that RNAi may tolerate even more extensive amide modification, which may be useful for optimization of siRNAs for in vivo applications. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Analysis of whole exome sequencing with cardiometabolic traits using family-based linkage and association in the IRAS Family Study

PubMed Central

Tabb, Keri L.; Hellwege, Jacklyn N.; Palmer, Nicholette D.; Dimitrov, Latchezar; Sajuthi, Satria; Taylor, Kent D.; NG, Maggie C.Y.; Hawkins, Gregory A.; Chen, Yii-Der Ida; Brown, W. Mark; McWilliams, David; Williams, Adrienne; Lorenzo, Carlos; Norris, Jill M.; Long, Jirong; Rotter, Jerome I.; Curran, Joanne E.; Blangero, John; Wagenknecht, Lynne E.; Langefeld, Carl D.; Bowden, Donald W.

2017-01-01

Summary Family-based methods are a potentially powerful tool to identify trait-defining genetic variants in extended families, particularly when used to complement conventional association analysis. We utilized two-point linkage analysis and single variant association analysis to evaluate whole exome sequencing (WES) data from 1,205 Hispanic Americans (78 families) from the Insulin Resistance Atherosclerosis Family Study. WES identified 211,612 variants above the minor allele frequency threshold of ≥0.005. These variants were tested for linkage and/or association with 50 cardiometabolic traits after quality control checks. Two-point linkage analysis yielded 10,580,600 LOD scores with 1,148 LOD scores ≥3, 183 LOD scores ≥4, and 29 LOD scores ≥5. The maximal novel LOD score was 5.50 for rs2289043:T>C, in UNC5C with subcutaneous adipose tissue volume. Association analysis identified 13 variants attaining genome-wide significance (p<5×10-08), with the strongest association between rs651821:C>T in APOA5, and triglyceride levels (p=3.67×10-10). Overall, there was a 5.2-fold increase in the number of informative variants detected by WES compared to exome chip analysis in this population, nearly 30% of which were novel variants relative to dbSNP build 138. Thus, integration of results from two-point linkage and single-variant association analysis from WES data enabled identification of novel signals potentially contributing to cardiometabolic traits. PMID:28067407

Linkage disequilibrium and signatures of positive selection around LINE-1 retrotransposons in the human genome.

PubMed

Kuhn, Alexandre; Ong, Yao Min; Cheng, Ching-Yu; Wong, Tien Yin; Quake, Stephen R; Burkholder, William F

2014-06-03

Insertions of the human-specific subfamily of LINE-1 (L1) retrotransposon are highly polymorphic across individuals and can critically influence the human transcriptome. We hypothesized that L1 insertions could represent genetic variants determining important human phenotypic traits, and performed an integrated analysis of L1 elements and single nucleotide polymorphisms (SNPs) in several human populations. We found that a large fraction of L1s were in high linkage disequilibrium with their surrounding genomic regions and that they were well tagged by SNPs. However, L1 variants were only partially captured by SNPs on standard SNP arrays, so that their potential phenotypic impact would be frequently missed by SNP array-based genome-wide association studies. We next identified potential phenotypic effects of L1s by looking for signatures of natural selection linked to L1 insertions; significant extended haplotype homozygosity was detected around several L1 insertions. This finding suggests that some of these L1 insertions may have been the target of recent positive selection.

Evaluation of Healthcare Interventions and Big Data: Review of Associated Data Issues.

PubMed

Asche, Carl V; Seal, Brian; Kahler, Kristijan H; Oehrlein, Elisabeth M; Baumgartner, Meredith Greer

2017-08-01

Although the analysis of 'big data' holds tremendous potential to improve patient care, there remain significant challenges before it can be realized. Accuracy and completeness of data, linkage of disparate data sources, and access to data are areas that require particular focus. This article discusses these areas and shares strategies to promote progress. Improvement in clinical coding, innovative matching methodologies, and investment in data standardization are potential solutions to data validation and linkage problems. Challenges to data access still require significant attention with data ownership, security needs, and costs representing significant barriers to access.

Combined linkage and association mapping of flowering time in Sunflower (Helianthus annuus L.).

PubMed

Cadic, Elena; Coque, Marie; Vear, Felicity; Grezes-Besset, Bruno; Pauquet, Jerôme; Piquemal, Joël; Lippi, Yannick; Blanchard, Philippe; Romestant, Michel; Pouilly, Nicolas; Rengel, David; Gouzy, Jerôme; Langlade, Nicolas; Mangin, Brigitte; Vincourt, Patrick

2013-05-01

Association mapping and linkage mapping were used to identify quantitative trait loci (QTL) and/or causative mutations involved in the control of flowering time in cultivated sunflower Helianthus annuus. A panel of 384 inbred lines was phenotyped through testcrosses with two tester inbred lines across 15 location × year combinations. A recombinant inbred line (RIL) population comprising 273 lines was phenotyped both per se and through testcrosses with one or two testers in 16 location × year combinations. In the association mapping approach, kinship estimation using 5,923 single nucleotide polymorphisms was found to be the best covariate to correct for effects of panel structure. Linkage disequilibrium decay ranged from 0.08 to 0.26 cM for a threshold of 0.20, after correcting for structure effects, depending on the linkage group (LG) and the ancestry of inbred lines. A possible hitchhiking effect is hypothesized for LG10 and LG08. A total of 11 regions across 10 LGs were found to be associated with flowering time, and QTLs were mapped on 11 LGs in the RIL population. Whereas eight regions were demonstrated to be common between the two approaches, the linkage disequilibrium approach did not detect a documented QTL that was confirmed using the linkage mapping approach.

A pH-responsive carboxymethyl dextran-based conjugate as a carrier of docetaxel for cancer therapy.

PubMed

Han, Hwa Seung; Lee, Minchang; An, Jae Yoon; Son, Soyoung; Ko, Hyewon; Lee, Hansang; Chae, Yee Soo; Kang, Young Mo; Park, Jae Hyung

2016-05-01

Although docetaxel is available for the treatment of various cancers, its clinical applications are limited by its poor water solubility and toxicity to normal cells, resulting in severe adverse effects. In this study, we synthesized a polymeric conjugate with an acid-labile ester linkage, consisting of carboxymethyl dextran (CMD) and docetaxel (DTX), as a potential anticancer drug delivery system. The conjugate exhibited sustained release of DTX in physiological buffer (pH 7.4), whereas its release rate increased remarkably under mildly acidic conditions (pH < 6.5), mimicking the intracellular environment. Cytotoxicity tests conducted in vitro demonstrated that the conjugate exhibited much higher toxicity to cancer cells under mildly acidic conditions than at physiological buffer (pH 7.4). These results implied that the ester linkage in the conjugate allowed for selective release of biologically active DTX under mildly acidic conditions. The in vivo biodistribution of a Cy5.5-labeled conjugate was observed using the noninvasive optical imaging technique after its systemic administration into tumor-bearing mice. The conjugate was effectively accumulated into the tumor site, which may have been because of an enhanced permeability and retention effect. In addition, in vivo antitumor efficacy of the conjugate was significantly higher than that of free DTX. Overall, the CMD-based conjugate might have promising potential as a carrier of DTX for cancer therapy. © 2015 Wiley Periodicals, Inc.

Distribution of lod scores in oligogenic linkage analysis.

PubMed

Williams, J T; North, K E; Martin, L J; Comuzzie, A G; Göring, H H; Blangero, J

2001-01-01

In variance component oligogenic linkage analysis it can happen that the residual additive genetic variance bounds to zero when estimating the effect of the ith quantitative trait locus. Using quantitative trait Q1 from the Genetic Analysis Workshop 12 simulated general population data, we compare the observed lod scores from oligogenic linkage analysis with the empirical lod score distribution under a null model of no linkage. We find that zero residual additive genetic variance in the null model alters the usual distribution of the likelihood-ratio statistic.

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.

Speech sound disorder influenced by a locus in 15q14 region.

PubMed

Stein, Catherine M; Millard, Christopher; Kluge, Amy; Miscimarra, Lara E; Cartier, Kevin C; Freebairn, Lisa A; Hansen, Amy J; Shriberg, Lawrence D; Taylor, H Gerry; Lewis, Barbara A; Iyengar, Sudha K

2006-11-01

Despite a growing body of evidence indicating that speech sound disorder (SSD) has an underlying genetic etiology, researchers have not yet identified specific genes predisposing to this condition. The speech and language deficits associated with SSD are shared with several other disorders, including dyslexia, autism, Prader-Willi Syndrome (PWS), and Angelman's Syndrome (AS), raising the possibility of gene sharing. Furthermore, we previously demonstrated that dyslexia and SSD share genetic susceptibility loci. The present study assesses the hypothesis that SSD also shares susceptibility loci with autism and PWS. To test this hypothesis, we examined linkage between SSD phenotypes and microsatellite markers on the chromosome 15q14-21 region, which has been associated with autism, PWS/AS, and dyslexia. Using SSD as the phenotype, we replicated linkage to the 15q14 region (P=0.004). Further modeling revealed that this locus influenced oral-motor function, articulation and phonological memory, and that linkage at D15S118 was potentially influenced by a parent-of-origin effect (LOD score increase from 0.97 to 2.17, P=0.0633). These results suggest shared genetic determinants in this chromosomal region for SSD, autism, and PWS/AS.

Linkage Disequilibrium in a Finite Population That Is Partially Selfing

PubMed Central

Golding, G. B.; Strobeck, C.

1980-01-01

The linkage disequilibrium expected in a finite, partially selfing population is analyzed, assuming the infinite allele model. Formulas for the expected sum of squares of the linkage disequilibria and the squared standard linkage disequilibrium are derived from the equilibrium values of sixteen inbreeding coefficients required to describe the behavior of the system. These formulas are identical to those obtained with random mating if the effective population size Ne = (1-½S)N and the effective recombination value re = (1-S)r/(1-½S), where S is the proportion of selfing, are substituted for the population size and the recombination value. Therefore, the effect of partial selfing at equilibrium is to reduce the population size by a factor 1-½S and the recombination value by a factor (1-S)/(1-½S). PMID:17249017

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.

Keep your opponents close: social context affects EEG and fEMG linkage in a turn-based computer game.

PubMed

Spapé, Michiel M; Kivikangas, J Matias; Järvelä, Simo; Kosunen, Ilkka; Jacucci, Giulio; Ravaja, Niklas

2013-01-01

In daily life, we often copy the gestures and expressions of those we communicate with, but recent evidence shows that such mimicry has a physiological counterpart: interaction elicits linkage, which is a concordance between the biological signals of those involved. To find out how the type of social interaction affects linkage, pairs of participants played a turn-based computer game in which the level of competition was systematically varied between cooperation and competition. Linkage in the beta and gamma frequency bands was observed in the EEG, especially when the participants played directly against each other. Emotional expression, measured using facial EMG, reflected this pattern, with the most competitive condition showing enhanced linkage over the facial muscle-regions involved in smiling. These effects were found to be related to self-reported social presence: linkage in positive emotional expression was associated with self-reported shared negative feelings. The observed effects confirmed the hypothesis that the social context affected the degree to which participants had similar reactions to their environment and consequently showed similar patterns of brain activity. We discuss the functional resemblance between linkage, as an indicator of a shared physiology and affect, and the well-known mirror neuron system, and how they relate to social functions like empathy.

Construction of an SSR and RAD-Marker Based Molecular Linkage Map of Vigna vexillata (L.) A. Rich

PubMed Central

Chankaew, Sompong; Kaga, Akito; Naito, Ken; Ehara, Hiroshi; Tomooka, Norihiko

2015-01-01

Vigna vexillata (L.) A. Rich. (tuber cowpea) is an underutilized crop for consuming its tuber and mature seeds. Wild form of V. vexillata is a pan-tropical perennial herbaceous plant which has been used by local people as a food. Wild V. vexillata has also been considered as useful gene(s) source for V. unguiculata (cowpea), since it was reported to have various resistance gene(s) for insects and diseases of cowpea. To exploit the potential of V. vexillata, an SSR-based linkage map of V. vexillata was developed. A total of 874 SSR markers successfully amplified single DNA fragment in V. vexillata among 1,336 SSR markers developed from Vigna angularis (azuki bean), V. unguiculata and Phaseolus vulgaris (common bean). An F2 population of 300 plants derived from a cross between salt resistant (V1) and susceptible (V5) accessions was used for mapping. A genetic linkage map was constructed using 82 polymorphic SSR markers loci, which could be assigned to 11 linkage groups spanning 511.5 cM in length with a mean distance of 7.2 cM between adjacent markers. To develop higher density molecular linkage map and to confirm SSR markers position in a linkage map, RAD markers were developed and a combined SSR and RAD markers linkage map of V. vexillata was constructed. A total of 559 (84 SSR and 475 RAD) markers loci could be assigned to 11 linkage groups spanning 973.9 cM in length with a mean distance of 1.8 cM between adjacent markers. Linkage and genetic position of all SSR markers in an SSR linkage map were confirmed. When an SSR genetic linkage map of V. vexillata was compared with those of V. radiata and V. unguiculata, it was suggested that the structure of V. vexillata chromosome was considerably differentiated. This map is the first SSR and RAD marker-based V. vexillata linkage map which can be used for the mapping of useful traits. PMID:26398819

For the Common Good. A Guide for Developing Local Interagency Linkage Teams.

ERIC Educational Resources Information Center

Imel, Susan

Developed from the Ohio At-Risk Linkage Team experiences, this guide assists local communities in organizing and strengthening effective collaborative interagency linkage teams for at-risk youth and adults. The guide proposes a series of steps, poses a number of questions relating to each step, and provides information about additional resources.…

A review and framework for understanding the potential impact of poor solid waste management on health in developing countries.

PubMed

Ziraba, Abdhalah K; Haregu, Tilahun Nigatu; Mberu, Blessing

2016-01-01

The increase in solid waste generated per capita in Africa has not been accompanied by a commensurate growth in the capacity and funding to manage it. It is reported that less than 30% of urban waste in developing countries is collected and disposed appropriately. The implications of poorly managed waste on health are numerous and depend on the nature of the waste, individuals exposed, duration of exposure and availability of interventions for those exposed. To present a framework for understanding the linkages between poor solid waste management, exposure and associated adverse health outcomes. The framework will aid understanding of the relationships, interlinkages and identification of the potential points for intervention. Development of the framework was informed by a review of literature on solid waste management policies, practices and its impact on health in developing countries. A configurative synthesis of literature was applied to develop the framework. Several iterations of the framework were reviewed by experts in the field. Each linkage and outcomes are described in detail as outputs of this study. The resulting framework identifies groups of people at a heightened risk of exposure and the potential health consequences. Using the iceberg metaphor, the framework illustrates the pathways and potential burden of ill-health related to solid waste that is hidden but rapidly unfolding with our inaction. The existing evidence on the linkage between poor solid waste management and adverse health outcomes calls to action by all stakeholders in understanding, prioritizing, and addressing the issue of solid waste in our midst to ensure that our environment and health are preserved. A resulting framework developed in this study presents a clearer picture of the linkages between poor solid waste management and could guide research, policy and action.

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.

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.

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.

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…

In vitro Studies of Sandfly Fever Viruses and Their Potential Significance for Vaccine Development.

DTIC Science & Technology

1980-02-01

more 14C-canavanine (DL-guanido-1LC-canavanine hydrochloride , Research Products International, Elk Grove, Illinois) than other viral proteins (data not...several laboratories have suggested that N-acetyl- glucosamine , glucose, and mannose residues are preassembled on dolichol phosphate (an isoprenoid...described below. Unlike the 0-glycosidic linkage between galactosamine and serine, the N-glycosidic linkage between N-acetyl glucosamine and asparagine

ECOTOXICOGENOMICS: LINKAGES BETWEEN EXPOSURE AND EFFECTS IN ASSESSING RISKS OF AQUATIC CONTAMINANTS TO FISH

EPA Science Inventory

Understanding the biological effects of exposures to chemicals in the environment relies on classical and emerging technologies in the areas of genomics, proteomics, and metabonomics. Linkages between the historical and newer toxicological tools are currently being developed in o...

Developing Effective Linkages between Job Corps and One-Stop Systems: A Technical Assistance Guide.

ERIC Educational Resources Information Center

Dickinson, Katherine; Soukamneuth, Sengsouvanh

This document is intended to help Job Corps centers and Office of Acquisition Policy contractors establish linkages with one-stop systems. Chapter 1 summarizes the requirements for linkages between Job Corps and one-stop systems that are specified in the Workforce Investment Act (WIA) of 1998 and compares one-stop delivery systems before and under…

Roadmap for Early Childhood and K-12 Data Linkages: Key Focus Areas to Ensure Quality Implementation. Quality Implementation Roadmaps

ERIC Educational Resources Information Center

Data Quality Campaign, 2016

2016-01-01

Every state can create secure, robust linkages between early childhood and K-12 data systems, and effectively use the information from these linkages to implement initiatives to support programs and children, answer key policy questions, and be transparent about how the state's early childhood investments prepare students for success in school and…

Design and analysis of an underactuated anthropomorphic finger for upper limb prosthetics.

PubMed

Omarkulov, Nurdos; Telegenov, Kuat; Zeinullin, Maralbek; Begalinova, Ainur; Shintemirov, Almas

2015-01-01

This paper presents the design of a linkage based finger mechanism ensuring extended range of anthropomorphic gripping motions. The finger design is done using a path-point generation method based on geometrical dimensions and motion of a typical index human finger. Following the design description, and its kinematics analysis, the experimental evaluation of the finger gripping performance is presented using the finger 3D printed prototype. The finger underactuation is achieved by utilizing mechanical linkage system, consisting of two crossed four-bar linkage mechanisms. It is shown that the proposed finger design can be used to design a five-fingered anthropomorphic hand and has the potential for upper limb prostheses development.

Selective cleavage of the C(α)-C(β) linkage in lignin model compounds via Baeyer-Villiger oxidation.

PubMed

Patil, Nikhil D; Yao, Soledad G; Meier, Mark S; Mobley, Justin K; Crocker, Mark

2015-03-21

Lignin is an amorphous aromatic polymer derived from plants and is a potential source of fuels and bulk chemicals. Herein, we present a survey of reagents for selective stepwise oxidation of lignin model compounds. Specifically, we have targeted the oxidative cleavage of Cα-Cβ bonds as a means to depolymerize lignin and obtain useful aromatic compounds. In this work, we prepared several lignin model compounds that possess structures, characteristic reactivity, and linkages closely related to the parent lignin polymer. We observed that selective oxidation of benzylic hydroxyl groups, followed by Baeyer-Villiger oxidation of the resulting ketones, successfully cleaves the Cα-Cβ linkage in these model compounds.

Near-IR-induced dissociation of thermally-sensitive star polymers.

PubMed

Dai, Yuqiong; Sun, Hao; Pal, Sunirmal; Zhang, Yunlu; Park, Sangwoo; Kabb, Christopher P; Wei, Wei David; Sumerlin, Brent S

2017-03-01

Responsive systems sensitive to near-infrared (NIR) light are promising for triggered release due to efficient deep tissue penetration of NIR irradiation relative to higher energy sources ( e.g. , UV), allowing for spatiotemporal control over triggering events with minimal potential for tissue damage. Herein, we report star polymers containing thermally-labile azo linkages that dissociate during conventional heating or during localized heating via the photothermal effect upon NIR irradiation. Controlled release during conventional heating was investigated for the star polymers loaded with a model dye, with negligible release being observed at 25 °C and >80% release at 90 °C. Star polymers co-loaded with NIR-responsive indocyanine green showed rapid dye release upon NIR irradiation ( λ ≥ 715 nm) due to the photothermally-induced degradation of azo linkages within the cores of the star polymers. This approach provides access to a new class of delivery and release systems that can be triggered by noninvasive external stimulation.

Family-Peer Linkages for Children with Intellectual Disability and Children with Learning Disabilities.

PubMed

Floyd, Frank J; Olsen, Darren L

2017-09-01

Family interactions are potential contexts for children with intellectual and learning disabilities to develop skillful social behaviors needed to relate effectively with peers. This study examined problem solving interactions within families of elementary school-age children (7-11 years) with intellectual disability (n = 37), specific learning disabilities (n =48), and without disabilities (n = 22). After accounting for group differences in children's behaviors and peer acceptance, across all groups, mothers' behaviors that encouraged egalitarian problem solving predicted more engaged and skillful problem solving by the children. However, mothers' controlling, directive behaviors predicted fewer of these behaviors by the children. Fathers' behaviors had mixed associations with the children's actions, possibly because they were reactive to children's unengaged and negative behaviors. For the children, greater involvement, more facilitative behaviors, and less negativity with their families were associated with greater acceptance from their peers, supporting family-peer linkages for children at risk for peer rejection.

Ensuring Privacy When Integrating Patient-Based Datasets: New Methods and Developments in Record Linkage.

PubMed

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

2017-01-01

In an era where the volume of structured and unstructured digital data has exploded, there has been an enormous growth in the creation of data about individuals that can be used for understanding and treating disease. Joining these records together at an individual level provides a complete picture of a patient's interaction with health services and allows better assessment of patient outcomes and effectiveness of treatment and services. Record linkage techniques provide an efficient and cost-effective method to bring individual records together as patient profiles. These linkage procedures bring their own challenges, especially relating to the protection of privacy. The development and implementation of record linkage systems that do not require the release of personal information can reduce the risks associated with record linkage and overcome legal barriers to data sharing. Current conceptual and experimental privacy-preserving record linkage (PPRL) models show promise in addressing data integration challenges. Enhancing and operationalizing PPRL protocols can help address the dilemma faced by some custodians between using data to improve quality of life and dealing with the ethical, legal, and administrative issues associated with protecting an individual's privacy. These methods can reduce the risk to privacy, as they do not require personally identifying information to be shared. PPRL methods can improve the delivery of record linkage services to the health and broader research community.

Ensuring Privacy When Integrating Patient-Based Datasets: New Methods and Developments in Record Linkage

PubMed Central

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

2017-01-01

In an era where the volume of structured and unstructured digital data has exploded, there has been an enormous growth in the creation of data about individuals that can be used for understanding and treating disease. Joining these records together at an individual level provides a complete picture of a patient’s interaction with health services and allows better assessment of patient outcomes and effectiveness of treatment and services. Record linkage techniques provide an efficient and cost-effective method to bring individual records together as patient profiles. These linkage procedures bring their own challenges, especially relating to the protection of privacy. The development and implementation of record linkage systems that do not require the release of personal information can reduce the risks associated with record linkage and overcome legal barriers to data sharing. Current conceptual and experimental privacy-preserving record linkage (PPRL) models show promise in addressing data integration challenges. Enhancing and operationalizing PPRL protocols can help address the dilemma faced by some custodians between using data to improve quality of life and dealing with the ethical, legal, and administrative issues associated with protecting an individual’s privacy. These methods can reduce the risk to privacy, as they do not require personally identifying information to be shared. PPRL methods can improve the delivery of record linkage services to the health and broader research community. PMID:28303240

ECOTOXICOGENOMICS: LINKAGES BETWEEN EXPOSURE AND EFFECTS IN ASSESSING RISKS OF AQUATIC CONTAMINANTS TO FISH (JOURNAL ARTICLE)

EPA Science Inventory

Understanding the biological effects of exposures to chemicals in the environment relies on classical methods and emerging technologies in the areas of genomics, proteomics, and metabonomics. Linkages between the historical and newer toxicological tools are currently being devel...

Genome-wide distribution of genetic diversity and linkage disequilibrium in a mass-selected population of maritime pine

PubMed Central

2014-01-01

Background The accessibility of high-throughput genotyping technologies has contributed greatly to the development of genomic resources in non-model organisms. High-density genotyping arrays have only recently been developed for some economically important species such as conifers. The potential for using genomic technologies in association mapping and breeding depends largely on the genome wide patterns of diversity and linkage disequilibrium in current breeding populations. This study aims to deepen our knowledge regarding these issues in maritime pine, the first species used for reforestation in south western Europe. Results Using a new map merging algorithm, we first established a 1,712 cM composite linkage map (comprising 1,838 SNP markers in 12 linkage groups) by bringing together three already available genetic maps. Using rigorous statistical testing based on kernel density estimation and resampling we identified cold and hot spots of recombination. In parallel, 186 unrelated trees of a mass-selected population were genotyped using a 12k-SNP array. A total of 2,600 informative SNPs allowed to describe historical recombination, genetic diversity and genetic structure of this recently domesticated breeding pool that forms the basis of much of the current and future breeding of this species. We observe very low levels of population genetic structure and find no evidence that artificial selection has caused a reduction in genetic diversity. By combining these two pieces of information, we provided the map position of 1,671 SNPs corresponding to 1,192 different loci. This made it possible to analyze the spatial pattern of genetic diversity (H e ) and long distance linkage disequilibrium (LD) along the chromosomes. We found no particular pattern in the empirical variogram of H e across the 12 linkage groups and, as expected for an outcrossing species with large effective population size, we observed an almost complete lack of long distance LD. Conclusions These results are a stepping stone for the development of strategies for studies in population genomics, association mapping and genomic prediction in this economical and ecologically important forest tree species. PMID:24581176

Genetic linkage map and QTL identification for adventitious rooting traits in red gum eucalypts.

PubMed

Sumathi, Murugan; Bachpai, Vijaya Kumar Waman; Mayavel, A; Dasgupta, Modhumita Ghosh; Nagarajan, Binai; Rajasugunasekar, D; Sivakumar, Veerasamy; Yasodha, Ramasamy

2018-05-01

The eucalypt species, Eucalyptus tereticornis and Eucalyptus camaldulensis , show tolerance to drought and salinity conditions, respectively, and are widely cultivated in arid and semiarid regions of tropical countries. In this study, genetic linkage map was developed for interspecific cross E. tereticornis  ×  E. camaldulensis using pseudo-testcross strategy with simple sequence repeats (SSRs), intersimple sequence repeats (ISSRs), and sequence-related amplified polymorphism (SRAP) markers. The consensus genetic map comprised totally 283 markers with 84 SSRs, 94 ISSRs, and 105 SRAP markers on 11 linkage groups spanning 1163.4 cM genetic distance. Blasting the SSR sequences against E. grandis sequences allowed an alignment of 64% and the average ratio of genetic-to-physical distance was 1.7 Mbp/cM, which strengths the evidence that high amount of synteny and colinearity exists among eucalypts genome. Blast searches also revealed that 37% of SSRs had homologies with genes, which could potentially be used in the variety of downstream applications including candidate gene polymorphism. Quantitative trait loci (QTL) analysis for adventitious rooting traits revealed six QTL for rooting percent and root length on five chromosomes with interval and composite interval mapping. All the QTL explained 12.0-14.7% of the phenotypic variance, showing the involvement of major effect QTL on adventitious rooting traits. Increasing the density of markers would facilitate the detection of more number of small-effect QTL and also underpinning the genes involved in rooting process.

Dissection of expression-quantitative trait locus and allele specificity using a haploid/diploid plant system - insights into compensatory evolution of transcriptional regulation within populations.

PubMed

Verta, Jukka-Pekka; Landry, Christian R; MacKay, John

2016-07-01

Regulation of gene expression plays a central role in translating genotypic variation into phenotypic variation. Dissection of the genetic basis of expression variation is key to understanding how expression regulation evolves. Such analyses remain challenging in contexts where organisms are outbreeding, highly heterozygous and long-lived such as in the case of conifer trees. We developed an RNA sequencing (RNA-seq)-based approach for both expression-quantitative trait locus (eQTL) mapping and the detection of cis-acting (allele-specific) vs trans-acting (non-allele-specific) eQTLs. This method can be potentially applied to many conifers. We used haploid and diploid meiotic seed tissues of a single self-fertilized white spruce (Picea glauca) individual to dissect eQTLs according to linkage and allele specificity. The genetic architecture of local eQTLs linked to the expressed genes was particularly complex, consisting of cis-acting, trans-acting and, surprisingly, compensatory cis-trans effects. These compensatory effects influence expression in opposite directions and are neutral when combined in homozygotes. Nearly half of local eQTLs were under compensation, indicating that close linkage between compensatory cis-trans factors is common in spruce. Compensated genes were overrepresented in developmental and cell organization functions. Our haploid-diploid eQTL analysis in spruce revealed that compensatory cis-trans eQTLs segregate within populations and evolve in close genetic linkage. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

A mathematical/physics model to measure the role of information and communication technology in some economies: the Chinese case

NASA Astrophysics Data System (ADS)

Lin, Xuchen; Lu, Ting-Jie; Chen, Xia

2017-03-01

Since the Reform and Opening-up in 1978, China has experienced a huge sustainable growth of gross domestic product (GDP) and an incredible development in Information and Communication Technology (ICT). This study aims to utilize an input-output (I-O) approach to explore the role of ICT in Chinese national economy. Specifically, we employ a static I-O framework, and analyze three topics in its application: the inter-industry linkage effect, the production inducing effect, and the supply shortage effect. We pay particular attention to the ICT manufacturing sector and ICT service-providing sector by taking the sectors as exogenous and investigating their economic impacts, respectively. The results suggest that (1) the ICT manufacturing sector has a high backward linkage effect, an intermediate forward linkage effect, a relatively low production inducing effect, and a low supply shortage effect, it suggests that ICT manufacturing sector has a powerful capacity for pulling the production activities of the whole economy. (2) The inter-industry linkage effect and supply shortage effect of ICT service-providing is low, but the production inducing effect of ICT service-providing is high, which suggests that the impact of an increase in ICT service-providing investment on the total output of all other sectors is large.

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.

Context matters: sexual signaling loss in digital organisms

PubMed Central

Weigel, Emily G; Testa, Nicholas D; Peer, Alex; Garnett, Sara C

2015-01-01

Sexual signals are important in attracting and choosing mates; however, these signals and their associated preferences are often costly and frequently lost. Despite the prevalence of signaling system loss in many taxa, the factors leading to signal loss remain poorly understood. Here, we test the hypothesis that complexity in signal loss scenarios is due to the context-dependent nature of the many factors affecting signal loss itself. Using the Avida digital life platform, we evolved 50 replicates of ∼250 lineages, each with a unique combination of parameters, including whether signaling is obligate or facultative; genetic linkage between signaling and receiving genes; population size; and strength of preference for signals. Each of these factors ostensibly plays a crucial role in signal loss, but was found to do so only under specific conditions. Under obligate signaling, genetic linkage, but not population size, influenced signal loss; under facultative signaling, genetic linkage does not have significant influence. Somewhat surprisingly, only a total loss of preference in the obligate signaling populations led to total signal loss, indicating that even a modest amount of preference is enough to maintain signaling systems. Strength of preference proved to be the strongest single force preventing signal loss, as it consistently overcame the potential effects of drift within our study. Our findings suggest that signaling loss is often dependent on not just preference for signals, population size, and genetic linkage, but also whether signals are required to initiate mating. These data provide an understanding of the factors (and their interactions) that may facilitate the maintenance of sexual signals. PMID:26380700

Online-to-offline models in HIV service delivery.

PubMed

Anand, Tarandeep; Nitpolprasert, Chattiya; Phanuphak, Nittaya

2017-09-01

Half the world's population has access to Internet and technologies, and utilization is near-ubiquitous among providers and key populations. Despite being so well connected; identifying, reaching and linking vulnerable populations to HIV clinical services remains a global challenge. This review highlights the emerging online-to-offline (O2O) models, their potential in scaling up services, and evaluating impact, and implications for future research. Globally, four major types of O2O models have been implemented, primarily in the West and Asia, especially among MSM and transgender women. These models have varying levels of impact in terms of reach, engagement, participation, linkage, and ability to track and monitor participants, and assess outcomes. Those integrated with offline sites enable seamless transition, dramatically reduce the O2O linkage time and demonstrate high linkage success (>73%). O2O models are ideal for at-risk, stigmatized, criminalized populations and for scaling-up biomedical prevention interventions such as preexposure and postexposure prophylaxis. O2O models represent novel and powerful solutions to reverse the pandemic and could help fill significant programmatic gaps in tracking individuals through HIV cascades. Providers, especially in resource-limited settings, could choose between a variety of current approaches highlighted in this review and employ no-cost or cost-effective technologies to transform their traditional models and leverage O2O models.

Vestibular short-latency evoked potential abolished by low-frequency noise exposure in rats.

PubMed

Stewart, Courtney E; Kanicki, Ariane C; Altschuler, Richard A; King, W M

2018-02-01

The vestibular system plays a critical role in detection of head movements and is essential for normal postural control. Because of their anatomical proximity to the cochlea, the otolith organs are selectively exposed to sound pressure and are at risk for noise overstimulation. Clinical reports suggest a link between noise exposure and balance problems, but the structural and physiological basis for this linkage is not well understood. The goal of this study was to determine the effects of low-frequency noise (LFN) on the otolith organs by correlating changes in vestibular short-latency evoked potentials (VsEPs) with changes in saccular afferent endings following noise exposure. LFN exposure transiently abolished the VsEP and reduced the number of stained calyces within the sacculus. Although some recovery of the VsEP waveform could be observed within 3 days after noise, at 3 wk recovery was only partial in most animals, consistent with a reduced number of afferents with calyceal endings. These data show that a single intense noise exposure is capable of causing a vestibular deficit that appears to mirror the synaptic deficit associated with hidden hearing loss after noise-induced cochlear injury. NEW & NOTEWORTHY This is the first study to explore the effects of low-frequency high-intensity noise on vestibular short-latency evoked potential (VsEP) responses, which shows a linkage between attenuated noise-induced VsEPs and pathological changes to otolith organ afferents. This finding suggests a potential limitation of the VsEP for evaluation of vestibular dysfunction, since the VsEP measurement may assess the activity of a specific class rather than all afferents.

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

Video-conferencing Telehealth Linkage attempts to Schools to Facilitate Mental Health Consultation.

PubMed

McLennan, John D

2018-04-01

Telehealth to schools may be a strategic approach to expand child mental health service delivery, however, there are only a few published examples. This report describes video-conferencing telehealth linkage attempts to schools to facilitate mental health consultation. A series of synchronous video-conferencing linkage strategies were attempted to connect a mental health consultation service to multiple schools in a Canadian setting. Consultation to support the implementation of the Daily Report Card, for students with attentional and behavioural problems, was the core content of this pilot linkage attempt. Synchronous video conference consultations were successfully delivered to six elementary schools across three school districts. Two of three linkage strategies were functional. One used existing health centre-based telehealth units to connect to school-based dedicated tablets with a video collaboration app and reliance on existing school Wi-Fi. A second used existing laptops in both the health and school system linked through a communication platform. A third connection, using 3G/4G hotspots to obviate the need to access school Wi-Fi, was deemed too expensive in this setting. The potential to use existing computer hardware to connect mental health providers and schools could facilitate scale-up. However, it is unknown whether mental health systems and school sectors will invest in such linkages and reorganize core mental health services to be delivered in this way.

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.

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

Whole-lake invasive crayfish removal and qualitative modeling reveal habitat-specific food web topology

DOE PAGES

Hansen, Gretchen J. A.; Tunney, Tyler D.; Winslow, Luke A.; ...

2017-02-10

Patterning of the presence/absence of food web linkages (hereafter topology) is a fundamental characteristic of ecosystems that can influence species responses to perturbations. However, the insight from food web topology into dynamic effects of perturbations on species is potentially hindered because most described topologies represent data integrated across spatial and temporal scales. We conducted a 10-year, whole-lake experiment in which we removed invasive rusty crayfish ( Orconectes rusticus) from a 64-ha north-temperate lake and monitored responses of multiple trophic levels. We compared species responses observed in two sub-habitats to the responses predicted from all topologies of an integrated, literature-informed basemore » food web model of 32 potential links. Out of 4.3 billion possible topologies, only 308,833 (0.0072%) predicted responses that qualitatively matched observed species responses in cobble habitat, and only 12,673 (0.0003%) matched observed responses in sand habitat. Furthermore, when constrained to predictions that both matched observed responses and were highly reliable (i.e., predictions were robust to link strength values), only 5040 (0.0001%) and 140 (0.000003%) topologies were identified for cobble and sand habitats, respectively. A small number of linkages were nearly always present in these valid, reliable networks in sand, while a greater variety of possible network configurations were possible in cobble. Direct links involving invasive rusty crayfish were more important in cobble, while indirect effects involving Lepomis spp. were more important in sand. Importantly, the importance of individual species linkages differed dramatically among cobble and sand sub-habitats within a single lake, even though species composition was identical. Furthermore the true topology of food webs is difficult to determine, constraining topologies to include spatial resolution that matches observed experimental outcomes may reduce possibilities to a small number of plausible alternatives.« less

Whole-lake invasive crayfish removal and qualitative modeling reveal habitat-specific food web topology

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

Hansen, Gretchen J. A.; Tunney, Tyler D.; Winslow, Luke A.

Patterning of the presence/absence of food web linkages (hereafter topology) is a fundamental characteristic of ecosystems that can influence species responses to perturbations. However, the insight from food web topology into dynamic effects of perturbations on species is potentially hindered because most described topologies represent data integrated across spatial and temporal scales. We conducted a 10-year, whole-lake experiment in which we removed invasive rusty crayfish ( Orconectes rusticus) from a 64-ha north-temperate lake and monitored responses of multiple trophic levels. We compared species responses observed in two sub-habitats to the responses predicted from all topologies of an integrated, literature-informed basemore » food web model of 32 potential links. Out of 4.3 billion possible topologies, only 308,833 (0.0072%) predicted responses that qualitatively matched observed species responses in cobble habitat, and only 12,673 (0.0003%) matched observed responses in sand habitat. Furthermore, when constrained to predictions that both matched observed responses and were highly reliable (i.e., predictions were robust to link strength values), only 5040 (0.0001%) and 140 (0.000003%) topologies were identified for cobble and sand habitats, respectively. A small number of linkages were nearly always present in these valid, reliable networks in sand, while a greater variety of possible network configurations were possible in cobble. Direct links involving invasive rusty crayfish were more important in cobble, while indirect effects involving Lepomis spp. were more important in sand. Importantly, the importance of individual species linkages differed dramatically among cobble and sand sub-habitats within a single lake, even though species composition was identical. Furthermore the true topology of food webs is difficult to determine, constraining topologies to include spatial resolution that matches observed experimental outcomes may reduce possibilities to a small number of plausible alternatives.« less

Replication of linkage to quantitative trait loci: variation in location and magnitude of the lod score.

PubMed

Hsueh, W C; Göring, H H; Blangero, J; Mitchell, B D

2001-01-01

Replication of linkage signals from independent samples is considered an important step toward verifying the significance of linkage signals in studies of complex traits. The purpose of this empirical investigation was to examine the variability in the precision of localizing a quantitative trait locus (QTL) by analyzing multiple replicates of a simulated data set with the use of variance components-based methods. Specifically, we evaluated across replicates the variation in both the magnitude and the location of the peak lod scores. We analyzed QTLs whose effects accounted for 10-37% of the phenotypic variance in the quantitative traits. Our analyses revealed that the precision of QTL localization was directly related to the magnitude of the QTL effect. For a QTL with effect accounting for > 20% of total phenotypic variation, > 90% of the linkage peaks fall within 10 cM from the true gene location. We found no evidence that, for a given magnitude of the lod score, the presence of interaction influenced the precision of QTL localization.

Hidden linkages between urbanization and food systems.

PubMed

Seto, Karen C; Ramankutty, Navin

2016-05-20

Global societies are becoming increasingly urban. This shift toward urban living is changing our relationship with food, including how we shop and what we buy, as well as ideas about sanitation and freshness. Achieving food security in an era of rapid urbanization will require considerably more understanding about how urban and food systems are intertwined. Here we discuss some potential understudied linkages that are ripe for further examination. Copyright © 2016, American Association for the Advancement of Science.

Common evolutionary trends underlie the four-bar linkage systems of sunfish and mantis shrimp.

PubMed

Hu, Yinan; Nelson-Maney, Nathan; Anderson, Philip S L

2017-05-01

Comparative biomechanics offers an opportunity to explore the evolution of disparate biological systems that share common underlying mechanics. Four-bar linkage modeling has been applied to various biological systems such as fish jaws and crustacean appendages to explore the relationship between biomechanics and evolutionary diversification. Mechanical sensitivity states that the functional output of a mechanical system will show differential sensitivity to changes in specific morphological components. We document similar patterns of mechanical sensitivity in two disparate four-bar systems from different phyla: the opercular four-bar system in centrarchid fishes and the raptorial appendage of stomatopods. We built dynamic linkage models of 19 centrarchid and 36 stomatopod species and used phylogenetic generalized least squares regression (PGLS) to compare evolutionary shifts in linkage morphology and mechanical outputs derived from the models. In both systems, the kinematics of the four-bar mechanism show significant evolutionary correlation with the output link, while travel distance of the output arm is correlated with the coupler link. This common evolutionary pattern seen in both fish and crustacean taxa is a potential consequence of the mechanical principles underlying four-bar systems. Our results illustrate the potential influence of physical principles on morphological evolution across biological systems with different structures, behaviors, and ecologies. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.

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…

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

A case study of the Secure Anonymous Information Linkage (SAIL) Gateway: a privacy-protecting remote access system for health-related research and evaluation.

PubMed

Jones, Kerina H; Ford, David V; Jones, Chris; Dsilva, Rohan; Thompson, Simon; Brooks, Caroline J; Heaven, Martin L; Thayer, Daniel S; McNerney, Cynthia L; Lyons, Ronan A

2014-08-01

With the current expansion of data linkage research, the challenge is to find the balance between preserving the privacy of person-level data whilst making these data accessible for use to their full potential. We describe a privacy-protecting safe haven and secure remote access system, referred to as the Secure Anonymised Information Linkage (SAIL) Gateway. The Gateway provides data users with a familiar Windows interface and their usual toolsets to access approved anonymously-linked datasets for research and evaluation. We outline the principles and operating model of the Gateway, the features provided to users within the secure environment, and how we are approaching the challenges of making data safely accessible to increasing numbers of research users. The Gateway represents a powerful analytical environment and has been designed to be scalable and adaptable to meet the needs of the rapidly growing data linkage community. Copyright © 2014 The Aurthors. Published by Elsevier Inc. All rights reserved.

A case study of the Secure Anonymous Information Linkage (SAIL) Gateway: A privacy-protecting remote access system for health-related research and evaluation☆

PubMed Central

Jones, Kerina H.; Ford, David V.; Jones, Chris; Dsilva, Rohan; Thompson, Simon; Brooks, Caroline J.; Heaven, Martin L.; Thayer, Daniel S.; McNerney, Cynthia L.; Lyons, Ronan A.

2014-01-01

With the current expansion of data linkage research, the challenge is to find the balance between preserving the privacy of person-level data whilst making these data accessible for use to their full potential. We describe a privacy-protecting safe haven and secure remote access system, referred to as the Secure Anonymised Information Linkage (SAIL) Gateway. The Gateway provides data users with a familiar Windows interface and their usual toolsets to access approved anonymously-linked datasets for research and evaluation. We outline the principles and operating model of the Gateway, the features provided to users within the secure environment, and how we are approaching the challenges of making data safely accessible to increasing numbers of research users. The Gateway represents a powerful analytical environment and has been designed to be scalable and adaptable to meet the needs of the rapidly growing data linkage community. PMID:24440148

Assessing Hepatitis C Burden and Treatment Effectiveness through the British Columbia Hepatitis Testers Cohort (BC-HTC): Design and Characteristics of Linked and Unlinked Participants

PubMed Central

Janjua, Naveed Zafar; Kuo, Margot; Chong, Mei; Yu, Amanda; Alvarez, Maria; Cook, Darrel; Armour, Rosemary; Aiken, Ciaran; Li, Karen; Mussavi Rizi, Seyed Ali; Woods, Ryan; Godfrey, David; Wong, Jason; Gilbert, Mark; Tyndall, Mark W.; Krajden, Mel

2016-01-01

Background The British Columbia (BC) Hepatitis Testers Cohort (BC-HTC) was established to assess and monitor hepatitis C (HCV) epidemiology, cost of illness and treatment effectiveness in BC, Canada. In this paper, we describe the cohort construction, data linkage process, linkage yields, and comparison of the characteristics of linked and unlinked individuals. Methods The BC-HTC includes all individuals tested for HCV and/or HIV or reported as a case of HCV, hepatitis B (HBV), HIV or active tuberculosis (TB) in BC linked with the provincial health insurance client roster, medical visits, hospitalizations, drug prescriptions, the cancer registry and mortality data using unique personal health numbers. The cohort includes data since inception (1990/1992) of each database until 2012/2013 with plans for annual updates. We computed linkage rates by year and compared the characteristics of linked and unlinked individuals. Results Of 2,656,323 unique individuals available in the laboratory and surveillance data, 1,427,917(54%) were included in the final linked cohort, including about 1.15 million tested for HCV and about 1.02 million tested for HIV. The linkage rate was 86% for HCV tests, 89% for HCV cases, 95% for active TB cases, 48% for HIV tests and 36% for HIV cases. Linkage rates increased from 40% for HCV negatives and 70% for HCV positives in 1992 to ~90% after 2005. Linkage rates were lower for males, younger age at testing, and those with unknown residence location. Linkage rates for HCV testers co-infected with HIV, HBV or TB were very high (90–100%). Conclusion Linkage rates increased over time related to improvements in completeness of identifiers in laboratory, surveillance, and registry databases. Linkage rates were higher for HCV than HIV testers, those testing positive, older individuals, and females. Data from the cohort provide essential information to support the development of prevention, care and treatment initiatives for those infected with HCV. PMID:26954020

Assessing Hepatitis C Burden and Treatment Effectiveness through the British Columbia Hepatitis Testers Cohort (BC-HTC): Design and Characteristics of Linked and Unlinked Participants.

PubMed

Janjua, Naveed Zafar; Kuo, Margot; Chong, Mei; Yu, Amanda; Alvarez, Maria; Cook, Darrel; Armour, Rosemary; Aiken, Ciaran; Li, Karen; Mussavi Rizi, Seyed Ali; Woods, Ryan; Godfrey, David; Wong, Jason; Gilbert, Mark; Tyndall, Mark W; Krajden, Mel

2016-01-01

The British Columbia (BC) Hepatitis Testers Cohort (BC-HTC) was established to assess and monitor hepatitis C (HCV) epidemiology, cost of illness and treatment effectiveness in BC, Canada. In this paper, we describe the cohort construction, data linkage process, linkage yields, and comparison of the characteristics of linked and unlinked individuals. The BC-HTC includes all individuals tested for HCV and/or HIV or reported as a case of HCV, hepatitis B (HBV), HIV or active tuberculosis (TB) in BC linked with the provincial health insurance client roster, medical visits, hospitalizations, drug prescriptions, the cancer registry and mortality data using unique personal health numbers. The cohort includes data since inception (1990/1992) of each database until 2012/2013 with plans for annual updates. We computed linkage rates by year and compared the characteristics of linked and unlinked individuals. Of 2,656,323 unique individuals available in the laboratory and surveillance data, 1,427,917(54%) were included in the final linked cohort, including about 1.15 million tested for HCV and about 1.02 million tested for HIV. The linkage rate was 86% for HCV tests, 89% for HCV cases, 95% for active TB cases, 48% for HIV tests and 36% for HIV cases. Linkage rates increased from 40% for HCV negatives and 70% for HCV positives in 1992 to ~90% after 2005. Linkage rates were lower for males, younger age at testing, and those with unknown residence location. Linkage rates for HCV testers co-infected with HIV, HBV or TB were very high (90-100%). Linkage rates increased over time related to improvements in completeness of identifiers in laboratory, surveillance, and registry databases. Linkage rates were higher for HCV than HIV testers, those testing positive, older individuals, and females. Data from the cohort provide essential information to support the development of prevention, care and treatment initiatives for those infected with HCV.

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

Sexual selection and sex linkage.

PubMed

Kirkpatrick, Mark; Hall, David W

2004-04-01

Some animal groups, such as birds, seem prone to extreme forms of sexual selection. One contributing factor may be sex linkage of genes affecting male displays and female preferences. Here we show that sex linkage can have substantial effects on the genetic correlation between these traits and consequently for Fisher's runaway and the good-genes mechanisms of sexual selection. Under some kinds of sex linkage (e.g. Z-linked preferences), a runaway is more likely than under autosomal inheritance, while under others (e.g., X-linked preferences and autosomal displays), the good-genes mechanism is particularly powerful. These theoretical results suggest empirical tests based on the comparative method.

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

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.

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 genomewide screen for late-onset Alzheimer disease in a genetically isolated Dutch population.

PubMed

Liu, Fan; Arias-Vásquez, Alejandro; Sleegers, Kristel; Aulchenko, Yurii S; Kayser, Manfred; Sanchez-Juan, Pascual; Feng, Bing-Jian; Bertoli-Avella, Aida M; van Swieten, John; Axenovich, Tatiana I; Heutink, Peter; van Broeckhoven, Christine; Oostra, Ben A; van Duijn, Cornelia M

2007-07-01

Alzheimer disease (AD) is the most common cause of dementia. We conducted a genome screen of 103 patients with late-onset AD who were ascertained as part of the Genetic Research in Isolated Populations (GRIP) program that is conducted in a recently isolated population from the southwestern area of The Netherlands. All patients and their 170 closely related relatives were genotyped using 402 microsatellite markers. Extensive genealogy information was collected, which resulted in an extremely large and complex pedigree of 4,645 members. The pedigree was split into 35 subpedigrees, to reduce the computational burden of linkage analysis. Simulations aiming to evaluate the effect of pedigree splitting on false-positive probabilities showed that a LOD score of 3.64 corresponds to 5% genomewide type I error. Multipoint analysis revealed four significant and one suggestive linkage peaks. The strongest evidence of linkage was found for chromosome 1q21 (heterogeneity LOD [HLOD]=5.20 at marker D1S498). Approximately 30 cM upstream of this locus, we found another peak at 1q25 (HLOD=4.0 at marker D1S218). These two loci are in a previously established linkage region. We also confirmed the AD locus at 10q22-24 (HLOD=4.15 at marker D10S185). There was significant evidence of linkage of AD to chromosome 3q22-24 (HLOD=4.44 at marker D3S1569). For chromosome 11q24-25, there was suggestive evidence of linkage (HLOD=3.29 at marker D11S1320). We next tested for association between cognitive function and 4,173 single-nucleotide polymorphisms in the linked regions in an independent sample consisting of 197 individuals from the GRIP region. After adjusting for multiple testing, we were able to detect significant associations for cognitive function in four of five AD-linked regions, including the new region on chromosome 3q22-24 and regions 1q25, 10q22-24, and 11q25. With use of cognitive function as an endophenotype of AD, our study indicates the that the RGSL2, RALGPS2, and C1orf49 genes are the potential disease-causing genes at 1q25. Our analysis of chromosome 10q22-24 points to the HTR7, MPHOSPH1, and CYP2C cluster. This is the first genomewide screen that showed significant linkage to chromosome 3q23 markers. For this region, our analysis identified the NMNAT3 and CLSTN2 genes. Our findings confirm linkage to chromosome 11q25. We were unable to confirm SORL1; instead, our analysis points to the OPCML and HNT genes.

The Peace Movement: An Exercise in Micro-Macro Linkages.

ERIC Educational Resources Information Center

Galtung, Johan

1988-01-01

Contends that the basic assumption of the peace movement is the abuse of military power by the state. Argues that the peace movement is most effective through linkages with cultural, political, and economic forces in society. (BSR)

The benefits of sexual orientation diversity in sport organizations.

PubMed

Cunningham, George B; Melton, E Nicole

2011-01-01

While sexual orientation diversity can potentially serve as a source of competitive advantage, researchers have largely failed to fully articulate the theoretical linkage between this diversity form and organizational effectiveness. As such, we propose a theoretical framework to understand these dynamics. Sexual orientation diversity is posited to positively contribute to organizational effectiveness through three mechanisms: enhanced decision making capabilities, improved marketplace understanding, and goodwill associated with engaging in socially responsible practices. We also propose two approaches to leveraging the benefits of sexual orientation diversity: targeting the categorization process and creating a proactive and inclusive diversity culture. Contributions and implications are discussed.

Moving Beyond Boron: The Emergence of New Linkage Chemistries in Covalent Organic Frameworks

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

DeBlase, Catherine R.; Dichtel, William R.

Since their discovery in 2005, covalent organic frameworks (COFs) have attracted interest as potential materials for gas storage, catalysis, energy storage, and other applications because of their ability to periodically and reliably organize designed functionality into high surface area materials. Most of the first examples relied on boron-containing linkages, which suffer from hydrolytic and oxidative instability that limit their utility. In this Perspective, we describe the trend toward more robust linkages by highlighting the design, synthesis, and properties of several recent examples. Finally, the continued development of new COF chemistries, along with improved understanding of their formation and control ofmore » their final form, will provide a means to harness their molecularly precise solidstate structures for useful purposes.« less

Moving Beyond Boron: The Emergence of New Linkage Chemistries in Covalent Organic Frameworks

DOE PAGES

DeBlase, Catherine R.; Dichtel, William R.

2016-06-21

Since their discovery in 2005, covalent organic frameworks (COFs) have attracted interest as potential materials for gas storage, catalysis, energy storage, and other applications because of their ability to periodically and reliably organize designed functionality into high surface area materials. Most of the first examples relied on boron-containing linkages, which suffer from hydrolytic and oxidative instability that limit their utility. In this Perspective, we describe the trend toward more robust linkages by highlighting the design, synthesis, and properties of several recent examples. Finally, the continued development of new COF chemistries, along with improved understanding of their formation and control ofmore » their final form, will provide a means to harness their molecularly precise solidstate structures for useful purposes.« less

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.

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.

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

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

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 .

Development and evaluation of an instrumented linkage system for total knee surgery.

PubMed

Walker, Peter S; Wei, Chih-Shing; Forman, Rachel E; Balicki, M A

2007-10-01

The principles and application of total knee surgery using optical tracking have been well demonstrated, but electromagnetic tracking may offer further advantages. We asked whether an instrumented linkage that attaches directly to the bone can maintain the accuracy of the optical and electromagnetic systems but be quicker, more convenient, and less expensive to use. Initial testing using a table-mounted digitizer to navigate a drill guide for placing pins to mount a cutting guide demonstrated the feasibility in terms of access and availability. A first version (called the Mark 1) instrumented linkage designed to fix directly to the bone was constructed and software was written to carry out a complete total knee replacement procedure. The results showed the system largely fulfilled these goals, but some surgeons found that using a visual display for pin placement was difficult and time consuming. As a result, a second version of a linkage system (called the K-Link) was designed to further develop the concept. User-friendly flexible software was developed for facilitating each step quickly and accurately while the placement of cutting guides was facilitated. We concluded that an instrumented linkage system could be a useful and potentially lower-cost option to the current systems for total knee replacement and could possibly have application to other surgical procedures.

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.

Upland Forest Linkages to Seasonal Wetlands: Litter Flux, Processing, and Food Quality

Treesearch

Brian J. Palik; Darold P. Batzer; Christel Kern

2005-01-01

The flux of materials across ecosystem boundaries has significant effects on recipient systems. Because of edge effects, seasonal wetlands in upland forest are good systems to explore these linkages. The purpose of this study was to examine flux of coarse particulate organic matter as litter fall into seasonal wetlands in Minnesota, and the relationship of this flux to...

Toward Efficient Enzymes for the Generation of Universal Blood through Structure-Guided Directed Evolution.

PubMed

Kwan, David H; Constantinescu, Iren; Chapanian, Rafi; Higgins, Melanie A; Kötzler, Miriam P; Samain, Eric; Boraston, Alisdair B; Kizhakkedathu, Jayachandran N; Withers, Stephen G

2015-05-06

Blood transfusions are critically important in many medical procedures, but the presence of antigens on red blood cells (RBCs, erythrocytes) means that careful blood-typing must be carried out prior to transfusion to avoid adverse and sometimes fatal reactions following transfusion. Enzymatic removal of the terminal N-acetylgalactosamine or galactose of A- or B-antigens, respectively, yields universal O-type blood, but is inefficient. Starting with the family 98 glycoside hydrolase from Streptococcus pneumoniae SP3-BS71 (Sp3GH98), which cleaves the entire terminal trisaccharide antigenic determinants of both A- and B-antigens from some of the linkages on RBC surface glycans, through several rounds of evolution, we developed variants with vastly improved activity toward some of the linkages that are resistant to cleavage by the wild-type enzyme. The resulting enzyme effects more complete removal of blood group antigens from cell surfaces, demonstrating the potential for engineering enzymes to generate antigen-null blood from donors of various types.

Opportunities and challenges for real-world studies on chronic inflammatory joint diseases through data enrichment and collaboration between national registers: the Nordic example

PubMed Central

Chatzidionysiou, Katerina; Hetland, Merete Lund; Frisell, Thomas; Di Giuseppe, Daniela; Hellgren, Karin; Glintborg, Bente; Nordström, Dan; Aaltonen, Kalle; Törmänen, Minna RK; Klami Kristianslund, Eirik; Kvien, Tore K; Provan, Sella A; Guðbjörnsson, Bjorn; Dreyer, Lene; Kristensen, Lars Erik; Jørgensen, Tanja Schjødt; Jacobsson, Lennart; Askling, Johan

2018-01-01

There are increasing needs for detailed real-world data on rheumatic diseases and their treatments. Clinical register data are essential sources of information that can be enriched through linkage to additional data sources such as national health data registers. Detailed analyses call for international collaborative observational research to increase the number of patients and the statistical power. Such linkages and collaborations come with legal, logistic and methodological challenges. In collaboration between registers of inflammatory arthritides in Sweden, Denmark, Norway, Finland and Iceland, we plan to enrich, harmonise and standardise individual data repositories to investigate analytical approaches to multisource data, to assess the viability of different logistical approaches to data protection and sharing and to perform collaborative studies on treatment effectiveness, safety and health-economic outcomes. This narrative review summarises the needs and potentials and the challenges that remain to be overcome in order to enable large-scale international collaborative research based on clinical and other types of data. PMID:29682328

Violent Victimization Among Disadvantaged Young Adults Exposed to Early Family Conflict and Abuse: A 24-Year Prospective Study of the Victimization Cycle Across Gender.

PubMed

Voith, Laura A; Topitzes, James; Reynolds, Arthur J

2016-01-01

Significant associations between childhood victimization and later revictimization have materialized in previous literature; yet, the victimization cycle has been primarily explored with indicators of sexual assault, although insight into linkages between other forms of victimization remains limited. This study examined connections from family conflict exposure and physical abuse in childhood to violent crime victimization in adulthood, assessing also gender differences and neighborhood influences. Results from logistic regression and hierarchical linear modeling with data from the Chicago Longitudinal Study, a panel of 1,539 low-income, ethnic/racial minority children, unearthed a significant relation between family conflict exposure and later revictimization. Moderated by gender, these analyses showed girls exposed to frequent family conflict are particularly vulnerable to revictimization in adulthood. Exploratory analyses unveiled a potential linkage between childhood physical abuse and later revictimization for men. Neighborhood effects marginally influenced results in one instance. Public health implications are discussed.

Solid-Phase Synthesis of RNA Analogs Containing Phosphorodithioate Linkages.

PubMed

Yang, Xianbin

2017-09-18

The oligoribonucleotide phosphorodithioate (PS2-RNA) modification uses two sulfur atoms to replace two non-bridging oxygen atoms at an internucleotide phosphorodiester backbone linkage. Like a natural phosphodiester RNA backbone linkage, a PS2-modified backbone linkage is achiral at phosphorus. PS2-RNAs are highly stable to nucleases and several in vitro assays have demonstrated their biological activity. For example, PS2-RNAs silenced mRNA in vitro and bound to protein targets in the form of PS2-aptamers (thioaptamers). Thus, the interest in and promise of PS2-RNAs has drawn attention to synthesizing, isolating, and characterizing these compounds. RNA-thiophosphoramidite monomers are commercially available from AM Biotechnologies and this unit describes an effective methodology for solid-phase synthesis, deprotection, and purification of RNAs having PS2 internucleotide linkages. © 2017 by John Wiley & Sons, Inc. Copyright © 2017 John Wiley & Sons, Inc.

A Novel Patient Recruitment Strategy: Patient Selection Directly from the Community through Linkage to Clinical Data.

PubMed

Zimmerman, Lindsay P; Goel, Satyender; Sathar, Shazia; Gladfelter, Charon E; Onate, Alejandra; Kane, Lindsey L; Sital, Shelly; Phua, Jasmin; Davis, Paris; Margellos-Anast, Helen; Meltzer, David O; Polonsky, Tamar S; Shah, Raj C; Trick, William E; Ahmad, Faraz S; Kho, Abel N

2018-01-01

This article presents and describes our methods in developing a novel strategy for recruitment of underrepresented, community-based participants, for pragmatic research studies leveraging routinely collected electronic health record (EHR) data. We designed a new approach for recruiting eligible patients from the community, while also leveraging affiliated health systems to extract clinical data for community participants. The strategy involves methods for data collection, linkage, and tracking. In this workflow, potential participants are identified in the community and surveyed regarding eligibility. These data are then encrypted and deidentified via a hashing algorithm for linkage of the community participant back to a record at a clinical site. The linkage allows for eligibility verification and automated follow-up. Longitudinal data are collected by querying the EHR data and surveying the community participant directly. We discuss this strategy within the context of two national research projects, a clinical trial and an observational cohort study. The community-based recruitment strategy is a novel, low-touch, clinical trial enrollment method to engage a diverse set of participants. Direct outreach to community participants, while utilizing EHR data for clinical information and follow-up, allows for efficient recruitment and follow-up strategies. This new strategy for recruitment links data reported from community participants to clinical data in the EHR and allows for eligibility verification and automated follow-up. The workflow has the potential to improve recruitment efficiency and engage traditionally underrepresented individuals in research. Schattauer GmbH Stuttgart.

The Genetic Linkage Map of the Medicinal Mushroom Agaricus subrufescens Reveals Highly Conserved Macrosynteny with the Congeneric Species Agaricus bisporus

PubMed Central

Foulongne-Oriol, Marie; Rocha de Brito, Manuela; Cabannes, Delphine; Clément, Aurélien; Spataro, Cathy; Moinard, Magalie; Dias, Eustáquio Souza; Callac, Philippe; Savoie, Jean-Michel

2016-01-01

Comparative linkage mapping can rapidly facilitate the transfer of genetic information from model species to orphan species. This macrosynteny analysis approach has been extensively used in plant species, but few example are available in fungi, and even fewer in mushroom crop species. Among the latter, the Agaricus genus comprises the most cultivable or potentially cultivable species. Agaricus bisporus, the button mushroom, is the model for edible and cultivable mushrooms. We have developed the first genetic linkage map for the basidiomycete A. subrufescens, an emerging mushroom crop known for its therapeutic properties and potential medicinal applications. The map includes 202 markers distributed over 16 linkage groups (LG), and covers a total length of 1701 cM, with an average marker spacing of 8.2 cM. Using 96 homologous loci, we also demonstrated the high level of macrosynteny with the genome of A. bisporus. The 13 main LG of A. subrufescens were syntenic to the 13 A. bisporus chromosomes. A disrupted synteny was observed for the three remaining A. subrufescens LG. Electronic mapping of a collection of A. subrufescens expressed sequence tags on A. bisporus genome showed that the homologous loci were evenly spread, with the exception of a few local hot or cold spots of homology. Our results were discussed in the light of Agaricus species evolution process. The map provides a framework for future genetic or genomic studies of the medicinal mushroom A. subrufescens. PMID:26921302

Cointegration and causal linkages in fertilizer markets across different regimes

NASA Astrophysics Data System (ADS)

Lahmiri, Salim

2017-04-01

Cointegration and causal linkages among five different fertilizer markets are investigated during low and high market regimes. The database includes prices of rock phosphate (RP), triple super phosphate (TSP), diammonium phosphate (DAP), urea, and potassium chloride (PC). It is found that fertilizer markets are closely linked to each other during low and high regimes; and, particularly during high regime (after 2007 international financial crisis). In addition, there is no evidence of bidirectional linear relationship between markets during low and high regime time periods. Furthermore, all significant linkages are only unidirectional. Moreover, some causality effects have emerged during high regime. Finally, the effect of an impulse during high regime time period persists longer and is stronger than the effect of an impulse during low regime time period (before 2007 international financial crisis).

Drought susceptibility of modern rice varieties: an effect of linkage of drought tolerance with undesirable traits

PubMed Central

Vikram, Prashant; Swamy, B. P. Mallikarjuna; Dixit, Shalabh; Singh, Renu; Singh, Bikram P.; Miro, Berta; Kohli, Ajay; Henry, Amelia; Singh, N. K.; Kumar, Arvind

2015-01-01

Green Revolution (GR) rice varieties are high yielding but typically drought sensitive. This is partly due to the tight linkage between the loci governing plant height and drought tolerance. This linkage is illustrated here through characterization of qDTY1.1, a QTL for grain yield under drought that co-segregates with the GR gene sd1 for semi-dwarf plant height. We report that the loss of the qDTY1.1 allele during the GR was due to its tight linkage in repulsion with the sd1 allele. Other drought-yield QTLs (qDTY) also showed tight linkage with traits rejected in GR varieties. Genetic diversity analysis for 11 different qDTY regions grouped GR varieties separately from traditional drought-tolerant varieties, and showed lower frequency of drought tolerance alleles. The increased understanding and breaking of the linkage between drought tolerance and undesirable traits has led to the development of high-yielding drought-tolerant dwarf lines with positive qDTY alleles and provides new hope for extending the benefits of the GR to drought-prone rice-growing regions. PMID:26458744

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

A new model of care collaboration for community-dwelling elders: findings and lessons learned from the NORC-Health Care linkage evaluation

PubMed Central

Kyriacou, Corinne; Vladeck, Fredda

2011-01-01

Introduction and background Few financial incentives in the United States encourage coordination across the health and social care systems. Supportive Service Programs (SSPs), operating in Naturally Occurring Retirement Communities (NORCs), attempt to increase access to care and enhance care quality for aging residents. This article presents findings from an evaluation conducted from 2004 to 2006 looking at the feasibility, quality and outcomes of linking health and social services through innovative NORC-SSP and health organization micro-collaborations. Methods Four NORC-SSPs participated in the study by finding a health care organization or community-based physicians to collaborate with on addressing health conditions that could benefit from a biopsychosocial approach. Each site focused on a specific population, addressed a specific condition or problem, and created different linkages to address the target problem. Using a case study approach, incorporating both qualitative and quantitative methods, this evaluation sought to answer the following two primary questions: 1) Have the participating sites created viable linkages between their organizations that did not exist prior to the study; and, 2) To what extent have the linkages resulted in improvements in clinical and other health and social outcomes? Results Findings suggest that immediate outcomes were widely achieved across sites: knowledge of other sector providers’ capabilities and services increased; communication across providers increased; identification of target population increased; and, awareness of risks, symptoms and health seeking behaviors among clients/patients increased. Furthermore, intermediate outcomes were also widely achieved: shared care planning, continuity of care, disease management and self care among clients improved. Evidence of improvements in distal outcomes was also found. Discussion Using simple, familiar and relatively low-tech approaches to sharing critical patient information among collaborating organizations, inter-sector linkages were successfully established at all four sites. Seven critical success factors emerged that increase the likelihood that linkages will be implemented, effective and sustained: 1) careful goal selection; 2) meaningful collaboration; 3) appropriate role for patients/clients; 4) realistic interventions; 5) realistic expectations for implementation environment; 6) continuous focus on outcomes; and, 7) stable leadership. Focused, micro-level collaborations have the potential to improve care, increasing the chance that organizations will undertake such endeavors. PMID:21637704

Orientations of Pre-existing Structures along the Scarp of the Bilila-Mtakataka Fault in the Central Malawi Rift.

NASA Astrophysics Data System (ADS)

Elifritz, E. A.; Johnson, S.; Beresh, S. C. M.; Mendez, K.; Mynatt, W. G.; Mayle, M.; Laó-Dávila, D. A.; Atekwana, E. A.; Chindandali, P. R. N.; Chisenga, C.; Gondwe, S.; Mkumbwa, M.; Kalindekafe, L.; Kalaguluka, D.; Salima, J.

2017-12-01

The NW-SE Bilila-Mtakataka Fault is suggested to be 100 km in length and is located in the Malawi Rift, a portion of the magma-poor Western Branch of the East African Rift System. This fault is exposed south of Lake Malawi and occurs close to the epicenter of the 1989 6.2 magnitude Salima Earthquake. Moreover, it traverses rocks with inherited Precambrian fabrics that may control the modern rifting process. The effect of the orientation of the pre-existing fabric on the formation of this potentially seismogenic fault has not been well studied. In this project, we measured the older foliations, dikes, and joints in addition to younger faults and striations to understand how the active faulting of the Bilila-Mtakataka Fault is affected by the older fabric. The Fault is divided into 5 segments and 4 linkage zones. All four linkage zones were studied in detail and a Brunton compass was used to determine orientations of structures. The linkage zone between segments 1 and 2 occurs between a regional WNW-ESE joint and the border fault, which is identified by a zig-zag pattern in SRTM data. Precambrian gneiss is cut by oblique steeply-dipping faults in this area. Striations and layer offsets suggest both right-lateral and normal components. This segment strikes NE-SW, in contrast with the NW-SE average strike of the entire fault. The foliations, faults, dikes, and joints collected in this area strike NE-SW, therefore running parallel to the segment. The last 3 southern linkage zones all strike NW-SE and the linkage zone between segment 3 and 4 has a steep dip angle. Dip angles of structures vary from segment to segment, having a wide range of results. Nonetheless, all four linkage zones show structures striking parallel to its segment direction. The results show that pre-existing meso-scale and regional structures and faults strike parallel to the fault scarp. The parallelism of the structures suggest that they serve as planes of weakness, controlling the localization of extension expressed as the border fault. Thus, further studies of the Precambrian foliation in the subsurface are necessary to understand the characterization of the fault where it is unexposed at depth.

Growing and navigating the small world Web by local content

PubMed Central

Menczer, Filippo

2002-01-01

Can we model the scale-free distribution of Web hypertext degree under realistic assumptions about the behavior of page authors? Can a Web crawler efficiently locate an unknown relevant page? These questions are receiving much attention due to their potential impact for understanding the structure of the Web and for building better search engines. Here I investigate the connection between the linkage and content topology of Web pages. The relationship between a text-induced distance metric and a link-based neighborhood probability distribution displays a phase transition between a region where linkage is not determined by content and one where linkage decays according to a power law. This relationship is used to propose a Web growth model that is shown to accurately predict the distribution of Web page degree, based on textual content and assuming only local knowledge of degree for existing pages. A qualitatively similar phase transition is found between linkage and semantic distance, with an exponential decay tail. Both relationships suggest that efficient paths can be discovered by decentralized Web navigation algorithms based on textual and/or categorical cues. PMID:12381792

Growing and navigating the small world Web by local content

NASA Astrophysics Data System (ADS)

Menczer, Filippo

2002-10-01

Can we model the scale-free distribution of Web hypertext degree under realistic assumptions about the behavior of page authors? Can a Web crawler efficiently locate an unknown relevant page? These questions are receiving much attention due to their potential impact for understanding the structure of the Web and for building better search engines. Here I investigate the connection between the linkage and content topology of Web pages. The relationship between a text-induced distance metric and a link-based neighborhood probability distribution displays a phase transition between a region where linkage is not determined by content and one where linkage decays according to a power law. This relationship is used to propose a Web growth model that is shown to accurately predict the distribution of Web page degree, based on textual content and assuming only local knowledge of degree for existing pages. A qualitatively similar phase transition is found between linkage and semantic distance, with an exponential decay tail. Both relationships suggest that efficient paths can be discovered by decentralized Web navigation algorithms based on textual and/or categorical cues.

Growing and navigating the small world Web by local content.

PubMed

Menczer, Filippo

2002-10-29

Can we model the scale-free distribution of Web hypertext degree under realistic assumptions about the behavior of page authors? Can a Web crawler efficiently locate an unknown relevant page? These questions are receiving much attention due to their potential impact for understanding the structure of the Web and for building better search engines. Here I investigate the connection between the linkage and content topology of Web pages. The relationship between a text-induced distance metric and a link-based neighborhood probability distribution displays a phase transition between a region where linkage is not determined by content and one where linkage decays according to a power law. This relationship is used to propose a Web growth model that is shown to accurately predict the distribution of Web page degree, based on textual content and assuming only local knowledge of degree for existing pages. A qualitatively similar phase transition is found between linkage and semantic distance, with an exponential decay tail. Both relationships suggest that efficient paths can be discovered by decentralized Web navigation algorithms based on textual and/or categorical cues.

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.

HealthNavigator: a mobile application for chronic disease screening and linkage to services at an urban Primary Health Network.

PubMed

Seneviratne, Martin G; Hersch, Fred; Peiris, David P

2018-03-26

Mobile applications (apps) are promising tools to support chronic disease screening and linkage to health services. They have the potential to increase healthcare access for vulnerable populations. The HealthNavigator app was developed to provide chronic disease risk assessments, linkage to local general practitioners (GPs) and lifestyle programs, and a personalised health report for discussion with a GP. Assessments were either self-administered or facilitated by community health workers through a Primary Health Network (PHN) initiative targeting ethnically diverse communities. In total, 1492 assessments (80.4% self-administered, 19.6% facilitated) were conducted over a 12-month period in Queensland, Australia. Of these, 26% of people screened came from postcodes representing the lowest quartile of socioeconomic disadvantage. When compared against self-administered assessments, subjects screened by the facilitated program were more likely to be born outside Australia (80.5 v. 33.2%, P<0.001), and to fall within a high risk category based on cardiovascular risk scores (19.8 v. 13.7%, P<0.01) and type 2 diabetes mellitus risk scores (58.0 v. 40.1%, P<0.001). Mobile apps embedded into PHN programs may be a useful adjunct for the implementation of community screening programs. Further research is needed to determine their effect on health service access and health outcomes.

Surface engineering of macrophages with nanoparticles to generate a cell-nanoparticle hybrid vehicle for hypoxia-targeted drug delivery.

PubMed

Holden, Christopher A; Yuan, Quan; Yeudall, W Andrew; Lebman, Deborah A; Yang, Hu

2010-02-02

Tumors frequently contain hypoxic regions that result from a shortage of oxygen due to poorly organized tumor vasculature. Cancer cells in these areas are resistant to radiation- and chemotherapy, limiting the treatment efficacy. Macrophages have inherent hypoxia-targeting ability and hold great advantages for targeted delivery of anticancer therapeutics to cancer cells in hypoxic areas. However, most anticancer drugs cannot be directly loaded into macrophages because of their toxicity. In this work, we designed a novel drug delivery vehicle by hybridizing macrophages with nanoparticles through cell surface modification. Nanoparticles immobilized on the cell surface provide numerous new sites for anticancer drug loading, hence potentially minimizing the toxic effect of anticancer drugs on the viability and hypoxia-targeting ability of the macrophage vehicles. In particular, quantum dots and 5-(aminoacetamido) fluorescein-labeled polyamidoamine dendrimer G4.5, both of which were coated with amine-derivatized polyethylene glycol, were immobilized to the sodium periodate-treated surface of RAW264.7 macrophages through a transient Schiff base linkage. Further, a reducing agent, sodium cyanoborohydride, was applied to reduce Schiff bases to stable secondary amine linkages. The distribution of nanoparticles on the cell surface was confirmed by fluorescence imaging, and it was found to be dependent on the stability of the linkages coupling nanoparticles to the cell surface.

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.

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

Enhanced reporting of deaths among Aboriginal and Torres Strait Islander peoples using linked administrative health datasets.

PubMed

Taylor, Lee K; Bentley, Jason; Hunt, Jennifer; Madden, Richard; McKeown, Sybille; Brandt, Peter; Baker, Deborah

2012-07-02

Aboriginal and Torres Strait Islander peoples are under-reported in administrative health datasets in NSW, Australia. Correct reporting of Aboriginal and Torres Strait Islander peoples is essential to measure the effectiveness of policies and programmes aimed at reducing the health disadvantage experienced by Aboriginal and Torres Strait Islander peoples. This study investigates the potential of record linkage to enhance reporting of deaths among Aboriginal and Torres Strait Islander peoples in NSW, Australia. Australian Bureau of Statistics death registration data for 2007 were linked with four population health datasets relating to hospitalisations, emergency department attendances and births. Reporting of deaths was enhanced from linked records using two methods, and effects on patterns of demographic characteristics and mortality indicators were examined. Reporting of deaths increased by 34.5% using an algorithm based on a weight of evidence of a person being Aboriginal or Torres Strait Islander, and by 56.6% using an approach based on 'at least one report' of a person being Aboriginal or Torres Strait Islander. The increase was relatively greater in older persons and those living in less geographically remote areas. Enhancement resulted in a reduction in the urban-remote differential in median age at death and increases in standardised mortality ratios particularly for chronic conditions. Record linkage creates a statistical construct that helps to correct under-reporting of deaths and potential bias in mortality statistics for Aboriginal and Torres Strait Islander peoples.

Some Aspects of Thermal Transport across the Interface between Graphene and Epoxy in Nanocomposites.

PubMed

Wang, Yu; Yang, Chunhui; Pei, Qing-Xiang; Zhang, Yingyan

2016-03-01

Owing to the superior thermal properties of graphene, graphene-reinforced polymer nanocomposites hold great potential as the thermal interface materials (TIMs) dissipating heat for electronic packages. However, this application is greatly hindered by the high thermal resistance at the interface between graphene and polymer. In this paper, some important aspects of the improvement of the thermal transport across the interface between graphene and epoxy in graphene-epoxy nanocomposites, including the effectiveness of covalent and noncovalent functionalization, isotope doping, and acetylenic linkage in graphene are systematically investigated using molecular dynamics (MD) simulations. The simulation results show that the covalent and noncovalent functionalization techniques could considerably reduce the graphene-epoxy interfacial thermal resistance in the nanocomposites. Among different covalent functional groups, butyl is more effective than carboxyl and hydroxyl in reducing the interfacial thermal resistance. Different noncovalent functional molecules, including 1-pyrenebutyl, 1-pyrenebutyric acid, and 1-pyrenebutylamine, yield a similar amount of reductions. Moreover, it is found that the graphene-epoxy interfacial thermal resistance is insensitive to the carbon isotope doping in graphene, while it can be reduced moderately by replacing the sp(2) bonds in graphene with acetylenic linkages.

Spatial and seasonal patterns in stream water contamination across mountainous watersheds: Linkage with landscape characteristics

NASA Astrophysics Data System (ADS)

Ai, L.; Shi, Z. H.; Yin, W.; Huang, X.

2015-04-01

Landscape characteristics are widely accepted as strongly influencing stream water quality in heterogeneous watersheds. Understanding the relationships between landscape and specific water contaminant can greatly improve the predictability of potential contamination and the assessment of contaminant export. In this work, we examined the combined effects of watershed complexity, in terms of land use and physiography, on specific water contaminant across watersheds close to the Danjiangkou Reservoir. The land use composition, land use pattern, morphometric variables and soil properties were calculated at the watershed scale and considered potential factors of influence. Due to high co-dependence of these watershed characteristics, partial least squares regression was used to elucidate the linkages between some specific water contaminants and the 16 selected watershed characteristic variables. Water contaminant maps revealed spatial and seasonal heterogeneity. The dissolved oxygen values in the dry season were higher than those in the wet season, whereas the other contaminant concentrations displayed the opposite trend. The studied watersheds which are influenced strongly by urbanization, showed higher levels of ammonia nitrogen, total phosphorus, potassium permanganate index and petroleum, and lower levels of dissolved oxygen. The urban land use, largest patch index and the hypsometric integral were the dominant factors affecting specific water contaminant.

Avoiding false discoveries in association studies.

PubMed

Sabatti, Chiara

2007-01-01

We consider the problem of controlling false discoveries in association studies. We assume that the design of the study is adequate so that the "false discoveries" are potentially only because of random chance, not to confounding or other flaws. Under this premise, we review the statistical framework for hypothesis testing and correction for multiple comparisons. We consider in detail the currently accepted strategies in linkage analysis. We then examine the underlying similarities and differences between linkage and association studies and document some of the most recent methodological developments for association mapping.

Exome sequencing of a large family identifies potential candidate genes contributing risk to bipolar disorder.

PubMed

Zhang, Tianxiao; Hou, Liping; Chen, David T; McMahon, Francis J; Wang, Jen-Chyong; Rice, John P

2018-03-01

Bipolar disorder is a mental illness with lifetime prevalence of about 1%. Previous genetic studies have identified multiple chromosomal linkage regions and candidate genes that might be associated with bipolar disorder. The present study aimed to identify potential susceptibility variants for bipolar disorder using 6 related case samples from a four-generation family. A combination of exome sequencing and linkage analysis was performed to identify potential susceptibility variants for bipolar disorder. Our study identified a list of five potential candidate genes for bipolar disorder. Among these five genes, GRID1(Glutamate Receptor Delta-1 Subunit), which was previously reported to be associated with several psychiatric disorders and brain related traits, is particularly interesting. Variants with functional significance in this gene were identified from two cousins in our bipolar disorder pedigree. Our findings suggest a potential role for these genes and the related rare variants in the onset and development of bipolar disorder in this one family. Additional research is needed to replicate these findings and evaluate their patho-biological significance. Copyright © 2017 Elsevier B.V. All rights reserved.

HIV self-testing in Peru: questionable availability, high acceptability but potential low linkage to care among men who have sex with men and transgender women.

PubMed

Bustamante, Maria Jose; Konda, Kelika A; Joseph Davey, Dvora; León, Segundo R; Calvo, Gino M; Salvatierra, Javier; Brown, Brandon; Caceres, Carlos F; Klausner, Jeffrey D

2017-02-01

HIV status awareness is key to prevention, linkage-to-care and treatment. Our study evaluated the accessibility and potential willingness of HIV self-testing among men who have sex with men (MSM) and transgender women in Peru. We surveyed four pharmacy chains in Peru to ascertain the commercial availability of the oral HIV self-test. The pharmacies surveyed confirmed that HIV self-test kits were available; however, those available were not intended for individual use, but for clinician use. We interviewed 147 MSM and 45 transgender women; nearly all (82%) reported willingness to perform the oral HIV self-test. However, only 55% of participants would definitely seek a confirmatory test in a clinic after an HIV-positive test result. Further, price may be a barrier, as HIV self-test kits were available for 18 USD, and MSM and transgender women were only willing to pay an average of 5 USD. HIV self-testing may facilitate increased access to HIV testing among some MSM/transgender women in Peru. However, price may prevent use, and poor uptake of confirmatory testing may limit linkage to HIV treatment and care.

A Homozygous TPO Gene Duplication (c.1184_1187dup4) Causes Congenital Hypothyroidism in Three Siblings Born to a Consanguineous Family

PubMed Central

Cangul, Hakan; Aydin, Banu K.; Bas, Firdevs

2015-01-01

Congenital hypothyroidism (CH) is the most common neonatal endocrine disease, and germ-line mutations in the TPO gene cause the inherited form of the disease. Our aim in this study was to determine the genetic basis of congenital hypothyroidism in three affected children coming from a consanguineous Turkish family. Because CH is usually inherited in autosomal recessive manner in consanguineous/multicase families, we adopted a two-stage strategy of genetic linkage studies and targeted sequencing of the candidate genes. First, we investigated the potential genetic linkage of the family to any known CH locus, using microsatellite markers, and then screened for mutations in linked-gene by conventional sequencing. The family showed potential linkage to the TPO gene and we detected a homozygous duplication (c.1184_1187dup4) in all cases. The mutation segregated with disease status in the family. This study confirms the pathogenicity of the c.1184_1187dup4 mutation in the TPO gene and helps establish a genotype/phenotype correlation associated with this mutation. It also highlights the importance of molecular genetic studies in the definitive diagnosis and accurate classification of CH. PMID:27617131

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.

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 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

Teaching Principles of Linkage and Gene Mapping with the Tomato.

ERIC Educational Resources Information Center

Hawk, James A.; And Others

1980-01-01

A three-point linkage system in tomatoes is used to explain concepts of gene mapping, linking and statistical analysis. The system is designed for teaching the effective use of statistics, and the power of genetic analysis from statistical analysis of phenotypic ratios. (Author/SA)

Developing Telecommunication Linkages for Microcomputer-Aided Instruction. TDC Research Report No. 1.

ERIC Educational Resources Information Center

Blinn, Charles R.; And Others

A project undertaken at the University of Minnesota evaluated two microcomputer teletraining systems (audiographic conferencing) to determine the effectiveness of this technology for point-to-point and multipoint distance education. System design requirements included broadcast keystrokes, error checking, master-slave linkages, simultaneous voice…

An improved recommendation algorithm via weakening indirect linkage effect

NASA Astrophysics Data System (ADS)

Chen, Guang; Qiu, Tian; Shen, Xiao-Quan

2015-07-01

We propose an indirect-link-weakened mass diffusion method (IMD), by considering the indirect linkage and the source object heterogeneity effect in the mass diffusion (MD) recommendation method. Experimental results on the MovieLens, Netflix, and RYM datasets show that, the IMD method greatly improves both the recommendation accuracy and diversity, compared with a heterogeneity-weakened MD method (HMD), which only considers the source object heterogeneity. Moreover, the recommendation accuracy of the cold objects is also better elevated in the IMD than the HMD method. It suggests that eliminating the redundancy induced by the indirect linkages could have a prominent effect on the recommendation efficiency in the MD method. Project supported by the National Natural Science Foundation of China (Grant No. 11175079) and the Young Scientist Training Project of Jiangxi Province, China (Grant No. 20133BCB23017).

The effect of missing data on linkage disequilibrium mapping and haplotype association analysis in the GAW14 simulated datasets

PubMed Central

McCaskie, Pamela A; Carter, Kim W; McCaskie, Simon R; Palmer, Lyle J

2005-01-01

We used our newly developed linkage disequilibrium (LD) plotting software, JLIN, to plot linkage disequilibrium between pairs of single-nucleotide polymorphisms (SNPs) for three chromosomes of the Genetic Analysis Workshop 14 Aipotu simulated population to assess the effect of missing data on LD calculations. Our haplotype analysis program, SIMHAP, was used to assess the effect of missing data on haplotype-phenotype association. Genotype data was removed at random, at levels of 1%, 5%, and 10%, and the LD calculations and haplotype association results for these levels of missingness were compared to those for the complete dataset. It was concluded that ignoring individuals with missing data substantially affects the number of regions of LD detected which, in turn, could affect tagging SNPs chosen to generate haplotypes. PMID:16451612

Rigid aromatic linking moiety in cationic lipids for enhanced gene transfection efficiency.

PubMed

Wang, Bing; Zhao, Rui-Mo; Zhang, Ji; Liu, Yan-Hong; Huang, Zheng; Yu, Qing-Ying; Yu, Xiao-Qi

2017-08-18

Although numerous cationic lipids have been developed as non-viral gene vectors, the structure-activity relationship (SAR) of these materials remains unclear and needs further investigation. In this work, a series of lysine-derived cationic lipids containing linkages with different rigidity were designed and synthesized. SAR studies showed that lipids with rigid aromatic linkage could promote the formation of tight liposomes and enhance DNA condensation, which is essential for the gene delivery process. These lipids could give much higher transfection efficiency than those containing more flexible aliphatic linkage in various cell lines. Moreover, the rigid aromatic linkage also affords the material higher serum tolerance ability. Flow cytometry assay revealed that the target lipids have good cellular uptake, while confocal microscopy observation showed weaker endosome escape than Lipofectamine 2000. To solve such problem and further increase the transfection efficiency, some lysosomotropic reagents were used to improve the endosome escape of lipoplex. As expected, higher transfection efficiency than Lipofectamine 2000 could be obtained via this strategy. Cytotoxicity assay showed that these lipids have lower toxicity in various cell lines than Lipofectamine 2000, suggesting their potential for further application. This work demonstrates that a rigid aromatic linkage might distinctly improve the gene transfection abilities of cationic lipids and affords information to construct safe and efficient gene vector towards practical application. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Genome-Wide Linkage and Association Analysis Identifies Major Gene Loci for Guttural Pouch Tympany in Arabian and German Warmblood Horses

PubMed Central

Metzger, Julia; Ohnesorge, Bernhard; Distl, Ottmar

2012-01-01

Equine guttural pouch tympany (GPT) is a hereditary condition affecting foals in their first months of life. Complex segregation analyses in Arabian and German warmblood horses showed the involvement of a major gene as very likely. Genome-wide linkage and association analyses including a high density marker set of single nucleotide polymorphisms (SNPs) were performed to map the genomic region harbouring the potential major gene for GPT. A total of 85 Arabian and 373 German warmblood horses were genotyped on the Illumina equine SNP50 beadchip. Non-parametric multipoint linkage analyses showed genome-wide significance on horse chromosomes (ECA) 3 for German warmblood at 16–26 Mb and 34–55 Mb and for Arabian on ECA15 at 64–65 Mb. Genome-wide association analyses confirmed the linked regions for both breeds. In Arabian, genome-wide association was detected at 64 Mb within the region with the highest linkage peak on ECA15. For German warmblood, signals for genome-wide association were close to the peak region of linkage at 52 Mb on ECA3. The odds ratio for the SNP with the highest genome-wide association was 0.12 for the Arabian. In conclusion, the refinement of the regions with the Illumina equine SNP50 beadchip is an important step to unravel the responsible mutations for GPT. PMID:22848553

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.

Untied Efforts: The Challenges for Improved Research, Extension and Education Linkages

ERIC Educational Resources Information Center

Eneyew, Adugna

2013-01-01

Ethiopian agriculture is characterized by smallholders farming whose access to modern technology and basic education is very limited. Research, extension, education and farmers are the main pillars of agricultural knowledge systems and their effectiveness largely depends on strong linkage among each other. However, the existing…

University-Industry Linkages in Developing Countries: Perceived Effect on Innovation

ERIC Educational Resources Information Center

Vaaland, Terje I.; Ishengoma, Esther

2016-01-01

Purpose: The purpose of this paper is to assess the perceptions of both universities and the resource-extractive companies on the influence of university-industry linkages (UILs) on innovation in a developing country. Design/Methodology/Approach: A total of 404 respondents were interviewed. Descriptive analysis and multinomial logistic regression…

MEETING IN PORTUGAL: LINKAGE OF EXPOSURE AND EFFECTS USING GENOMICS, PROTEOMICS AND METABOLOMICS IN SMALL FISH MODELS

EPA Science Inventory

With an interdisciplinary team of scientists from U.S. Government Agencies and Universities, we are utilizing zebrafish and fathead minnow to develop techniques for extrapolation of chemical stressor impacts across species, chemicals and endpoints. The linkage of responses acros...

Stakeholder perceptions of Environmental Management Plans as an environmental protection tool for major developments in the UK

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

Bennett, Sophie; Kemp, Simon; Hudson, Malcolm D., E-mail: mdh@soton.ac.uk

Insufficient implementation and the lack of legislative requirements for follow-up measures following the approval of projects are consistently highlighted as major shortcomings of Environmental Impact Assessment (EIA). Although adopted over 15 years ago by the World Bank, Environmental Management Plans (EMPs) were only semi-formalised in the UK in 2008 and arguably provide a continuous link or ‘bridge’ between the EIA process pre-consent and an Environmental Management System (EMS) post-consent. Drawing on twenty-one semi-structured interviews with stakeholders and thematic analysis of their responses, and a broad-scale practitioner survey, this study aimed to assess the effectiveness of EMPs as an environmental protectionmore » tool across the project lifecycle for major developments. The findings revealed a mixed picture of EMP effectiveness in practice, with EMPs only partially fulfilling a bridging role between EIA and EMS. There is no ‘gold standard’ terminology for EMPs, all having slightly different uses, thus presenting different focuses to different stakeholders and further enhancing variation in practice. For many stakeholders, the effectiveness was simply not known, due to the lack of communication and follow-up that still exists. EMP–EMS linkages were shown to be effective from the developer's perspective when a single organisation has involvement across all project phases, though weaknesses occur when multiple parties are involved. Among other stakeholders, knowledge varied significantly; whilst some were in agreement that the linkages worked, many were unaware of the connections and thought of them as two quite separate tools. Stakeholders advocated for the need to make EMPs a legal requirement; for improved communication between stakeholders during EMP implementation and increased documentation of project outcomes; and for EMPs to be consistently written by environmental professionals. Furthermore, weak links in the current process may be improved by providing detailed guidance for organisations on the potential for EMP–EMS linkages, with the additional aim of encouraging stakeholders to broaden their current specialist knowledge on environmental protection tools. - Highlights: • We assessed the effectiveness of Environmental Management Plans (EMPs) for major developments, focusing on delivery of mitigation and monitoring. • EIA and Environmental Management Systems (EMS) post-consent are weakly linked. • The use of EMPs varies significantly in practise, partly due to the range of terminology used. • Linkages are hampered by poor communication and follow-up • More detailed guidance on how EMPs can successfully link with EMS is required.« less

Mitochondrial FAD-glycerophosphate dehydrogenase and G-protein-coupled inwardly rectifying K+ channel: No evidence for linkage in maturity-onset diabetes of the young or NIDDM.

PubMed

Warren-Perry, M G; Stoffel, M; Saker, P J; Zhang, Y; Brown, L J; MacDonald, M J; Turner, R C

1996-05-01

Two genes that have potentially important regulatory roles in insulin secretion are both located on chromosome 2q24.1. G-protein-coupled muscarinic potassium channel (GIRK1) is an inwardly rectifying K+ channel that helps to maintain the resting potential and excitability of cells. Mitochondrial FAD-linked glycerophosphate dehydrogenase (m-GDH) catalyzes a rate-limiting step of the glycerol phosphate shuttle in pancreatic islets. Reduced m-GDH activity has been demonstrated in islets isolated from diabetic subjects compared with islets from nondiabetic control subjects and from the diabetic GK rat. To study the relationship between these candidate genes and NIDDM, we have examined a simple tandem-repeat polymorphism (STRP) close to both the KCN J3 (GIRK1) locus and the m-GDH locus. In a linkage study of three maturity-onset diabetes of the young (MODY) pedigrees, not linked to MODY1, MODY2, or MODY3, a cumulative score of - 9.6 at a recombination fraction of theta = 0 excluded linkage. In a population-association study, no linkage disequilibrium for the STRP was found between 190 unselected NIDDM patients and 60 geographically and age-matched white nondiabetic subjects (chi2 = 1.51 on 3 df, P = 0.68). Thus, mutations involving the genes for GIRK1 or FAD-glycerophosphate dehydrogenase are unlikely to cause MODY, and a common mutation in either gene is unlikely to contribute to NIDDM in whites. These data do not exclude mutations in some families or other ethnic groups.

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.

Linkage mapping of beta 2 EEG waves via non-parametric regression.

PubMed

Ghosh, Saurabh; Begleiter, Henri; Porjesz, Bernice; Chorlian, David B; Edenberg, Howard J; Foroud, Tatiana; Goate, Alison; Reich, Theodore

2003-04-01

Parametric linkage methods for analyzing quantitative trait loci are sensitive to violations in trait distributional assumptions. Non-parametric methods are relatively more robust. In this article, we modify the non-parametric regression procedure proposed by Ghosh and Majumder [2000: Am J Hum Genet 66:1046-1061] to map Beta 2 EEG waves using genome-wide data generated in the COGA project. Significant linkage findings are obtained on chromosomes 1, 4, 5, and 15 with findings at multiple regions on chromosomes 4 and 15. We analyze the data both with and without incorporating alcoholism as a covariate. We also test for epistatic interactions between regions of the genome exhibiting significant linkage with the EEG phenotypes and find evidence of epistatic interactions between a region each on chromosome 1 and chromosome 4 with one region on chromosome 15. While regressing out the effect of alcoholism does not affect the linkage findings, the epistatic interactions become statistically insignificant. Copyright 2003 Wiley-Liss, Inc.

Revealing the role of glutathione S-transferase omega in age-at-onset of Alzheimer and Parkinson diseases.

PubMed

Li, Yi-Ju; Scott, William K; Zhang, Ling; Lin, Ping-I; Oliveira, Sofia A; Skelly, Tara; Doraiswamy, Maurali P; Welsh-Bohmer, Kathleen A; Martin, Eden R; Haines, Jonathan L; Pericak-Vance, Margaret A; Vance, Jeffery M

2006-08-01

We previously reported a linkage region on chromosome 10q for age-at-onset (AAO) of Alzheimer (AD) and Parkinson (PD) diseases. Glutathione S-transferase, omega-1 (GSTO1) and the adjacent gene GSTO2, located in this linkage region, were then reported to associate with AAO of AD and PD. To examine whether GSTO1 and GSTO2 (hereafter referred to as GSTO1h) are responsible for the linkage evidence, we identified 39 families in AD that lead to our previous linkage and association findings. The evidence of linkage and association was markedly diminished after removing these 39 families from the analyses, thus providing support that GSTO1h drives the original linkage results. The maximum average AAO delayed by GSTO1h SNP 7-1 (rs4825, A nucleotide) was 6.8 (+/-4.41) years for AD and 8.6(+/-5.71) for PD, respectively. This is comparable to the magnitude of AAO difference by APOE-4 in these same AD and PD families. These findings suggest the presence of genetic heterogeneity for GSTO1h's effect on AAO, and support GSTO1h's role in modifying AAO in these two disorders.

Understanding the linkages between social safety nets and childhood violence: a review of the evidence from low- and middle-income countries

PubMed Central

Peterman, Amber; Neijhoft, Anastasia (Naomi); Cook, Sarah; Palermo, Tia M

2017-01-01

Abstract As many as one billion children experience violence every year, and household- and community-level poverty are among the risk factors for child protection violations. Social safety nets (SSNs) are a main policy tool to address poverty and vulnerability, and there is substantial evidence demonstrating positive effects on children’s health and human capital. This paper reviews evidence and develops a framework to understand linkages between non-contributory SSNs and the experience of childhood emotional, physical and sexual violence in low- and middle-income countries. We catalogue 14 rigorous impact evaluations, 11 of which are completed, analysing 57 unique impacts on diverse violence indicators. Among these impacts, approximately one in five represent statistically significant protective effects on childhood violence. Promising evidence relates to sexual violence among female adolescents in Africa, while there is less clear evidence of significant impacts in other parts of the developing world, and on young child measures, including violent discipline. Further, few studies are set up to meaningfully unpack mechanisms between SSNs and childhood violence; however, those most commonly hypothesized operate at the household level (through increases in economic security and reductions in poverty-related stress), the interpersonal level (improved parental behaviours, caregiving practices, improved psychosocial well-being) and at the child-level (protective education and decreases in problem or risky behaviours). It is important to emphasize that traditional SSNs are never designed with violence prevention as primary objectives, and thus should not be considered as standalone interventions to reduce risks for childhood violence. However, SSNs, particularly within integrated protection systems, appear to have potential to reduce violence risk. Linkages between SSNs and childhood violence are understudied, and investments should be made to close this evidence gap. PMID:28444197

Montmorillonite catalysis of RNA oligomer formation in aqueous solution. A model for the prebiotic formation of RNA

NASA Technical Reports Server (NTRS)

Ferris, J. P.; Ertem, G.

1993-01-01

Oligomers of adenylic acid of up to the 11-mer in length are formed by the reaction of the phosphorimidazolide of adenosine (ImpA) in pH 8 aqueous solution at room temperature in the presence of Na(+)-montmorillonite. These oligomers are joined by phosphodiester bonds in which the 3',5'-linkage predominates over the 2',5'-linkage by a 2:1 ratio. Reaction of a 9:1 mixture of ImpA, A5'ppA results in the formation of oligomers with a 3:1 ratio of 3',5'- to 2',5'-linked phosphodiester bonds. A high proportion of these oligomers contain the A5'ppA grouping. A5'ppA reacts much more rapidly with ImpA than does 5'-ADP (ppA) or 5'-ATP (pppA). The exchangeable cation associated with the montmorillonite effects the observed catalysis with Li+, Na+, NH4+, and Ca2+ being the more effective while Mg2+ and Al3+ are almost ineffective catalysts. 2',5'-Linked oligomers, up to the tetramer in length, are formed using UO2(2+)-montmorillonite. The structure analysis of individual oligomer fractions was performed by selective enzymatic and KOH hydrolytic studies followed by HPLC analysis of the reaction products. It is concluded from the composition of the oligomers that the rate of addition ImpA to a 3'-terminus containing a 2',5'-linkage is slower than the addition to a nucleoside joined by a 3',5'-linked phosphodiester bond. The potential importance of mineral catalysis of the formation of RNA and other oligomers on primitive Earth is discussed.

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.

Effects of urban sprawl and vehicle miles traveled on traffic fatalities.

PubMed

Yeo, Jiho; Park, Sungjin; Jang, Kitae

2015-01-01

Previous research suggests that urban sprawl increases auto-dependency and that excessive auto use increases the risk of traffic fatalities. This indirect effect of urban sprawl on traffic fatalities is compared to non-vehicle miles traveled (VMT)-related direct effect of sprawl on fatalities. We conducted a path analysis to examine the causal linkages among urban sprawl, VMT, traffic fatalities, income, and fuel cost. The path diagram includes 2 major linkages: the direct relationship between urban sprawl and traffic fatalities and the indirect effect on fatalities through increased VMT in sprawling urban areas. To measure the relative strength of these causal linkages, path coefficients are estimated using data collected nationally from 147 urbanized areas in the United States. Through both direct and indirect paths, urban sprawl is associated with greater numbers of traffic fatalities, but the direct effect of sprawl on fatalities is more influential than the indirect effect. Enhancing traffic safety can be achieved by impeding urban sprawl and encouraging compact development. On the other hand, policy tools reducing VMT may be less effective than anticipated for traffic safety.

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).

Power of a Labrador Retriever-Greyhound pedigree for linkage analysis of hip dysplasia and osteoarthritis.

PubMed

Todhunter, Rory J; Casella, George; Bliss, Stuart P; Lust, George; Williams, Alma Jo; Hamilton, Samuel; Dykes, Nathan L; Yeager, Amy E; Gilbert, Robert O; Burton-Wurster, Nancy I; Mellersh, Cathryn C; Acland, Gregory M

2003-04-01

To estimate the number of dogs required to find linkage to heritable traits of hip dysplasia in dogs from an experimental pedigree. 147 Labrador Retrievers, Greyhounds, and their crossbreed offspring. Labrador Retrievers with hip dysplasia were crossed with unaffected Greyhounds. Age at detection of femoral capital ossification, distraction index (DI), hip joint dorsolateral subluxation (DLS) score, and hip joint osteoarthritis (OA) were recorded. Power to find linkage of a single marker to a quantitative trait locus (QTL) controlling 100% of the variation in a dysplastic trait in the backcross dogs was determined. For the DI at the observed effect size, recombination fraction of 0.05, and heterozygosity of 0.75, 35 dogs in the backcross of the F1 to the Greyhound generation would yield linkage at a power of 0.8. For the DLS score, 35 dogs in the backcross to the Labrador Retriever generation would be required for linkage at the same power. For OSS, 45 dogs in the backcross to the founding Labrador Retrievers would yield linkage at the same power. Fewer dogs were projected to be necessary to find linkage to hip OA. Testing for linkage to the DLS at 4 loci simultaneously, each controlling 25% of the phenotypic variation, yielded an overall power of 0.7 CONCLUSIONS AND CLINICAL SIGNIFICANCE: Based on this conservative single-marker estimate, this pedigree has the requisite power to find microsatellites linked to susceptibility loci for hip dysplasia and hip OA by breeding a reasonable number of backcross dogs.

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

Success and failure in replication of genotype-phenotype associations: How does replication help in understanding the genetic basis of phenotypic variation in outbred populations?

PubMed

Schielzeth, Holger; Rios Villamil, Alejandro; Burri, Reto

2018-03-25

Recent developments in sequencing technologies have facilitated genomewide mapping of phenotypic variation in natural populations. Such mapping efforts face a number of challenges potentially leading to low reproducibility. However, reproducible research forms the basis of scientific progress. We here discuss the options for replication and the reasons for potential nonreproducibility. We then review the evidence for reproducible quantitative trait loci (QTL) with a focus on natural animal populations. Existing case studies of replication fall into three categories: (i) traits that have been mapped to major effect loci (including chromosomal inversion and supergenes) by independent research teams; (ii) QTL fine-mapped in discovery populations; and (iii) attempts to replicate QTL across multiple populations. Major effect loci, in particular those associated with inversions, have been successfully replicated in several cases within and across populations. Beyond such major effect variants, replication has been more successful within than across populations, suggesting that QTL discovered in natural populations may often be population-specific. This suggests that biological causes (differences in linkage patterns, allele frequencies or context-dependencies of QTL) contribute to nonreproducibility. Evidence from other fields, notably animal breeding and QTL mapping in humans, suggests that a significant fraction of QTL is indeed reproducible in direction and magnitude at least within populations. However, there is also a large number of QTL that cannot be easily reproduced. We put forward that more studies should explicitly address the causes and context-dependencies of QTL signals, in particular to disentangle linkage differences, allele frequency differences and gene-by-environment interactions as biological causes of nonreproducibility of QTL, especially between populations. © 2018 John Wiley & Sons Ltd.

Integrating HIV Surveillance and Field Services: Data Quality and Care Continuum in King County, Washington, 2010-2015.

PubMed

Hood, Julia E; Katz, David A; Bennett, Amy B; Buskin, Susan E; Dombrowski, Julia C; Hawes, Stephen E; Golden, Matthew R

2017-12-01

To assess how integration of HIV surveillance and field services might influence surveillance data and linkage to care metrics. We used HIV surveillance and field services data from King County, Washington, to assess potential impact of misclassification of prior diagnoses on numbers of new diagnoses. The relationship between partner services and linkage to care was evaluated with multivariable log-binomial regression models. Of the 2842 people who entered the King County HIV Surveillance System in 2010 to 2015, 52% were newly diagnosed, 41% had a confirmed prior diagnosis in another state, and 7% had an unconfirmed prior diagnosis. Twelve percent of those classified as newly diagnosed for purposes of national HIV surveillance self-reported a prior HIV diagnosis that was unconfirmed. Partner services recipients were more likely than nonrecipients to link to care within 30 days (adjusted risk ratio [RR] = 1.10; 95% confidence interval [CI] = 1.03, 1.18) and 90 days (adjusted RR = 1.07; 95% CI = 1.01, 1.14) of diagnosis. Integration of HIV surveillance, partner services, and care linkage efforts may improve the accuracy of HIV surveillance data and facilitate timely linkage to care.

Examination of the Effects of an Intervention Aiming to Link Patients Receiving Addiction Treatment With Health Care: The LINKAGE Clinical Trial.

PubMed

Weisner, Constance M; Chi, Felicia W; Lu, Yun; Ross, Thekla B; Wood, Sabrina B; Hinman, Agatha; Pating, David; Satre, Derek; Sterling, Stacy A

2016-08-01

Research has shown that higher activation and engagement with health care is associated with better self-management. To our knowledge, the linkage intervention (LINKAGE) is the first to engage patients receiving addiction treatment with health care using the electronic health record and a patient activation approach. To examine the effects of an intervention aiming to link patients receiving addiction treatment with health care. A nonrandomized clinical trial evaluating the LINKAGE intervention vs usual care by applying an alternating 3-month off-and-on design over 30 months. Participants were recruited from an outpatient addiction treatment clinic in a large health system between April 7, 2011, and October 2, 2013. Six group-based, manual-guided sessions on patient engagement in health care and the use of health information technology resources in the electronic health record, as well as facilitated communication with physicians, vs usual care. Primary outcomes, measured at 6 months after enrollment, were patient activation (by interview using the Patient Activation Measure), patient engagement in health care (by interview and electronic health record), and alcohol, drug, and depression outcomes (by interview using the Addiction Severity Index for alcohol and drug outcomes and Patient Health Questionnaire (PHQ) for depression). A total of 503 patients were recruited and assigned to the LINKAGE (n = 252) or usual care (n = 251) conditions, with no differences in baseline characteristics between conditions. The mean (SD) age of the patients was 42.5 (11.8) years, 31.0% (n = 156) were female, and 455 (90.5%) completed the 6-month interview. Compared with usual care participants, LINKAGE participants showed an increase in the mean number of log-in days (incidence rate ratio, 1.53; 95% CI, 1.19-1.97; P = .001). Similar results were found across types of patient portal use (communicating by email, viewing laboratory test results and information, and obtaining medical advice). LINKAGE participants were more likely to talk with their physicians about addiction problems (odds ratio, 2.30; 95% CI, 1.52-3.49; P < .001). Although 6-month abstinence rates were high for both conditions (≥70.0% for both) and depression symptoms improved (the proportion with scores ≥15 on the 9-item PHQ dropped from 15.1% [38 of 252] to 8.0% [18 of 225] among LINKAGE participants), there were no differences between conditions. Those who received all intervention components had significantly better alcohol and other drug outcomes than those who received fewer intervention components. Findings support the feasibility and effectiveness of the LINKAGE intervention in helping patients receiving addiction treatment engage in health care and increase communication with their physicians. The intervention did not affect short-term abstinence or depression outcomes. Understanding if the LINKAGE intervention helps prevent relapse and manage long-term recovery will be important. clinicaltrials.gov Identifier: NCT01621711.

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.

A Model for Mapping Linkages between Health and Education Agencies To Improve School Health.

ERIC Educational Resources Information Center

St. Leger, Lawrence; Nutbeam, Don

2000-01-01

Reviews the evolution of efforts to develop effective, sustainable school health programs, arguing that efforts were significantly driven by public health priorities and have not adequately accounted for educational perspectives. A model illustrating linkages between different school-based inputs and strategies and long-term health and educational…

Linking stressors and ecological responses

USGS Publications Warehouse

Gentile, J.H.; Solomon, K.R.; Butcher, J.B.; Harrass, M.; Landis, W.G.; Power, M.; Rattner, B.A.; Warren-Hicks, W.J.; Wenger, R.; Foran, Jeffery A.; Ferenc, Susan A.

1999-01-01

To characterize risk, it is necessary to quantify the linkages and interactions between chemical, physical and biological stressors and endpoints in the conceptual framework for ecological risk assessment (ERA). This can present challenges in a multiple stressor analysis, and it will not always be possible to develop a quantitative stressor-response profile. This review commences with a conceptual representation of the problem of developing a linkage analysis for multiple stressors and responses. The remainder of the review surveys a variety of mathematical and statistical methods (e.g., ranking methods, matrix models, multivariate dose-response for mixtures, indices, visualization, simulation modeling and decision-oriented methods) for accomplishing the linkage analysis for multiple stressors. Describing the relationships between multiple stressors and ecological effects are critical components of 'effects assessment' in the ecological risk assessment framework.

The effects of carbon nanotubes on lung and dermal cellular behaviors

PubMed Central

Luanpitpong, Sudjit; Wang, Liying; Rojanasakul, Yon

2016-01-01

Carbon nanotubes (CNTs) hold great promise to create new and better products, but their adverse health effect is a major concern. Human exposure to CNTs is primarily through inhalation and dermal contact, especially during the manufacturing and handling processes. Numerous animal studies have demonstrated the potential pulmonary and dermal hazards associated with CNT exposure, while in vitro studies have assessed the effects of CNT exposure on various cellular behaviors and have been used to perform mechanistic studies. In this review, we provide an overview of the pathological effects of CNTs and examine the acute and chronic effects of CNT exposure on lung and dermal cellular behaviors, beyond the generally discussed cytotoxicity. We then examine the linkage of cellular behaviors and disease pathogenesis, and discuss the pertinent mechanisms. PMID:24981653

Sources of global climate data and visualization portals

USGS Publications Warehouse

Douglas, David C.

2014-01-01

Climate is integral to the geophysical foundation upon which ecosystems are structured. Knowledge about mechanistic linkages between the geophysical and biological environments is essential for understanding how global warming may reshape contemporary ecosystems and ecosystem services. Numerous global data sources spanning several decades are available that document key geophysical metrics such as temperature and precipitation, and metrics of primary biological production such as vegetation phenology and ocean phytoplankton. This paper provides an internet directory to portals for visualizing or servers for downloading many of the more commonly used global datasets, as well as a description of how to write simple computer code to efficiently retrieve these data. The data are broadly useful for quantifying relationships between climate, habitat availability, and lower-trophic-level habitat quality - especially in Arctic regions where strong seasonality is accompanied by intrinsically high year-to-year variability. If defensible linkages between the geophysical (climate) and the biological environment can be established, general circulation model (GCM) projections of future climate conditions can be used to infer future biological responses. Robustness of this approach is, however, complicated by the number of direct, indirect, or interacting linkages involved. For example, response of a predator species to climate change will be influenced by the responses of its prey and competitors, and so forth throughout a trophic web. The complexities of ecological systems warrant sensible and parsimonious approaches for assessing and establishing the role of natural climate variability in order to substantiate inferences about the potential effects of global warming.

Novel linkage disequilibrium clustering algorithm identifies new lupus genes on meta-analysis of GWAS datasets.

PubMed

Saeed, Mohammad

2017-05-01

Systemic lupus erythematosus (SLE) is a complex disorder. Genetic association studies of complex disorders suffer from the following three major issues: phenotypic heterogeneity, false positive (type I error), and false negative (type II error) results. Hence, genes with low to moderate effects are missed in standard analyses, especially after statistical corrections. OASIS is a novel linkage disequilibrium clustering algorithm that can potentially address false positives and negatives in genome-wide association studies (GWAS) of complex disorders such as SLE. OASIS was applied to two SLE dbGAP GWAS datasets (6077 subjects; ∼0.75 million single-nucleotide polymorphisms). OASIS identified three known SLE genes viz. IFIH1, TNIP1, and CD44, not previously reported using these GWAS datasets. In addition, 22 novel loci for SLE were identified and the 5 SLE genes previously reported using these datasets were verified. OASIS methodology was validated using single-variant replication and gene-based analysis with GATES. This led to the verification of 60% of OASIS loci. New SLE genes that OASIS identified and were further verified include TNFAIP6, DNAJB3, TTF1, GRIN2B, MON2, LATS2, SNX6, RBFOX1, NCOA3, and CHAF1B. This study presents the OASIS algorithm, software, and the meta-analyses of two publicly available SLE GWAS datasets along with the novel SLE genes. Hence, OASIS is a novel linkage disequilibrium clustering method that can be universally applied to existing GWAS datasets for the identification of new genes.

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.

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.

A comprehensive screen for SNP associations on chromosome region 5q31-33 in Swedish/Norwegian celiac disease families.

PubMed

Amundsen, Silja Svanstrøm; Adamovic, Svetlana; Hellqvist, Asa; Nilsson, Staffan; Gudjónsdóttir, Audur H; Ascher, Henry; Ek, Johan; Larsson, Kristina; Wahlström, Jan; Lie, Benedicte A; Sollid, Ludvig M; Naluai, Asa Torinsson

2007-09-01

Celiac disease (CD) is a gluten-induced enteropathy, which results from the interplay between environmental and genetic factors. There is a strong human leukocyte antigen (HLA) association with the disease, and HLA-DQ alleles represent a major genetic risk factor. In addition to HLA-DQ, non-HLA genes appear to be crucial for CD development. Chromosomal region 5q31-33 has demonstrated linkage with CD in several genome-wide studies, including in our Swedish/Norwegian cohort. In a European meta-analysis 5q31-33 was the only region that reached a genome-wide level of significance except for the HLA region. To identify the genetic variant(s) responsible for this linkage signal, we performed a comprehensive single nucleotide polymorphism (SNP) association screen in 97 Swedish/Norwegian multiplex families who demonstrate linkage to the region. We selected tag SNPs from a 16 Mb region representing the 95% confidence interval of the linkage peak. A total of 1,404 SNPs were used for the association analysis. We identified several regions with SNPs demonstrating moderate single- or multipoint associations. However, the isolated association signals appeared insufficient to account for the linkage signal seen in our cohort. Collective effects of multiple risk genes within the region, incomplete genetic coverage or effects related to copy number variation are possible explanations for our findings.

Selective digestion of Ba2+/Ca2+ alginate gel microdroplets for single-cell handling

NASA Astrophysics Data System (ADS)

Odaka, Masao; Hattori, Akihiro; Matsuura, Kenji; Yasuda, Kenji

2018-06-01

Cells encapsuled by polymer microdroplets are an effective platform for the identification and separation of individual cells for single-cell-based analysis. However, a key challenge is to maintain and release the captured cells in the microdroplets selectively, nondestructively, and noninvasively. We developed a simple method of encapsulating cells in alginate microdroplets having different digestion characteristics. Cells were diluted with an alginate polymer of sol state and encapsulated into microdroplets with Ba2+ and Ca2+ by a spray method. When a chelating buffer was applied, alginate gel microdroplets were digested according to the difference in chelating efficiency of linkage-divalent cations; hence, two types of alginate microdroplets were formed. Moreover, we examined the capability of the alginate gel to exchange linkage-divalent cations and found that both Ca2+ exchange in Ba-alginate microdroplets and Ba2+ exchange in Ca-alginate microdroplets occurred. These results indicate that the potential applications of a mixture of alginate microdroplets with different divalent cations control the selective digestion of microdroplets to improve the high-throughput, high-content microdroplet-based separation, analysis, or storage of single cells.

Corporate Investors Increased Common Ownership In Hospitals And The Postacute Care And Hospice Sectors.

PubMed

Fowler, Annabelle C; Grabowski, David C; Gambrel, Robert J; Huskamp, Haiden A; Stevenson, David G

2017-09-01

The sharing of investors across firms is a new antitrust focus because of its potential negative effects on competition. Historically, the ability to track common investors across the continuum of health care providers has been limited. Thus, little is known about common investor ownership structures that might exist across health care delivery systems and how these linkages have evolved over time. We used data from the Provider Enrollment, Chain, and Ownership System of the Centers for Medicare and Medicaid Services to identify common investor ownership linkages across the acute care, postacute care, and hospice sectors within the same geographic markets. To our knowledge, this study provides the first description of common investor ownership trends in these sectors. We found that the percentage of acute care hospitals having common investor ties to the postacute or hospice sectors increased from 24.6 percent in 2005 to 48.9 percent in 2015. These changes have important implications for antitrust, payment, and regulatory policies. Project HOPE—The People-to-People Health Foundation, Inc.

Coastal livelihood transitions under globalization with implications for trans-ecosystem interactions.

PubMed

Kramer, Daniel B; Stevens, Kara; Williams, Nicholas E; Sistla, Seeta A; Roddy, Adam B; Urquhart, Gerald R

2017-01-01

Anthropogenic threats to natural systems can be exacerbated due to connectivity between marine, freshwater, and terrestrial ecosystems, complicating the already daunting task of governance across the land-sea interface. Globalization, including new access to markets, can change social-ecological, land-sea linkages via livelihood responses and adaptations by local people. As a first step in understanding these trans-ecosystem effects, we examined exit and entry decisions of artisanal fishers and smallholder farmers on the rapidly globalizing Caribbean coast of Nicaragua. We found that exit and entry decisions demonstrated clear temporal and spatial patterns and that these decisions differed by livelihood. In addition to household characteristics, livelihood exit and entry decisions were strongly affected by new access to regional and global markets. The natural resource implications of these livelihood decisions are potentially profound as they provide novel linkages and spatially-explicit feedbacks between terrestrial and marine ecosystems. Our findings support the need for more scientific inquiry in understanding trans-ecosystem tradeoffs due to linked-livelihood transitions as well as the need for a trans-ecosystem approach to natural resource management and development policy in rapidly changing coastal regions.

A Linkage Map and QTL Analysis for Pyrethroid Resistance in the Bed Bug Cimex lectularius

PubMed Central

Fountain, Toby; Ravinet, Mark; Naylor, Richard; Reinhardt, Klaus; Butlin, Roger K.

2016-01-01

The rapid evolution of insecticide resistance remains one of the biggest challenges in the control of medically and economically important pests. Insects have evolved a diverse range of mechanisms to reduce the efficacy of the commonly used classes of insecticides, and finding the genetic basis of resistance is a major aid to management. In a previously unstudied population, we performed an F2 resistance mapping cross for the common bed bug, Cimex lectularius, for which insecticide resistance is increasingly widespread. Using 334 SNP markers obtained through RAD-sequencing, we constructed the first linkage map for the species, consisting of 14 putative linkage groups (LG), with a length of 407 cM and an average marker spacing of 1.3 cM. The linkage map was used to reassemble the recently published reference genome, facilitating refinement and validation of the current genome assembly. We detected a major QTL on LG12 associated with insecticide resistance, occurring in close proximity (1.2 Mb) to a carboxylesterase encoding candidate gene for pyrethroid resistance. This provides another example of this candidate gene playing a major role in determining survival in a bed bug population following pesticide resistance evolution. The recent availability of the bed bug genome, complete with a full list of potential candidate genes related to insecticide resistance, in addition to the linkage map generated here, provides an excellent resource for future research on the development and spread of insecticide resistance in this resurging pest species. PMID:27733453

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

Tracking a northern fulmar from a Scottish nesting site to the Charlie-Gibbs Fracture Zone: Evidence of linkage between coastal breeding seabirds and Mid-Atlantic Ridge feeding sites

NASA Astrophysics Data System (ADS)

Edwards, Ewan W. J.; Quinn, Lucy R.; Wakefield, Ewan D.; Miller, Peter I.; Thompson, Paul M.

2013-12-01

The seas above mid-ocean ridges are biodiversity hotspots in an otherwise largely oligotrophic environment, but the nature and extent of linkage between these offshore regimes and coastal ecosystems remains uncertain. Using a combination of GPS and geolocation tracking data, we show that a male fulmar, breeding on the Scottish coast, foraged over areas of persistent thermal fronts along the Charlie-Gibbs Fracture Zone (CGFZ) of the Mid-Atlantic Ridge during the incubation period. The bird travelled over 6200 km in 14.9 days. First-passage time analysis identified seven areas of restricted search, four on the shelf and three in the vicinity of the Mid-Atlantic Ridge. Previous studies of incubation foraging trip durations at this site suggest that a trip of this duration is unusual, and further work is required to assess the extent to which different individuals use these offshore resources. Nevertheless, these data highlight the potential importance of high sea areas beyond the limits of national jurisdiction when considering the management and conservation of seabirds breeding in NW Europe, and raises the potential for even greater linkage between the CGFZ and seabirds breeding colonies in other regions.

Background selection as null hypothesis in population genomics: insights and challenges from Drosophila studies

PubMed Central

2017-01-01

The consequences of selection at linked sites are multiple and widespread across the genomes of most species. Here, I first review the main concepts behind models of selection and linkage in recombining genomes, present the difficulty in parametrizing these models simply as a reduction in effective population size (Ne) and discuss the predicted impact of recombination rates on levels of diversity across genomes. Arguments are then put forward in favour of using a model of selection and linkage with neutral and deleterious mutations (i.e. the background selection model, BGS) as a sensible null hypothesis for investigating the presence of other forms of selection, such as balancing or positive. I also describe and compare two studies that have generated high-resolution landscapes of the predicted consequences of selection at linked sites in Drosophila melanogaster. Both studies show that BGS can explain a very large fraction of the observed variation in diversity across the whole genome, thus supporting its use as null model. Finally, I identify and discuss a number of caveats and challenges in studies of genetic hitchhiking that have been often overlooked, with several of them sharing a potential bias towards overestimating the evidence supporting recent selective sweeps to the detriment of a BGS explanation. One potential source of bias is the analysis of non-equilibrium populations: it is precisely because models of selection and linkage predict variation in Ne across chromosomes that demographic dynamics are not expected to be equivalent chromosome- or genome-wide. Other challenges include the use of incomplete genome annotations, the assumption of temporally stable recombination landscapes, the presence of genes under balancing selection and the consequences of ignoring non-crossover (gene conversion) recombination events. This article is part of the themed issue ‘Evolutionary causes and consequences of recombination rate variation in sexual organisms’. PMID:29109230

Study design elements for rigorous quasi-experimental comparative effectiveness research.

PubMed

Maciejewski, Matthew L; Curtis, Lesley H; Dowd, Bryan

2013-03-01

Quasi-experiments are likely to be the workhorse study design used to generate evidence about the comparative effectiveness of alternative treatments, because of their feasibility, timeliness, affordability and external validity compared with randomized trials. In this review, we outline potential sources of discordance in results between quasi-experiments and experiments, review study design choices that can improve the internal validity of quasi-experiments, and outline innovative data linkage strategies that may be particularly useful in quasi-experimental comparative effectiveness research. There is an urgent need to resolve the debate about the evidentiary value of quasi-experiments since equal consideration of rigorous quasi-experiments will broaden the base of evidence that can be brought to bear in clinical decision-making and governmental policy-making.

Selective DNA Pooling for Determination of Linkage between a Molecular Marker and a Quantitative Trait Locus

PubMed Central

Darvasi, A.; Soller, M.

1994-01-01

Selective genotyping is a method to reduce costs in marker-quantitative trait locus (QTL) linkage determination by genotyping only those individuals with extreme, and hence most informative, quantitative trait values. The DNA pooling strategy (termed: ``selective DNA pooling'') takes this one step further by pooling DNA from the selected individuals at each of the two phenotypic extremes, and basing the test for linkage on marker allele frequencies as estimated from the pooled samples only. This can reduce genotyping costs of marker-QTL linkage determination by up to two orders of magnitude. Theoretical analysis of selective DNA pooling shows that for experiments involving backcross, F(2) and half-sib designs, the power of selective DNA pooling for detecting genes with large effect, can be the same as that obtained by individual selective genotyping. Power for detecting genes with small effect, however, was found to decrease strongly with increase in the technical error of estimating allele frequencies in the pooled samples. The effect of technical error, however, can be markedly reduced by replication of technical procedures. It is also shown that a proportion selected of 0.1 at each tail will be appropriate for a wide range of experimental conditions. PMID:7896115

Nitrogen availability drives priming effect by altering microbial carbon-use efficiency after permafrost thaw

NASA Astrophysics Data System (ADS)

Chen, L.; Liu, L.; Zhang, Q.; Mao, C.; Liu, F.; Yang, Y.

2017-12-01

Enhanced vegetation growth can potentially aggravate soil C loss by accelerating the decomposition of soil organic matter (SOM) ("priming effect"), thereby reinforcing the positive C-climate feedback in permafrost ecosystems. However, the degree to which priming effect alters permafrost C dynamics is expected to be modified by nitrogen (N) availability after permafrost thaw. Despite this recognition, experimental evidence for the linkage between priming effect and post-thaw N availability is still lacking. Particularly, the microbial mechanisms involved remain unknown. Here, using a thermokarst-induced natural N gradient combined with an isotope-labeled glucose and N addition experiment, we presented a strong linkage between soil N availability and priming effect in Tibetan permafrost. We observed that the magnitude of priming effect along the thaw gradient was negatively associated with soil total dissolved nitrogen (TDN) concentration. This negative effect of post-thaw N availability was further proved by a sharply reduced priming effect following mineral N supply. These two lines of evidence jointly illustrated that the priming effect along the thaw chronosequence was controlled by N availability, supporting the `N mining theory'. In contrast to the prevailing assumption, this N-regulated priming effect was independent from changes in C- or N-acquiring enzyme activities, but positively associated with the change in metabolic quotients (△SOM-qCO2), highlighting that decreased microbial metabolism efficiency rather than increased enzyme activities account for greater priming effect under reduced N availability. Taken together, these findings demonstrate that C dynamics in melting permafrost largely depends on post-thaw N availability due to its effect of retarding SOM mineralization. This C-N interaction and the relevant microbial metabolic efficiency should be considered in Earth System Models for a better understanding of soil C dynamics after permafrost thaw.

Shout-It-Now: A Mobile HCT Model Employing Technology and Edutainment in South Africa.

PubMed

Daniels, Joseph; Komarek, Arnost; Forgreive, Bruce; Pahl, Kathryn; Stafford, Stephen; Bruns, Laurie Campbell; Coates, Thomas

Mobile HIV counseling and testing (HCT) has been effective in reaching men, women, and adolescents in South Africa. However, there is limited understanding of effective mobile HCT programs utilizing tools like technology and edutainment to increase HIV counseling and testing rates. The authors examine data from the Shout-It-Now (S-N) program that uses such tools in South Africa. The S-N program utilizes various forms of technology and ongoing telephonic counseling within a 6-step program of HIV testing and linkage-to-care support, and program data were analyzed over an 18-month period. Data were analyzed from women, men, and adolescent program participants. Summative statistics was conducted on participant registration, HIV risk assessment, and HIV testing profiles. HIV prevalence were estimated along with the related 95% confidence intervals using the Clopper-Pearson method. Over an 18-month period, there were 72 220 program participants with high representation of men, women, and adolescents and 40% of the participants being men at each site. There were 3343 participants who tested HIV positive, and a higher proportion of women tested positive. Integrating technology, quality assurance measures, and edutainment with mobile HCT has the potential to increase the number of those who test within communities. Research is needed to understand the effectiveness of this model in facilitating regular testing and linkage to care.

Kineto-dynamic design optimisation for vehicle-specific seat-suspension systems

NASA Astrophysics Data System (ADS)

Shangguan, Wen-Bin; Shui, Yijie; Rakheja, Subhash

2017-11-01

Designs and analyses of seat-suspension systems are invariably performed considering effective vertical spring rate and damping properties, while neglecting important contributions due to kinematics of the widely used cross-linkage mechanism. In this study, a kineto-dynamic model of a seat-suspension is formulated to obtain relations for effective vertical suspension stiffness and damping characteristics as functions of those of the air spring and the hydraulic damper, respectively. The proposed relations are verified through simulations of the multi-body dynamic model of the cross-linkage seat-suspension in the ADAMS platform. The validity of the kineto-dynamic model is also demonstrated through comparisons of its vibration transmission response with the experimental data. The model is used to identify optimal air spring coordinates to attain nearly constant natural frequency of the suspension, irrespective of the seated body mass and seated height. A methodology is further proposed to identify optimal damping requirements for vehicle-specific suspension designs to achieve minimal seat effective amplitude transmissibility (SEAT) and vibration dose value (VDV) considering vibration spectra of different classes of earthmoving vehicles. The shock and vibration isolation performance potentials of the optimal designs are evaluated under selected vehicle vibration superimposed with shock motions. Results show that the vehicle-specific optimal designs could provide substantial reductions in the SEAT and VDV values for the vehicle classes considered.

Tertiary structure in N-linked oligosaccharides.

PubMed

Homans, S W; Dwek, R A; Rademacher, T W

1987-10-06

Distance constraints derived from two-dimensional nuclear Overhauser effect measurements have been used to define the orientation of the Man alpha 1-3Man beta linkage in seven different N-linked oligosaccharides, all containing the common pentasaccharide core Man alpha 1-6(Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc. Conformational invariance of the Man alpha 1-3Man beta linkage was found for those structures bearing substitutions on the Man alpha 1-3Man beta antenna. However, the presence of either a GlcNAc residue in the beta 1-4 linkage to Man beta ("bisecting GlcNAc") or a xylose residue in the beta 1-2 linkage to Man beta of the trimannosyl core was found to generate conformational transitions that were similar. These transitions were accompanied by characteristic chemical shift perturbations of proton resonances in the vicinity of the Man alpha 1-3Man beta linkage. Molecular orbital energy calculations suggest that the conformational transition between the unsubstituted and substituted cores arises from energetic constraints in the vicinity of the Man alpha 1-3Man beta linkage, rather than specific long-range interactions. These data taken together with our previous results on the Man alpha 1-6Man beta linkage [Homans, S. W., Dwek R. A., Boyd, J., Mahmoudian, M., Richards, W. G., & Rademacher, T. W. (1986) Biochemistry 25, 6342] allow us to discuss the consequences of the modulation of oligosaccharide solution conformations.

Heavy ion mutagenesis: linear energy transfer effects and genetic linkage

NASA Technical Reports Server (NTRS)

Kronenberg, A.; Gauny, S.; Criddle, K.; Vannais, D.; Ueno, A.; Kraemer, S.; Waldren, C. A.; Chatterjee, A. (Principal Investigator)

1995-01-01

We have characterized a series of 69 independent mutants at the endogenous hprt locus of human TK6 lymphoblasts and over 200 independent S1-deficient mutants of the human x hamster hybrid cell line AL arising spontaneously or following low-fluence exposures to densely ionizing Fe ions (600 MeV/amu, linear energy transfer = 190 keV/microns). We find that large deletions are common. The entire hprt gene (> 44 kb) was missing in 19/39 Fe-induced mutants, while only 2/30 spontaneous mutants lost the entire hprt coding sequence. When the gene of interest (S1 locus = M1C1 gene) is located on a nonessential human chromosome 11, multilocus deletions of several million base pairs are observed frequently. The S1 mutation frequency is more than 50-fold greater than the frequency of hprt mutants in the same cells. Taken together, these results suggest that low-fluence exposures to Fe ions are often cytotoxic due to their ability to create multilocus deletions that may often include the loss of essential genes. In addition, the tumorigenic potential of these HZE heavy ions may be due to the high potential for loss of tumor suppressor genes. The relative insensitivity of the hprt locus to mutation is likely due to tight linkage to a gene that is required for viability.

Quantification of type I error probabilities for heterogeneity LOD scores.

PubMed

Abreu, Paula C; Hodge, Susan E; Greenberg, David A

2002-02-01

Locus heterogeneity is a major confounding factor in linkage analysis. When no prior knowledge of linkage exists, and one aims to detect linkage and heterogeneity simultaneously, classical distribution theory of log-likelihood ratios does not hold. Despite some theoretical work on this problem, no generally accepted practical guidelines exist. Nor has anyone rigorously examined the combined effect of testing for linkage and heterogeneity and simultaneously maximizing over two genetic models (dominant, recessive). The effect of linkage phase represents another uninvestigated issue. Using computer simulation, we investigated type I error (P value) of the "admixture" heterogeneity LOD (HLOD) score, i.e., the LOD score maximized over both recombination fraction theta and admixture parameter alpha and we compared this with the P values when one maximizes only with respect to theta (i.e., the standard LOD score). We generated datasets of phase-known and -unknown nuclear families, sizes k = 2, 4, and 6 children, under fully penetrant autosomal dominant inheritance. We analyzed these datasets (1) assuming a single genetic model, and maximizing the HLOD over theta and alpha; and (2) maximizing the HLOD additionally over two dominance models (dominant vs. recessive), then subtracting a 0.3 correction. For both (1) and (2), P values increased with family size k; rose less for phase-unknown families than for phase-known ones, with the former approaching the latter as k increased; and did not exceed the one-sided mixture distribution xi = (1/2) chi1(2) + (1/2) chi2(2). Thus, maximizing the HLOD over theta and alpha appears to add considerably less than an additional degree of freedom to the associated chi1(2) distribution. We conclude with practical guidelines for linkage investigators. Copyright 2002 Wiley-Liss, Inc.

A genome scan for quantitative trait loci affecting cyanogenic potential of cassava root in an outbred population.

PubMed

Whankaew, Sukhuman; Poopear, Supannee; Kanjanawattanawong, Supanath; Tangphatsornruang, Sithichoke; Boonseng, Opas; Lightfoot, David A; Triwitayakorn, Kanokporn

2011-05-25

Cassava (Manihot esculenta Crantz) can produce cyanide, a toxic compound, without self-injury. That ability was called the cyanogenic potential (CN). This project aimed to identify quantitative trait loci (QTL) associated with the CN in an outbred population derived from 'Hanatee' × 'Huay Bong 60', two contrasting cultivars. CN was evaluated in 2008 and in 2009 at Rayong province, and in 2009 at Lop Buri province, Thailand. CN was measured using a picrate paper kit. QTL analysis affecting CN was performed with 303 SSR markers. The phenotypic values showed continuous variation with transgressive segregation events with more (115 ppm) and less CN (15 ppm) than either parent ('Hanatee' had 33 ppm and 'Huay Bong 60' had 95 ppm). The linkage map consisted of 303 SSR markers, on 27 linkage groups with a map that encompassed 1,328 cM. The average marker interval was 5.8 cM. Five QTL underlying CN were detected. CN08R1from 2008 at Rayong, CN09R1and CN09R2 from 2009 at Rayong, and CN09L1 and CN09L2 from 2009 at Lop Buri were mapped on linkage group 2, 5, 10 and 11, respectively. Among all the identified QTL, CN09R1 was the most significantly associated with the CN trait with LOD score 5.75 and explained the greatest percentage of phenotypic variation (%Expl.) of 26%. Five new QTL affecting CN were successfully identified from 4 linkage groups. Discovery of these QTL can provide useful markers to assist in cassava breeding and studying genes affecting the trait.

A genome scan for quantitative trait loci affecting cyanogenic potential of cassava root in an outbred population

PubMed Central

2011-01-01

Background Cassava (Manihot esculenta Crantz) can produce cyanide, a toxic compound, without self-injury. That ability was called the cyanogenic potential (CN). This project aimed to identify quantitative trait loci (QTL) associated with the CN in an outbred population derived from 'Hanatee' × 'Huay Bong 60', two contrasting cultivars. CN was evaluated in 2008 and in 2009 at Rayong province, and in 2009 at Lop Buri province, Thailand. CN was measured using a picrate paper kit. QTL analysis affecting CN was performed with 303 SSR markers. Results The phenotypic values showed continuous variation with transgressive segregation events with more (115 ppm) and less CN (15 ppm) than either parent ('Hanatee' had 33 ppm and 'Huay Bong 60' had 95 ppm). The linkage map consisted of 303 SSR markers, on 27 linkage groups with a map that encompassed 1,328 cM. The average marker interval was 5.8 cM. Five QTL underlying CN were detected. CN08R1from 2008 at Rayong, CN09R1and CN09R2 from 2009 at Rayong, and CN09L1 and CN09L2 from 2009 at Lop Buri were mapped on linkage group 2, 5, 10 and 11, respectively. Among all the identified QTL, CN09R1 was the most significantly associated with the CN trait with LOD score 5.75 and explained the greatest percentage of phenotypic variation (%Expl.) of 26%. Conclusions Five new QTL affecting CN were successfully identified from 4 linkage groups. Discovery of these QTL can provide useful markers to assist in cassava breeding and studying genes affecting the trait. PMID:21609492

Screening for Multiple Genes Influencing Dyslexia.

ERIC Educational Resources Information Center

Smith, Shelley D.; And Others

1991-01-01

Examines the "sib pair" method of linkage analysis designed to locate genes influencing dyslexia, which has several advantages over the "LOD" score method. Notes that the sib pair analysis was able to detect the same linkages as the LOD method, plus a possible third region. Confirms that the sib pair method is an effective means of screening. (RS)

75 FR 8421 - Self-Regulatory Organizations; Notice of Filing and Immediate Effectiveness of Proposed Rule...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-24

... $.0035 per contract to each member for all options transactions executed or cleared by the member that... Options Intermarket Linkage Plan (``Linkage'').\\3\\ The ORF is imposed upon all such transactions executed by a member, even if such transactions do not take place on the Exchange.\\4\\ The ORF also includes...

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.

pH-triggered chitosan nanogels via an ortho ester-based linkage for efficient chemotherapy.

PubMed

Yang, Guanqing; Wang, Xin; Fu, Shengxiang; Tang, Rupei; Wang, Jun

2017-09-15

We report on new types of chitosan-based nanogels via an ortho ester-based linkage, used as drug carriers for efficient chemotherapy. First, we synthesized a novel diacrylamide containing ortho ester (OEAM) as an acid-labile cross-linker. Subsequently, methacrylated succinyl-chitosan (MASCS) was prepared and polymerized with OEAM at different molar ratios to give a series of pH-triggered MASCS nanogels. Doxorubicin (DOX) as a model anticancer drug was loaded into MASCS nanogels with a loading content of 16.5%. As expected, with the incorporation of ortho ester linkages, these nanogels showed pH-triggered degradation and drug release at acidic pH values. In vitro cellular uptake shows that the DOX-loaded nanogels could be preferentially internalized by two-dimensional (2D) cells and three-dimensional (3D) multicellular spheroids (MCs), resulting in higher inhibition of the proliferation of tumor cells. In vivo biodistribution and anti-tumor effect were determined in H22 tumor-bearing mice, and the results demonstrate that the acid-labile MASCS nanogels can significantly prolong the blood circulation time of DOX and improve the accumulation in tumor areas, leading to higher therapeutic efficacy. We designed new pH-triggered chitosan nanogels via an ortho ester-based cross-linker for efficient drug-loading and chemotherapy. These drug-loaded nanogels exhibit excellent pH-triggered drug release behavior due to the degradation of ortho ester linkages in mildly acidic environments. In vitro and in vivo results demonstrate that the nanogels could be efficiently internalized by 2D cells and 3D-MCs, improve drug concentration in solid tumors, and lead to higher therapeutic efficacy. To the best of our knowledge, this is the first report on using an ortho ester-based cross-linker to prepare pH-triggered chitosan nanogels as tumor carriers, which may provide a potential route for improved safety and to increase the therapeutic efficacy of anticancer therapy. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Fine mapping of the chromosome 12 late-onset Alzheimer disease locus: potential genetic and phenotypic heterogeneity.

PubMed

Scott, W K; Grubber, J M; Conneally, P M; Small, G W; Hulette, C M; Rosenberg, C K; Saunders, A M; Roses, A D; Haines, J L; Pericak-Vance, M A

2000-03-01

Apolipoprotein E (APOE) is the only confirmed susceptibility gene for late-onset Alzheimer disease (AD). In a recent genomic screen of 54 families with late-onset AD, we detected significant evidence for a second late-onset AD locus located on chromosome 12 between D12S373 and D12S390. Linkage to this region was strongest in 27 large families with at least one affected individual without an APOE-4 allele, suggesting that APOE and the chromosome 12 locus might have independent effects. We have since genotyped several additional markers across the region, to refine the linkage results. In analyzing these additional data, we have addressed the issue of heterogeneity in the data set by weighting results by clinical and neuropathologic features, sibship size, and APOE genotype. When considering all possible affected sib pairs (ASPs) per nuclear family, we obtained a peak maximum LOD score between D12S1057 and D12S1042. The magnitude and location of the maximum LOD score changed when different weighting schemes were used to control for the number of ASPs contributed by each nuclear family. Using the affected-relative-pair method implemented in GENEHUNTER-PLUS, we obtained a maximum LOD score between D12S398 and D12S1632, 25 cM from the original maximum LOD score. These results indicate that family size influences the location estimate for the chromosome 12 AD gene. The results of conditional linkage analysis by use of GENEHUNTER-PLUS indicated that evidence for linkage to chromosome 12 was stronger in families with affected individuals lacking an APOE-4 allele; much of this evidence came from families with affected individuals with neuropathologic diagnosis of dementia with Lewy bodies (DLB). Taken together, these results indicate that the chromosome 12 locus acts independently of APOE to increase the risk of late-onset familial AD and that it may be associated with the DLB variant of AD.

Mexican mestizo population sub-structure: effects on genetic and forensic statistical parameters.

PubMed

Noris, Gino; Santana, Carla; Meraz-Ríos, Marco Antonio; de Lourdes Munoz, María; Majluf-Cruz, Abraham; Magaña, Jonathan J; Granados, Julio; Quezada, Rosa; Revilla, María Cristina; Martínez-Salas, Sergio; Xihuitl, Salvador; Martínez de la Escalera, Gonzalo; Díaz-Badillo, Alvaro; Calderon-Aranda, Emma S; Gómez, Rocío

2012-12-01

Since Mexican mestizos are an admixed population, it is necessary to determine the effects that the substructure of the population has on genetic and forensic parameters. With this aim, a study was performed with 15 STR loci (CODIS plus D2S1338 and D19S433) on 1,640 unrelated Mexican mestizos. We determine allele and genotypic frequencies observing departure from Hardy-Weinberg expectation (12 out of 15 loci, with an excess of homozygotes, Fis > 0), as well as pairs of loci in an apparent linkage disequilibrium (13 of 92 loci). We conducted a test for genetic population stratification, the results show that the Mexican mestizo population is substructured into three subgroups, which are in HW and linkage equilibrium. The combination of the 15 loci in the whole population has high forensic efficiency with the capacity to genetically discriminate one individual in one quintillion (1/10(18)). Our data potentially validates the use of these 15 STR loci to establish forensic identity and parentage testing for legal purposes, and offers a powerful tool for genetic variation analysis. However, given that the population is stratified, we highly recommend applying a correction with the inbreeding coefficient in calculations of paternity and forensic studies to avoid erroneous assumptions.

Monoglycoconjugated phthalocyanines: effect of sugar and linkage on photodynamic activity.

PubMed

Lafont, Dominique; Zorlu, Yunus; Savoie, Huguette; Albrieux, Florian; Ahsen, Vefa; Boyle, Ross W; Dumoulin, Fabienne

2013-09-01

Click chemistry can be advantageously used to graft carbohydrates on phthalocyanines which are potent photosensitisers, but the effect of the presence of triazole moieties on photodynamic efficiency was not investigated systematically to date. The nature and linkage of the sugar were investigated in order to define structure-activity relationships. Two sets of monoglycoconjugated water-soluble phthalocyanines have been designed and their photodynamic activity and uptake investigated in HT-29 human colon adenocarcinoma cells. Carbohydrates: galactose, mannose or lactose were grafted onto Zn(II) phthalocyanines either by glycosylation or by click reaction. The triazole linkage formed by click conjugation lowered the biological efficiency for mannose and galactose, compared to classical glycosylation grafting. The mannose conjugate formed by glycosylation was the most photodynamically active, without correlation with the photosensitiser cell uptake. Copyright © 2012 Elsevier B.V. All rights reserved.

Conjugation of isoniazid to a zinc phthalocyanine via hydrazone linkage for pH-dependent liposomal controlled release

NASA Astrophysics Data System (ADS)

Nkanga, Christian Isalomboto; Krause, Rui Werner Maçedo

2018-05-01

Tuberculosis (TB) remains the leading cause of mortality from infectious diseases. Extended TB treatment and frequent adverse effects, due to poor bioavailability of anti-tubercular drugs (ATBDs), represent the main rationales behind liposomal encapsulation for controlled delivery. Liposomes have been reported as potential vehicles for targeted delivery of ATBDs due to their rapid uptake by macrophages, which are known as the main host cells for TB causative agent (Mycobacterium tuberculosis). Additionally, the need for controlled release of ATBDs arises because leakage is part of the key liposome challenges for hydrophilic compounds like isoniazid (INH). In this study, INH was conjugated to a highly hydrophobic photosensitizer, zinc (II) phthalocyanine (PC), through hydrazone bonding. The obtained conjugate (PC-INH) was encapsulated in liposomes by film hydration method. PC-INH loaded liposomes (PILs) were characterized using dynamic light scattering, transmission electron microscopy, energy-dispersive X-ray spectrometry and UV-Vis absorption spectrometry, which was used also for estimation of encapsulation efficiency (%EE). INH release was evaluated in different pH media using dialysis. Particle size, zeta potential and %EE of PILs were about 506 nm, - 55 mV and 72%, respectively. Over 12 h, PILs exhibited 22, 41, 97 and 100% of INH, respectively, released in pH 7.4, 6.4, 5.4 and 4.4 media. This pH-dependent behavior is attractive for site-specific delivery. These findings suggest the conjugation of chemotherapeutics to phthalocyanines using pH-labile linkages as a potential strategy for liposomal controlled release.

The clinical and economic impact of point-of-care CD4 testing in mozambique and other resource-limited settings: a cost-effectiveness analysis.

PubMed

Hyle, Emily P; Jani, Ilesh V; Lehe, Jonathan; Su, Amanda E; Wood, Robin; Quevedo, Jorge; Losina, Elena; Bassett, Ingrid V; Pei, Pamela P; Paltiel, A David; Resch, Stephen; Freedberg, Kenneth A; Peter, Trevor; Walensky, Rochelle P

2014-09-01

Point-of-care CD4 tests at HIV diagnosis could improve linkage to care in resource-limited settings. Our objective is to evaluate the clinical and economic impact of point-of-care CD4 tests compared to laboratory-based tests in Mozambique. We use a validated model of HIV testing, linkage, and treatment (CEPAC-International) to examine two strategies of immunological staging in Mozambique: (1) laboratory-based CD4 testing (LAB-CD4) and (2) point-of-care CD4 testing (POC-CD4). Model outcomes include 5-y survival, life expectancy, lifetime costs, and incremental cost-effectiveness ratios (ICERs). Input parameters include linkage to care (LAB-CD4, 34%; POC-CD4, 61%), probability of correctly detecting antiretroviral therapy (ART) eligibility (sensitivity: LAB-CD4, 100%; POC-CD4, 90%) or ART ineligibility (specificity: LAB-CD4, 100%; POC-CD4, 85%), and test cost (LAB-CD4, US$10; POC-CD4, US$24). In sensitivity analyses, we vary POC-CD4-specific parameters, as well as cohort and setting parameters to reflect a range of scenarios in sub-Saharan Africa. We consider ICERs less than three times the per capita gross domestic product in Mozambique (US$570) to be cost-effective, and ICERs less than one times the per capita gross domestic product in Mozambique to be very cost-effective. Projected 5-y survival in HIV-infected persons with LAB-CD4 is 60.9% (95% CI, 60.9%-61.0%), increasing to 65.0% (95% CI, 64.9%-65.1%) with POC-CD4. Discounted life expectancy and per person lifetime costs with LAB-CD4 are 9.6 y (95% CI, 9.6-9.6 y) and US$2,440 (95% CI, US$2,440-US$2,450) and increase with POC-CD4 to 10.3 y (95% CI, 10.3-10.3 y) and US$2,800 (95% CI, US$2,790-US$2,800); the ICER of POC-CD4 compared to LAB-CD4 is US$500/year of life saved (YLS) (95% CI, US$480-US$520/YLS). POC-CD4 improves clinical outcomes and remains near the very cost-effective threshold in sensitivity analyses, even if point-of-care CD4 tests have lower sensitivity/specificity and higher cost than published values. In other resource-limited settings with fewer opportunities to access care, POC-CD4 has a greater impact on clinical outcomes and remains cost-effective compared to LAB-CD4. Limitations of the analysis include the uncertainty around input parameters, which is examined in sensitivity analyses. The potential added benefits due to decreased transmission are excluded; their inclusion would likely further increase the value of POC-CD4 compared to LAB-CD4. POC-CD4 at the time of HIV diagnosis could improve survival and be cost-effective compared to LAB-CD4 in Mozambique, if it improves linkage to care. POC-CD4 could have the greatest impact on mortality in settings where resources for HIV testing and linkage are most limited. Please see later in the article for the Editors' Summary.

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.

An approach to investigating linkage for bipolar disorder using large Costa Rican pedigrees

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

Freimer, N.B.; Reus, V.I.; Vinogradov, S.

1996-05-31

Despite the evidence that major gene effects exist for bipolar disorder (BP), efforts to map BP loci have so far been unsuccessful. A strategy for mapping BP loci is described, focused on investigation of large pedigrees from a genetically homogenous population, that of Costa Rica. This approach is based on the use of a conservative definition of the BP phenotype in preparation for whole genome screening with polymorphic markers. Linkage simulation analyses are utilized to indicate the probability of detecting evidence suggestive of linkage, using these pedigrees. These analyses are performed under a series of single locus models, ranging formmore » recessive to nearly dominant, utilizing both lod score and affected pedigree member analyses. Additional calculations demonstrate that with any of the models employed, most of the information for linkage derives from affected rather than unaffected individuals. 26 refs., 2 figs., 5 tabs.« less

Genetic Predisposition to Self-Curing Infection with the Protozoan Leishmania chagasi: A Genome Wide Scan

PubMed Central

Jeronimo, Selma M. B.; Duggal, Priya; Ettinger, Nicholas A.; Nascimento, Eliana T.; Monteiro, Gloria R.; Cabral, Angela P.; Pontes, Núbia N.; Lacerda, Hênio G.; Queiroz, Paula V.; Maia, Carlos G.; Pearson, Richard D.; Blackwell, Jenefer M.; Beaty, Terri H.; Wilson, Mary E.

2008-01-01

The protozoan Leishmania chagasi can cause disseminated, fatal visceral leishmaniasis (VL) or asymptomatic human infection. We hypothesized that genetic factors contribute to this variable response to infection. A family study was performed in endemic neighborhoods near Natal, northeast Brazil. Subjects were assessed for VL or asymptomatic infection, defined as a positive delayed type hypersensitivity (DTH) skin test response to Leishmania antigen without disease symptoms. A genome scan of 405 microsatellite markers in 1254 subjects was analyzed for regions of linkage. The results indicated loci of potential linkage to DTH response on chromosomes 2, 13, 15 and 19, and a novel region of potential interest for VL on chromosome 9. An understanding of the genetic factors determining whether an individual will develop symptomatic or asymptomatic infection with L. chagasi may illuminate proteins essential for immune protection against this parasitic disease; findings could reveal strategies for immunotherapy or prevention. PMID:17955446

Click nucleic acid ligation: applications in biology and nanotechnology.

PubMed

El-Sagheer, Afaf H; Brown, Tom

2012-08-21

Biochemical strategies that use a combination of synthetic oligonucleotides, thermostable DNA polymerases, and DNA ligases can produce large DNA constructs up to 1 megabase in length. Although these ambitious targets are feasible biochemically, comparable technologies for the chemical synthesis of long DNA strands lag far behind. The best available chemical approach is the solid-phase phosphoramidite method, which can be used to assemble DNA strands up to 150 bases in length. Beyond this point, deficiencies in the chemistry make it impossible to produce pure DNA. A possible alternative approach to the chemical synthesis of large DNA strands is to join together carefully purified synthetic oligonucleotides by chemical methods. Click ligation by the copper-catalyzed azide-alkyne (CuAAC) reaction could facilitate this process. In this Account, we describe the synthesis, characterization, and applications of oligonucleotides prepared by click ligation. The alkyne and azide oligonucleotide strands can be prepared by standard protocols, and the ligation reaction is compatible with a wide range of chemical modifications to DNA and RNA. We have employed click ligation to synthesize DNA constructs up to 300 bases in length and much longer sequences are feasible. When the resulting triazole linkage is placed in a PCR template, various DNA polymerases correctly copy the entire base sequence. We have also successfully demonstrated both in vitro transcription and rolling circle amplification through the modified linkage. This linkage has shown in vivo biocompatibility: an antibiotic resistance gene containing triazole linkages functions in E. coli . Using click ligation, we have synthesized hairpin ribozymes up to 100 nucleotides in length and a hammerhead ribozyme with the triazole linkage located at the substrate cleavage site. At the opposite end of the length scale, click-ligated, cyclic mini-DNA duplexes have been used as models to study base pairing. Cyclic duplexes have potential therapeutic applications. They have extremely high thermodynamic stability, have increased resistance to enzymatic degradation, and have been investigated as decoys for regulatory proteins. For potential nanotechnology applications, we have synthesized double stranded DNA catenanes by click ligation. Other researchers have studied covalently fixed multistranded DNA constructs including triplexes and quadruplexes.

regSNPs: a strategy for prioritizing regulatory single nucleotide substitutions

PubMed Central

Teng, Mingxiang; Ichikawa, Shoji; Padgett, Leah R.; Wang, Yadong; Mort, Matthew; Cooper, David N.; Koller, Daniel L.; Foroud, Tatiana; Edenberg, Howard J.; Econs, Michael J.; Liu, Yunlong

2012-01-01

Motivation: One of the fundamental questions in genetics study is to identify functional DNA variants that are responsible to a disease or phenotype of interest. Results from large-scale genetics studies, such as genome-wide association studies (GWAS), and the availability of high-throughput sequencing technologies provide opportunities in identifying causal variants. Despite the technical advances, informatics methodologies need to be developed to prioritize thousands of variants for potential causative effects. Results: We present regSNPs, an informatics strategy that integrates several established bioinformatics tools, for prioritizing regulatory SNPs, i.e. the SNPs in the promoter regions that potentially affect phenotype through changing transcription of downstream genes. Comparing to existing tools, regSNPs has two distinct features. It considers degenerative features of binding motifs by calculating the differences on the binding affinity caused by the candidate variants and integrates potential phenotypic effects of various transcription factors. When tested by using the disease-causing variants documented in the Human Gene Mutation Database, regSNPs showed mixed performance on various diseases. regSNPs predicted three SNPs that can potentially affect bone density in a region detected in an earlier linkage study. Potential effects of one of the variants were validated using luciferase reporter assay. Contact: yunliu@iupui.edu Supplementary information: Supplementary data are available at Bioinformatics online PMID:22611130

Effect of aqueous environment in chemical reactivity of monolignols. A New Fukui Function Study.

PubMed

Martínez, Carmen; Sedano, Miriam; Mendoza, Jorge; Herrera, Rafael; Rutiaga, Jose G; Lopez, Pablo

2009-09-01

The free radical reactivity of monolignols can be explained in terms of the Fukui function and the local hard and soft acids and bases (HSAB) principle to determine the potential linkages among them for reactions involving free radicals. Our results in gas-phase and aqueous environment elucidate the most probable free radical resonance structures in monolignols. Their reactivity toward nucleophilic or electrophilic species was described applying the Fukui function after a second analysis of the selected resonance structures. Methodology herein described could differentiate the inherent nature of one radical from another.

[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.

Linkage of mike she to wetland-dndc for carbon budgeting and anaerobic biogeochemistry simulation

Treesearch

Jianbo Cui; Changsheng Li; Ge Sun; Carl Trettin

2005-01-01

This study reports the linkage between MIKE SHE and Wetland-DNDC for carbon dynamics and greenhouse gases (GHGs) emissions simulation in forested wetland.Wet1and-DNDC was modified by parameterizing management measures, refining anaerobic biogeochemical processes, and was linked to the hydrological model - MIKE SHE. As a preliminary application, we simulated the effect...

Depth gradients in food-web processes linking habitats in large lakes: Lake Superior as an exemplar ecosystem

USGS Publications Warehouse

Sierszen, Michael E.; Hrabik, Thomas R.; Stockwell, Jason D.; Cotter, Anne M; Hoffman, Joel C.; Yule, Daniel L.

2014-01-01

Support of whole-lake food webs through trophic linkages among pelagic, profundal and littoral habitats appears to be integral to the functioning of large lakes. These linkages can be disrupted though ecosystem disturbance such as eutrophication or the effects of invasive species and should be considered in native species restoration efforts.

Hausdorff clustering

NASA Astrophysics Data System (ADS)

Basalto, Nicolas; Bellotti, Roberto; de Carlo, Francesco; Facchi, Paolo; Pantaleo, Ester; Pascazio, Saverio

2008-10-01

A clustering algorithm based on the Hausdorff distance is analyzed and compared to the single, complete, and average linkage algorithms. The four clustering procedures are applied to a toy example and to the time series of financial data. The dendrograms are scrutinized and their features compared. The Hausdorff linkage relies on firm mathematical grounds and turns out to be very effective when one has to discriminate among complex structures.

Non-coding genomic regions possessing enhancer and silencer potential are associated with healthy aging and exceptional survival.

PubMed

Kim, Sangkyu; Welsh, David A; Myers, Leann; Cherry, Katie E; Wyckoff, Jennifer; Jazwinski, S Michal

2015-02-28

We have completed a genome-wide linkage scan for healthy aging using data collected from a family study, followed by fine-mapping by association in a separate population, the first such attempt reported. The family cohort consisted of parents of age 90 or above and their children ranging in age from 50 to 80. As a quantitative measure of healthy aging, we used a frailty index, called FI34, based on 34 health and function variables. The linkage scan found a single significant linkage peak on chromosome 12. Using an independent cohort of unrelated nonagenarians, we carried out a fine-scale association mapping of the region suggestive of linkage and identified three sites associated with healthy aging. These healthy-aging sites (HASs) are located in intergenic regions at 12q13-14. HAS-1 has been previously associated with multiple diseases, and an enhancer was recently mapped and experimentally validated within the site. HAS-2 is a previously uncharacterized site possessing genomic features suggestive of enhancer activity. HAS-3 contains features associated with Polycomb repression. The HASs also contain variants associated with exceptional longevity, based on a separate analysis. Our results provide insight into functional genomic networks involving non-coding regulatory elements that are involved in healthy aging and longevity.

Non-coding genomic regions possessing enhancer and silencer potential are associated with healthy aging and exceptional survival

PubMed Central

Kim, Sangkyu; Welsh, David A.; Myers, Leann; Cherry, Katie E.; Wyckoff, Jennifer; Jazwinski, S. Michal

2015-01-01

We have completed a genome-wide linkage scan for healthy aging using data collected from a family study, followed by fine-mapping by association in a separate population, the first such attempt reported. The family cohort consisted of parents of age 90 or above and their children ranging in age from 50 to 80. As a quantitative measure of healthy aging, we used a frailty index, called FI34, based on 34 health and function variables. The linkage scan found a single significant linkage peak on chromosome 12. Using an independent cohort of unrelated nonagenarians, we carried out a fine-scale association mapping of the region suggestive of linkage and identified three sites associated with healthy aging. These healthy-aging sites (HASs) are located in intergenic regions at 12q13–14. HAS-1 has been previously associated with multiple diseases, and an enhancer was recently mapped and experimentally validated within the site. HAS-2 is a previously uncharacterized site possessing genomic features suggestive of enhancer activity. HAS-3 contains features associated with Polycomb repression. The HASs also contain variants associated with exceptional longevity, based on a separate analysis. Our results provide insight into functional genomic networks involving non-coding regulatory elements that are involved in healthy aging and longevity. PMID:25682868

Biochemical characterization of two GH70 family 4,6-α-glucanotransferases with distinct product specificity from Lactobacillus aviarius subsp. aviarius DSM 20655.

PubMed

Meng, Xiangfeng; Gangoiti, Joana; de Kok, Niels; van Leeuwen, Sander S; Pijning, Tjaard; Dijkhuizen, Lubbert

2018-07-01

Nine GtfB-like 4,6-α-glucanotransferases (4,6-α-GTs) (represented by GtfX of L. aviarius subsp. aviarius DSM 20655) were identified to show distinct characteristics in conserved motifs I-IV. In particular, the "fingerprint" Tyr in motif III of these nine GtfB-type 4,6-α-GTs was found to be replaced by a Trp. In L. aviarius subsp. aviarius DSM20655, a second GtfB-like protein (GtfY), containing the canonical GtfB Tyr residue in motif III, was located directly upstream of GtfX. Biochemical characterization revealed that both GtfX and GtfY showed GtfB-like 4,6-α-GT activity, cleaving (α1→4) linkages and catalyzing the synthesis of (α1→6) linkages. Nonetheless, they differ in product specificity; GtfY only synthesizes consecutive (α1→6) linkages, yielding linear α-glucan products, but GtfX catalyzes the synthesis of (α1→6) linkages predominantly at branch points (22%) rather than in linear segments (10%). The highly branched α-glucan produced by GtfX from amylose V is resistant to digestion by α-amylase, offering great potential as dietary fibers. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Aboveground-belowground biodiversity linkages differ in early and late successional temperate forests

PubMed Central

Li, Hui; Wang, Xugao; Liang, Chao; Hao, Zhanqing; Zhou, Lisha; Ma, Sam; Li, Xiaobin; Yang, Shan; Yao, Fei; Jiang, Yong

2015-01-01

Understanding ecological linkages between above- and below-ground biota is critical for deepening our knowledge on the maintenance and stability of ecosystem processes. Nevertheless, direct comparisons of plant-microbe diversity at the community level remain scarce due to the knowledge gap between microbial ecology and plant ecology. We compared the α- and β- diversities of plant and soil bacterial communities in two temperate forests that represented early and late successional stages. We documented different patterns of aboveground-belowground diversity relationships in these forests. We observed no linkage between plant and bacterial α-diversity in the early successional forest, and even a negative correlation in the late successional forest, indicating that high bacterial α-diversity is not always linked to high plant α-diversity. Beta-diversity coupling was only found at the late successional stage, while in the early successional forest, the bacterial β-diversity was closely correlated with soil property distances. Additionally, we showed that the dominant competitive tree species in the late successional forest may play key roles in driving forest succession by shaping the soil bacterial community in the early successional stage. This study sheds new light on the potential aboveground-belowground linkage in natural ecosystems, which may help us understand the mechanisms that drive ecosystem succession. PMID:26184121

Identifying common pressure pathways from a complex network of human activities to support ecosystem-based management.

PubMed

Knights, Antony M; Koss, Rebecca S; Robinson, Leonie A

2013-06-01

The marine environment is heavily exploited, but unintentional consequences cause wide-ranging negative effects to its characteristics. Linkage frameworks (e.g., DPSIR [driver-pressure-state-impact-response]) are commonly used to describe an interaction between human activities and ecological characteristics of the ecosystem, but as each linkage is viewed independently, the diversity of pressures that affect those characteristics may not be identified or managed effectively. Here we demonstrate an approach for using linkages to build a simple network to capture the complex relationships arising from multiple sectors and their activities. Using data-analysis tools common to ecology, we show how linkages can be placed into mechanistically similar groups. Management measures can be combined into fewer and more simplified measures that target groups of pressures rather than individual pressures, which is likely to increase compliance and the success of the measure while reducing the cost of enforcement. Given that conservation objectives (regional priorities) can vary, we also demonstrate by way of a case study example from the Marine Strategy Framework Directive, how management priorities might change, and illustrate how the approach can be used to identify sectors for control that best support the conservation objectives.

Glycan Reader: Automated Sugar Identification and Simulation Preparation for Carbohydrates and Glycoproteins

PubMed Central

Jo, Sunhwan; Song, Kevin C.; Desaire, Heather; MacKerell, Alexander D.; Im, Wonpil

2011-01-01

Understanding how glycosylation affects protein structure, dynamics, and function is an emerging and challenging problem in biology. As a first step toward glycan modeling in the context of structural glycobiology, we have developed Glycan Reader and integrated it into the CHARMM-GUI, http://www.charmm-gui.org/input/glycan. Glycan Reader greatly simplifies the reading of PDB structure files containing glycans through (i) detection of carbohydrate molecules, (ii) automatic annotation of carbohydrates based on their three-dimensional structures, (iii) recognition of glycosidic linkages between carbohydrates as well as N-/O-glycosidic linkages to proteins, and (iv) generation of inputs for the biomolecular simulation program CHARMM with the proper glycosidic linkage setup. In addition, Glycan Reader is linked to other functional modules in CHARMM-GUI, allowing users to easily generate carbohydrate or glycoprotein molecular simulation systems in solution or membrane environments and visualize the electrostatic potential on glycoprotein surfaces. These tools are useful for studying the impact of glycosylation on protein structure and dynamics. PMID:21815173

An update on the effects of playing violent video games.

PubMed

Anderson, Craig A

2004-02-01

This article presents a brief overview of existing research on the effects of exposure to violent video games. An updated meta-analysis reveals that exposure to violent video games is significantly linked to increases in aggressive behaviour, aggressive cognition, aggressive affect, and cardiovascular arousal, and to decreases in helping behaviour. Experimental studies reveal this linkage to be causal. Correlational studies reveal a linkage to serious, real-world types of aggression. Methodologically weaker studies yielded smaller effect sizes than methodologically stronger studies, suggesting that previous meta-analytic studies of violent video games underestimate the true magnitude of observed deleterious effects on behaviour, cognition, and affect.

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

Ensemble Learning of QTL Models Improves Prediction of Complex Traits

PubMed Central

Bian, Yang; Holland, James B.

2015-01-01

Quantitative trait locus (QTL) models can provide useful insights into trait genetic architecture because of their straightforward interpretability but are less useful for genetic prediction because of the difficulty in including the effects of numerous small effect loci without overfitting. Tight linkage between markers introduces near collinearity among marker genotypes, complicating the detection of QTL and estimation of QTL effects in linkage mapping, and this problem is exacerbated by very high density linkage maps. Here we developed a thinning and aggregating (TAGGING) method as a new ensemble learning approach to QTL mapping. TAGGING reduces collinearity problems by thinning dense linkage maps, maintains aspects of marker selection that characterize standard QTL mapping, and by ensembling, incorporates information from many more markers-trait associations than traditional QTL mapping. The objective of TAGGING was to improve prediction power compared with QTL mapping while also providing more specific insights into genetic architecture than genome-wide prediction models. TAGGING was compared with standard QTL mapping using cross validation of empirical data from the maize (Zea mays L.) nested association mapping population. TAGGING-assisted QTL mapping substantially improved prediction ability for both biparental and multifamily populations by reducing both the variance and bias in prediction. Furthermore, an ensemble model combining predictions from TAGGING-assisted QTL and infinitesimal models improved prediction abilities over the component models, indicating some complementarity between model assumptions and suggesting that some trait genetic architectures involve a mixture of a few major QTL and polygenic effects. PMID:26276383

Effects of the Ordering of Natural Selection and Population Regulation Mechanisms on Wright-Fisher Models

PubMed Central

He, Zhangyi; Beaumont, Mark; Yu, Feng

2017-01-01

We explore the effect of different mechanisms of natural selection on the evolution of populations for one- and two-locus systems. We compare the effect of viability and fecundity selection in the context of the Wright-Fisher model with selection under the assumption of multiplicative fitness. We show that these two modes of natural selection correspond to different orderings of the processes of population regulation and natural selection in the Wright-Fisher model. We find that under the Wright-Fisher model these two different orderings can affect the distribution of trajectories of haplotype frequencies evolving with genetic recombination. However, the difference in the distribution of trajectories is only appreciable when the population is in significant linkage disequilibrium. We find that as linkage disequilibrium decays the trajectories for the two different models rapidly become indistinguishable. We discuss the significance of these findings in terms of biological examples of viability and fecundity selection, and speculate that the effect may be significant when factors such as gene migration maintain a degree of linkage disequilibrium. PMID:28500051

Extension of the lod score: the mod score.

PubMed

Clerget-Darpoux, F

2001-01-01

In 1955 Morton proposed the lod score method both for testing linkage between loci and for estimating the recombination fraction between them. If a disease is controlled by a gene at one of these loci, the lod score computation requires the prior specification of an underlying model that assigns the probabilities of genotypes from the observed phenotypes. To address the case of linkage studies for diseases with unknown mode of inheritance, we suggested (Clerget-Darpoux et al., 1986) extending the lod score function to a so-called mod score function. In this function, the variables are both the recombination fraction and the disease model parameters. Maximizing the mod score function over all these parameters amounts to maximizing the probability of marker data conditional on the disease status. Under the absence of linkage, the mod score conforms to a chi-square distribution, with extra degrees of freedom in comparison to the lod score function (MacLean et al., 1993). The mod score is asymptotically maximum for the true disease model (Clerget-Darpoux and Bonaïti-Pellié, 1992; Hodge and Elston, 1994). Consequently, the power to detect linkage through mod score will be highest when the space of models where the maximization is performed includes the true model. On the other hand, one must avoid overparametrization of the model space. For example, when the approach is applied to affected sibpairs, only two constrained disease model parameters should be used (Knapp et al., 1994) for the mod score maximization. It is also important to emphasize the existence of a strong correlation between the disease gene location and the disease model. Consequently, there is poor resolution of the location of the susceptibility locus when the disease model at this locus is unknown. Of course, this is true regardless of the statistics used. The mod score may also be applied in a candidate gene strategy to model the potential effect of this gene in the disease. Since, however, it ignores the information provided both by disease segregation and by linkage disequilibrium between the marker alleles and the functional disease alleles, its power of discrimination between genetic models is weak. The MASC method (Clerget-Darpoux et al., 1988) has been designed to address more efficiently the objectives of a candidate gene approach.

Implementing microbicides in low income countries

PubMed Central

Gengiah, Tanuja; Karim, Quarraisha Abdool

2012-01-01

The magnitude of the global HIV epidemic is determined by women from lower income countries, specifically sub-Saharan Africa. Microbicides offer women who are unable to negotiate safe sex practices a self-initiated HIV prevention method. Of note, is its potential to yield significant public health benefits even with relatively conservative efficacy, coverage and user adherence estimates, making microbicides an effective intervention to invest scarce health care resources. Existing health care delivery systems provide an excellent opportunity to identify women at highest risk for infection and to also provide an access point to initiate microbicide use. Innovative quality improvement approaches, which strengthen existing sexual reproductive health services and include HIV testing, and linkages to care and treatment services provide an opportunity to lay the foundations for wide-scale provision of microbicides. The potential to enhance health outcomes in women and infants and potentially impact rates of new HIV infection may soon be realised. PMID:22498040

7 CFR 3430.908 - Review criteria.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Agriculture Regulations of the Department of Agriculture (Continued) COOPERATIVE STATE RESEARCH, EDUCATION... to the following factors: (a) Potential for Advancing Quality of Technology Development, Applied Research, and/or Training/Significance of the Program. (b) Proposed Approach and Cooperative Linkages. (c...

Eco-Health Relationship Browser

EPA Science Inventory

The Eco-Health Relationship Browser (Browser) is a web tool designed to portray, in an engaging and intuitive way, the linkages between ecosystems, their services, and potential health outcomes that have been associated with those services in the literature. It functions an inte...

[Construction of genetic linkage map and localization of NBS-LRR like resistance gene analogues in cauliflower (Brassica oleracea var. botrytis)].

PubMed

Gu, Yu; Zhao, Qian-Cheng; Sun, De-Ling; Song, Wen-Qin

2007-06-01

Nucleotide binding site (NBS) profiling, a new method was used to map resistance gene analogues (RGAs) in cauliflower (Brassica oleracea var. botrytis). This method allows amplification and the mapping of genetic markers anchored in the conserved NBS encoding domain of plant disease resistance genes. AFLP was also performed to construct the cauliflower intervarietal genetic map. The aim of constructing genetic map was to identify potential molecular markers linked to important agronomic traits that would be particularly useful for development and improving the species. Using 17 AFLP primer combinations and two degeneration primer/enzyme combinations, a total of 234 AFLP markers and 21 NBS markers were mapped in the F2 population derived from self-pollinating a single F1 plant of the cross AD White Flower x C-8. The markers were mapped in 9 of major linkage groups spanning 668.4 cM, with an average distance of 2.9 cM between adjacent mapped markers. The AFLP markers were well distributed throughout the linkage groups. The linkage groups contained from 12 to 47 loci each and the distance between two consecutive loci ranged from 0 to 14.9 cM. NBS markers were mapped on 8 of the 9 linkage groups of the genetic map. Most of these markers were organized in clusters. This result demonstrates the feasibility of the NBS-profiling method for generating NBS markers for resistance loci in cauliflower. The clustering of the markers mapped in this study adds to the evidence that most of them could be real RGAs.

Interfacial charge-transfer transitions in a TiO2-benzenedithiol complex with Ti-S-C linkages.

PubMed

Fujisawa, Jun-ichi; Muroga, Ryuki; Hanaya, Minoru

2015-11-28

Interfacial charge-transfer (ICT) transitions between organic materials and inorganic semiconductors are a new mechanism for light absorption at organic-semiconductor interfaces. ICT transitions cause one-step interfacial charge separation without loss of energy. This feature is potentially useful to realize efficient organic-inorganic hybrid solar cells. ICT transitions have been examined by employing titanium dioxide (TiO2) nanoparticles chemisorbed with π-conjugated molecules via Ti-O-C linkages. Here, we report ICT transitions in a TiO2 and 1,2-benzenedithiol (BDT) complex with Ti-S-C linkages. BDT adsorbs on TiO2 by the bridging bidentate coordination of the sulfur atoms to surface titanium atoms. The TiO2-BDT complex shows ICT transitions from the BDT moiety to the conduction band of TiO2 in the visible region. The ICT transitions occur by orbital overlaps between the d orbitals of the surface titanium atoms and the π orbitals of the benzene ring. Our density-functional-theory (DFT) analysis reveals that the 3p valence orbitals of the sulfur bridging atoms contribute to more than 50% of the highest occupied molecular orbital (HOMO) and the 3d-3p(sulfur)-π interaction via the Ti-S-C linkage enhances the electronic mixing between the titanium atoms and the benzene moiety as compared to the 3d-2p(oxygen)-πvia the Ti-O-C linkage. This result indicates the important role of the heavier-atom linkers for strong organic-inorganic electronic couplings.

A Linkage Map and QTL Analysis for Pyrethroid Resistance in the Bed Bug Cimex lectularius.

PubMed

Fountain, Toby; Ravinet, Mark; Naylor, Richard; Reinhardt, Klaus; Butlin, Roger K

2016-12-07

The rapid evolution of insecticide resistance remains one of the biggest challenges in the control of medically and economically important pests. Insects have evolved a diverse range of mechanisms to reduce the efficacy of the commonly used classes of insecticides, and finding the genetic basis of resistance is a major aid to management. In a previously unstudied population, we performed an F 2 resistance mapping cross for the common bed bug, Cimex lectularius, for which insecticide resistance is increasingly widespread. Using 334 SNP markers obtained through RAD-sequencing, we constructed the first linkage map for the species, consisting of 14 putative linkage groups (LG), with a length of 407 cM and an average marker spacing of 1.3 cM. The linkage map was used to reassemble the recently published reference genome, facilitating refinement and validation of the current genome assembly. We detected a major QTL on LG12 associated with insecticide resistance, occurring in close proximity (1.2 Mb) to a carboxylesterase encoding candidate gene for pyrethroid resistance. This provides another example of this candidate gene playing a major role in determining survival in a bed bug population following pesticide resistance evolution. The recent availability of the bed bug genome, complete with a full list of potential candidate genes related to insecticide resistance, in addition to the linkage map generated here, provides an excellent resource for future research on the development and spread of insecticide resistance in this resurging pest species. Copyright © 2016 Fountain et al.

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

Toward a Molecular Cytogenetic Map for Cultivated Sunflower (Helianthus annuus L.) by Landed BAC/BIBAC Clones

PubMed Central

Feng, Jiuhuan; Liu, Zhao; Cai, Xiwen; Jan, Chao-Chien

2013-01-01

Conventional karyotypes and various genetic linkage maps have been established in sunflower (Helianthus annuus L., 2n = 34). However, the relationship between linkage groups and individual chromosomes of sunflower remains unknown and has considerable relevance for the sunflower research community. Recently, a set of linkage group-specific bacterial /binary bacterial artificial chromosome (BAC/BIBAC) clones was identified from two complementary BAC and BIBAC libraries constructed for cultivated sunflower cv. HA89. In the present study, we used these linkage group-specific clones (∼100 kb in size) as probes to in situ hybridize to HA89 mitotic chromosomes at metaphase using the BAC- fluorescence in situ hybridization (FISH) technique. Because a characteristic of the sunflower genome is the abundance of repetitive DNA sequences, a high ratio of blocking DNA to probe DNA was applied to hybridization reactions to minimize the background noise. As a result, all sunflower chromosomes were anchored by one or two BAC/BIBAC clones with specific FISH signals. FISH analysis based on tandem repetitive sequences, such as rRNA genes, has been previously reported; however, the BAC-FISH technique developed here using restriction fragment length polymorphism (RFLP)−derived BAC/BIBAC clones as probes to apply genome-wide analysis is new for sunflower. As chromosome-specific cytogenetic markers, the selected BAC/BIBAC clones that encompass the 17 linkage groups provide a valuable tool for identifying sunflower cytogenetic stocks (such as trisomics) and tracking alien chromosomes in interspecific crosses. This work also demonstrates the potential of using a large-insert DNA library for the development of molecular cytogenetic resources. PMID:23316437

Impact of population structure, effective bottleneck time, and allele frequency on linkage disequilibrium maps

PubMed Central

Zhang, Weihua; Collins, Andrew; Gibson, Jane; Tapper, William J.; Hunt, Sarah; Deloukas, Panos; Bentley, David R.; Morton, Newton E.

2004-01-01

Genetic maps in linkage disequilibrium (LD) units play the same role for association mapping as maps in centimorgans provide at much lower resolution for linkage mapping. Association mapping of genes determining disease susceptibility and other phenotypes is based on the theory of LD, here applied to relations with three phenomena. To test the theory, markers at high density along a 10-Mb continuous segment of chromosome 20q were studied in African-American, Asian, and Caucasian samples. Population structure, whether created by pooling samples from divergent populations or by the mating pattern in a mixed population, is accurately bioassayed from genotype frequencies. The effective bottleneck time for Eurasians is substantially less than for migration out of Africa, reflecting later bottlenecks. The classical dependence of allele frequency on mutation age does not hold for the generally shorter time span of inbreeding and LD. Limitation of the classical theory to mutation age justifies the assumption of constant time in a LD map, except for alleles that were rare at the effective bottleneck time or have arisen since. This assumption is derived from the Malecot model and verified in all samples. Tested measures of relative efficiency, support intervals, and localization error determine the operating characteristics of LD maps that are applicable to every sexually reproducing species, with implications for association mapping, high-resolution linkage maps, evolutionary inference, and identification of recombinogenic sequences. PMID:15604137

Impact of population structure, effective bottleneck time, and allele frequency on linkage disequilibrium maps.

PubMed

Zhang, Weihua; Collins, Andrew; Gibson, Jane; Tapper, William J; Hunt, Sarah; Deloukas, Panos; Bentley, David R; Morton, Newton E

2004-12-28

Genetic maps in linkage disequilibrium (LD) units play the same role for association mapping as maps in centimorgans provide at much lower resolution for linkage mapping. Association mapping of genes determining disease susceptibility and other phenotypes is based on the theory of LD, here applied to relations with three phenomena. To test the theory, markers at high density along a 10-Mb continuous segment of chromosome 20q were studied in African-American, Asian, and Caucasian samples. Population structure, whether created by pooling samples from divergent populations or by the mating pattern in a mixed population, is accurately bioassayed from genotype frequencies. The effective bottleneck time for Eurasians is substantially less than for migration out of Africa, reflecting later bottlenecks. The classical dependence of allele frequency on mutation age does not hold for the generally shorter time span of inbreeding and LD. Limitation of the classical theory to mutation age justifies the assumption of constant time in a LD map, except for alleles that were rare at the effective bottleneck time or have arisen since. This assumption is derived from the Malecot model and verified in all samples. Tested measures of relative efficiency, support intervals, and localization error determine the operating characteristics of LD maps that are applicable to every sexually reproducing species, with implications for association mapping, high-resolution linkage maps, evolutionary inference, and identification of recombinogenic sequences.

Common subtypes of idiopathic generalized epilepsies: Lack of linkage to D20S19 close to candidate loci (EBN1, EEGV1) on chromosome 20

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

Sander, T.; Schmitz, B.; Janz, D.

1996-02-16

Hereditary factors play a major role in the etiology of idiopathic generalized epilepsies (IGEs). A trait locus (EBN1) for a rare subtype of IGEs, the benign neonatal familial convulsions, and a susceptibility gene (EEGV1) for the common human low-voltage electroencephalogram have been mapped close together with D20S19 to the chromosomal region 20q13.2. Both loci are potential candidates for the susceptibility to IGE spectra with age-related onset beyond the neonatal period. The present study tested the hypothesis that a putative susceptibility locus linked to D20S19 predisposes to spectra of IGEs with age-related onset from childhood to adolescence. Linkage analyses were conductedmore » in 60 families ascertained through IGE patients with juvenile myoclonic epilepsy, juvenile absence epilepsy or childhood absence epilepsy. Our results provide evidence against linkage of a putative susceptibility gene for four hierarchically broadened IGE spectra with D20S19 assuming tentative single-locus genetic models. The extent of an {open_quotes}exclusion region{close_quotes} (lod scores below -2) varied from 0.5 cM up to 22 cM on either side of D2OSl9 depending on the trait assumed. These results are contrary to the expectation that a susceptibility gene in vicinity to D20S19 confers a common major gene effect to the expression of IGE spectra with age-related onset from childhood to adolescence. 50 refs., 1 fig., 1 tab.« less

Dihydro-5,6-dehydrokavain (DDK) from Alpinia zerumbet: Its Isolation, Synthesis, and Characterization.

PubMed

Xuan, Tran Dang; Teschke, Rolf

2015-09-09

Dihydro-5,6-dehydrokavain (DDK) is the major and most promising component of the tropical plant Alpinia zerumbet (shell ginger), a species of the ginger family Zingiberaceae. Alpinia zerumbet is known for its human use as a traditional herbal medicine, food, and dietary supplement. With its α-lactone ring, DDK belongs to the large chemical group of kavalactones, which are also found in kava (Piper methysticum), another herbal medicine; DDK is characterized by a double-bond linkage at positions 5,6 and the absence of a double-bond linkage at positions 7,8. This dissociates DDK from other kavalactones with their linkages at positions 7,8 and 5,6 that are both either completely saturated or unsaturated, or may have an unsaturated bond at the position 7,8 as well as a saturated bond at the position 5,6. DDK is easily identified and quantified by HPLC and GC. DDK contents in fresh leaves, stems and rhizomes range from 80 to 410 mg/g, requiring solvent extraction procedures to ensure high DDK yield. This is best achieved by hexane extraction from fresh rhizomes that were previously boiled in water, allowing DDK yields of up to 424 mg/g. Successful synthesis of DDK can be achieved by asymmetric pathways, whereas its simple chemical structure facilitates the synthesis of DDK derivatives by HCl hydrolysis. Thus, all synthesized products may be used for various commercial purposes, including the potential development of promising antiobesity pharmaceutical drugs, preparation of specific and safe dietary supplements, and use as effective natural herbicides or fungicides.

Hydroxyl radical generation in electro-Fenton process with a gas-diffusion electrode: Linkages with electro-chemical generation of hydrogen peroxide and iron redox cycle.

PubMed

Yatagai, Tomonori; Ohkawa, Yoshiko; Kubo, Daichi; Kawase, Yoshinori

2017-01-02

The hydroxyl radical generation in an electro-Fenton process with a gas-diffusion electrode which is strongly linked with electro-chemical generation of hydrogen peroxide and iron redox cycle was studied. The OH radical generation subsequent to electro-chemical generations of H 2 O 2 was examined under the constant potential in the range of Fe 2+ dosage from 0 to 1.0 mM. The amount of generated OH radical initially increased and gradually decreased after the maximum was reached. The initial rate of OH radical generation increased for the Fe 2+ dosage <0.25 mM and at higher Fe 2+ dosages remained constant. At higher Fe 2+ dosages the precipitation of Fe might inhibit the enhancement of OH radical generation. The experiments for decolorization and total organic carbon (TOC) removal of azo-dye Orange II by the electro-Fenton process were conducted and the quick decolorization and slow TOC removal of Orange II were found. To quantify the linkages of OH radical generation with dynamic behaviors of electro-chemically generated H 2 O 2 and iron redox cycle and to investigate effects of OH radical generation on the decolorization and TOC removal of Orange II, novel reaction kinetic models were developed. The proposed models could satisfactory clarify the linkages of OH radical generation with electro-chemically generated H 2 O 2 and iron redox cycle and simulate the decolorization and TOC removal of Orange II by the electro-Fenton process.

Multilocus patterns of polymorphism and selection across the X chromosome of Caenorhabditis remanei.

PubMed

Cutter, Asher D

2008-03-01

Natural selection and neutral processes such as demography, mutation, and gene conversion all contribute to patterns of polymorphism within genomes. Identifying the relative importance of these varied components in evolution provides the principal challenge for population genetics. To address this issue in the nematode Caenorhabditis remanei, I sampled nucleotide polymorphism at 40 loci across the X chromosome. The site-frequency spectrum for these loci provides no evidence for population size change, and one locus presents a candidate for linkage to a target of balancing selection. Selection for codon usage bias leads to the non-neutrality of synonymous sites, and despite its weak magnitude of effect (N(e)s approximately 0.1), is responsible for profound patterns of diversity and divergence in the C. remanei genome. Although gene conversion is evident for many loci, biased gene conversion is not identified as a significant evolutionary process in this sample. No consistent association is observed between synonymous-site diversity and linkage-disequilibrium-based estimators of the population recombination parameter, despite theoretical predictions about background selection or widespread genetic hitchhiking, but genetic map-based estimates of recombination are needed to rigorously test for a diversity-recombination relationship. Coalescent simulations also illustrate how a spurious correlation between diversity and linkage-disequilibrium-based estimators of recombination can occur, due in part to the presence of unbiased gene conversion. These results illustrate the influence that subtle natural selection can exert on polymorphism and divergence, in the form of codon usage bias, and demonstrate the potential of C. remanei for detecting natural selection from genomic scans of polymorphism.

Nanoparticle bioconjugate for controlled cellular delivery of doxorubicin

NASA Astrophysics Data System (ADS)

Sangtani, Ajmeeta; Petryayeva, Eleonora; Wu, Miao; Susumu, Kimihiro; Oh, Eunkeu; Huston, Alan L.; Lasarte-Aragones, Guillermo; Medintz, Igor L.; Algar, W. Russ; Delehanty, James B.

2018-02-01

Nanoparticle (NP)-mediated drug delivery offers the potential to overcome limitations of systemic delivery, including the ability to specifically target cargo and control release of NP-associated drug cargo. Doxorubicin (DOX) is a widely used FDA-approved cancer therapeutic; however, multiple side effects limit its utility. Thus, there is wide interest in modulating toxicity after cell delivery. Our goal here was to realize a NP-based DOX-delivery system that can modulate drug toxicity by controlling the release kinetics of DOX from the surface of a hard NP carrier. To achieve this, we employed a quantum dot (QD) as a central scaffold which DOX was appended via three different peptidyl linkages (ester, disulfide, hydrazone) that are cleavable in response to various intracellular conditions. Attachment of a cell penetrating peptide (CPP) containing a positively charged polyarginine sequence facilitates endocytosis of the ensemble. Polyhistidine-driven metal affinity coordination was used to self-assemble both peptides to the QD surface, allowing for fine control over both the ratio of peptides attached to the QD as well as DOX dose delivered to cells. Microplate-based Förster resonance energy transfer assays confirmed the successful ratiometric assembly of the conjugates and functionality of the linkages. Cell delivery experiments and cytotoxicity assays were performed to compare the various cleavable linkages to a control peptide where DOX is attached through an amide bond. The role played by various attachment chemistries used in QD-peptide-drug assemblies and their implications for the rationale in design of NPbased constructs for drug delivery is described here.

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?

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

Linkage design effect on the reliability of surface-micromachined microengines driving a load

NASA Astrophysics Data System (ADS)

Tanner, Danelle M.; Peterson, Kenneth A.; Irwin, Lloyd W.; Tangyunyong, Paiboon; Miller, William M.; Eaton, William P.; Smith, Norman F.; Rodgers, M. Steven

1998-09-01

The reliability of microengines is a function of the design of the mechanical linkage used to connect the electrostatic actuator to the drive. We have completed a series of reliability stress tests on surface micromachined microengines driving an inertial load. In these experiments, we used microengines that had pin mechanisms with guides connecting the drive arms to the electrostatic actuators. Comparing this data to previous results using flexure linkages revealed that the pin linkage design was less reliable. The devices were stressed to failure at eight frequencies, both above and below the measured resonance frequency of the microengine. Significant amounts of wear debris were observed both around the hub and pin joint of the drive gear. Additionally, wear tracks were observed in the area where the moving shuttle rubbed against the guides of the pin linkage. At each frequency, we analyzed the statistical data yielding a lifetime (t50) for median cycles to failure and (sigma) , the shape parameter of the distribution. A model was developed to describe the failure data based on fundamental wear mechanisms and forces exhibited in mechanical resonant systems. The comparison to the model will be discussed.

Genotyping-by-sequencing markers facilitate the identification of quantitative trait loci controlling resistance to Penicillium expansum in Malus sieversii

PubMed Central

Wisniewski, Michael; Fazio, Gennaro; Burchard, Erik; Gutierrez, Benjamin; Levin, Elena; Droby, Samir

2017-01-01

Blue mold caused by Penicillium expansum is the most important postharvest disease of apple worldwide and results in significant financial losses. There are no defined sources of resistance to blue mold in domesticated apple. However, resistance has been described in wild Malus sieversii accessions, including plant introduction (PI)613981. The objective of the present study was to identify the genetic loci controlling resistance to blue mold in this accession. We describe the first quantitative trait loci (QTL) reported in the Rosaceae tribe Maleae conditioning resistance to P. expansum on genetic linkage group 3 (qM-Pe3.1) and linkage group 10 (qM-Pe10.1). These loci were identified in a M.× domestica ‘Royal Gala’ X M. sieversii PI613981 family (GMAL4593) based on blue mold lesion diameter seven days post-inoculation in mature, wounded apple fruit inoculated with P. expansum. Phenotypic analyses were conducted in 169 progeny over a four year period. PI613981 was the source of the resistance allele for qM-Pe3.1, a QTL with a major effect on blue mold resistance, accounting for 27.5% of the experimental variability. The QTL mapped from 67.3 to 74 cM on linkage group 3 of the GMAL4593 genetic linkage map. qM-Pe10.1 mapped from 73.6 to 81.8 cM on linkage group 10. It had less of an effect on resistance, accounting for 14% of the experimental variation. ‘Royal Gala’ was the primary contributor to the resistance effect of this QTL. However, resistance-associated alleles in both parents appeared to contribute to the least square mean blue mold lesion diameter in an additive manner at qM-Pe10.1. A GMAL4593 genetic linkage map composed of simple sequence repeats and ‘Golden Delicious’ single nucleotide polymorphism markers was able to detect qM-Pe10.1, but failed to detect qM-Pe3.1. The subsequent addition of genotyping-by-sequencing markers to the linkage map provided better coverage of the PI613981 genome on linkage group 3 and facilitated discovery of qM-Pe3.1. A DNA test for qM-Pe3.1 has been developed and is currently being evaluated for its ability to predict blue mold resistance in progeny segregating for qM-Pe3.1. Due to the long juvenility of apple, the availability of a DNA test to screen for the presence of qM-Pe3.1 at the seedling stage will greatly improve efficiency of breeding apple for blue mold resistance. PMID:28257442

Molecular mapping of QTLs for plant type and earliness traits in pigeonpea (Cajanus cajan L. Millsp.).

PubMed

Kumawat, Giriraj; Raje, Ranjeet S; Bhutani, Shefali; Pal, Jitendra K; Mithra, Amitha S V C R; Gaikwad, Kishor; Sharma, Tilak R; Singh, Nagendra K

2012-10-08

Pigeonpea is an important grain legume of the semi-arid tropics and sub-tropical regions where it plays a crucial role in the food and nutritional security of the people. The average productivity of pigeonpea has remained very low and stagnant for over five decades due to lack of genomic information and intensive breeding efforts. Previous SSR-based linkage maps of pigeonpea used inter-specific crosses due to low inter-varietal polymorphism. Here our aim was to construct a high density intra-specific linkage map using genic-SNP markers for mapping of major quantitative trait loci (QTLs) for key agronomic traits, including plant height, number of primary and secondary branches, number of pods, days to flowering and days to maturity in pigeonpea. A population of 186 F2:3 lines derived from an intra-specific cross between inbred lines 'Pusa Dwarf' and 'HDM04-1' was used to construct a dense molecular linkage map of 296 genic SNP and SSR markers covering a total adjusted map length of 1520.22 cM for the 11 chromosomes of the pigeonpea genome. This is the first dense intra-specific linkage map of pigeonpea with the highest genome length coverage. Phenotypic data from the F2:3 families were used to identify thirteen QTLs for the six agronomic traits. The proportion of phenotypic variance explained by the individual QTLs ranged from 3.18% to 51.4%. Ten of these QTLs were clustered in just two genomic regions, indicating pleiotropic effects or close genetic linkage. In addition to the main effects, significant epistatic interaction effects were detected between the QTLs for number of pods per plant. A large amount of information on transcript sequences, SSR markers and draft genome sequence is now available for pigeonpea. However, there is need to develop high density linkage maps and identify genes/QTLs for important agronomic traits for practical breeding applications. This is the first report on identification of QTLs for plant type and maturity traits in pigeonpea. The QTLs identified in this study provide a strong foundation for further validation and fine mapping for utilization in the pigeonpea improvement.

Linkage to HIV care and its determinants in the late HAART era: a systematic review and meta-analysis.

PubMed

Perelman, Julian; Rosado, Ricardo; Ferro, Adriana; Aguiar, Pedro

2018-06-01

Poor engagement into HIV care limits the effectiveness of highly active antiretroviral therapies (HAART) to improve survival and reduce transmission. The design of effective interventions to enhance linkage to care is dependent on evidence about rates of entry into HIV care. This is a systematic review and meta-analysis on linkage measurement and its determinants in the late era of HAART (post-2003), in high-income countries. We searched the PubMed and Web of Science databases, restricting our sample to the late HAART era (post-2003) until February 2016, and to high-income countries. We retained only studies that produced quantified outcomes. We rejected the studies with a high risk of bias, and followed a standard meta-analytic approach. Because there was a high heterogeneity ( I 2  > 90%), the aggregated findings were based on a random-effects model. A total of 43 studies were identified, all of them following a cohort of patients newly diagnosed until referred to specialized care. For a one-month period, the meta-proportion was 71.1% (IC95%: 61.0%-81.2). For a three-month duration, the meta-proportion of linkage to care was 77.0% (IC95%: 75.0%-79.0). For a one-year period, the meta-proportion was 76.3% (IC95%: 54.2%-98.4%). The proportions were lower when lab tests were used as referral indicator, with a pooled meta-proportion of 76.7% (IC95%: 73.0%-80.4), in comparison to a value of 80.8% (IC95%: 68.7%-92.9) for consultations. Being black or male were the most commonly observed determinants of delayed entry into care. Young people, injecting drug users, people with low socioeconomic status, or at a less advanced stage of disease also experienced lower proportions of timely linkage. Timely engagement into care is below 80% and specific sub-groups are particularly at risk of late entry. These findings confirm earlier evidence that linkage to care remains low, and that efforts should focus on vulnerable populations.

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.

Analyzing the Relative Linkages of Land Use and Hydrologic Variables with Urban Surface Water Quality using Multivariate Techniques

NASA Astrophysics Data System (ADS)

Ahmed, S.; Abdul-Aziz, O. I.

2015-12-01

We used a systematic data-analytics approach to analyze and quantify relative linkages of four stream water quality indicators (total nitrogen, TN; total phosphorus, TP; chlorophyll-a, Chla; and dissolved oxygen, DO) with six land use and four hydrologic variables, along with the potential external (upstream in-land and downstream coastal) controls in highly complex coastal urban watersheds of southeast Florida, U.S.A. Multivariate pattern recognition techniques of principle component and factor analyses, in concert with Pearson correlation analysis, were applied to map interrelations and identify latent patterns of the participatory variables. Relative linkages of the in-stream water quality variables with their associated drivers were then quantified by developing dimensionless partial least squares (PLS) regression model based on standardized data. Model fitting efficiency (R2=0.71-0.87) and accuracy (ratio of root-mean-square error to the standard deviation of the observations, RSR=0.35-0.53) suggested good predictions of the water quality variables in both wet and dry seasons. Agricultural land and groundwater exhibited substantial controls on surface water quality. In-stream TN concentration appeared to be mostly contributed by the upstream water entering from Everglades in both wet and dry seasons. In contrast, watershed land uses had stronger linkages with TP and Chla than that of the watershed hydrologic and upstream (Everglades) components for both seasons. Both land use and hydrologic components showed strong linkages with DO in wet season; however, the land use linkage appeared to be less in dry season. The data-analytics method provided a comprehensive empirical framework to achieve crucial mechanistic insights into the urban stream water quality processes. Our study quantitatively identified dominant drivers of water quality, indicating key management targets to maintain healthy stream ecosystems in complex urban-natural environments near the coast.

Using Object Oriented Bayesian Networks to Model Linkage, Linkage Disequilibrium and Mutations between STR Markers

PubMed Central

Kling, Daniel; Egeland, Thore; Mostad, Petter

2012-01-01

In a number of applications there is a need to determine the most likely pedigree for a group of persons based on genetic markers. Adequate models are needed to reach this goal. The markers used to perform the statistical calculations can be linked and there may also be linkage disequilibrium (LD) in the population. The purpose of this paper is to present a graphical Bayesian Network framework to deal with such data. Potential LD is normally ignored and it is important to verify that the resulting calculations are not biased. Even if linkage does not influence results for regular paternity cases, it may have substantial impact on likelihood ratios involving other, more extended pedigrees. Models for LD influence likelihoods for all pedigrees to some degree and an initial estimate of the impact of ignoring LD and/or linkage is desirable, going beyond mere rules of thumb based on marker distance. Furthermore, we show how one can readily include a mutation model in the Bayesian Network; extending other programs or formulas to include such models may require considerable amounts of work and will in many case not be practical. As an example, we consider the two STR markers vWa and D12S391. We estimate probabilities for population haplotypes to account for LD using a method based on data from trios, while an estimate for the degree of linkage is taken from the literature. The results show that accounting for haplotype frequencies is unnecessary in most cases for this specific pair of markers. When doing calculations on regular paternity cases, the markers can be considered statistically independent. In more complex cases of disputed relatedness, for instance cases involving siblings or so-called deficient cases, or when small differences in the LR matter, independence should not be assumed. (The networks are freely available at http://arken.umb.no/~dakl/BayesianNetworks.) PMID:22984448

Stratified Whole Genome Linkage Analysis of Chiari Type I Malformation Implicates Known Klippel-Feil Syndrome Genes as Putative Disease Candidates

PubMed Central

Markunas, Christina A.; Soldano, Karen; Dunlap, Kaitlyn; Cope, Heidi; Asiimwe, Edgar; Stajich, Jeffrey; Enterline, David; Grant, Gerald; Fuchs, Herbert

2013-01-01

Chiari Type I Malformation (CMI) is characterized by displacement of the cerebellar tonsils below the base of the skull, resulting in significant neurologic morbidity. Although multiple lines of evidence support a genetic contribution to disease, no genes have been identified. We therefore conducted the largest whole genome linkage screen to date using 367 individuals from 66 families with at least two individuals presenting with nonsyndromic CMI with or without syringomyelia. Initial findings across all 66 families showed minimal evidence for linkage due to suspected genetic heterogeneity. In order to improve power to localize susceptibility genes, stratified linkage analyses were performed using clinical criteria to differentiate families based on etiologic factors. Families were stratified on the presence or absence of clinical features associated with connective tissue disorders (CTDs) since CMI and CTDs frequently co-occur and it has been proposed that CMI patients with CTDs represent a distinct class of patients with a different underlying disease mechanism. Stratified linkage analyses resulted in a marked increase in evidence of linkage to multiple genomic regions consistent with reduced genetic heterogeneity. Of particular interest were two regions (Chr8, Max LOD = 3.04; Chr12, Max LOD = 2.09) identified within the subset of “CTD-negative” families, both of which harbor growth differentiation factors (GDF6, GDF3) implicated in the development of Klippel-Feil syndrome (KFS). Interestingly, roughly 3–5% of CMI patients are diagnosed with KFS. In order to investigate the possibility that CMI and KFS are allelic, GDF3 and GDF6 were sequenced leading to the identification of a previously known KFS missense mutation and potential regulatory variants in GDF6. This study has demonstrated the value of reducing genetic heterogeneity by clinical stratification implicating several convincing biological candidates and further supporting the hypothesis that multiple, distinct mechanisms are responsible for CMI. PMID:23620759

Triazole-linked DNA as a primer surrogate in the synthesis of first-strand cDNA.

PubMed

Fujino, Tomoko; Yasumoto, Ken-ichi; Yamazaki, Naomi; Hasome, Ai; Sogawa, Kazuhiro; Isobe, Hiroyuki

2011-11-04

A phosphate-eliminated nonnatural oligonucleotide serves as a primer surrogate in reverse transcription reaction of mRNA. Despite of the nonnatural triazole linkages in the surrogate, the reverse transcriptase effectively elongated cDNA sequences on the 3'-downstream of the primer by transcription of the complementary sequence of mRNA. A structure-activity comparison with the reference natural oligonucleotides shows the superior priming activity of the surrogate containing triazole-linkages. The nonnatural linkages also protect the transcribed cDNA from digestion reactions with 5'-exonuclease and enable us to remove noise transcripts of unknown origins. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Globalization and health: a framework for analysis and action.

PubMed Central

Woodward, D.; Drager, N.; Beaglehole, R.; Lipson, D.

2001-01-01

Globalization is a key challenge to public health, especially in developing countries, but the linkages between globalization and health are complex. Although a growing amount of literature has appeared on the subject, it is piecemeal, and suffers from a lack of an agreed framework for assessing the direct and indirect health effects of different aspects of globalization. This paper presents a conceptual framework for the linkages between economic globalization and health, with the intention that it will serve as a basis for synthesizing existing relevant literature, identifying gaps in knowledge, and ultimately developing national and international policies more favourable to health. The framework encompasses both the indirect effects on health, operating through the national economy, household economies and health-related sectors such as water, sanitation and education, as well as more direct effects on population-level and individual risk factors for health and on the health care system. Proposed also is a set of broad objectives for a programme of action to optimize the health effects of economic globalization. The paper concludes by identifying priorities for research corresponding with the five linkages identified as critical to the effects of globalization on health. PMID:11584737

Use of MODIS Satellite Images and an Atmospheric Dust Transport Model to Evaluate Juniperus spp. Pollen Phenology and Transport

NASA Technical Reports Server (NTRS)

Luvall, J. C.; Sprigg, W. A.; Levetin, E.; Huete, A.; Nickovic, S.; Pejanovic, G. A.; Vukovic, A.; Van de Water, P. K.; Myers, O. B.; Budge, A. M.;

Use Of MODIS Satellite Images And An Atmospheric Dust Transport Model To Evaluate Juniperus Spp. Pollen Phenology And Transport

NASA Astrophysics Data System (ADS)

Luvall, J. C.; Sprigg, W. A.; Levetin, E.; Huete, A. R.; Nickovic, S.; Crimmins, T. M.; Van De Water, P. K.; Pejanovic, G.; Vukovic, A. J.; Myers, O.; Budge, A.; Zelicoff, A.; Bunderson, L.; Ponce-Campos, G.

2011-12-01

Pollen can be transported great distances. Van de Water et al., 2003 reported Juniperus spp. pollen, a significant aeroallergen was transported 200-600 km. Hence local observations of plant phenology may not be consistent with the timing and source of pollen collected by pollen sampling instruments. Direct detection of pollen via satellite is not practical. A practical alternative combines modeling and phenological observations using ground based sampling and satellite data. The DREAM (Dust REgional Atmospheric Model) is a verified model for atmospheric dust transport modeling using MODIS data products to identify source regions and quantities of dust (Nickovic et al. 2001). The use of satellite data products for studying phenology is well documented (White and Nemani 2006). In the current project MODIS data will provide critical input to the PREAM model providing pollen source location, timing of pollen release, and vegetation type. We are modifying the DREAM model (PREAM - Pollen REgional Atmospheric Model) to incorporate pollen transport. The linkages already exist with DREAM through PHAiRS (Public Health Applications in Remote Sensing) to the public health community. This linkage has the potential to fill this data gap so that the potential association of health effects of pollen can better be tracked for possible linkage with health outcome data which may be associated with asthma, respiratory effects, myocardial infarction, and lost workdays. Juniperus spp. pollen phenology may respond to a wide range of environmental factors such as day length, growing degree-days, precipitation patterns and soil moisture. Species differences are also important. These environmental factors vary over both time and spatial scales. Ground based networks such as the USA National Phenology Network have been established to provide national wide observations of vegetation phenology. However, the density of observers is not adequate to sufficiently document the phenology variability over large regions. Hence the use of satellite data is critical to observe Juniperus spp. pollen phenology. MODIS data was used to observe Juniperus spp. pollen phenology. The MODIS surface reflectance product(MOD09) provided information on the Juniper spp. cone formation and cone density. Ground based observational records of pollen release timing and quantities were used as verification. Techniques developed using MOD09 surface reflectance products will be directly applicable to the next generation sensors such as VIIRS.

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

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.

Linkage of Viral Sequences among HIV-Infected Village Residents in Botswana: Estimation of Linkage Rates in the Presence of Missing Data

PubMed Central

Carnegie, Nicole Bohme; Wang, Rui; Novitsky, Vladimir; De Gruttola, Victor

2014-01-01

Linkage analysis is useful in investigating disease transmission dynamics and the effect of interventions on them, but estimates of probabilities of linkage between infected people from observed data can be biased downward when missingness is informative. We investigate variation in the rates at which subjects' viral genotypes link across groups defined by viral load (low/high) and antiretroviral treatment (ART) status using blood samples from household surveys in the Northeast sector of Mochudi, Botswana. The probability of obtaining a sequence from a sample varies with viral load; samples with low viral load are harder to amplify. Pairwise genetic distances were estimated from aligned nucleotide sequences of HIV-1C env gp120. It is first shown that the probability that randomly selected sequences are linked can be estimated consistently from observed data. This is then used to develop estimates of the probability that a sequence from one group links to at least one sequence from another group under the assumption of independence across pairs. Furthermore, a resampling approach is developed that accounts for the presence of correlation across pairs, with diagnostics for assessing the reliability of the method. Sequences were obtained for 65% of subjects with high viral load (HVL, n = 117), 54% of subjects with low viral load but not on ART (LVL, n = 180), and 45% of subjects on ART (ART, n = 126). The probability of linkage between two individuals is highest if both have HVL, and lowest if one has LVL and the other has LVL or is on ART. Linkage across groups is high for HVL and lower for LVL and ART. Adjustment for missing data increases the group-wise linkage rates by 40–100%, and changes the relative rates between groups. Bias in inferences regarding HIV viral linkage that arise from differential ability to genotype samples can be reduced by appropriate methods for accommodating missing data. PMID:24415932

Linkage of viral sequences among HIV-infected village residents in Botswana: estimation of linkage rates in the presence of missing data.

PubMed

Carnegie, Nicole Bohme; Wang, Rui; Novitsky, Vladimir; De Gruttola, Victor

2014-01-01

Linkage analysis is useful in investigating disease transmission dynamics and the effect of interventions on them, but estimates of probabilities of linkage between infected people from observed data can be biased downward when missingness is informative. We investigate variation in the rates at which subjects' viral genotypes link across groups defined by viral load (low/high) and antiretroviral treatment (ART) status using blood samples from household surveys in the Northeast sector of Mochudi, Botswana. The probability of obtaining a sequence from a sample varies with viral load; samples with low viral load are harder to amplify. Pairwise genetic distances were estimated from aligned nucleotide sequences of HIV-1C env gp120. It is first shown that the probability that randomly selected sequences are linked can be estimated consistently from observed data. This is then used to develop estimates of the probability that a sequence from one group links to at least one sequence from another group under the assumption of independence across pairs. Furthermore, a resampling approach is developed that accounts for the presence of correlation across pairs, with diagnostics for assessing the reliability of the method. Sequences were obtained for 65% of subjects with high viral load (HVL, n = 117), 54% of subjects with low viral load but not on ART (LVL, n = 180), and 45% of subjects on ART (ART, n = 126). The probability of linkage between two individuals is highest if both have HVL, and lowest if one has LVL and the other has LVL or is on ART. Linkage across groups is high for HVL and lower for LVL and ART. Adjustment for missing data increases the group-wise linkage rates by 40-100%, and changes the relative rates between groups. Bias in inferences regarding HIV viral linkage that arise from differential ability to genotype samples can be reduced by appropriate methods for accommodating missing data.

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.

PolyUbiquitin Chain Linkage Topology Selects the Functions from the Underlying Binding Landscape

PubMed Central

Wang, Yong; Tang, Chun; Wang, Erkang; Wang, Jin

2014-01-01

Ubiquitin (Ub) can generate versatile molecular signals and lead to different celluar fates. The functional poly-valence of Ub is believed to be resulted from its ability to form distinct polymerized chains with eight linkage types. To provide a full picture of ubiquitin code, we explore the binding landscape of two free Ub monomers and also the functional landscapes of of all eight linkage types by theoretical modeling. Remarkably, we found that most of the compact structures of covalently connected dimeric Ub chains (diUbs) pre-exist on the binding landscape. These compact functional states were subsequently validated by corresponding linkage models. This leads to the proposal that the folding architecture of Ub monomer has encoded all functional states into its binding landscape, which is further selected by different topologies of polymeric Ub chains. Moreover, our results revealed that covalent linkage leads to symmetry breaking of interfacial interactions. We further propose that topological constraint not only limits the conformational space for effective switching between functional states, but also selects the local interactions for realizing the corresponding biological function. Therefore, the topological constraint provides a way for breaking the binding symmetry and reaching the functional specificity. The simulation results also provide several predictions that qualitatively and quantitatively consistent with experiments. Importantly, the K48 linkage model successfully predicted intermediate states. The resulting multi-state energy landscape was further employed to reconcile the seemingly contradictory experimental data on the conformational equilibrium of K48-diUb. Our results further suggest that hydrophobic interactions are dominant in the functional landscapes of K6-, K11-, K33- and K48 diUbs, while electrostatic interactions play a more important role in the functional landscapes of K27, K29, K63 and linear linkages. PMID:24992446

PolyUbiquitin chain linkage topology selects the functions from the underlying binding landscape.

PubMed

Wang, Yong; Tang, Chun; Wang, Erkang; Wang, Jin

2014-07-01

Ubiquitin (Ub) can generate versatile molecular signals and lead to different celluar fates. The functional poly-valence of Ub is believed to be resulted from its ability to form distinct polymerized chains with eight linkage types. To provide a full picture of ubiquitin code, we explore the binding landscape of two free Ub monomers and also the functional landscapes of of all eight linkage types by theoretical modeling. Remarkably, we found that most of the compact structures of covalently connected dimeric Ub chains (diUbs) pre-exist on the binding landscape. These compact functional states were subsequently validated by corresponding linkage models. This leads to the proposal that the folding architecture of Ub monomer has encoded all functional states into its binding landscape, which is further selected by different topologies of polymeric Ub chains. Moreover, our results revealed that covalent linkage leads to symmetry breaking of interfacial interactions. We further propose that topological constraint not only limits the conformational space for effective switching between functional states, but also selects the local interactions for realizing the corresponding biological function. Therefore, the topological constraint provides a way for breaking the binding symmetry and reaching the functional specificity. The simulation results also provide several predictions that qualitatively and quantitatively consistent with experiments. Importantly, the K48 linkage model successfully predicted intermediate states. The resulting multi-state energy landscape was further employed to reconcile the seemingly contradictory experimental data on the conformational equilibrium of K48-diUb. Our results further suggest that hydrophobic interactions are dominant in the functional landscapes of K6-, K11-, K33- and K48 diUbs, while electrostatic interactions play a more important role in the functional landscapes of K27, K29, K63 and linear linkages.

Genetic dissection of MHC-associated susceptibility to Lepeophtheirus salmonis in Atlantic salmon

PubMed Central

Gharbi, Karim; Glover, Kevin A; Stone, Louise C; MacDonald, Elizabeth S; Matthews, Louise; Grimholt, Unni; Stear, Michael J

2009-01-01

Background Genetic variation has been shown to play a significant role in determining susceptibility to the salmon louse, Lepeophtheirus salmonis. However, the mechanisms involved in differential response to infection remain poorly understood. Recent findings in Atlantic salmon (Salmo salar) have provided evidence for a potential link between marker variation at the major histocompatibility complex (MHC) and differences in lice abundance among infected siblings, suggesting that MHC genes can modulate susceptibility to the parasite. In this study, we used quantitative trait locus (QTL) analysis to test the effect of genomic regions linked to MHC class I and II on linkage groups (LG) 15 and 6, respectively. Results Significant QTL effects were detected on both LG 6 and LG 15 in sire-based analysis but the QTL regions remained unresolved due to a lack of recombination between markers. In dam-based analysis, a significant QTL was identified on LG 6, which accounted for 12.9% of within-family variance in lice abundance. However, the QTL was located at the opposite end of DAA, with no significant overlap with the MHC class II region. Interestingly, QTL modelling also revealed evidence of sex-linked differences in lice abundance, indicating that males and females may have different susceptibility to infection. Conclusion Overall, QTL analysis provided relatively weak support for a proximal effect of classical MHC regions on lice abundance, which can partly be explained by linkage to other genes controlling susceptibility to L. salmonis on the same chromosome. PMID:19397823

Clickable and imageable multiblock polymer micelles with magnetically guided and PEG-switched targeting and release property for precise tumor theranosis.

PubMed

Wei, Jing; Shuai, Xiaoyu; Wang, Rui; He, Xueling; Li, Yiwen; Ding, Mingming; Li, Jiehua; Tan, Hong; Fu, Qiang

2017-11-01

Targeted delivery of therapeutics and diagnostics using nanotechnology holds great promise to minimize the side effects of conventional chemotherapy and enable specific and real-time detection of diseases. To realize this goal, we report a clickable and imageable nanovehicle assembled from multiblock polyurethanes (MPUs). The soft segments of the polymers are based on detachable poly(ethylene glycol) (PEG) and degradable poly(ε-caprolactone) (PCL), and the hard segments are constructed from lysine- and cystine-derivatives bearing reduction-responsive disulfide linkages and click-active alkynyl moieties, allowing for post-conjugation of targeting ligands via a click chemistry. It was found that the cleavage of PEG corona bearing a pH-sensitive benzoic-imine linkage (BPEG) could act as an on-off switch, which is capable of activating the clicked targeting ligands under extracellular acidic condition, followed by triggering the core degradation and payload release within tumor cells. In combination with superparamagnetic iron oxide nanoparticles (SPION) clustered within the micellar core, the MPUs exhibit excellent magnetic resonance imaging (MRI) contrast effects and T 2 relaxation in vitro, as well as magnetically guided MR imaging and multimodal targeting of therapeutics to tumor precisely, leading to significant inhibition of cancer with minimal side effect. This work provides a safe and versatile platform for the further development of smart theranostic systems for potential magnetically-targeted and imaging-guided personalized medicine. Copyright © 2017 Elsevier Ltd. All rights reserved.

Petrographic and Vitrinite Reflectance Analyses of a Suite of High Volatile Bituminous Coal Samples from the United States and Venezuela

USGS Publications Warehouse

Hackley, Paul C.; Kolak, Jonathan J.

2008-01-01

This report presents vitrinite reflectance and detailed organic composition data for nine high volatile bituminous coal samples. These samples were selected to provide a single, internally consistent set of reflectance and composition analyses to facilitate the study of linkages among coal composition, bitumen generation during thermal maturation, and geochemical characteristics of generated hydrocarbons. Understanding these linkages is important for addressing several issues, including: the role of coal as a source rock within a petroleum system, the potential for conversion of coal resources to liquid hydrocarbon fuels, and the interactions between coal and carbon dioxide during enhanced coalbed methane recovery and(or) carbon dioxide sequestration in coal beds.

Towards a more versatile alpha-glucan biosynthesis in plants.

PubMed

Kok-Jacon, Géraldine A; Ji, Qin; Vincken, Jean-Paul; Visser, Richard G F

2003-07-01

Starch is an important storage polysaccharide in many plants. It is composed of densely packed alpha-glucans, consisting of 1,4- and 1,4,6-linked glucose residues. The starch polymers are used in many industrial applications. The biosynthetic machinery for assembling the granule has been manipulated in many different ways to gain insight into the process of starch biosynthesis and to engineer starches with improved functionalities. With respect to the latter, two generic technologies with great potential have been developed: (i) introduction of new linkage types in starch polymers (1,3- and 1,6-linkages), and (ii) engineering granule-boundness. The toolbox to engineer this new generation of starch polymers is discussed.

From Manaus to Maputo: toward a public health and biodiversity framework.

PubMed

Romanelli, Cristina; Corvalan, Carlos; Cooper, H David; Manga, Lucien; Maiero, Marina; Campbell-Lendrum, Diarmid

2014-09-01

The linkages between human health, biodiversity, ecosystems, and the life-supporting services that they provide are varied and complex. The traditional neglect of this nexus by policy-makers perpetuates threats posed to ecosystems with potentially critical impacts on global health. The Convention on Biological Diversity and the World Health Organization recently co-convened two regional workshops on these intricate but vital linkages. From discussions held with policy-makers and experts in the biodiversity and health sectors, spanning some 50 countries in Africa and the Americas, we derive a broad framework for the development of national and regional public health and biodiversity strategies relevant to strategic planning processes in the emerging post-2015 development context.

When water saving limits recycling: Modelling economy-wide linkages of wastewater use.

PubMed

Luckmann, Jonas; Grethe, Harald; McDonald, Scott

2016-01-01

The reclamation of wastewater is an increasingly important water source in parts of the world. It is claimed that wastewater recycling is a cheap and reliable form of water supply, which preserves water resources and is economically efficient. However, the quantity of reclaimed wastewater depends on water consumption by economic agents connected to a sewage system. This study uses a Computable General Equilibrium (CGE) model to analyse such a cascading water system. A case study of Israel shows that failing to include this linkage can lead to an overestimation of the potential of wastewater recycling, especially when economic agents engage in water saving. Copyright © 2015 Elsevier Ltd. All rights reserved.

A High-Density Linkage Map Reveals Sexual Dimorphism in Recombination Landscapes in Red Deer (Cervus elaphus)

PubMed Central

Johnston, Susan E.; Huisman, Jisca; Ellis, Philip A.; Pemberton, Josephine M.

2017-01-01

High-density linkage maps are an important tool to gain insight into the genetic architecture of traits of evolutionary and economic interest, and provide a resource to characterize variation in recombination landscapes. Here, we used information from the cattle genome and the 50 K Cervine Illumina BeadChip to inform and refine a high-density linkage map in a wild population of red deer (Cervus elaphus). We constructed a predicted linkage map of 38,038 SNPs and a skeleton map of 10,835 SNPs across 34 linkage groups. We identified several chromosomal rearrangements in the deer lineage relative to sheep and cattle, including six chromosome fissions, one fusion, and two large inversions. Otherwise, our findings showed strong concordance with map orders in the cattle genome. The sex-averaged linkage map length was 2739.7 cM and the genome-wide autosomal recombination rate was 1.04 cM/Mb. The female autosomal map length was 1.21 longer than that of males (2767.4 cM vs. 2280.8 cM, respectively). Sex differences in map length were driven by high female recombination rates in peri-centromeric regions, a pattern that is unusual relative to other mammal species. This effect was more pronounced in fission chromosomes that would have had to produce new centromeres. We propose two hypotheses to explain this effect: (1) that this mechanism may have evolved to counteract centromeric drive associated with meiotic asymmetry in oocyte production; and/or (2) that sequence and structural characteristics suppressing recombination in close proximity to the centromere may not have evolved at neo-centromeres. Our study provides insight into how recombination landscapes vary and evolve in mammals, and will provide a valuable resource for studies of evolution, genetic improvement, and population management in red deer and related species. PMID:28667018

Transancestral fine-mapping of four type 2 diabetes susceptibility loci highlights potential causal regulatory mechanisms

PubMed Central

Horikoshi, Momoko; Pasquali, Lorenzo; Wiltshire, Steven; Huyghe, Jeroen R.; Mahajan, Anubha; Asimit, Jennifer L.; Ferreira, Teresa; Locke, Adam E.; Robertson, Neil R.; Wang, Xu; Sim, Xueling; Fujita, Hayato; Hara, Kazuo; Young, Robin; Zhang, Weihua; Choi, Sungkyoung; Chen, Han; Kaur, Ismeet; Takeuchi, Fumihiko; Fontanillas, Pierre; Thuillier, Dorothée; Yengo, Loic; Below, Jennifer E.; Tam, Claudia H.T.; Wu, Ying; Abecasis, Gonçalo; Altshuler, David; Bell, Graeme I.; Blangero, John; Burtt, Noél P.; Duggirala, Ravindranath; Florez, Jose C.; Hanis, Craig L.; Seielstad, Mark; Atzmon, Gil; Chan, Juliana C.N.; Ma, Ronald C.W.; Froguel, Philippe; Wilson, James G.; Bharadwaj, Dwaipayan; Dupuis, Josee; Meigs, James B.; Cho, Yoon Shin; Park, Taesung; Kooner, Jaspal S.; Chambers, John C.; Saleheen, Danish; Kadowaki, Takashi; Tai, E. Shyong; Mohlke, Karen L.; Cox, Nancy J.; Ferrer, Jorge; Zeggini, Eleftheria; Kato, Norihiro; Teo, Yik Ying; Boehnke, Michael; McCarthy, Mark I.; Morris, Andrew P.

2016-01-01

To gain insight into potential regulatory mechanisms through which the effects of variants at four established type 2 diabetes (T2D) susceptibility loci (CDKAL1, CDKN2A-B, IGF2BP2 and KCNQ1) are mediated, we undertook transancestral fine-mapping in 22 086 cases and 42 539 controls of East Asian, European, South Asian, African American and Mexican American descent. Through high-density imputation and conditional analyses, we identified seven distinct association signals at these four loci, each with allelic effects on T2D susceptibility that were homogenous across ancestry groups. By leveraging differences in the structure of linkage disequilibrium between diverse populations, and increased sample size, we localised the variants most likely to drive each distinct association signal. We demonstrated that integration of these genetic fine-mapping data with genomic annotation can highlight potential causal regulatory elements in T2D-relevant tissues. These analyses provide insight into the mechanisms through which T2D association signals are mediated, and suggest future routes to understanding the biology of specific disease susceptibility loci. PMID:26911676

Maltase Has Most Versatile α-Hydrolytic Activity Among the Mucosal α-Glucosidases of the Small Intestine.

PubMed

Lee, Byung-Hoo; Hamaker, Bruce R

2018-06-01

Complete digestion of the glycemic carbohydrates to glucose takes place through the combined action of the 4 mucosal α-glucosidases (maltase-glucoamylase and sucrase-isomaltase) in the small intestine. Maltase digests α-1,2- and α-1,3-disaccharides better than the other α-glucosidases, and has, as well, the capability to effectively hydrolyze α-1,4 and α-1,6 linkages that form the major backbone of a starch molecule. This broad hydrolytic activity on α-linkages makes it an enzyme that has the most versatile α-hydrolytic activity among the 4mucosal α-glucosidases. The slowly digestible properties of the unusual linkages from this research suggest the development of new glycemic oligosaccharides which will be hydrolyzed slowly, compared to α-1,4 linkages, for modulating the postprandial glycemic response. In addition, using mammalian mucosal α-glucosidases is a better fit to characterize carbohydrate digestion properties, compared to fungal amyloglucosidase which is currently applied in in vitro assays.

Understanding the linkages between social safety nets and childhood violence: a review of the evidence from low- and middle-income countries.

PubMed

Peterman, Amber; Neijhoft, Anastasia Naomi; Cook, Sarah; Palermo, Tia M

2017-09-01

As many as one billion children experience violence every year, and household- and community-level poverty are among the risk factors for child protection violations. Social safety nets (SSNs) are a main policy tool to address poverty and vulnerability, and there is substantial evidence demonstrating positive effects on children's health and human capital. This paper reviews evidence and develops a framework to understand linkages between non-contributory SSNs and the experience of childhood emotional, physical and sexual violence in low- and middle-income countries. We catalogue 14 rigorous impact evaluations, 11 of which are completed, analysing 57 unique impacts on diverse violence indicators. Among these impacts, approximately one in five represent statistically significant protective effects on childhood violence. Promising evidence relates to sexual violence among female adolescents in Africa, while there is less clear evidence of significant impacts in other parts of the developing world, and on young child measures, including violent discipline. Further, few studies are set up to meaningfully unpack mechanisms between SSNs and childhood violence; however, those most commonly hypothesized operate at the household level (through increases in economic security and reductions in poverty-related stress), the interpersonal level (improved parental behaviours, caregiving practices, improved psychosocial well-being) and at the child-level (protective education and decreases in problem or risky behaviours). It is important to emphasize that traditional SSNs are never designed with violence prevention as primary objectives, and thus should not be considered as standalone interventions to reduce risks for childhood violence. However, SSNs, particularly within integrated protection systems, appear to have potential to reduce violence risk. Linkages between SSNs and childhood violence are understudied, and investments should be made to close this evidence gap. © The Author 2017. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine.

Coastal livelihood transitions under globalization with implications for trans-ecosystem interactions

PubMed Central

Stevens, Kara; Williams, Nicholas E.; Sistla, Seeta A.; Roddy, Adam B.; Urquhart, Gerald R.

2017-01-01

Anthropogenic threats to natural systems can be exacerbated due to connectivity between marine, freshwater, and terrestrial ecosystems, complicating the already daunting task of governance across the land-sea interface. Globalization, including new access to markets, can change social-ecological, land-sea linkages via livelihood responses and adaptations by local people. As a first step in understanding these trans-ecosystem effects, we examined exit and entry decisions of artisanal fishers and smallholder farmers on the rapidly globalizing Caribbean coast of Nicaragua. We found that exit and entry decisions demonstrated clear temporal and spatial patterns and that these decisions differed by livelihood. In addition to household characteristics, livelihood exit and entry decisions were strongly affected by new access to regional and global markets. The natural resource implications of these livelihood decisions are potentially profound as they provide novel linkages and spatially-explicit feedbacks between terrestrial and marine ecosystems. Our findings support the need for more scientific inquiry in understanding trans-ecosystem tradeoffs due to linked-livelihood transitions as well as the need for a trans-ecosystem approach to natural resource management and development policy in rapidly changing coastal regions. PMID:29077748

Biscarbamate Cross-Linked Low-Molecular-Weight Polyethylenimine for Delivering Anti-chordin siRNA into Human Mesenchymal Stem Cells for Improving Bone Regeneration.

PubMed

Wang, Chuandong; Yuan, Weien; Xiao, Fei; Gan, Yaokai; Zhao, Xiaotian; Zhai, Zhanjing; Zhao, Xiaoying; Zhao, Chen; Cui, Penglei; Jin, Tuo; Chen, Xiaodong; Zhang, Xiaoling

2017-01-01

Small-interfering RNA (siRNA) provides a rapid solution for drug design and provides new methods to develop customizable medicines. Polyethyleneimine 25 kDa (PEI25kDa) is an effective transfection agent used in siRNA delivery. However, the lack of degradable linkage causes undesirable toxicity, hindering its clinical application. We designed a low-molecular-weight cross-linked polyethylenimine named PEI-Et (Mn:1220, Mw:2895) by using degradable ethylene biscarbamate linkage with lower cytotoxicity and higher knockdown efficiency than PEI25kDa in delivery Chordin siRNA to human bone mesenchymal stem cells (hBMSCs). Suppression of Chordin by using anti-Chordin siRNA delivered by PEI-Et improved bone regeneration in vitro and in vivo associated with the bone morphogenetic protein-2 (BMP-2) mediated smad1/5/8 signaling pathway. Results of this study suggest that Chordin siRNA can be potentially used to improve osteogenesis associated with the BMP-2-mediated Smad1/5/8 signaling pathway and biodegradable biscarbamate cross-linked low-molecular-weight polyethylenimine (PEI-Et) is a therapeutically feasible carrier material to deliver anti-Chordin siRNA to hBMSCs.

Linkage disequilibrium between STRPs and SNPs across the human genome.

PubMed

Payseur, Bret A; Place, Michael; Weber, James L

2008-05-01

Patterns of linkage disequilibrium (LD) reveal the action of evolutionary processes and provide crucial information for association mapping of disease genes. Although recent studies have described the landscape of LD among single nucleotide polymorphisms (SNPs) from across the human genome, associations involving other classes of molecular variation remain poorly understood. In addition to recombination and population history, mutation rate and process are expected to shape LD. To test this idea, we measured associations between short-tandem-repeat polymorphisms (STRPs), which can mutate rapidly and recurrently, and SNPs in 721 regions across the human genome. We directly compared STRP-SNP LD with SNP-SNP LD from the same genomic regions in the human HapMap populations. The intensity of STRP-SNP LD, measured by the average of D', was reduced, consistent with the action of recurrent mutation. Nevertheless, a higher fraction of STRP-SNP pairs than SNP-SNP pairs showed significant LD, on both short (up to 50 kb) and long (cM) scales. These results reveal the substantial effects of mutational processes on LD at STRPs and provide important measures of the potential of STRPs for association mapping of disease genes.

Beyond genome-wide scan: Association of a cis-regulatory NCR3 variant with mild malaria in a population living in the Republic of Congo.

PubMed

Baaklini, Sabrina; Afridi, Sarwat; Nguyen, Thy Ngoc; Koukouikila-Koussounda, Felix; Ndounga, Mathieu; Imbert, Jean; Torres, Magali; Pradel, Lydie; Ntoumi, Francine; Rihet, Pascal

2017-01-01

Linkage studies have revealed a linkage of mild malaria to chromosome 6p21 that contains the NCR3 gene encoding a natural killer cell receptor, whereas NCR3-412G>C (rs2736191) located in its promoter region was found to be associated with malaria in Burkina Faso. Here we confirmed the association of rs2736191 with mild malaria in a Congolese cohort and investigated its potential cis-regulatory effect. Luciferase assay results indicated that rs2736191-G allele had a significantly increased promoter activity compared to rs2736191-C allele. Furthermore, EMSAs demonstrated an altered binding of two nuclear protein complexes to the rs2736191-C allele in comparison to rs2736191-G allele. Finally, after in silico identification of transcription factor candidates, pull-down western blot experiments confirmed that both STAT4 and RUNX3 bind the region encompassing rs2736191 with a higher affinity for the G allele. To our knowledge, this is the first report that explored the functional role of rs2736191. These results support the hypothesis that genetic variation within natural killer cell receptors alters malaria resistance in humans.

Diagnosis of potential stressors adversely affecting benthic ...

EPA Pesticide Factsheets

Greenwich Bay is an urbanized embayment of Narragansett Bay potentially impacted by multiple stressors. The present study identified the important stressors affecting Greenwich Bay benthic fauna. First, existing data and information were used to confirm that the waterbody was impaired. Second, the presence of source, stressor, and effect were established. Then linkages between source, stressor, and effect were developed. This allows identification of probable stressors adversely affecting the waterbody. Three pollutant categories were assessed: chemicals, nutrients, and suspended sediments. This weight of evidence approach indicated that Greenwich Bay was primarily impacted by eutrophication-related stressors. The sediments of Greenwich Bay were carbon enriched and low dissolved oxygen concentrations were commonly seen, especially in the western portions of Greenwich Bay. The benthic community was depauperate, as would be expected under oxygen stress. Although our analysis indicated that contaminant loads in Greenwich Bay were at concentrations where adverse effects might be expected, no toxicity was observed, as a result of high levels of organic carbon in these sediments reducing contaminant bioavailability. Our analysis also indicated that suspended sediment impacts were likely nonexistent for much of the Bay. This analysis demonstrates that the diagnostic procedure was useful to organize and assess the potential stressors impacting the ecological well-being

Evidence of linkage of HDL level variation to APOC3 in two samples with different ascertainment.

PubMed

Gagnon, France; Jarvik, Gail P; Motulsky, Arno G; Deeb, Samir S; Brunzell, John D; Wijsman, Ellen M

2003-11-01

The APOA1-C3-A4-A5 gene complex encodes genes whose products are implicated in the metabolism of HDL and/or triglycerides. Although the relationship between polymorphisms in this gene cluster and dyslipidemias was first reported more than 15 years ago, association and linkage results have remained inconclusive. This is due, in part, to the oligogenic and multivariate nature of dyslipidemic phenotypes. Therefore, we investigate evidence of linkage of APOC3 and HDL using two samples of dyslipidemic pedigrees: familial combined hyperlipidemia (FCHL) and isolated low-HDL (ILHDL). We used a strategy that deals with several difficulties inherent in the study of complex traits: by using a Bayesian Markov Chain Monte Carlo (MCMC) approach we allow for oligogenic trait models, as well as simultaneous incorporation of covariates, in the context of multipoint analysis. By using this approach on extended pedigrees we provide evidence of linkage of APOC3 and HDL level variation in two samples with different ascertainment. In addition to APOC3, we estimate that two to three genes, each with a substantial effect on total variance, are responsible for HDL variation in both data sets. We also provide evidence, using the FCHL data set, for a pleiotropic effect between HDL, HDL3 and triglycerides at the APOC3 locus.

Effect of Linkage Disequilibrium on the Identification of Functional Variants

PubMed Central

Thomas, Alun; Abel, Haley J; Di, Yanming; Faye, Laura L; Jin, Jing; Liu, Jin; Wu, Zheyan; Paterson, Andrew D

2011-01-01

We summarize the contributions of Group 9 of Genetic Analysis Workshop 17. This group addressed the problems of linkage disequilibrium and other longer range forms of allelic association when evaluating the effects of genotypes on phenotypes. Issues raised by long-range associations, whether a result of selection, stratification, possible technical errors, or chance, were less expected but proved to be important. Most contributors focused on regression methods of various types to illustrate problematic issues or to develop adaptations for dealing with high-density genotype assays. Study design was also considered, as was graphical modeling. Although no method emerged as uniformly successful, most succeeded in reducing false-positive results either by considering clusters of loci within genes or by applying smoothing metrics that required results from adjacent loci to be similar. Two unexpected results that questioned our assumptions of what is required to model linkage disequilibrium were observed. The first was that correlations between loci separated by large genetic distances can greatly inflate single-locus test statistics, and, whether the result of selection, stratification, possible technical errors, or chance, these correlations seem overabundant. The second unexpected result was that applying principal components analysis to genome-wide genotype data can apparently control not only for population structure but also for linkage disequilibrium. PMID:22128051

Live births after simultaneous avoidance of monogenic diseases and chromosome abnormality by next-generation sequencing with linkage analyses.

PubMed

Yan, Liying; Huang, Lei; Xu, Liya; Huang, Jin; Ma, Fei; Zhu, Xiaohui; Tang, Yaqiong; Liu, Mingshan; Lian, Ying; Liu, Ping; Li, Rong; Lu, Sijia; Tang, Fuchou; Qiao, Jie; Xie, X Sunney

2015-12-29

In vitro fertilization (IVF), preimplantation genetic diagnosis (PGD), and preimplantation genetic screening (PGS) help patients to select embryos free of monogenic diseases and aneuploidy (chromosome abnormality). Next-generation sequencing (NGS) methods, while experiencing a rapid cost reduction, have improved the precision of PGD/PGS. However, the precision of PGD has been limited by the false-positive and false-negative single-nucleotide variations (SNVs), which are not acceptable in IVF and can be circumvented by linkage analyses, such as short tandem repeats or karyomapping. It is noteworthy that existing methods of detecting SNV/copy number variation (CNV) and linkage analysis often require separate procedures for the same embryo. Here we report an NGS-based PGD/PGS procedure that can simultaneously detect a single-gene disorder and aneuploidy and is capable of linkage analysis in a cost-effective way. This method, called "mutated allele revealed by sequencing with aneuploidy and linkage analyses" (MARSALA), involves multiple annealing and looping-based amplification cycles (MALBAC) for single-cell whole-genome amplification. Aneuploidy is determined by CNVs, whereas SNVs associated with the monogenic diseases are detected by PCR amplification of the MALBAC product. The false-positive and -negative SNVs are avoided by an NGS-based linkage analysis. Two healthy babies, free of the monogenic diseases of their parents, were born after such embryo selection. The monogenic diseases originated from a single base mutation on the autosome and the X-chromosome of the disease-carrying father and mother, respectively.

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.

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

Complementary genetic and genomic approaches help characterize the linkage group I seed protein QTL in soybean

PubMed Central

2010-01-01

Background The nutritional and economic value of many crops is effectively a function of seed protein and oil content. Insight into the genetic and molecular control mechanisms involved in the deposition of these constituents in the developing seed is needed to guide crop improvement. A quantitative trait locus (QTL) on Linkage Group I (LG I) of soybean (Glycine max (L.) Merrill) has a striking effect on seed protein content. Results A soybean near-isogenic line (NIL) pair contrasting in seed protein and differing in an introgressed genomic segment containing the LG I protein QTL was used as a resource to demarcate the QTL region and to study variation in transcript abundance in developing seed. The LG I QTL region was delineated to less than 8.4 Mbp of genomic sequence on chromosome 20. Using Affymetrix® Soy GeneChip and high-throughput Illumina® whole transcriptome sequencing platforms, 13 genes displaying significant seed transcript accumulation differences between NILs were identified that mapped to the 8.4 Mbp LG I protein QTL region. Conclusions This study identifies gene candidates at the LG I protein QTL for potential involvement in the regulation of protein content in the soybean seed. The results demonstrate the power of complementary approaches to characterize contrasting NILs and provide genome-wide transcriptome insight towards understanding seed biology and the soybean genome. PMID:20199683

Genetic and Genomic Analysis of a Fat Mass Trait with Complex Inheritance Reveals Marked Sex Specificity

PubMed Central

Wang, Hui; Drake, Thomas A; Lusis, Aldons J

2006-01-01

The integration of expression profiling with linkage analysis has increasingly been used to identify genes underlying complex phenotypes. The effects of gender on the regulation of many physiological traits are well documented; however, “genetical genomic” analyses have not yet addressed the degree to which their conclusions are affected by sex. We constructed and densely genotyped a large F2 intercross derived from the inbred mouse strains C57BL/6J and C3H/HeJ on an apolipoprotein E null (ApoE−/−) background. This BXH.ApoE−/− population recapitulates several “metabolic syndrome” phenotypes. The cross consists of 334 animals of both sexes, allowing us to specifically test for the dependence of linkage on sex. We detected several thousand liver gene expression quantitative trait loci, a significant proportion of which are sex-biased. We used these analyses to dissect the genetics of gonadal fat mass, a complex trait with sex-specific regulation. We present evidence for a remarkably high degree of sex-dependence on both the cis and trans regulation of gene expression. We demonstrate how these analyses can be applied to the study of the genetics underlying gonadal fat mass, a complex trait showing significantly female-biased heritability. These data have implications on the potential effects of sex on the genetic regulation of other complex traits. PMID:16462940

Storage related changes of cell wall based dietary fiber components of broccoli (Brassica oleracea var. italica) stems.

PubMed

Schäfer, Judith; Stanojlovic, Luisa; Trierweiler, Bernhard; Bunzel, Mirko

2017-03-01

Storage related changes in the cell wall composition potentially affect the texture of plant-based foods and the physiological effects of cell wall based dietary fiber components. Therefore, a detailed characterization of cell wall polysaccharides and lignins from broccoli stems was performed. Freshly harvested broccoli and broccoli stored at 20°C and 1°C for different periods of time were analyzed. Effects on dietary fiber contents, polysaccharide composition, and on lignin contents/composition were much more pronounced during storage at 20°C than at 1°C. During storage, insoluble dietary fiber contents of broccoli stems increased up to 13%. Storage related polysaccharide modifications include an increase of the portions of cellulose, xylans, and homogalacturonans and a decrease of the neutral pectic side-chains arabinans and galactans. Broccoli stem lignins are generally rich in guaiacyl units. Lignins from freshly harvested broccoli stems contain slightly larger amounts of p-hydroxyphenyl units than syringyl units. Syringyl units are predominantly incorporated into the lignin polymers during storage, resulting in increased acetyl bromide soluble lignin contents. NMR-based analysis of the interunit linkage types of broccoli stem lignins revealed comparably large portions of resinol structures for a guaiacyl rich lignin. Incorporation of syringyl units into the polymers over storage predominantly occurs through β-O-4-linkages. Copyright © 2017 Elsevier Ltd. 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.

Securizing data linkage in french public statistics.

PubMed

Guesdon, Maxence; Benzenine, Eric; Gadouche, Kamel; Quantin, Catherine

2016-10-06

Administrative records in France, especially medical and social records, have huge potential for statistical studies. The NIR (a national identifier) is widely used in medico-social administrations, and this would theoretically provide considerable scope for data matching, on condition that the legislation on such matters was respected.The law, however, forbids the processing of non-anonymized medical data, thus making it difficult to carry out studies that require several sources of social and medical data.We would like to benefit from computer techniques introduced since the 70 s to provide safe linkage of anonymized files, to release the current constraints of such procedures.We propose an organization and a data workflow, based on hashing and cyrptographic techniques, to strongly compartmentalize identifying and not-identifying data.The proposed method offers a strong control over who is in possession of which information, using different hashing keys for each linkage. This allows to prevent unauthorized linkage of data, to protect anonymity, by preventing cumulation of not-identifying data which can become identifying data when linked.Our proposal would make it possible to conduct such studies more easily, more regularly and more precisely while preserving a high enough level of anonymity.The main obstacle to setting up such a system, in our opinion, is not technical, but rather organizational in that it is based on the existence of a Key-Management Authority.

Genomewide Scan for Nonsyndromic Cleft Lip and Palate in Multigenerational Indian Families Reveals Significant Evidence of Linkage at 13q33.1-34

PubMed Central

Radhakrishna, Uppala; Ratnamala, Uppala; Gaines, Mathew; Beiraghi, Soraya; Hutchings, David; Golla, Jeffrey; Husain, Syed A.; Gambhir, Prakash S.; Sheth, Jayesh J.; Sheth, Frenny J.; Chetan, Ghati K.; Naveed, Mohammed; Solanki, Jitendra V.; Patel, Uday C.; Master, Dilipkumar C.; Memon, Rafiq; Antonarakis, Gregory S.; Antonarakis, Stylianos E.; Nath, Swapan K.

2006-01-01

Nonsyndromic cleft lip with or without cleft palate (CL-P) is a common congenital anomaly with incidence ranging from 1 in 300 to 1 in 2,500 live births. We analyzed two Indian pedigrees (UR017 and UR019) with isolated, nonsyndromic CL-P, in which the anomaly segregates as an autosomal dominant trait. The phenotype was variable, ranging from unilateral to bilateral CL-P. A genomewide linkage scan that used ∼10,000 SNPs was performed. Nonparametric linkage (NPL) analysis identified 11 genomic regions (NPL>3.5; P<.005) that could potentially harbor CL-P susceptibility variations. Among those, the most significant evidence was for chromosome 13q33.1-34 at marker rs1830756 (NPL=5.57; P=.00024). This was also supported by parametric linkage; MOD score (LOD scores maximized over genetic model parameters) analysis favored an autosomal dominant model. The maximum LOD score was 4.45, and heterogeneity LOD was 4.45 (α=100%). Haplotype analysis with informative crossovers enabled the mapping of the CL-P locus to a region of ∼20.17 cM (7.42 Mb) between SNPs rs951095 and rs726455. Thus, we have identified a novel genomic region on 13q33.1-34 that harbors a high-risk variant for CL-P in these Indian families. PMID:16909398

Understanding Local Spatial Variation Along the Care Continuum: The Potential Impact of Transportation Vulnerability on HIV Linkage to Care and Viral Suppression in High-Poverty Areas, Atlanta, Georgia.

PubMed

Goswami, Neela D; Schmitz, Michelle M; Sanchez, Travis; Dasgupta, Sharoda; Sullivan, Patrick; Cooper, Hannah; Rane, Deepali; Kelly, Jane; Del Rio, Carlos; Waller, Lance A

2016-05-01

Engagement in care is central to reducing mortality for HIV-infected persons and achieving the White House National AIDS Strategy of 80% viral suppression in the US by 2020. Where an HIV-infected person lives impacts his or her ability to achieve viral suppression. Reliable transportation access for healthcare may be a key determinant of this place-suppression relationship. ZIP code tabulation areas (ZCTAs) were the units of analysis. We used geospatial and ecologic analyses to examine spatial distributions of neighborhood-level variables (eg, transportation accessibility) and associations with: (1) community linkage to care, and (2) community viral suppression. Among Atlanta ZCTAs with data for newly diagnosed HIV cases (2006-2010), we used Moran I to evaluate spatial clustering and linear regression models to evaluate associations between neighborhood variables and outcomes. In 100 ZCTAs with 8413 newly diagnosed HIV-positive residents, a median of 60 HIV cases were diagnosed per ZCTA during the 5-year period. We found significant clustering of ZCTAs with low linkage to care and viral suppression (Moran I = 0.218, P < 0.05). In high-poverty ZCTAs, a 10% point increase in ZCTA-level household vehicle ownership was associated with a 4% point increase in linkage to care (P = 0.02, R = 0.16). In low-poverty ZCTAs, a 10% point increase in ZCTA-level household vehicle ownership was associated with a 30% point increase in ZCTA-level viral suppression (P = 0.01, R = 0.08). Correlations between transportation variables and community-level care linkage and viral suppression vary by area poverty level and provide opportunities for interventions beyond individual-level factors.

Improving linkage to HIV care at low-threshold STI/HIV testing sites: An evaluation of the Immediate Staging Pilot Project in Vancouver, British Columbia.

PubMed

Brownrigg, Bobbi; Taylor, Darlene; Phan, Felicia; Sandstra, Irvine; Stimpson, Rochelle; Barrios, Rolando; Lester, Richard; Ogilvie, Gina

2017-04-20

The objective of the Immediate Staging Pilot Project (ISPP) was to improve linkage to human immunodeficiency virus (HIV) care by increasing the number of referrals made to HIV care, and to decrease the time between diagnosis and linkage to care for newly diagnosed HIV clients. This pilot had the potential to decrease HIV transmission at a population level by engaging clients in treatment earlier. The Bute Street Clinic and Health Initiative for Men Clinic on Davie in Vancouver, British Columbia are low-threshold public health facilities providing HIV/STI testing primarily to men who have sex with men (MSM). To improve engagement of MSM in the cascade of HIV care, the BC Centre for Disease Control implemented a 12-month ISPP in 2012 for clients newly diagnosed with HIV. The pilot offered CD4 and viral load testing at the time of diagnosis, implemented improved referral procedures and enhanced nursing support for clients. Comparing linkage to care outcomes between a group that received the standard of care (SOC) and an intervention group that received immediate staging, the median linkage to care time decreased from 21.5 to 14.0 days respectively (p = 0.053). The referral rates to HIV care were 56.1% in the SOC group and 94.1% in the intervention group (p < 0.001). Creating best practices that include offering CD4 and viral load testing at the time of diagnosis, enhanced nursing support and standardized referral processes has facilitated an improvement in the quality of HIV services provided to MSM clients attending low-threshold clinics.

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.

Financial Incentives for Linkage to Care and Viral Suppression Among HIV-Positive Patients: A Randomized Clinical Trial (HPTN 065).

PubMed

El-Sadr, Wafaa M; Donnell, Deborah; Beauchamp, Geetha; Hall, H Irene; Torian, Lucia V; Zingman, Barry; Lum, Garret; Kharfen, Michael; Elion, Richard; Leider, Jason; Gordin, Fred M; Elharrar, Vanessa; Burns, David; Zerbe, Allison; Gamble, Theresa; Branson, Bernard

2017-08-01

Achieving linkage to care and viral suppression in human immunodeficiency virus (HIV)-positive patients improves their well-being and prevents new infections. Current gaps in the HIV care continuum substantially limit such benefits. To evaluate the effectiveness of financial incentives on linkage to care and viral suppression in HIV-positive patients. A large community-based clinical trial that randomized 37 HIV test and 39 HIV care sites in the Bronx, New York, and Washington, DC, to financial incentives or standard of care. Participants at financial incentive test sites who had positive test results for HIV received coupons redeemable for $125 cash-equivalent gift cards upon linkage to care. HIV-positive patients receiving antiretroviral therapy at financial incentive care sites received $70 gift cards quarterly, if virally suppressed. Linkage to care: proportion of HIV-positive persons at the test site who linked to care within 3 months, as indicated by CD4+ and/or viral load test results done at a care site. Viral suppression: proportion of established patients at HIV care sites with suppressed viral load (<400 copies/mL), assessed at each calendar quarter. Outcomes assessed through laboratory test results reported to the National HIV Surveillance System. A total of 1061 coupons were dispensed for linkage to care at 18 financial incentive test sites and 39 359 gift cards were dispensed to 9641 HIV-positive patients eligible for gift cards at 17 financial incentive care sites. Financial incentives did not increase linkage to care (adjusted odds ratio, 1.10; 95% CI, 0.73-1.67; P = .65). However, financial incentives significantly increased viral suppression. The overall proportion of patients with viral suppression was 3.8% higher (95% CI, 0.7%-6.8%; P = .01) at financial incentive sites compared with standard of care sites. Among patients not previously consistently virally suppressed, the proportion virally suppressed was 4.9% higher (95% CI, 1.4%-8.5%; P = .007) at financial incentive sites. In addition, continuity in care was 8.7% higher (95% CI, 4.2%-13.2%; P < .001) at financial incentive sites. Financial incentives, as used in this study (HPTN 065), significantly increased viral suppression and regular clinic attendance among HIV-positive patients in care. No effect was noted on linkage to care. Financial incentives offer promise for improving adherence to treatment and viral suppression among HIV-positive patients. clinicaltrials.gov Identifier: NCT01152918.

A Symmetric Two-Locus Fertility Model

PubMed Central

Feldman, Marcus W.; Liberman, Uri

1985-01-01

A model in which selection is mediated by differential fertilities among the genotypes at two diallelic loci is proposed. Fertility depends only on the number of heterozygous loci participating in the mating. Classes analogous to symmetric equilibria in symmetric viability models are determined explicitly and shown to exhibit stability behavior very different from the viability results. Linkage equilibrium is shown to occur in a relatively asymmetric fashion and to overlap in stability with linkage disequilibrium. In many cases single-locus or two-locus polymorphism is shown to be stable simultaneously with chromosome fixation even under very tight linkage. It is suggested that historical effects may be of great significance in the evolution of systems in which fertility is the primary agent of natural selection. PMID:3967817

[Concept for Planning the Nurse-Patient Ratio and Nursing Fee Payment Linkage System].

PubMed

Lu, Meei-Shiow; Tseng, Hsiu-Yi; Liang, Shu-Yuan; Lin, Chiou-Fen

2017-02-01

This article describes the current situation in Taiwan with regard to the nurse-patient ratio and nursing fee payments, reviews the related policies and results in developed countries, and then proposes a plan for improving the domestic situation. Direct relationships exist between patient nursing quality and patient safety and the nurse-patient ratio as well as between nursing fee payments and the nurse-patient ratio. Therefore, in order to enhance the quality and safety of nursing care, it will be necessary to develop and institute a payment linkage system that links nursing fee payments to the nurse-patient ratio. This process requires public consensus and planning in order to institute an equitable and effective payment linkage system in the future.

Community-Clinical Linkages With Community Health Workers in the United States: A Scoping Review.

PubMed

Lohr, Abby M; Ingram, Maia; Nuñez, Annabelle V; Reinschmidt, Kerstin M; Carvajal, Scott C

2018-05-01

Despite the proliferation of community-clinical linkage (CCL) interventions with community health workers (CHWs), little is known about the components of these programs or how linkages are realized. In this scoping review, we synthesize evidence concerning the role of CHWs in creating and sustaining CCLs aimed at improving individual health outcomes. Our inclusion criteria included peer-reviewed articles that described a CHW intervention in the United States that used a CCL model. A total of 2,776 titles and/or abstracts were screened and 47 articles underwent full text review. Two independent reviewers rated the screened articles based on additional criteria including the CHW connection to community and evidence of linkage follow up rather than simple referral. For the 11 peer-reviewed articles included in the final review, we describe the CHW's relationship to the community, training, and role within the intervention, linkage, and outcomes. We used a standardized framework to determine commonalities in CHW roles across the interventions. CCLs with CHWs positively affect the delivery of both clinical care and community resources across a range of disease areas in a variety of contexts. To identify effective CCL models, additional information on CHW training, CCL follow-up methods, and the CHW role in CCLs is recommended.

Formation of contact active antimicrobial surfaces by covalent grafting of quaternary ammonium compounds.

PubMed

Elena, Poverenov; Miri, Klein

2018-05-16

Different synthetic strategies for the formation of contact active antimicrobial materials utilizing covalent linkage of quaternary ammonium compounds (QACs) were reviewed. There is a demand to find methods that will prevent bacterial fouling without the release of antimicrobial agents, because biocides cause environment pollution and promote the development of bacteria resistance mechanisms. The contact active antimicrobial surfaces may provide a useful tool for this purpose. The covalent surface grafting of QACs seems to be a feasible and promising approach for the formation of safe and effective antimicrobial materials that could be utilized for medical devices, food industry, water treatment systems and other applications. This manuscript reviews covalent attachment of QACs to form contact active antimicrobial materials based on glass, metals, synthetic and natural polymers. The review emphasizes the description of different synthetic methods that are used for the covalent linkage. Direct covalent linkage of QACs to the material surfaces, a linkage via auxiliary nanoparticles (NPs), or spacers, controlled radical polymerization techniques and a linkage to pre-activated surfaces are discussed. The physico-chemical properties and biological activity of the modified surfaces are also described. This review does not cover non-covalent grafting of QACs and incorporation of QACs into a bulk material. Copyright © 2018 Elsevier B.V. All rights reserved.

Mapping of angular leaf spot resistance QTL in common bean (Phaseolus vulgaris L.) under different environments

PubMed Central

2012-01-01

Background Common bean (Phaseolus vulgaris L.) is the most important grain legume for human diet worldwide and the angular leaf spot (ALS) is one of the most devastating diseases of this crop, leading to yield losses as high as 80%. In an attempt to breed resistant cultivars, it is important to first understand the inheritance mode of resistance and to develop tools that could be used in assisted breeding. Therefore, the aim of this study was to identify quantitative trait loci (QTL) controlling resistance to ALS under natural infection conditions in the field and under inoculated conditions in the greenhouse. Results QTL analyses were made using phenotypic data from 346 recombinant inbreed lines from the IAC-UNA x CAL 143 cross, gathered in three experiments, two of which were conducted in the field in different seasons and one in the greenhouse. Joint composite interval mapping analysis of QTL x environment interaction was performed. In all, seven QTLs were mapped on five linkage groups. Most of them, with the exception of two, were significant in all experiments. Among these, ALS10.1DG,UC presented major effects (R2 between 16% - 22%). This QTL was found linked to the GATS11b marker of linkage group B10, which was consistently amplified across a set of common bean lines and was associated with the resistance. Four new QTLs were identified. Between them the ALS5.2 showed an important effect (9.4%) under inoculated conditions in the greenhouse. ALS4.2 was another major QTL, under natural infection in the field, explaining 10.8% of the variability for resistance reaction. The other QTLs showed minor effects on resistance. Conclusions The results indicated a quantitative inheritance pattern of ALS resistance in the common bean line CAL 143. QTL x environment interactions were observed. Moreover, the major QTL identified on linkage group B10 could be important for bean breeding, as it was stable in all the environments. Thereby, the GATS11b marker is a potential tool for marker assisted selection for ALS resistance. PMID:22738188

Evolutionary versatility of eukaryotic protein domains revealed by their bigram networks

PubMed Central

2011-01-01

Background Protein domains are globular structures of independently folded polypeptides that exert catalytic or binding activities. Their sequences are recognized as evolutionary units that, through genome recombination, constitute protein repertoires of linkage patterns. Via mutations, domains acquire modified functions that contribute to the fitness of cells and organisms. Recent studies have addressed the evolutionary selection that may have shaped the functions of individual domains and the emergence of particular domain combinations, which led to new cellular functions in multi-cellular animals. This study focuses on modeling domain linkage globally and investigates evolutionary implications that may be revealed by novel computational analysis. Results A survey of 77 completely sequenced eukaryotic genomes implies a potential hierarchical and modular organization of biological functions in most living organisms. Domains in a genome or multiple genomes are modeled as a network of hetero-duplex covalent linkages, termed bigrams. A novel computational technique is introduced to decompose such networks, whereby the notion of domain "networking versatility" is derived and measured. The most and least "versatile" domains (termed "core domains" and "peripheral domains" respectively) are examined both computationally via sequence conservation measures and experimentally using selected domains. Our study suggests that such a versatility measure extracted from the bigram networks correlates with the adaptivity of domains during evolution, where the network core domains are highly adaptive, significantly contrasting the network peripheral domains. Conclusions Domain recombination has played a major part in the evolution of eukaryotes attributing to genome complexity. From a system point of view, as the results of selection and constant refinement, networks of domain linkage are structured in a hierarchical modular fashion. Domains with high degree of networking versatility appear to be evolutionary adaptive, potentially through functional innovations. Domain bigram networks are informative as a model of biological functions. The networking versatility indices extracted from such networks for individual domains reflect the strength of evolutionary selection that the domains have experienced. PMID:21849086

Evolutionary versatility of eukaryotic protein domains revealed by their bigram networks.

PubMed

Xie, Xueying; Jin, Jing; Mao, Yongyi

2011-08-18

Protein domains are globular structures of independently folded polypeptides that exert catalytic or binding activities. Their sequences are recognized as evolutionary units that, through genome recombination, constitute protein repertoires of linkage patterns. Via mutations, domains acquire modified functions that contribute to the fitness of cells and organisms. Recent studies have addressed the evolutionary selection that may have shaped the functions of individual domains and the emergence of particular domain combinations, which led to new cellular functions in multi-cellular animals. This study focuses on modeling domain linkage globally and investigates evolutionary implications that may be revealed by novel computational analysis. A survey of 77 completely sequenced eukaryotic genomes implies a potential hierarchical and modular organization of biological functions in most living organisms. Domains in a genome or multiple genomes are modeled as a network of hetero-duplex covalent linkages, termed bigrams. A novel computational technique is introduced to decompose such networks, whereby the notion of domain "networking versatility" is derived and measured. The most and least "versatile" domains (termed "core domains" and "peripheral domains" respectively) are examined both computationally via sequence conservation measures and experimentally using selected domains. Our study suggests that such a versatility measure extracted from the bigram networks correlates with the adaptivity of domains during evolution, where the network core domains are highly adaptive, significantly contrasting the network peripheral domains. Domain recombination has played a major part in the evolution of eukaryotes attributing to genome complexity. From a system point of view, as the results of selection and constant refinement, networks of domain linkage are structured in a hierarchical modular fashion. Domains with high degree of networking versatility appear to be evolutionary adaptive, potentially through functional innovations. Domain bigram networks are informative as a model of biological functions. The networking versatility indices extracted from such networks for individual domains reflect the strength of evolutionary selection that the domains have experienced.

Carbohydrate intake, obesity, metabolic syndrome and cancer risk? A two-part systematic review and meta-analysis protocol to estimate attributability

PubMed Central

Sartorius, B; Sartorius, K; Aldous, C; Madiba, T E; Stefan, C; Noakes, T

2016-01-01

Introduction Linkages between carbohydrates, obesity and cancer continue to demonstrate conflicting results. Evidence suggests inconclusive direct linkages between carbohydrates and specific cancers. Conversely, obesity has been strongly linked to a wide range of cancers. The purpose of the study is to explore linkages between carbohydrate intake and cancer types using a two-step approach. First the study will evaluate the linkages between carbohydrate intake and obesity, potentially stratified by metabolic syndrome status. Second, the estimated attributable fraction of obesity ascribed to carbohydrate intake will be multiplied against obesity attributable fractions for cancer types to give estimated overall attributable fraction for carbohydrate versus cancer type. Methods and analysis We will perform a comprehensive search to identify all possible published and unpublished studies that have assessed risk factors for obesity including dietary carbohydrate intake. Scientific databases, namely PubMed MEDLINE, EMBASE, EBSCOhost and ISI Web of Science will be searched. Following study selection, paper/data acquisition, and data extraction and synthesis, we will appraise the quality of studies and risk of bias, as well as assess heterogeneity. Meta-weighted attributable fractions of obesity due to carbohydrate intake will be estimated after adjusting for other potential confounding factors (eg, physical inactivity, other dietary intake). Furthermore, previously published systematic reviews assessing the cancer-specific risk associated with obesity will also be drawn. These estimates will be linked with the attributability of carbohydrate intake in part 1 to estimate the cancer-specific burden that can be attributed to dietary carbohydrates. This systematic review protocol has been developed according to the ‘Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P) 2015’. Ethics and dissemination The current study will be based on published literature and data, and, as such, ethics approval is not required. The final results of this two part systematic review (plus multiplicative calculations) will be published in a relevant international peer-reviewed journal. Trial registration number PROSPERO CRD42015023257. PMID:26729382

School Psychology Awareness: Making Connections

ERIC Educational Resources Information Center

Cohn, Andrea; Cowan, Katherine C.

2011-01-01

A day in the life of a student at school is filled with potential connections (relationships, linkages in learning, behavioral choices, etc.). Friendships with peers, relationships with teachers, acknowledgements from administrators, encouragement from coaches: These are all interpersonal connections that are essential not only to making school an…

TRIPLE-VALUE SIMULATION MODELING CASES TACKLE NUTRIENT AND WATERSHED MANAGEMENT FROM A SOCIAL-ECOLOGICAL SYSTEMS PERSPECTIVE

EPA Science Inventory

Decision makers often need assistance in understanding dynamic interactions and linkages among economic, environmental and social systems in coastal watersheds. They also need scientific input to better evaluate potential costs and benefits of alternative policy interventions. EP...

Importance of Watershed Land Use in Predicting Benthic Invertebrate Condition in the Virginian Biogeographic Province, USA.

EPA Science Inventory

Estuaries are dynamic transition zones linking freshwater and oceanic habitats. These productive ecosystems are threatened by a variety of stressors including human modification of coastal watersheds. In this study we examined potential linkages between estuarine condition and...

Bridging the Knowledge Gaps between Richards' Equation and Budyko Equation

NASA Astrophysics Data System (ADS)

Wang, D.

2017-12-01

The empirical Budyko equation represents the partitioning of mean annual precipitation into evaporation and runoff. Richards' equation, based on Darcy's law, represents the movement of water in unsaturated soils. The linkage between Richards' equation and Budyko equation is presented by invoking the empirical Soil Conservation Service curve number (SCS-CN) model for computing surface runoff at the event-scale. The basis of the SCS-CN method is the proportionality relationship, i.e., the ratio of continuing abstraction to its potential is equal to the ratio of surface runoff to its potential value. The proportionality relationship can be derived from the Richards' equation for computing infiltration excess and saturation excess models at the catchment scale. Meanwhile, the generalized proportionality relationship is demonstrated as the common basis of SCS-CN method, monthly "abcd" model, and Budyko equation. Therefore, the linkage between Darcy's law and the emergent pattern of mean annual water balance at the catchment scale is presented through the proportionality relationship.

Further evidence of no linkage between schizophrenia and the dopamine D{sub 3} receptor gene locus

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

Nanko, S.; Fukuda, R.; Hattori, M.

The dopamine hypothesis of schizophrenia proposed that dopaminergic pathways are involved in the etiology of the disease. In particular, interest among psychiatrists has focused on the D{sub 2} receptor because of its affinity to antipsychotic drugs. Recently a new dopamine receptor gene has been cloned and named the dopamine D{sub 3} receptor. The D{sub 3} receptor is a potential site for antipsychotic drug action and may be involved in the pathophysiology of schizophrenia. We have carried out a linkage study between the susceptibility gene for schizophrenia and polymorphism of the dopamine D{sub 3} receptor gene in two Japanese pedigrees. Themore » LOD scores were negative for all genetic models and for all affective status at a recombination fraction {theta} = 0. Linkage of DRD{sub 3} has been excluded for the model 1 (dominant model) and the model 3 (recessive model). The LOD score was -3.43 at {theta} = 0 for model 1 (dominant model) and broad definition of affected status. These results were consistent with previous studies. 19 refs., 2 figs., 3 tabs.« less

The Norwegian Family Based Life Course (NFLC) study: data structure and potential for public health research.

PubMed

Næss, Øyvind; Hoff, Dominic Anthony

2013-02-01

To present details of the Norwegian Family Based Life Course Study. All Norwegians participating in censuses from 1960 to 2001 were included. In addition to the personal identity number, we used household and family information from the 1960 census to link family members together. The NFLC study is further linked to other health registers and surveys. The proportion included and alive in 1960 increased from 67 % among those born in 1900 to more than 90 % for those born after 1940. In all, 5,266,270 were included. This combined family linkage approach gave 85 % parental linkage for those born in 1940 that dropped to 20 % of those born in 1930. The proportion with misclassified parents was less than 0.5 %. In all, 3,564,582 individuals were linked to their parents. The NFLC is one of the largest follow-up of individuals over several decades in their life course. The comprehensive multigenerational, family linkage within the database contributes to large-scale use of various designs for investigating life course determinants.

Extending the Fellegi-Sunter probabilistic record linkage method for approximate field comparators.

PubMed

DuVall, Scott L; Kerber, Richard A; Thomas, Alun

2010-02-01

Probabilistic record linkage is a method commonly used to determine whether demographic records refer to the same person. The Fellegi-Sunter method is a probabilistic approach that uses field weights based on log likelihood ratios to determine record similarity. This paper introduces an extension of the Fellegi-Sunter method that incorporates approximate field comparators in the calculation of field weights. The data warehouse of a large academic medical center was used as a case study. The approximate comparator extension was compared with the Fellegi-Sunter method in its ability to find duplicate records previously identified in the data warehouse using different demographic fields and matching cutoffs. The approximate comparator extension misclassified 25% fewer pairs and had a larger Welch's T statistic than the Fellegi-Sunter method for all field sets and matching cutoffs. The accuracy gain provided by the approximate comparator extension grew as less information was provided and as the matching cutoff increased. Given the ubiquity of linkage in both clinical and research settings, the incremental improvement of the extension has the potential to make a considerable impact.

A linkage and family-based association analysis of a potential neurocognitive endophenotype of bipolar disorder.

PubMed

Savitz, Jonathan; van der Merwe, Lize; Solms, Mark; Ramesar, Rajkumar

2007-01-01

The identification of the genetic variants underpinning bipolar disorder (BPD) has been impeded by a complex pattern of inheritance characterized by genetic and phenotypic heterogeneity, genetic epistasis, and gene-environment interactions. In this paper two strategies were used to ameliorate these confounding factors. A unique South African sample including 190 individuals of the relatively, reproductively isolated Afrikaner population was assessed with a battery of neuropsychological tests in an attempt to identify a BPD-associated quantitative trait or endophenotype. BPD individuals performed significantly worse than their unaffected relatives on visual and verbal memory tasks, a finding congruent with the literature. Afocused linkage and family-based association study was carried out using this memory-related endophenotype. In the largest 77-strong Afrikaner pedigree significant evidence for linkage was detected on chromosome 22q11, a region previously implicated in BPD. The quantitative transmission disequilibrium tests-based association analysis suggested that functional variants of the DRD4 and MAO-A genes modulate memory-related cognition. We speculate that polymorphisms at these loci may predispose to a subtype of BPD characterized by memory-related deficits.

Automated electrochemical assembly of the protected potential TMG-chitotriomycin precursor based on rational optimization of the carbohydrate building block.

PubMed

Nokami, Toshiki; Isoda, Yuta; Sasaki, Norihiko; Takaiso, Aki; Hayase, Shuichi; Itoh, Toshiyuki; Hayashi, Ryutaro; Shimizu, Akihiro; Yoshida, Jun-ichi

2015-03-20

The anomeric arylthio group and the hydroxyl-protecting groups of thioglycosides were optimized to construct carbohydrate building blocks for automated electrochemical solution-phase synthesis of oligoglucosamines having 1,4-β-glycosidic linkages. The optimization study included density functional theory calculations, measurements of the oxidation potentials, and the trial synthesis of the chitotriose trisaccharide. The automated synthesis of the protected potential N,N,N-trimethyl-d-glucosaminylchitotriomycin precursor was accomplished by using the optimized building block.

Linkage disequilibrium at the SCA2 locus

PubMed Central

Didierjean, O.; Cancel, G.; Stevanin, G.; Durr, A.; Burk, K.; Benomar, A.; Lezin, A.; Belal, S.; Abada-Bendid, M.; Klockgether, T.; Brice, A.

1999-01-01

Spinocerebellar ataxia type 2 (SCA2) is caused by the expansion of an unstable CAG repeat encoding a polyglutamine tract. Repeats with 32 to 200 CAGs are associated with the disease, whereas normal chromosomes contain 13 to 33 repeats. We tested 220 families of different geographical origins for the SCA2 mutation. Thirty three were positive (15%). Twenty three families with at least two affected subjects were tested for linkage disequilibium (LD) between the SCA2 mutation and three microsatellite markers, two of which (D12S1332-D12S1333) closely flanked the mutation; the other (D12S1672) was intragenic. Many different haplotypes were observed, indicating the occurrence of several ancestral mutations. However, the same haplotype, not observed in controls, was detected in the German, the Serbian, and some of the French families, suggesting a founder effect or recurrent mutations on an at risk haplotype.


Keywords: linkage disequilibrium; SCA2; trinucleotide repeat expansion; founder effect PMID:10353790

Linkage of familial Alzheimer disease to chromosome 14 in two large early-onset pedigrees: effects of marker allele frequencies on lod scores.

PubMed

Nechiporuk, A; Fain, P; Kort, E; Nee, L E; Frommelt, E; Polinsky, R J; Korenberg, J R; Pulst, S M

1993-05-01

Alzheimer disease (AD) is a devastating neurodegenerative disease leading to global dementia. In addition to sporadic forms of AD, familial forms (FAD) have been recognized. Mutations in the amyloid precursor protein (APP) gene on chromosome (CHR) 21 have been shown to cause early-onset AD in a small number of pedigrees. Recently, linkage to markers on CHR 14 has been established in several early-onset FAD pedigrees. We now report lod scores for CHR 14 markers in two large early-onset FAD pedigrees. Pairwise linkage analysis suggested that in these pedigrees the mutation is tightly linked to the loci D14S43 and D14S53. However, assumptions regarding marker allele frequencies had a major and often unpredictable effect on calculated lod scores. Therefore, caution needs to be exercised when single pedigrees are analyzed with marker allele frequencies determined from the literature or from a pool of spouses.

A habitat assessment for Florida panther population expansion into central Florida

USGS Publications Warehouse

Thatcher, C.A.; Van Manen, F.T.; Clark, J.D.

2009-01-01

One of the goals of the Florida panther (Puma concolor coryi) recovery plan is to expand panther range north of the Caloosahatchee River in central Florida. Our objective was to evaluate the potential of that region to support panthers. We used a geographic information system and the Mahalanobis distance statistic to develop a habitat model based on landscape characteristics associated with panther home ranges. We used cross-validation and an independent telemetry data set to test the habitat model. We also conducted a least-cost path analysis to identify potential habitat linkages and to provide a relative measure of connectivity among habitat patches. Variables in our model were paved road density, major highways, human population density, percentage of the area permanently or semipermanently flooded, and percentage of the area in natural land cover. Our model clearly identified habitat typical of that found within panther home ranges based on model testing with recent telemetry data. We identified 4 potential translocation sites that may support a total of approximately 36 panthers. Although we identified potential habitat linkages, our least-cost path analyses highlighted the extreme isolation of panther habitat in portions of the study area. Human intervention will likely be required if the goal is to establish female panthers north of the Caloosahatchee in the near term.

A gp41-based heteroduplex mobility assay provides rapid and accurate assessment of intrasubtype epidemiological linkage in HIV type 1 heterosexual transmission Pairs.

PubMed

Manigart, Olivier; Boeras, Debrah I; Karita, Etienne; Hawkins, Paulina A; Vwalika, Cheswa; Makombe, Nathan; Mulenga, Joseph; Derdeyn, Cynthia A; Allen, Susan; Hunter, Eric

2012-12-01

A critical step in HIV-1 transmission studies is the rapid and accurate identification of epidemiologically linked transmission pairs. To date, this has been accomplished by comparison of polymerase chain reaction (PCR)-amplified nucleotide sequences from potential transmission pairs, which can be cost-prohibitive for use in resource-limited settings. Here we describe a rapid, cost-effective approach to determine transmission linkage based on the heteroduplex mobility assay (HMA), and validate this approach by comparison to nucleotide sequencing. A total of 102 HIV-1-infected Zambian and Rwandan couples, with known linkage, were analyzed by gp41-HMA. A 400-base pair fragment within the envelope gp41 region of the HIV proviral genome was PCR amplified and HMA was applied to both partners' amplicons separately (autologous) and as a mixture (heterologous). If the diversity between gp41 sequences was low (<5%), a homoduplex was observed upon gel electrophoresis and the transmission was characterized as having occurred between partners (linked). If a new heteroduplex formed, within the heterologous migration, the transmission was determined to be unlinked. Initial blind validation of gp-41 HMA demonstrated 90% concordance between HMA and sequencing with 100% concordance in the case of linked transmissions. Following validation, 25 newly infected partners in Kigali and 12 in Lusaka were evaluated prospectively using both HMA and nucleotide sequences. Concordant results were obtained in all but one case (97.3%). The gp41-HMA technique is a reliable and feasible tool to detect linked transmissions in the field. All identified unlinked results should be confirmed by sequence analyses.

Genetic Structure, Linkage Disequilibrium and Signature of Selection in Sorghum: Lessons from Physically Anchored DArT Markers

PubMed Central

Bouchet, Sophie; Pot, David; Deu, Monique; Rami, Jean-François; Billot, Claire; Perrier, Xavier; Rivallan, Ronan; Gardes, Laëtitia; Xia, Ling; Wenzl, Peter; Kilian, Andrzej; Glaszmann, Jean-Christophe

2012-01-01

Population structure, extent of linkage disequilibrium (LD) as well as signatures of selection were investigated in sorghum using a core sample representative of worldwide diversity. A total of 177 accessions were genotyped with 1122 informative physically anchored DArT markers. The properties of DArTs to describe sorghum genetic structure were compared to those of SSRs and of previously published RFLP markers. Model-based (STRUCTURE software) and Neighbor-Joining diversity analyses led to the identification of 6 groups and confirmed previous evolutionary hypotheses. Results were globally consistent between the different marker systems. However, DArTs appeared more robust in terms of data resolution and bayesian group assignment. Whole genome linkage disequilibrium as measured by mean r2 decreased from 0.18 (between 0 to 10 kb) to 0.03 (between 100 kb to 1 Mb), stabilizing at 0.03 after 1 Mb. Effects on LD estimations of sample size and genetic structure were tested using i. random sampling, ii. the Maximum Length SubTree algorithm (MLST), and iii. structure groups. Optimizing population composition by the MLST reduced the biases in small samples and seemed to be an efficient way of selecting samples to make the best use of LD as a genome mapping approach in structured populations. These results also suggested that more than 100,000 markers may be required to perform genome-wide association studies in collections covering worldwide sorghum diversity. Analysis of DArT markers differentiation between the identified genetic groups pointed out outlier loci potentially linked to genes controlling traits of interest, including disease resistance genes for which evidence of selection had already been reported. In addition, evidence of selection near a homologous locus of FAR1 concurred with sorghum phenotypic diversity for sensitivity to photoperiod. PMID:22428056

Lysosome-oriented, dual-stage pH-responsive polymeric micelles for β-Lapachone delivery.

PubMed

Zhou, Yinjian; Dong, Ying; Huang, Gang; Wang, Yiguang; Huang, Xiaonan; Zhang, Fayun; Boothman, David A; Gao, Jinming; Liang, Wei

2016-12-14

β-Lapachone (β-lap), a novel anticancer agent, is bioactivated by NADP(H):quinone oxidoreductase 1 (NQO1), an enzyme over-expressed in numerous tumors, including lung, pancreas, breast, and prostate cancers. Fast renal clearance and methemaglobinemia / hemolytic side-effects from the clinical formulation (β-lap-hydroxyl propyl-β-cyclodextrin complex) hindered its clinical translation. Here, we investigated a dual model pH responsive polymers for β-lap delivery. Three pH-sensitive linkages, including acylhydrazone, ketal and imine bonds for β-lap prodrug syntheses result in an aryl imine linkage the most optimal linkage. The conversion to β-lap was 2.8%, 4.5% and 100% at pH 7.4, 6.5 and 5.0 in 8 h, respectively. β-lap aryl imine prodrug conjugated ultra pH-sensitive (UPS) polymer reached high β-lap loading density (8.3%) and exhibited dual-stages responsiveness to pH variation. In pHs under pH t , at stage I, micelle immediately dissociation and subsequently entering stage II, micelles start quickly release β-lap. In vitro release study showed that the micelles constantly release β-lap (14.9 ± 0.1%) at pHs above pH t in 72 h, whereas boosted release of β-lap (79.4 ± 1.2%) at pH 5.0. Micelle intracellular distribution predominantly in the lysosome organelle guaranteed their pH responsive dissociation and subsequently β-lap controlled release. The M-P micelles retained NQO1-dependent cytotoxicity in A549 lung cancer cells, similar to free drug in both efficacy and mechanism of cell death. The lysosome-oriented dual-stage ultra pH responsive β-lap prodrug micelles potentially offer an alternative nanotherapeutic strategy for lung, as well as other NQO1+ cancer therapies.

Testing the sensitivity of trade linkages in Europe to compound drought events

NASA Astrophysics Data System (ADS)

Veldkamp, Ted; Koks, Elco; Thissen, Mark; Wahl, Thomas; Haigh, Ivan; Muis, Sanne; Ward, Philip

2017-04-01

Droughts can be defined as spatially extensive events that are characterized by temporal deficits in precipitation, soil moisture or streamflow, and have the potential to cause large direct and indirect economic losses. Many European countries face drought as an economically important hazard, with agriculture, livestock, forestry, energy, industry, and water sectors particularly at risk, causing economic losses of 139 billion US over the past 30 years. Apart from these direct impacts, business production and the flow of goods and services can be affected indirectly by droughts. With consequences that can propagate through the economic system affecting regions not directly hit by the drought event itself, or in time-periods long after the original drought event occurred. In this study, we evaluate the sensitivity of existing trade linkages between the different NUTS-2 regions in Europe to the coupled occurrence of hydro-meteorological drought events, and their associated production losses. Using a multi-regional supply-use model for Europe, we have, on a product level, insight in the existing trade linkages between NUTS-2 regions. Using this information in combination with historical drought data, we assessed and identified for a selection of water related products: 1) the dependency-structures of the NUTS-2 regions within Europe for the import and export of products (and therein water); 2) the coupled nature of drought events occurring in regions that are linked via these trade-patterns; 3) the probability of not meeting demands (on a product level) due to drought events and the associated (indirect economic) impacts; and 4) regions that lose or benefit from their selection of trade-partners given the coupled nature of drought events, as well as the net effects for Europe as a whole.

Genetic structure, linkage disequilibrium and signature of selection in Sorghum: lessons from physically anchored DArT markers.

PubMed

Bouchet, Sophie; Pot, David; Deu, Monique; Rami, Jean-François; Billot, Claire; Perrier, Xavier; Rivallan, Ronan; Gardes, Laëtitia; Xia, Ling; Wenzl, Peter; Kilian, Andrzej; Glaszmann, Jean-Christophe

2012-01-01

Population structure, extent of linkage disequilibrium (LD) as well as signatures of selection were investigated in sorghum using a core sample representative of worldwide diversity. A total of 177 accessions were genotyped with 1122 informative physically anchored DArT markers. The properties of DArTs to describe sorghum genetic structure were compared to those of SSRs and of previously published RFLP markers. Model-based (STRUCTURE software) and Neighbor-Joining diversity analyses led to the identification of 6 groups and confirmed previous evolutionary hypotheses. Results were globally consistent between the different marker systems. However, DArTs appeared more robust in terms of data resolution and bayesian group assignment. Whole genome linkage disequilibrium as measured by mean r(2) decreased from 0.18 (between 0 to 10 kb) to 0.03 (between 100 kb to 1 Mb), stabilizing at 0.03 after 1 Mb. Effects on LD estimations of sample size and genetic structure were tested using i. random sampling, ii. the Maximum Length SubTree algorithm (MLST), and iii. structure groups. Optimizing population composition by the MLST reduced the biases in small samples and seemed to be an efficient way of selecting samples to make the best use of LD as a genome mapping approach in structured populations. These results also suggested that more than 100,000 markers may be required to perform genome-wide association studies in collections covering worldwide sorghum diversity. Analysis of DArT markers differentiation between the identified genetic groups pointed out outlier loci potentially linked to genes controlling traits of interest, including disease resistance genes for which evidence of selection had already been reported. In addition, evidence of selection near a homologous locus of FAR1 concurred with sorghum phenotypic diversity for sensitivity to photoperiod.

Ultra-high density intra-specific genetic linkage maps accelerate identification of functionally relevant molecular tags governing important agronomic traits in chickpea

PubMed Central

Kujur, Alice; Upadhyaya, Hari D.; Shree, Tanima; Bajaj, Deepak; Das, Shouvik; Saxena, Maneesha S.; Badoni, Saurabh; Kumar, Vinod; Tripathi, Shailesh; Gowda, C. L. L.; Sharma, Shivali; Singh, Sube; Tyagi, Akhilesh K.; Parida, Swarup K.

2015-01-01

We discovered 26785 and 16573 high-quality SNPs differentiating two parental genotypes of a RIL mapping population using reference desi and kabuli genome-based GBS assay. Of these, 3625 and 2177 SNPs have been integrated into eight desi and kabuli chromosomes, respectively in order to construct ultra-high density (0.20–0.37 cM) intra-specific chickpea genetic linkage maps. One of these constructed high-resolution genetic map has potential to identify 33 major genomic regions harbouring 35 robust QTLs (PVE: 17.9–39.7%) associated with three agronomic traits, which were mapped within <1 cM mean marker intervals on desi chromosomes. The extended LD (linkage disequilibrium) decay (~15 cM) in chromosomes of genetic maps have encouraged us to use a rapid integrated approach (comparative QTL mapping, QTL-region specific haplotype/LD-based trait association analysis, expression profiling and gene haplotype-based association mapping) rather than a traditional QTL map-based cloning method to narrow-down one major seed weight (SW) robust QTL region. It delineated favourable natural allelic variants and superior haplotype-containing one seed-specific candidate embryo defective gene regulating SW in chickpea. The ultra-high-resolution genetic maps, QTLs/genes and alleles/haplotypes-related genomic information generated and integrated strategy for rapid QTL/gene identification developed have potential to expedite genomics-assisted breeding applications in crop plants, including chickpea for their genetic enhancement. PMID:25942004

Analysis and compensation of an aircraft simulator control loading system with compliant linkage. [using hydraulic equipment

NASA Technical Reports Server (NTRS)

Johnson, P. R.; Bardusch, R. E.

1974-01-01

A hydraulic control loading system for aircraft simulation was analyzed to find the causes of undesirable low frequency oscillations and loading effects in the output. The hypothesis of mechanical compliance in the control linkage was substantiated by comparing the behavior of a mathematical model of the system with previously obtained experimental data. A compensation scheme based on the minimum integral of the squared difference between desired and actual output was shown to be effective in reducing the undesirable output effects. The structure of the proposed compensation was computed by use of a dynamic programing algorithm and a linear state space model of the fixed elements in the system.

Refining the Use of Linkage Disequilibrium as a Robust Signature of Selective Sweeps

PubMed Central

Jacobs, Guy S.; Sluckin, Timothy J.; Kivisild, Toomas

2016-01-01

During a selective sweep, characteristic patterns of linkage disequilibrium can arise in the genomic region surrounding a selected locus. These have been used to infer past selective sweeps. However, the recombination rate is known to vary substantially along the genome for many species. We here investigate the effectiveness of current (Kelly’s ZnS and ωmax) and novel statistics at inferring hard selective sweeps based on linkage disequilibrium distortions under different conditions, including a human-realistic demographic model and recombination rate variation. When the recombination rate is constant, Kelly’s ZnS offers high power, but is outperformed by a novel statistic that we test, which we call Zα. We also find this statistic to be effective at detecting sweeps from standing variation. When recombination rate fluctuations are included, there is a considerable reduction in power for all linkage disequilibrium-based statistics. However, this can largely be reversed by appropriately controlling for expected linkage disequilibrium using a genetic map. To further test these different methods, we perform selection scans on well-characterized HapMap data, finding that all three statistics—ωmax, Kelly’s ZnS, and Zα—are able to replicate signals at regions previously identified as selection candidates based on population differentiation or the site frequency spectrum. While ωmax replicates most candidates when recombination map data are not available, the ZnS and Zα statistics are more successful when recombination rate variation is controlled for. Given both this and their higher power in simulations of selective sweeps, these statistics are preferred when information on local recombination rate variation is available. PMID:27516617

Refining the Use of Linkage Disequilibrium as a Robust Signature of Selective Sweeps.

PubMed

Jacobs, Guy S; Sluckin, Tim J; Kivisild, Toomas

2016-08-01

During a selective sweep, characteristic patterns of linkage disequilibrium can arise in the genomic region surrounding a selected locus. These have been used to infer past selective sweeps. However, the recombination rate is known to vary substantially along the genome for many species. We here investigate the effectiveness of current (Kelly's [Formula: see text] and [Formula: see text]) and novel statistics at inferring hard selective sweeps based on linkage disequilibrium distortions under different conditions, including a human-realistic demographic model and recombination rate variation. When the recombination rate is constant, Kelly's [Formula: see text] offers high power, but is outperformed by a novel statistic that we test, which we call [Formula: see text] We also find this statistic to be effective at detecting sweeps from standing variation. When recombination rate fluctuations are included, there is a considerable reduction in power for all linkage disequilibrium-based statistics. However, this can largely be reversed by appropriately controlling for expected linkage disequilibrium using a genetic map. To further test these different methods, we perform selection scans on well-characterized HapMap data, finding that all three statistics-[Formula: see text] Kelly's [Formula: see text] and [Formula: see text]-are able to replicate signals at regions previously identified as selection candidates based on population differentiation or the site frequency spectrum. While [Formula: see text] replicates most candidates when recombination map data are not available, the [Formula: see text] and [Formula: see text] statistics are more successful when recombination rate variation is controlled for. Given both this and their higher power in simulations of selective sweeps, these statistics are preferred when information on local recombination rate variation is available. Copyright © 2016 by the Genetics Society of America.

Genetic Candidate Variants in Two Multigenerational Families with Childhood Apraxia of Speech

PubMed Central

Wijsman, Ellen M.; Nato, Alejandro Q.; Matsushita, Mark M.; Chapman, Kathy L.; Stanaway, Ian B.; Wolff, John; Oda, Kaori; Gabo, Virginia B.; Raskind, Wendy H.

2016-01-01

Childhood apraxia of speech (CAS) is a severe and socially debilitating form of speech sound disorder with suspected genetic involvement, but the genetic etiology is not yet well understood. Very few known or putative causal genes have been identified to date, e.g., FOXP2 and BCL11A. Building a knowledge base of the genetic etiology of CAS will make it possible to identify infants at genetic risk and motivate the development of effective very early intervention programs. We investigated the genetic etiology of CAS in two large multigenerational families with familial CAS. Complementary genomic methods included Markov chain Monte Carlo linkage analysis, copy-number analysis, identity-by-descent sharing, and exome sequencing with variant filtering. No overlaps in regions with positive evidence of linkage between the two families were found. In one family, linkage analysis detected two chromosomal regions of interest, 5p15.1-p14.1, and 17p13.1-q11.1, inherited separately from the two founders. Single-point linkage analysis of selected variants identified CDH18 as a primary gene of interest and additionally, MYO10, NIPBL, GLP2R, NCOR1, FLCN, SMCR8, NEK8, and ANKRD12, possibly with additive effects. Linkage analysis in the second family detected five regions with LOD scores approaching the highest values possible in the family. A gene of interest was C4orf21 (ZGRF1) on 4q25-q28.2. Evidence for previously described causal copy-number variations and validated or suspected genes was not found. Results are consistent with a heterogeneous CAS etiology, as is expected in many neurogenic disorders. Future studies will investigate genome variants in these and other families with CAS. PMID:27120335

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

Construction of the model for the Genetic Analysis Workshop 14 simulated data: genotype-phenotype relationships, gene interaction, linkage, association, disequilibrium, and ascertainment effects for a complex phenotype.

PubMed

Greenberg, David A; Zhang, Junying; Shmulewitz, Dvora; Strug, Lisa J; Zimmerman, Regina; Singh, Veena; Marathe, Sudhir

2005-12-30

The Genetic Analysis Workshop 14 simulated dataset was designed 1) To test the ability to find genes related to a complex disease (such as alcoholism). Such a disease may be given a variety of definitions by different investigators, have associated endophenotypes that are common in the general population, and is likely to be not one disease but a heterogeneous collection of clinically similar, but genetically distinct, entities. 2) To observe the effect on genetic analysis and gene discovery of a complex set of gene x gene interactions. 3) To allow comparison of microsatellite vs. large-scale single-nucleotide polymorphism (SNP) data. 4) To allow testing of association to identify the disease gene and the effect of moderate marker x marker linkage disequilibrium. 5) To observe the effect of different ascertainment/disease definition schemes on the analysis. Data was distributed in two forms. Data distributed to participants contained about 1,000 SNPs and 400 microsatellite markers. Internet-obtainable data consisted of a finer 10,000 SNP map, which also contained data on controls. While disease characteristics and parameters were constant, four "studies" used varying ascertainment schemes based on differing beliefs about disease characteristics. One of the studies contained multiplex two- and three-generation pedigrees with at least four affected members. The simulated disease was a psychiatric condition with many associated behaviors (endophenotypes), almost all of which were genetic in origin. The underlying disease model contained four major genes and two modifier genes. The four major genes interacted with each other to produce three different phenotypes, which were themselves heterogeneous. The population parameters were calibrated so that the major genes could be discovered by linkage analysis in most datasets. The association evidence was more difficult to calibrate but was designed to find statistically significant association in 50% of datasets. We also simulated some marker x marker linkage disequilibrium around some of the genes and also in areas without disease genes. We tried two different methods to simulate the linkage disequilibrium.

Classroom Acoustics: Understanding Barriers to Learning.

ERIC Educational Resources Information Center

Crandell, Carl C., Ed.; Smaldino, Joseph J., Ed.

2001-01-01

This booklet explores classroom acoustics and their importance on the learning potential of children with hearing loss and related disabilities. The booklet also reviews research on classroom acoustics and the need for the development of classroom acoustics standards. Chapters examine: 1) a speech-perception model demonstrating the linkage between…

Education, Conflict and Development

ERIC Educational Resources Information Center

Paulson, Julia, Ed.

2011-01-01

Under various names--education and conflict, education and fragility, education and insecurity, etc.--the understanding of linkages between education and violent conflict has emerged as an important and pressing area of inquiry. Work and research by practitioners and scholars has clearly pointed to the negative potential of education to contribute…

Molecular mapping of QTLs for plant type and earliness traits in pigeonpea (Cajanus cajan L. Millsp.)

PubMed Central

2012-01-01

Background Pigeonpea is an important grain legume of the semi-arid tropics and sub-tropical regions where it plays a crucial role in the food and nutritional security of the people. The average productivity of pigeonpea has remained very low and stagnant for over five decades due to lack of genomic information and intensive breeding efforts. Previous SSR-based linkage maps of pigeonpea used inter-specific crosses due to low inter-varietal polymorphism. Here our aim was to construct a high density intra-specific linkage map using genic-SNP markers for mapping of major quantitative trait loci (QTLs) for key agronomic traits, including plant height, number of primary and secondary branches, number of pods, days to flowering and days to maturity in pigeonpea. Results A population of 186 F2:3 lines derived from an intra-specific cross between inbred lines ‘Pusa Dwarf’ and ‘HDM04-1’ was used to construct a dense molecular linkage map of 296 genic SNP and SSR markers covering a total adjusted map length of 1520.22 cM for the 11 chromosomes of the pigeonpea genome. This is the first dense intra-specific linkage map of pigeonpea with the highest genome length coverage. Phenotypic data from the F2:3 families were used to identify thirteen QTLs for the six agronomic traits. The proportion of phenotypic variance explained by the individual QTLs ranged from 3.18% to 51.4%. Ten of these QTLs were clustered in just two genomic regions, indicating pleiotropic effects or close genetic linkage. In addition to the main effects, significant epistatic interaction effects were detected between the QTLs for number of pods per plant. Conclusions A large amount of information on transcript sequences, SSR markers and draft genome sequence is now available for pigeonpea. However, there is need to develop high density linkage maps and identify genes/QTLs for important agronomic traits for practical breeding applications. This is the first report on identification of QTLs for plant type and maturity traits in pigeonpea. The QTLs identified in this study provide a strong foundation for further validation and fine mapping for utilization in the pigeonpea improvement. PMID:23043321

An empirical Bayes method for updating inferences in analysis of quantitative trait loci using information from related genome scans.

PubMed

Zhang, Kui; Wiener, Howard; Beasley, Mark; George, Varghese; Amos, Christopher I; Allison, David B

2006-08-01

Individual genome scans for quantitative trait loci (QTL) mapping often suffer from low statistical power and imprecise estimates of QTL location and effect. This lack of precision yields large confidence intervals for QTL location, which are problematic for subsequent fine mapping and positional cloning. In prioritizing areas for follow-up after an initial genome scan and in evaluating the credibility of apparent linkage signals, investigators typically examine the results of other genome scans of the same phenotype and informally update their beliefs about which linkage signals in their scan most merit confidence and follow-up via a subjective-intuitive integration approach. A method that acknowledges the wisdom of this general paradigm but formally borrows information from other scans to increase confidence in objectivity would be a benefit. We developed an empirical Bayes analytic method to integrate information from multiple genome scans. The linkage statistic obtained from a single genome scan study is updated by incorporating statistics from other genome scans as prior information. This technique does not require that all studies have an identical marker map or a common estimated QTL effect. The updated linkage statistic can then be used for the estimation of QTL location and effect. We evaluate the performance of our method by using extensive simulations based on actual marker spacing and allele frequencies from available data. Results indicate that the empirical Bayes method can account for between-study heterogeneity, estimate the QTL location and effect more precisely, and provide narrower confidence intervals than results from any single individual study. We also compared the empirical Bayes method with a method originally developed for meta-analysis (a closely related but distinct purpose). In the face of marked heterogeneity among studies, the empirical Bayes method outperforms the comparator.

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.

The Army’s Local Economic Effects

DTIC Science & Technology

2015-01-01

region. An I/O model is a representation of the linkages between major sectors of a regional economy in which each sector of the regional economy is...assumed to require inputs from the other sectors to produce output. These inputs can come from local sources within the region, from other domestic...ment of the Army in a congressional district. An I/O model is a representation of the linkages between major sectors of a regional economy (and, to a

Statistical aspects of evolution under natural selection, with implications for the advantage of sexual reproduction.

PubMed

Crouch, Daniel J M

2017-10-27

The prevalence of sexual reproduction remains mysterious, as it poses clear evolutionary drawbacks compared to reproducing asexually. Several possible explanations exist, with one of the most likely being that finite population size causes linkage disequilibria to randomly generate and impede the progress of natural selection, and that these are eroded by recombination via sexual reproduction. Previous investigations have either analysed this phenomenon in detail for small numbers of loci, or performed population simulations for many loci. Here we present a quantitative genetic model for fitness, based on the Price Equation, in order to examine the theoretical consequences of randomly generated linkage disequilibria when there are many loci. In addition, most previous work has been concerned with the long-term consequences of deleterious linkage disequilibria for population fitness. The expected change in mean fitness between consecutive generations, a measure of short-term evolutionary success, is shown under random environmental influences to be related to the autocovariance in mean fitness between the generations, capturing the effects of stochastic forces such as genetic drift. Interaction between genetic drift and natural selection, due to randomly generated linkage disequilibria, is demonstrated to be one possible source of mean fitness autocovariance. This suggests a possible role for sexual reproduction in reducing the negative effects of genetic drift, thereby improving the short-term efficacy of natural selection. Copyright © 2017 Elsevier Ltd. All rights reserved.

Markov chain Monte Carlo linkage analysis: effect of bin width on the probability of linkage.

PubMed

Slager, S L; Juo, S H; Durner, M; Hodge, S E

2001-01-01

We analyzed part of the Genetic Analysis Workshop (GAW) 12 simulated data using Monte Carlo Markov chain (MCMC) methods that are implemented in the computer program Loki. The MCMC method reports the "probability of linkage" (PL) across the chromosomal regions of interest. The point of maximum PL can then be taken as a "location estimate" for the location of the quantitative trait locus (QTL). However, Loki does not provide a formal statistical test of linkage. In this paper, we explore how the bin width used in the calculations affects the max PL and the location estimate. We analyzed age at onset (AO) and quantitative trait number 5, Q5, from 26 replicates of the general simulated data in one region where we knew a major gene, MG5, is located. For each trait, we found the max PL and the corresponding location estimate, using four different bin widths. We found that bin width, as expected, does affect the max PL and the location estimate, and we recommend that users of Loki explore how their results vary with different bin widths.

Synthesis of New Hyperbranched α-Glucans from Sucrose by Lactobacillus reuteri 180 Glucansucrase Mutants.

PubMed

Meng, Xiangfeng; Dobruchowska, Justyna M; Pijning, Tjaard; Gerwig, Gerrit J; Dijkhuizen, Lubbert

2016-01-20

α-Glucans produced by glucansucrase enzymes of lactic acid bacteria attract strong attention as novel ingredients and functional biopolymers in the food industry. In the present study, α-helix 4 amino acid residues D1085, R1088, and N1089 of glucansucrase GTF180 of Lactobacillus reuteri 180 were targeted for mutagenesis both jointly and separately. Analysis of the mutational effects on enzyme function revealed that all D1085 and R1088 mutants catalyzed the synthesis of hyperbranched α-glucans with 15-22% branching (α1→3,6) linkages, compared to 13% in the wild-type GTF180. In addition, besides native (α1→6) and (α1→3) linkages, all of the mutations introduced a small amount of (α1→4) linkages (5% at most) in the polysaccharides produced. We conclude that α-helix 4 residues, especially D1085 and R1088, constituting part of the +2 acceptor binding subsite, are important determinants for the linkage specificity. The new hyperbranched α-glucans provide very interesting structural diversities and may find applications in the food industry.

Genetic linkage analysis of schizophrenia using chromosome 11q13-24 markers in Israeli pedigrees

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

Mulcrone, J.; Marchblanks, R.; Whatley, S.A.

It is generally agreed that there is a genetic component in the etiology of schizophrenia which may be tested by the application of linkage analysis to multiply-affected families. One genetic region of interest is the long arm of chromosome 11 because of previously reported associations of genetic variation in this region with schizophrenia, and because of the fact that it contains the locus for the dopamine D2 receptor gene. In this study we have examined the segregation of schizophrenia with microsatellite dinucleotide repeat DNA markers along chromosome 11q in 5 Israeli families multiply-affected for schizophrenia. The hypothesis of linkage undermore » genetic homogeneity of causation was tested under a number of genetic models. Linkage analysis provided no evidence for significant causal mutations within the region bounded by INT and D11S420 on chromosome 11q. It is still possible, however, that a gene of major effect exists in this region, either with low penetrance or with heterogeneity. 32 refs., 2 figs., 4 tabs.« less

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.

The quality of Indigenous identification in administrative health data in Australia: insights from studies using data linkage

PubMed Central

2012-01-01

Background Missing or incorrect Indigenous status in health records hinders monitoring of Indigenous health indicators. Linkage of administrative data has been used to improve the ascertainment of Indigenous status. Data linkage was pioneered in Western Australia (WA) and is now being used in other Australian states. This systematic review appraises peer-reviewed Australian studies that used data linkage to elucidate the impact of under-ascertainment of Indigenous status on health indicators. Methods A PubMed search identified eligible studies that used Australian linked data to interrogate Indigenous identification using more than one identifier and interrogated the impact of the different identifiers on estimation of Indigenous health indicators. Results Eight papers were included, five from WA and three from New South Wales (NSW). The WA papers included a self-identified Indigenous community cohort and showed improved identification in hospital separation data after 2000. In CVD hospitalised patients (2000–05), under-identification was greater in urban residents, older people and socially more advantaged Indigenous people, with varying algorithms giving different estimates of under-count. Age-standardised myocardial infarction incidence rates (2000–2004) increased by about 10%-15% with improved identification. Under-ascertainment of Indigenous identification overestimated secular improvements in life expectancy and mortality whereas correcting infectious disease notifications resulted in lower Indigenous/ non-Indigenous rate ratios. NSW has a history of poor Indigenous identification in administrative data systems, but the NSW papers confirmed the usefulness of data linkage for improving Indigenous identification and the potential for very different estimates of Indigenous disease indicators depending upon the algorithm used for identification. Conclusions Under-identification of Indigenous status must be addressed in health analyses concerning Indigenous health differentials – they cannot be ignored or wished away. This problem can be substantially diminished through data linkage. Under-identification of Indigenous status impacts differently in different disease contexts, generally resulting in under-estimation of absolute and relative Indigenous health indicators, but may perversely overestimate Indigenous rates and differentials in the setting of stigma-associated conditions such as sexually-transmitted and blood-borne virus infections. Under-numeration in Census surveys also needs consideration to address the added problem of denominator undercounts. PMID:23157943

Evidence for Linkage of Bipolar Disorder to Chromosome 18 with a Parent-of-Origin Effect

PubMed Central

Stine, O. Colin; Xu, Jianfeng; Koskela, Rebecca; McMahon, Francis J.; Gschwend, Michele; Friddle, Carl; Clark, Chris D.; McInnis, Melvin G.; Simpson, Sylvia G.; Breschel, Theresa S.; Vishio, Eva; Riskin, Kelly; Feilotter, Harriet; Chen, Eugene; Shen, Susan; Folstein, Susan; Meyers, Deborah A.; Botstein, David; Marr, Thomas G.; DePaulo, J. Raymond

1995-01-01

A susceptibility gene on chromosome 18 and a parent-of-origin effect have been suggested for bipolar affective disorder (BPAD). We have studied 28 nuclear families selected for apparent unilineal transmission of the BPAD phenotype, by using 31 polymorphic markers spanning chromosome 18. Evidence for linkage was tested with affected-sib-pair and LOD score methods under two definitions of the affected phenotype. The affected-sib-pair analyses indicated excess allele sharing for markers on 18p within the region reported previously. The greatest sharing was at D18S37: 64% in bipolar and recurrent unipolar (RUP) sib pairs (P = .0006). In addition, excess sharing of the paternally, but not maternally, transmitted alleles was observed at three markers on 18q: at D18S41, 51 bipolar and RUP sib pairs were concordant for paternally transmitted alleles, and 21 pairs were discordant (P = .0004). The evidence for linkage to loci on both 18p and 18q was strongest in the 11 paternal pedigrees, i.e., those in which the father or one of the father's sibs is affected. In these pedigrees, the greatest allele sharing (81%; P = .00002) and the highest LOD score (3.51; θ = 0.0) were observed at D18S41. Our results provide further support for linkage of BPAD to chromosome 18 and the first molecular evidence for a parent-of-origin effect operating in this disorder. The number of loci involved, and their precise location, require further study. PMID:8533768

A Comparative Study of Dilute acid and Ionic Liquid Pretreatment of Biomass and Model Lignocellulosics

USDA-ARS?s Scientific Manuscript database

Lignocellulosic biomass has the great potential to serve as the low cost and abundant feedstock for bioconversion into fermentable sugars, which can be further utilized for biofuel production. However, high lignin content, crystalline cellulose structure and the presence of ester linkages between l...

Conceptualizing the Linkages between Diversity Experiences and Moral Development

ERIC Educational Resources Information Center

Engberg, Mark E.; Porter, Kamaria B.

2013-01-01

The purpose of this article is to advance an understanding of how diversity experiences can potentially foster moral development among college students. An overview of the research linking diversity experiences to moral development is discussed, followed by a presentation of a conceptual framework that demonstrates the nuances and challenges in…

Videotex 1983. An ERIC Fact Sheet.

ERIC Educational Resources Information Center

Olson, Michael

The capabilities and potential of videotex, a two-way interactive communication and information retrieval service, are briefly described in this fact sheet. Videotex refers to a two-way linkage between databases and individual consumers in home or office. It is currently being used for information retrieval, transactions (e.g., bill paying,…

Developing a Digital Assessment in Senior Secondary Physical Education

ERIC Educational Resources Information Center

Penney, Dawn; Jones, Andy; Newhouse, Paul; Cambell, Alistair

2012-01-01

Background: The Digital Forms of Assessment project is a three-year Australian Research Council Linkage research project being conducted by Edith Cowan University's Centre for Schooling and Learning Technologies (CSaLT) in partnership with the Curriculum Council of Western Australia. The project is investigating the potential for a digital format…

Intelligence and Schooling. Fueling the Education Explosion: Proceedings of Conference 2 (Cleveland, Ohio, November 17-18, 1983).

ERIC Educational Resources Information Center

Gardner, Mary, Ed.; Reed-Mundell, Charlene, Ed.

These proceedings contain presentations from a conference whose major topics were real-world intelligence, artificial intelligence, and linkage between the education and corporate sectors. "People, Perspectives...Potential and Possibilities" (Elyse S. Fleming), which was the conference's closing speech, briefly summarizes the information…

A Systems Approach to the Estimation of Ecosystem and Human Health Stressors in Air, Land and Water

EPA Science Inventory

A model linkage paradigm, based on the nitrogen cascade, is introduced. This general paradigm is then adapted to specific multi-media nitrogen issues and specific models to be linked. An example linked modeling system addressing potential nitrogen responses to biofuel-driven co...

INTEGRATING STAKEHOLDER PERSPECTIVES IN A SYSTEMS APPROACH TO EXPLORING SUSTAINABLE SOLUTIONS: TRIPLE VALUE SIMULATION (3VS) MODELS IN COASTAL WATERSHEDS

EPA Science Inventory

Decision makers often need assistance in understanding the dynamic interactions and linkages among economic, environmental and social systems in coastal watersheds. They also need scientific input to better evaluate the potential costs and benefits of intervention options. The US...

Beyond strategy: exploring the brokerage role of facilities manager in hospitals.

PubMed

Heng, H K S; McGeorge, W D; Loosemore, M

2005-01-01

Seeks to explore the brokerage role of facilities manager in hospitals, based on the premise that facilities management (FM) is largely concerned with "strategic brokerage". Strategic brokerage is the term coined by Akhaghi to explain the integration of a wide range of support services to ensure the effective operation of the core business of an organization. The research was conducted in the health service sector using a single case study approach to examine the brokerage potential for FM in a hospital in the Sydney Metropolitan area. A social network analysis technique was used to identify and analyse the communication networks of players in a hospital environment. Two general questions guided the analysis. First, what is the brokerage potential within the FM process? Second, where are the opportunities for brokerage? The results indicate that identifying relationship linkages between different functional units can create potential brokerage opportunities. The proposition is made that viewing FM from a brokerage perspective can add value to the delivery of health-care services.

Targeting estrogen/estrogen receptor alpha enhances Bacillus Calmette-Guérin efficacy in bladder cancer

PubMed Central

Shang, Zhiqun; Li, Yanjun; Hsu, Iawen; Zhang, Minghao; Tian, Jing; Wen, Simeng; Han, Ruifa; Messing, Edward M.; Chang, Chawnshang; Niu, Yuanjie; Yeh, Shuyuan

2016-01-01

Recent studies showed the potential linkage of estrogen/estrogen receptor signaling with bladder tumorigenesis, yet detailed mechanisms remain elusive. Here we found a new potential therapy with the combination of Bacillus Calmette Guerin (BCG) and the anti-estrogen ICI 182,780 led to better suppression of bladder cancer (BCa) than BCG alone. Mechanism dissection found ICI 182,780 could promote BCG attachment/internalization to the BCa cells through increased integrin-α5β1 expression and IL-6 release, which may enhance BCG-induced suppression of BCa cell growth via recruiting more monocytes/macrophages to BCa cells and increased TNF-α release. Consistently, in vivo studies found ICI 182,780 could potentiate the anti-BCa effects of BCG in the carcinogen-induced mouse BCa models. Together, these in vitro and in vivo results suggest that combining BCG with anti-estrogen may become a new therapeutic approach with better efficacy to suppress BCa progression and recurrence. PMID:27092883

Targeting estrogen/estrogen receptor alpha enhances Bacillus Calmette-Guérin efficacy in bladder cancer.

PubMed

Shang, Zhiqun; Li, Yanjun; Hsu, Iawen; Zhang, Minghao; Tian, Jing; Wen, Simeng; Han, Ruifa; Messing, Edward M; Chang, Chawnshang; Niu, Yuanjie; Yeh, Shuyuan

2016-05-10

Recent studies showed the potential linkage of estrogen/estrogen receptor signaling with bladder tumorigenesis, yet detailed mechanisms remain elusive. Here we found a new potential therapy with the combination of Bacillus Calmette-Guerin (BCG) and the anti-estrogen ICI 182,780 led to better suppression of bladder cancer (BCa) than BCG alone. Mechanism dissection found ICI 182,780 could promote BCG attachment/internalization to the BCa cells through increased integrin-α5β1 expression and IL-6 release, which may enhance BCG-induced suppression of BCa cell growth via recruiting more monocytes/macrophages to BCa cells and increased TNF-α release. Consistently, in vivo studies found ICI 182,780 could potentiate the anti-BCa effects of BCG in the carcinogen-induced mouse BCa models. Together, these in vitro and in vivo results suggest that combining BCG with anti-estrogen may become a new therapeutic approach with better efficacy to suppress BCa progression and recurrence.

State-Level Immunization Information Systems: Potential for Childhood Immunization Data Linkages.

PubMed

Fuller, Jill E; Walter, Emmanuel B; Dole, Nancy; O'Hara, Richard; Herring, Amy H; Durkin, Maureen S; Specker, Bonny; Wey, Betty

2017-01-01

Objectives Sources of immunization data include state registries or immunization information systems (IIS), medical records, and surveys. Little is known about the quality of these data sources or the feasibility of using IIS data for research. We assessed the feasibility of collecting immunization information for a national children's health study by accessing existing IIS data and comparing the completeness of these data against medical record abstractions (MRA) and parent report. Staff time needed to obtain IIS and MRA data was assessed. Methods We administered a questionnaire to state-level IIS representatives to ascertain availability and completeness of their data for research and gather information about data formats. We evaluated quality of data from IIS, medical records, and reports from parents of 119 National Children's Study participants at three locations. Results IIS data were comparable to MRA data and both were more complete than parental report. Agreement between IIS and MRA data was greater than between parental report and MRA, suggesting IIS and MRA are better sources than parental report. Obtaining IIS data took less staff time than chart review, making IIS data linkage for research a preferred choice. Conclusions IIS survey results indicate data can be obtained by researchers using data linkages. IIS are an accessible and feasible child immunization information source and these registries reduce reliance on parental report or medical record abstraction. Researchers seeking to link IIS data with large multi-site studies should consider acquiring IIS data, but may need strategies to overcome barriers to data completeness and linkage.

Sugars, obesity, and cardiovascular disease: results from recent randomized control trials.

PubMed

Rippe, James M; Angelopoulos, Theodore J

2016-11-01

The relationship between sugar consumption and various health-related sequelas is controversial. Some investigators have argued that excessive sugar consumption is associated with increased risk of obesity, coronary heart disease, diabetes (T2D), metabolic syndrome, non-alcoholic fatty liver disease, and stimulation of reward pathways in the brain potentially causing excessive caloric consumption. These concerns have influenced organizations such as the World Health Organization, the Scientific Advisory Committee on Nutrition in England not to exceed 5 % of total energy and the Dietary Guidelines for Americans Advisory Committee 2015 to recommend upper limits of sugar consumption not to exceed 10 % of calories. Data from many randomized control trials (RCTs) do not support linkages between sugar consumption at normal levels within the human diet and various adverse metabolic and health-related effects. Fructose and glucose are typically consumed together in roughly equal proportions from high-fructose corn syrup (also known as isoglucose in Europe) or sucrose. The purpose of this review is to present data from recent RCTs and findings from recent systematic reviews and meta-analyses related to sugar consumption and its putative health effects. This review evaluates findings from recent randomized controlled trials, systematic reviews and meta-analyses into the relationship of sugar consumption and a range of health-related issues including energy-regulating hormones, obesity, cardiovascular disease, diabetes, and accumulation of liver fat and neurologic responses. Data from these sources do not support linkages between sugar consumption at normal levels within the human diet and various adverse metabolic and health-related effects.

Optimising the use of linked administrative data for infectious diseases research in Australia.

PubMed

Moore, Hannah C; Blyth, Christopher C

2018-06-14

Infectious diseases remain a major cause of morbidity in Australia. A wealth of data exists in administrative datasets, which are linked through established data-linkage infrastructure in most Australian states and territories. These linkages can support robust studies to investigate the burden of disease, the relative contribution of various aetiological agents to disease, and the effectiveness of population-based prevention policies - research that is critical to the success of current and future vaccination programs. At a recent symposium in Perth, epidemiologists, clinicians and policy makers in the infectious diseases field discussed the various benefits of, and barriers to, data-linkage research, with a focus on respiratory infection research. A number of issues and recommendations emerged. The demand for data-linkage projects is starting to outweigh the capabilities of exisiting data-linkage infrastructure. There is a need to further streamline processes relating to data access, increase data sharing and conduct nationally collaborative projects. Concerns about data security and sharing across jurisdictional borders can be addressed through multiple safe data solutions. Researchers need to do more to ensure that the benefits of linking datasets to answer policy-relevant questions are being realised for the benefit of community groups, government authorities, funding bodies and policy makers. Increased collaboration and engagement across all sectors can optimise the use of linked data to help reduce the burden of infectious diseases.

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.

Linking effects of anthropogenic debris to ecological impacts

PubMed Central

Browne, Mark Anthony; Underwood, A. J.; Chapman, M. G.; Williams, Rob; Thompson, Richard C.; van Franeker, Jan A.

2015-01-01

Accelerated contamination of habitats with debris has caused increased effort to determine ecological impacts. Strikingly, most work on organisms focuses on sublethal responses to plastic debris. This is controversial because (i) researchers have ignored medical insights about the mechanisms that link effects of debris across lower levels of biological organization to disease and mortality, and (ii) debris is considered non-hazardous by policy-makers, possibly because individuals can be injured or removed from populations and assemblages without ecological impacts. We reviewed the mechanisms that link effects of debris across lower levels of biological organization to assemblages and populations. Using plastic, we show microplastics reduce the ‘health’, feeding, growth and survival of ecosystem engineers. Larger debris alters assemblages because fishing-gear and tyres kill animals and damage habitat-forming plants, and because floating bottles facilitate recruitment and survival of novel taxa. Where ecological linkages are not known, we show how to establish hypothetical links by synthesizing studies to assess the likelihood of impacts. We also consider how population models examine ecological linkages and guide management of ecological impacts. We show that by focusing on linkages to ecological impacts rather than the presence of debris and its sublethal impacts, we could reduce threats posed by debris. PMID:25904661

Dynamic linkages among the gold market, US dollar and crude oil market

NASA Astrophysics Data System (ADS)

Mo, Bin; Nie, He; Jiang, Yonghong

2018-02-01

This paper aims to examine the dynamic linkages among the gold market, US dollar and crude oil market. The analysis also delves more deeply into the effect of the global financial crisis on the short-term relationship. We use fractional cointegration to analyze the long-term memory feature of these volatility processes to investigate whether they are tied through a common long-term equilibrium. The DCC-MGARCH model is employed to investigate the time-varying long-term linkages among these markets. The Krystou-Labys non-linear asymmetric Granger causality method is used to examine the effect of the financial crisis. We find that (i) there is clearly a long-term dependence among these markets; (ii) the dynamic gold-oil relationship is always positive and the oil-dollar relationship is always negative; and (iii) after the crisis, we can observe evidence of a positive non-linear causal relationship from gold to US dollar and US dollar to crude oil, and a negative non-linear causal relationship from US dollar to gold. Investors who want to construct their optimal portfolios and policymakers who aim to make effective macroeconomic policies should take these findings into account.

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.

National Survey of Preventive Health Services in US Emergency Departments

PubMed Central

Delgado, M. Kit; Acosta, Colleen D.; Ginde, Adit A.; Wang, N. Ewen; Strehlow, Matthew C.; Khandwala, Yash S.; Camargo, Carlos A.

2012-01-01

Study objective We describe the availability of preventive health services in US emergency departments (EDs), as well as ED directors’ preferred service and perceptions of barriers to offering preventive services. Methods Using the 2007 National Emergency Department Inventory (NEDI)–USA, we randomly sampled 350 (7%) of 4,874 EDs. We surveyed directors of these EDs to determine the availability of (1) screening and referral programs for alcohol, tobacco, geriatric falls, intimate partner violence, HIV, diabetes, and hypertension; (2) vaccination programs for influenza and pneumococcus; and (3) linkage programs to primary care and health insurance. ED directors were asked to select the service they would most like to implement and to rate 5 potential barriers to offering preventive services. Results Two hundred seventy-seven EDs (80%) responded across 46 states. Availability of services ranged from 66% for intimate partner violence screening to 19% for HIV screening. ED directors wanted to implement primary care linkage most (17%) and HIV screening least (2%). ED directors “agreed/strongly agreed” that the following are barriers to ED preventive care: cost (74%), increased patient length of stay (64%), lack of follow-up (60%), resource shifting leading to worse patient outcomes (53%), and philosophical opposition (27%). Conclusion Most US EDs offer preventive services, but availability and ED director preference for type of service vary greatly. The majority of EDs do not routinely offer Centers for Disease Control and Prevention–recommended HIV screening. Most ED directors are not philosophically opposed to offering preventive services but are concerned with added costs, effects on ED operations, and potential lack of follow-up. PMID:20889237

Meta-Analysis of Reciprocal Linkages between Temperate Seagrasses and Waterfowl with Implications for Conservation.

PubMed

Kollars, Nicole M; Henry, Amy K; Whalen, Matthew A; Boyer, Katharyn E; Cusson, Mathieu; Eklöf, Johan S; Hereu, Clara M; Jorgensen, Pablo; Kiriakopolos, Stephanie L; Reynolds, Pamela L; Tomas, Fiona; Turner, Mo S; Ruesink, Jennifer L

2017-01-01

Multi-trophic conservation and management strategies may be necessary if reciprocal linkages between primary producers and their consumers are strong. While herbivory on aquatic plants is well-studied, direct top-down control of seagrass populations has received comparatively little attention, particularly in temperate regions. Herein, we used qualitative and meta-analytic approaches to assess the scope and consequences of avian (primarily waterfowl) herbivory on temperate seagrasses of the genus Zostera . Meta-analyses revealed widespread evidence of spatio-temporal correlations between Zostera and waterfowl abundances as well as strong top-down effects of grazing on Zostera . We also documented the identity and diversity of avian species reported to consume Zostera and qualitatively assessed their potential to exert top-down control. Our results demonstrate that Zostera and their avian herbivores are ecologically linked and we suggest that bird herbivory may influence the spatial structure, composition, and functioning of the seagrass ecosystem. Therefore, the consequences of avian herbivory should be considered in the management of seagrass populations. Of particular concern are instances of seagrass overgrazing by waterfowl which result in long-term reductions in seagrass biomass or coverage, with subsequent impacts on local populations of waterfowl and other seagrass-affiliated species. While our results showed that bird density and type may affect the magnitude of the top-down effects of avian herbivory, empirical research on the strength, context-dependency, and indirect effects of waterfowl- Zostera interactions remains limited. For example, increased efforts that explicitly measure the effects of different functional groups of birds on seagrass abundance and/or document how climate change-driven shifts in waterfowl migratory patterns impact seagrass phenology and population structure will advance research programs for both ecologists and managers concerned with the joint conservation of both seagrasses and their avian herbivores.

Measuring the economic effects of Japan's Mikawa Port: Pre- and-post disaster assessments

NASA Astrophysics Data System (ADS)

Shibusawa, Hiroyuki; Miyata, Yuzuru

2017-10-01

This study examines the economic effects of Japan's Mikawa Port on Aichi Prefecture before and after a natural disaster interrupts its operations for one year. Using a regional input-output model, backward and forward linkage impacts are calculated along the waterfront where the auto industry is concentrated. In addition, economic damage from natural disasters is estimated. We assess the economic implications on the hinterland of Mikawa Port. Density functions of the backward and forward linkage impacts are derived. A production stoppage along the waterfront of Mikawa Port generates large indirect negative effects on the regional economy. Results found that density functions of the total impacts are decreasing function of distance but that several sectors are characterized by non-decreasing functions.

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.

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.

Strategic issues in performance appraisal: theory and practice.

PubMed

Fombrun, C J; Laud, R L

1983-01-01

Performance appraisal systems have tremendous strategic potential for governing employee behavior and thus corporate direction through their links to selection, training and career planning, and reward systems. Authors Charles J. Fombrun, assistant professor of management at the University of Pennsylvania's Wharton School, and Robert P. Laud, senior vice-president of Drake Beam Morin, Inc., surveyed appraisal systems of Fortune 1300 corporations to find out how well companies are realizing this potential. Among their conclusions: (1) In most organizations, the typical performance appraisal system is focused on short-term goals. Strengthening the linkage between the appraisal system and the long-term implications of strategic planning could improve organizational effectiveness in the future. (2) The performance appraisal system's most prevalent use is as a feedback mechanism rather than as a management tool. Thus, the authors conclude, the role of the performance appraisal system as a strategic organizational tool is largely unappreciated by U.S. organizations.

The importance of including local correlation times in the calculation of inter-proton distances from NMR measurements: ignoring local correlation times leads to significant errors in the conformational analysis of the Glc alpha1-2Glc alpha linkage by NMR spectroscopy.

PubMed

Mackeen, Mukram; Almond, Andrew; Cumpstey, Ian; Enis, Seth C; Kupce, Eriks; Butters, Terry D; Fairbanks, Antony J; Dwek, Raymond A; Wormald, Mark R

2006-06-07

The experimental determination of oligosaccharide conformations has traditionally used cross-linkage 1H-1H NOE/ROEs. As relatively few NOEs are observed, to provide sufficient conformational constraints this method relies on: accurate quantification of NOE intensities (positive constraints); analysis of absent NOEs (negative constraints); and hence calculation of inter-proton distances using the two-spin approximation. We have compared the results obtained by using 1H 2D NOESY, ROESY and T-ROESY experiments at 500 and 700 MHz to determine the conformation of the terminal Glc alpha1-2Glc alpha linkage in a dodecasaccharide and a related tetrasaccharide. For the tetrasaccharide, the NOESY and ROESY spectra produced the same qualitative pattern of linkage cross-peaks but the quantitative pattern, the relative peak intensities, was different. For the dodecasaccharide, the NOESY and ROESY spectra at 500 MHz produced a different qualitative pattern of linkage cross-peaks, with fewer peaks in the NOESY spectrum. At 700 MHz, the NOESY and ROESY spectra of the dodecasaccharide produced the same qualitative pattern of peaks, but again the relative peak intensities were different. These differences are due to very significant differences in the local correlation times for different proton pairs across this glycosidic linkage. The local correlation time for each proton pair was measured using the ratio of the NOESY and T-ROESY cross-relaxation rates, leaving the NOESY and ROESY as independent data sets for calculating the inter-proton distances. The inter-proton distances calculated including the effects of differences in local correlation times give much more consistent results.

Genome-scan analysis for quantitative trait loci in an F2 tilapia hybrid.

PubMed

Cnaani, A; Zilberman, N; Tinman, S; Hulata, G; Ron, M

2004-09-01

We searched for genetic linkage between DNA markers and quantitative trait loci (QTLs) for innate immunity, response to stress, biochemical parameters of blood, and fish size in an F2 population derived from an interspecific tilapia hybrid (Oreochromis mossambicusx O. aureus). A family of 114 fish was scanned for 40 polymorphic microsatellite DNA markers and two polymorphic genes, covering approximately 80% of the tilapia genome. These fish had previously been phenotyped for seven immune-response traits and six blood parameters. Critical values for significance were P <0.05 with the false discovery rate (FDR) controlled at 40%. The genome-scan analysis resulted in 35 significant marker-trait associations, involving 26 markers in 16 linkage groups. In a second experiment, nine markers were re-sampled in a second family of 79 fish of the same species hybrid. Seven markers (GM180, GM553, MHC-I, UNH848, UNH868, UNH898 and UNH925) in five linkage groups (LG 1, 3, 4, 22 and 23) were associated with stress response traits. An additional six markers (GM47, GM552, UNH208, UNH881, UNH952, UNH998) in five linkage groups (LG 4, 16, 19, 20 and 23) were verified for their associations with immune response traits, by linkage to several different traits. The portion of variance explained by each QTL was 11% on average, with a maximum of 29%. The average additive effect of QTLs was 0.2 standard deviation units of stress response traits and fish size, with a maximum of 0.33. In three linkage groups (LG 1, 3 and 23) markers were associated with stress response, body weight and sex determination, confirming the location of QTLs reported by several other studies.

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

Genetic Mapping and QTL Analysis of Growth-Related Traits in Pinctada fucata Using Restriction-Site Associated DNA Sequencing

PubMed Central

Li, Yaoguo; He, Maoxian

2014-01-01

The pearl oyster, Pinctada fucata (P. fucata), is one of the marine bivalves that is predominantly cultured for pearl production. To obtain more genetic information for breeding purposes, we constructed a high-density linkage map of P. fucata and identified quantitative trait loci (QTL) for growth-related traits. One F1 family, which included the two parents, 48 largest progeny and 50 smallest progeny, was sampled to construct a linkage map using restriction site-associated DNA sequencing (RAD-Seq). With low coverage data, 1956.53 million clean reads and 86,342 candidate RAD loci were generated. A total of 1373 segregating SNPs were used to construct a sex-average linkage map. This spanned 1091.81 centimorgans (cM), with 14 linkage groups and an average marker interval of 1.41 cM. The genetic linkage map coverage, Coa, was 97.24%. Thirty-nine QTL-peak loci, for seven growth-related traits, were identified using the single-marker analysis, nonparametric mapping Kruskal-Wallis (KW) test. Parameters included three for shell height, six for shell length, five for shell width, four for hinge length, 11 for total weight, eight for soft tissue weight and two for shell weight. The QTL peak loci for shell height, shell length and shell weight were all located in linkage group 6. The genotype frequencies of most QTL peak loci showed significant differences between the large subpopulation and the small subpopulation (P<0.05). These results highlight the effectiveness of RAD-Seq as a tool for generation of QTL-targeted and genome-wide marker data in the non-model animal, P. fucata, and its possible utility in marker-assisted selection (MAS). PMID:25369421

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.

Sulfation effect on levan polysaccharide chains structure with molecular dynamics simulations

NASA Astrophysics Data System (ADS)

Coskunkan, Binnaz; Turgut, Deniz; Rende, Deniz; Malta, Seyda; Baysal, Nihat; Ozisik, Rahmi; Toksoy-Oner, Ebru

Diversity in conformations and structural heterogeneity make polysaccharides the most challenging biopolymer type for experimental and theoretical characterization studies. Levan is a biopolymer chain that consists of fructose rings with β(2-6) linkages. It is a glycan that has great potential as a functional biopolymer in foods, feeds, cosmetics, pharmaceutical and chemical industries. Sulfated polysaccharides are group of macromolecules with sulfated groups in their hydroxyl parts with a range of important biological properties. Sulfate groups and their positions have a major effect on anticoagulant activity. It is reported that sulfate modified levan has anticoagulant activity such as heparin. In the current study, the effect of sulfation on the structure and dynamics of unmodified and sulfate modified levan are investigated via fully atomistic Molecular Dynamics simulations in aqueous media and varying salt concentrations at 310 K. This material is based upon work supported by the National Science Foundation under Grant No. CMMI-1538730.

Response Inhibition, Peer Preference and Victimization, and Self-Harm: Longitudinal Associations in Young Adult Women with and without ADHD.

PubMed

Meza, Jocelyn I; Owens, Elizabeth B; Hinshaw, Stephen P

2016-02-01

Self-harm (suicidal ideation and attempts; non-suicidal self-injuries behavior) peaks in adolescence and early-adulthood, with rates higher for women than men. Young women with childhood psychiatric diagnoses appear to be at particular risk, yet more remains to be learned about the key predictors or mediators of self-harm outcomes. Our aims were to examine, with respect to self-harm-related outcomes in early adulthood, the predictive validity of childhood response inhibition, a cardinal trait of attention-deficit hyperactivity disorder (ADHD), as well as the potential mediating effects of social preference and peer victimization, ascertained in early adolescence. Participants were an ethnically and socioeconomically diverse sample of 228 girls with and without ADHD, an enriched sample for deficits in response inhibition. Childhood response inhibition (RI) predicted young-adult suicide ideation (SI), suicide attempts (SA), and non-suicidal self-injury (NSSI), over and above full-scale IQ, mother's education, household income, and age. Importantly, teacher-rated social preference in adolescence was a partial mediator of the RI-SI/SA linkages; self-reported peer victimization in adolescence emerged as a significant partial mediator of the RI-NSSI linkage. We discuss implications for conceptual models of self-harm and for needed clinical services designed to detect and reduce self-harm.

Suicidal Ideation on Higher Education Students: Influence of Some Psychosocial Variables.

PubMed

Gonçalves, Amadeu Matos; da Cruz Sequeira, Carlos Alberto; Duarte, João Carvalho; de Freitas, Paula Pinto

2016-04-01

While attending to higher education, multiple changes occur in the lives of young students. These changes make higher education students particularly more exposed and vulnerable to mental health problems, and therefore more likely to present suicidal behaviors. The aim of this study was to assess suicidal ideation in higher education students, and its relationship with some psychosocial variables. Exploratory, quantitative and descriptive study, applied on a sample of 1074 students of a higher education institution in Portugal. Some significant associations with suicidal ideation were found with self-concept factors (self-acceptance, self-effectiveness and impulsivity); stress, anxiety and clinical depression; linkage anxiety and social support activities dimensions; intimacy and total social support. In our sample we found 84 students with potential suicidal risk, and through the result analysis, the biopsychosocial profile of the student at risk for suicidal ideation exhibits the following traits: female, age 18/19, low self-concept, insecure linkage patterns and little involvement in social activities and intimacy relationships. All facts considered, higher education institutions should provide programs that promote mental health and suicide prevention in academic environments. The results of this study also have implications for policy makers, clinical practice, suicide prevention and higher education institutions. Copyright © 2015 Elsevier Inc. All rights reserved.

Impact of lignin polymer backbone esters on ionic liquid pretreatment of poplar

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

Kim, Kwang Ho; Dutta, Tanmoy; Ralph, John

Biomass pretreatment remains an essential step in lignocellulosic biofuel production, largely to facilitate the efficient removal of lignin and increase enzyme accessibility to the polysaccharides. In recent years, there have been significant efforts in planta to reduce lignin content or modify its composition to overcome the inherent recalcitrance that it imposes on lignocellulosic biomass during processing. Here, transgenic poplar lines in which monolignol ferulate conjugates were synthesized during cell wall development to introduce, during lignification, readily cleavable ester linkages into the lignin polymer backbone (i.e., "zip lignin"), along with wild-type (WT) controls, were pretreated with different ionic liquids (ILs). Themore » strategic introduction of ester bonds into the lignin backbone resulted in increased pretreatment efficiency and released more carbohydrates with lower energy input. After pretreatment with any of three different ILs, and after limited saccharification, the transgenic poplars, especially those with relatively higher amounts of incorporated monolignol ferulate conjugates, yielded up to 23% higher sugar levels compared to WT plants. Our findings clearly demonstrate that the introduction of ester linkages into the lignin polymer backbone decreases biomass recalcitrance in poplar has the potential to reduce the energy and/or amount of IL required for effective pretreatment, and could enable the development of an economically viable and sustainable biorefinery process.« less

Impact of lignin polymer backbone esters on ionic liquid pretreatment of poplar

DOE PAGES

Kim, Kwang Ho; Dutta, Tanmoy; Ralph, John; ...

2017-04-20

Biomass pretreatment remains an essential step in lignocellulosic biofuel production, largely to facilitate the efficient removal of lignin and increase enzyme accessibility to the polysaccharides. In recent years, there have been significant efforts in planta to reduce lignin content or modify its composition to overcome the inherent recalcitrance that it imposes on lignocellulosic biomass during processing. Here, transgenic poplar lines in which monolignol ferulate conjugates were synthesized during cell wall development to introduce, during lignification, readily cleavable ester linkages into the lignin polymer backbone (i.e., "zip lignin"), along with wild-type (WT) controls, were pretreated with different ionic liquids (ILs). Themore » strategic introduction of ester bonds into the lignin backbone resulted in increased pretreatment efficiency and released more carbohydrates with lower energy input. After pretreatment with any of three different ILs, and after limited saccharification, the transgenic poplars, especially those with relatively higher amounts of incorporated monolignol ferulate conjugates, yielded up to 23% higher sugar levels compared to WT plants. Our findings clearly demonstrate that the introduction of ester linkages into the lignin polymer backbone decreases biomass recalcitrance in poplar has the potential to reduce the energy and/or amount of IL required for effective pretreatment, and could enable the development of an economically viable and sustainable biorefinery process.« less

Sectoral linkage analysis of three main air pollutants in China's industry: Comparing 2010 with 2002.

PubMed

He, Weiwei; Wang, Yuan; Zuo, Jian; Luo, Yincheng

2017-11-01

To investigate the driving forces of air pollution in China, the changes in linkages amongst inter-industrial air pollutant emissions were analyzed by hypothetical extraction method under the input-output framework. Results showed that the emissions of SO 2 , soot and dust from industrial sources increased by 56.46%, 36.95% and 11.69% respectively in 2010, compared with 2002. As major contributors to emissions, the power and gas sectors were responsible for the growing SO 2 emissions, the nonmetal products sector for soot emissions, and the metals mining, smelting and pressing sectors for dust emissions. The increasing volume of emissions was mainly driven by the growing demand in the transport equipment and electrical equipment sectors. In addition, the expansion in the metals mining, smelting and pressing sectors could result in even more severe air pollution. Therefore, potential effective strategies to control air pollution in China are: (1) reducing the demand of major import sectors in the equipment manufacturing industry; (2) promoting R&D in low-emissions-production technologies to the power and gas sectors, the metals mining, smelting and pressing sectors, and the nonmetal products sector, and (3) auditing the considerable industrial scale expansion in the metals mining, smelting and pressing sectors and optimizing the industrial structure. Copyright © 2017 Elsevier Ltd. All rights reserved.

Ambient air pollution exposure and the incidence of related health effects among racial/ethnic minorities

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

Nieves, L.A.; Wernette, D.R.

1997-02-01

Differences among racial and ethnic groups in morbidity and mortality rates for diseases, including diseases with environmental causes, have been extensively documented. However, documenting the linkages between environmental contaminants, individual exposures, and disease incidence has been hindered by difficulties in measuring exposure for the population in general and for minority populations in particular. After briefly discussing research findings on associations of common air pollutants with disease incidence, the authors summarize recent studies of radial/ethnic subgroup differences in incidence of these diseases in the US. They then present evidence of both historic and current patterns of disproportionate minority group exposure tomore » air pollution as measured by residence in areas where ambient air quality standards are violated. The current indications of disproportionate potential exposures of minority and low-income populations to air pollutants represent the continuation of a historical trend. The evidence of linkage between disproportionate exposure to air pollution of racial/ethnic minorities and low-income groups and their higher rates of some air pollution-related diseases is largely circumstantial. Differences in disease incidence and mortality rates among racial/ethnic groups are discussed for respiratory diseases, cancers, and lead poisoning. Pollutants of concern include CO, Pb, SO{sub 2}, O{sub 3}, and particulates.« less

Transancestral fine-mapping of four type 2 diabetes susceptibility loci highlights potential causal regulatory mechanisms.

PubMed

Horikoshi, Momoko; Pasquali, Lorenzo; Wiltshire, Steven; Huyghe, Jeroen R; Mahajan, Anubha; Asimit, Jennifer L; Ferreira, Teresa; Locke, Adam E; Robertson, Neil R; Wang, Xu; Sim, Xueling; Fujita, Hayato; Hara, Kazuo; Young, Robin; Zhang, Weihua; Choi, Sungkyoung; Chen, Han; Kaur, Ismeet; Takeuchi, Fumihiko; Fontanillas, Pierre; Thuillier, Dorothée; Yengo, Loic; Below, Jennifer E; Tam, Claudia H T; Wu, Ying; Abecasis, Gonçalo; Altshuler, David; Bell, Graeme I; Blangero, John; Burtt, Noél P; Duggirala, Ravindranath; Florez, Jose C; Hanis, Craig L; Seielstad, Mark; Atzmon, Gil; Chan, Juliana C N; Ma, Ronald C W; Froguel, Philippe; Wilson, James G; Bharadwaj, Dwaipayan; Dupuis, Josee; Meigs, James B; Cho, Yoon Shin; Park, Taesung; Kooner, Jaspal S; Chambers, John C; Saleheen, Danish; Kadowaki, Takashi; Tai, E Shyong; Mohlke, Karen L; Cox, Nancy J; Ferrer, Jorge; Zeggini, Eleftheria; Kato, Norihiro; Teo, Yik Ying; Boehnke, Michael; McCarthy, Mark I; Morris, Andrew P

2016-05-15

To gain insight into potential regulatory mechanisms through which the effects of variants at four established type 2 diabetes (T2D) susceptibility loci (CDKAL1, CDKN2A-B, IGF2BP2 and KCNQ1) are mediated, we undertook transancestral fine-mapping in 22 086 cases and 42 539 controls of East Asian, European, South Asian, African American and Mexican American descent. Through high-density imputation and conditional analyses, we identified seven distinct association signals at these four loci, each with allelic effects on T2D susceptibility that were homogenous across ancestry groups. By leveraging differences in the structure of linkage disequilibrium between diverse populations, and increased sample size, we localised the variants most likely to drive each distinct association signal. We demonstrated that integration of these genetic fine-mapping data with genomic annotation can highlight potential causal regulatory elements in T2D-relevant tissues. These analyses provide insight into the mechanisms through which T2D association signals are mediated, and suggest future routes to understanding the biology of specific disease susceptibility loci. © The Author 2016. Published by Oxford University Press.

Regarding the unitary theory of agonist and antagonist action at presynaptic adrenoceptors.

PubMed

Kalsner, S; Abdali, S A

2001-06-01

1. The linkage between potentiation of field stimulation-induced noradrenaline release and blockade of the presynaptic inhibitory effect of exogenous noradrenaline by a presynaptic antagonist was examined in superfused rabbit aorta preparations. 2. Rauwolscine clearly potentiated the release of noradrenaline in response to 100 pulses at 2 Hz but reduced the capacity of noradrenaline to inhibit transmitter release to a questionable extent, and then only when comparisons were made with untreated, rather then to rauwolscine-treated, controls. 3. Aortic preparations exposed for 60 min to rauwolscine followed by superfusion with antagonist-free Krebs for 60 min retained the potentiation of stimulation-induced transmitter release but no antagonism of the noradrenaline-induced inhibition could be detected at either of two noradrenaline concentrations when comparisons were made with rauwolscine treated controls. 4. Comparisons of the inhibitory effect of exogenous noradrenaline (1.8 x 10-6 M) on transmitter efflux in the presence and absence of rauwolscine pretreatment revealed that the antagonist enhanced rather than antagonized the presynaptic inhibition by noradrenaline. 5 It is concluded that the unitary hypothesis that asserts that antagonist enhancement of transmitter release and its blockade of noradrenaline induced inhibition are manifestations of a unitary event are not supportable.

Sexual Contact in Childhood, Revictimization, and Lifetime Sexual and Psychological Outcomes.

PubMed

Das, Aniruddha; Otis, Nicholas

2016-07-01

Using data from the 2010 to 2011 wave of the National Social Life, Health, and Aging Project-a nationally representative probability sample of older U.S. adults-this study queried distinctive linkages of mild and of severe childhood sexual contact with lifetime sexual and psychological outcomes among women and men aged 60-99 years (N = 3283). In addition, we examined stratification of these associations by sexual revictimization (forced sex and/or harassment). Among women, sequelae of childhood contact seemed consistently negative for the mild rather than severe variant-but only in the co-presence of revictimization-a pattern that may have remained obscured in previous analysis of event effects. Men's results suggested lifelong eroticizing but not psychological effects of this early experience-with the co-presence of revictimization potentially enhancing rather than lowering their mental health. Overall, findings appeared to reflect gendered patterns of risk-with mild childhood contact potentially channeling women but not men into revictimization and finally to elevated sexuality and poor mental health in late life. Early sexual experiences should thus be conceptualized not as singular events, but as part of a lifelong career with regularities and rhythms that may influence their pathogenic potential.

Black Carbon (Biochar) In Water/Soil Environments: Molecular Structure, Sorption, Stability, and Potential Risk.

PubMed

Lian, Fei; Xing, Baoshan

2017-12-05

Black carbon (BC) is ubiquitous in the environments and participates in various biogeochemical processes. Both positive and negative effects of BC (especially biochar) on the ecosystem have been identified, which are mainly derived from its diverse physicochemical properties. Nevertheless, few studies systematically examined the linkage between the evolution of BC molecular structure with the resulted BC properties, environmental functions as well as potential risk, which is critical for understanding the BC environmental behavior and utilization as a multifunctional product. Thus, this review highlights the molecular structure evolution of BC during pyrolysis and the impact of BC physicochemical properties on its sorption behavior, stability, and potential risk in terrestrial and aqueous ecosystems. Given the wide application of BC and its important role in biogeochemical processes, future research should focus on the following: (1) establishing methodology to more precisely predict and design BC properties on the basis of pyrolysis and phase transformation of biomass; (2) developing an assessment system to evaluate the long-term effect of BC on stabilization and bioavailability of contaminants, agrochemicals, and nutrient elements in soils; and (3) elucidating the interaction mechanisms of BC with plant roots, microorganisms, and soil components.

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.

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.

Functional linear models for association analysis of quantitative traits.

PubMed

Fan, Ruzong; Wang, Yifan; Mills, James L; Wilson, Alexander F; Bailey-Wilson, Joan E; Xiong, Momiao

2013-11-01

Functional linear models are developed in this paper for testing associations between quantitative traits and genetic variants, which can be rare variants or common variants or the combination of the two. By treating multiple genetic variants of an individual in a human population as a realization of a stochastic process, the genome of an individual in a chromosome region is a continuum of sequence data rather than discrete observations. The genome of an individual is viewed as a stochastic function that contains both linkage and linkage disequilibrium (LD) information of the genetic markers. By using techniques of functional data analysis, both fixed and mixed effect functional linear models are built to test the association between quantitative traits and genetic variants adjusting for covariates. After extensive simulation analysis, it is shown that the F-distributed tests of the proposed fixed effect functional linear models have higher power than that of sequence kernel association test (SKAT) and its optimal unified test (SKAT-O) for three scenarios in most cases: (1) the causal variants are all rare, (2) the causal variants are both rare and common, and (3) the causal variants are common. The superior performance of the fixed effect functional linear models is most likely due to its optimal utilization of both genetic linkage and LD information of multiple genetic variants in a genome and similarity among different individuals, while SKAT and SKAT-O only model the similarities and pairwise LD but do not model linkage and higher order LD information sufficiently. In addition, the proposed fixed effect models generate accurate type I error rates in simulation studies. We also show that the functional kernel score tests of the proposed mixed effect functional linear models are preferable in candidate gene analysis and small sample problems. The methods are applied to analyze three biochemical traits in data from the Trinity Students Study. © 2013 WILEY PERIODICALS, INC.

African-specific variability in the acetylcholine muscarinic receptor M4: association with cocaine and heroin addiction.

PubMed

Levran, Orna; Randesi, Matthew; Peles, Einat; Correa da Rosa, Joel; Ott, Jurg; Rotrosen, John; Adelson, Miriam; Kreek, Mary Jeanne

2016-06-01

This study was designed to determine whether polymorphisms in acetylcholine receptors contribute to opioid dependence and/or cocaine dependence. The sample (n = 1860) was divided by drug and ancestry, and 55 polymorphisms (nine genes) were analyzed. Of the 20 SNPs that showed nominally significant associations, the association of the African-specific CHRM4 SNP rs2229163 (Asn417=) with cocaine dependence survived correction for multiple testing (Pcorrected = 0.047). CHRM4 is located in a region of strong linkage disequilibrium on chromosome 11 that includes genes associated with schizophrenia. CHRM4 SNP rs2229163 is in strong linkage disequilibrium with several African-specific SNPs in DGKZ and AMBRA1. Cholinergic receptors' variants may contribute to drug addiction and have a potential role as pharmacogenetic markers.

U.S. domestic cats as sentinels for perfluoroalkyl substances: Possible linkages with housing, obesity, and disease

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

Bost, Phillip C.

Perfluoroalkyl substances (PFAS), such as perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), are persistent, globally distributed, anthropogenic compounds. The primary source(s) for human exposure are not well understood although within home exposure is likely important since many consumer products have been treated with different PFAS, and people spend much of their lives indoors. Herein, domestic cats were used as sentinels to investigate potential exposure and health linkages. PFAS in serum samples of 72 pet and feral cats, including 11 healthy and 61 with one or more primary disease diagnoses, were quantitated using high-resolution time-of-flight mass spectroscopy. All but one samplemore » had detectable PFAS, with PFOS and perfluorohexane sulfonate (PFHxS) ranging from« less

Global change-driven effects on dissolved organic matter composition: Implications for food webs of northern lakes.

PubMed

Creed, Irena F; Bergström, Ann-Kristin; Trick, Charles G; Grimm, Nancy B; Hessen, Dag O; Karlsson, Jan; Kidd, Karen A; Kritzberg, Emma; McKnight, Diane M; Freeman, Erika C; Senar, Oscar E; Andersson, Agneta; Ask, Jenny; Berggren, Martin; Cherif, Mehdi; Giesler, Reiner; Hotchkiss, Erin R; Kortelainen, Pirkko; Palta, Monica M; Vrede, Tobias; Weyhenmeyer, Gesa A

2018-03-15

Northern ecosystems are experiencing some of the most dramatic impacts of global change on Earth. Rising temperatures, hydrological intensification, changes in atmospheric acid deposition and associated acidification recovery, and changes in vegetative cover are resulting in fundamental changes in terrestrial-aquatic biogeochemical linkages. The effects of global change are readily observed in alterations in the supply of dissolved organic matter (DOM)-the messenger between terrestrial and lake ecosystems-with potentially profound effects on the structure and function of lakes. Northern terrestrial ecosystems contain substantial stores of organic matter and filter or funnel DOM, affecting the timing and magnitude of DOM delivery to surface waters. This terrestrial DOM is processed in streams, rivers, and lakes, ultimately shifting its composition, stoichiometry, and bioavailability. Here, we explore the potential consequences of these global change-driven effects for lake food webs at northern latitudes. Notably, we provide evidence that increased allochthonous DOM supply to lakes is overwhelming increased autochthonous DOM supply that potentially results from earlier ice-out and a longer growing season. Furthermore, we assess the potential implications of this shift for the nutritional quality of autotrophs in terms of their stoichiometry, fatty acid composition, toxin production, and methylmercury concentration, and therefore, contaminant transfer through the food web. We conclude that global change in northern regions leads not only to reduced primary productivity but also to nutritionally poorer lake food webs, with discernible consequences for the trophic web to fish and humans. © 2018 John Wiley & Sons Ltd.

Characterization and bioactivities of a novel polysaccharide obtained from Gracilariopsis lemaneiformis.

PubMed

Shi, Chen-Shan; Sang, Ya-Xin; Sun, Gui-Qing; Li, Tian-Ye; Gong, Zheng-Si; Wang, Xiang-Hong

2017-01-01

Gracilariopsis lemaneiformis is a type of red alga that contains seaweed polysaccharide agar. In this study, a novel non-agar seaweed polysaccharide fraction named GCP (short of crude polysaccharide obtained from Gracilariopsis lemaneiformis) was isolated from Gracilariopsis lemaneiformis. Structural analysis showed that GCP shows triple helical chain conformation when dissolved in water and has many branches and long side chains. Also, 1→3 linkage is the major linkage and the sugar structures are galactopyranose configurations linked by β-type glycosidic linkages. Two macromolecular substance fractions (GCP-1 and GCP-2) were purified by DEAE Sepharose Fast Flow column chromatography. Moreover, a splenocyte damage assay and splenocyte proliferation assay were used to analyse the bioactivities of GCP, GCP-1 and GCP-2. It was demonstrated that polysaccharides could protect splenocyte damaged by H2O2; GCP-2 shows a greatest protection rate, that is, 92.8%, which significantly enhanced the splenocyte proliferation, and GCP showed the highest proliferation rate, 9.30%. The results suggested that this type of novel non-agar polysaccharide displayed remarkable antioxidant and immunomodulatory activities and early alkali treatment could decrease the activities. It may represent a potential material for health food and clinical medicines.

An integrative method for testing form–function linkages and reconstructed evolutionary pathways of masticatory specialization

PubMed Central

Tseng, Z. Jack; Flynn, John J.

2015-01-01

Morphology serves as a ubiquitous proxy in macroevolutionary studies to identify potential adaptive processes and patterns. Inferences of functional significance of phenotypes or their evolution are overwhelmingly based on data from living taxa. Yet, correspondence between form and function has been tested in only a few model species, and those linkages are highly complex. The lack of explicit methodologies to integrate form and function analyses within a deep-time and phylogenetic context weakens inferences of adaptive morphological evolution, by invoking but not testing form–function linkages. Here, we provide a novel approach to test mechanical properties at reconstructed ancestral nodes/taxa and the strength and direction of evolutionary pathways in feeding biomechanics, in a case study of carnivorous mammals. Using biomechanical profile comparisons that provide functional signals for the separation of feeding morphologies, we demonstrate, using experimental optimization criteria on estimation of strength and direction of functional changes on a phylogeny, that convergence in mechanical properties and degree of evolutionary optimization can be decoupled. This integrative approach is broadly applicable to other clades, by using quantitative data and model-based tests to evaluate interpretations of function from morphology and functional explanations for observed macroevolutionary pathways. PMID:25994295

Vibrational spectroscopic investigation of the gold complexation within the cascade structure of phosphorus-containing dendrimer.

PubMed

Furer, V L; Vandyukov, A E; Majoral, J P; Caminade, A M; Gottis, S; Laurent, R; Kovalenko, V I

2018-05-29

The interaction of the phosphoric dendrimer with gold was performed by means of vibrational spectroscopy and quantum chemistry. Stable complexes are formed with a PN-PS linkage, whereas with an isolated PS bond this does not occur. The change in geometric parameters and delocalization of electric charge under the influence of gold was discovered. The classification of bands in the experimental vibrational spectra of the dendrimer and its complex was carried out. HOMO of molecule of the dendrimer is localized on the SPNP linkage, whereas the LUMO is located on the terminal group. In the SPNP linkage there is a noticeable delocalization of the charge which leads to a change in the reactivity of this group. Interaction energy was estimated as the difference between the energies of the complex and the energies of the molecules of the dendrimer G' 0 and two molecules AuCl and is equal to 25.2 eV. The ionization energy IE and electron affinity EA for AuCl are higher than for dendrimer, therefore, when the complex is formed, these quantities increases. Chemical potential and the electrophilicity index in the complex also increases. Copyright © 2018 Elsevier B.V. All rights reserved.

Mixed-Linkage Glucan Oligosaccharides Produced by Automated Glycan Assembly Serve as Tools To Determine the Substrate Specificity of Lichenase.

PubMed

Dallabernardina, Pietro; Schuhmacher, Frank; Seeberger, Peter H; Pfrengle, Fabian

2017-03-02

The mixed-linkage (1→3),(1→4)-d-glucan (MLG) specific glycosyl hydrolase lichenase is an important biochemical tool for the structural characterization of MLGs. It holds potential for application in the brewery, animal feed, and biofuel industries. Several defined MLG oligosaccharides obtained by automated glycan assembly are used to analyze the substrate specificities of Bacillus subtilis lichenase. Two glucose building blocks (BBs), equipped with a temporary fluorenylmethyloxycarbonyl chloride (Fmoc) protecting group in the C-3 or C-4 position, served to assemble different oligosaccharides by using an automated oligosaccharide synthesizer. Light-induced cleavage of the glycan products from the solid support followed by global deprotection provided seven MLG oligosaccharides of different length and connectivity. After incubation of the MLG oligosaccharides with lichenase, the digestion products were analyzed by HPLC-MS. These digestion experiments provided insights into the enzyme's active site that is in line with other recent evidence suggesting that the substrate specificity of lichenases has to be reconsidered. These results demonstrate that synthetic MLG oligosaccharides are useful tools to analyze mixed-linkage β-glucanases. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Structure-Dependent Spectroscopic Properties of Yb3+-Doped Phosphosilicate Glasses Modified by SiO₂.

PubMed

Wang, Ling; Zeng, Huidan; Yang, Bin; Ye, Feng; Chen, Jianding; Chen, Guorong; Smith, Andew T; Sun, Luyi

2017-02-28

Yb 3+ -doped phosphate glasses containing different amounts of SiO₂ were successfully synthesized by the conventional melt-quenching method. The influence mechanism of SiO₂ on the structural and spectroscopic properties was investigated systematically using the micro-Raman technique. It was worth noting that the glass with 26.7 mol % SiO₂ possessed the longest fluorescence lifetime (1.51 ms), the highest gain coefficient (1.10 ms·pm²), the maximum Stark splitting manifold of ²F 7/2 level (781 cm -1 ), and the largest scalar crystal-field N J and Yb 3+ asymmetry degree. Micro-Raman spectra revealed that introducing SiO₂ promoted the formation of P=O linkages, but broke the P=O linkages when the SiO₂ content was greater than 26.7 mol %. Based on the previous 29 Si MAS NMR experimental results, these findings further demonstrated that the formation of [SiO₆] may significantly affect the formation of P=O linkages, and thus influences the spectroscopic properties of the glass. These results indicate that phosphosilicate glasses may have potential applications as a Yb 3+ -doped gain medium for solid-state lasers and optical fiber amplifiers.

Structure-Dependent Spectroscopic Properties of Yb3+-Doped Phosphosilicate Glasses Modified by SiO2

PubMed Central

Wang, Ling; Zeng, Huidan; Yang, Bin; Ye, Feng; Chen, Jianding; Chen, Guorong; Smith, Andew T.; Sun, Luyi

2017-01-01

Yb3+-doped phosphate glasses containing different amounts of SiO2 were successfully synthesized by the conventional melt-quenching method. The influence mechanism of SiO2 on the structural and spectroscopic properties was investigated systematically using the micro-Raman technique. It was worth noting that the glass with 26.7 mol % SiO2 possessed the longest fluorescence lifetime (1.51 ms), the highest gain coefficient (1.10 ms·pm2), the maximum Stark splitting manifold of 2F7/2 level (781 cm−1), and the largest scalar crystal-field NJ and Yb3+ asymmetry degree. Micro-Raman spectra revealed that introducing SiO2 promoted the formation of P=O linkages, but broke the P=O linkages when the SiO2 content was greater than 26.7 mol %. Based on the previous 29Si MAS NMR experimental results, these findings further demonstrated that the formation of [SiO6] may significantly affect the formation of P=O linkages, and thus influences the spectroscopic properties of the glass. These results indicate that phosphosilicate glasses may have potential applications as a Yb3+-doped gain medium for solid-state lasers and optical fiber amplifiers. PMID:28772601

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.

A linkage analysis toolkit for studying allosteric networks in ion channels

PubMed Central

2013-01-01

A thermodynamic approach to studying allosterically regulated ion channels such as the large-conductance voltage- and Ca2+-dependent (BK) channel is presented, drawing from principles originally introduced to describe linkage phenomena in hemoglobin. In this paper, linkage between a principal channel component and secondary elements is derived from a four-state thermodynamic cycle. One set of parallel legs in the cycle describes the “work function,” or the free energy required to activate the principal component. The second are “lever operations” activating linked elements. The experimental embodiment of this linkage cycle is a plot of work function versus secondary force, whose asymptotes are a function of the parameters (displacements and interaction energies) of an allosteric network. Two essential work functions play a role in evaluating data from voltage-clamp experiments. The first is the conductance Hill energy WH[g], which is a “local” work function for pore activation, and is defined as kT times the Hill transform of the conductance (G-V) curve. The second is the electrical capacitance energy WC[q], representing “global” gating charge displacement, and is equal to the product of total gating charge per channel times the first moment (VM) of normalized capacitance (slope of Q-V curve). Plots of WH[g] and WC[q] versus voltage and Ca2+ potential can be used to measure thermodynamic parameters in a model-independent fashion of the core gating constituents (pore, voltage-sensor, and Ca2+-binding domain) of BK channel. The method is easily generalized for use in studying other allosterically regulated ion channels. The feasibility of performing linkage analysis from patch-clamp data were explored by simulating gating and ionic currents of a 17-particle model BK channel in response to a slow voltage ramp, which yielded interaction energies deviating from their given values in the range of 1.3 to 7.2%. PMID:23250867

Use of linkage mapping and centrality analysis across habitat gradients to conserve connectivity of gray wolf populations in western North America.

PubMed

Carroll, Carlos; McRae, Brad H; Brookes, Allen

2012-02-01

Centrality metrics evaluate paths between all possible pairwise combinations of sites on a landscape to rank the contribution of each site to facilitating ecological flows across the network of sites. Computational advances now allow application of centrality metrics to landscapes represented as continuous gradients of habitat quality. This avoids the binary classification of landscapes into patch and matrix required by patch-based graph analyses of connectivity. It also avoids the focus on delineating paths between individual pairs of core areas characteristic of most corridor- or linkage-mapping methods of connectivity analysis. Conservation of regional habitat connectivity has the potential to facilitate recovery of the gray wolf (Canis lupus), a species currently recolonizing portions of its historic range in the western United States. We applied 3 contrasting linkage-mapping methods (shortest path, current flow, and minimum-cost-maximum-flow) to spatial data representing wolf habitat to analyze connectivity between wolf populations in central Idaho and Yellowstone National Park (Wyoming). We then applied 3 analogous betweenness centrality metrics to analyze connectivity of wolf habitat throughout the northwestern United States and southwestern Canada to determine where it might be possible to facilitate range expansion and interpopulation dispersal. We developed software to facilitate application of centrality metrics. Shortest-path betweenness centrality identified a minimal network of linkages analogous to those identified by least-cost-path corridor mapping. Current flow and minimum-cost-maximum-flow betweenness centrality identified diffuse networks that included alternative linkages, which will allow greater flexibility in planning. Minimum-cost-maximum-flow betweenness centrality, by integrating both land cost and habitat capacity, allows connectivity to be considered within planning processes that seek to maximize species protection at minimum cost. Centrality analysis is relevant to conservation and landscape genetics at a range of spatial extents, but it may be most broadly applicable within single- and multispecies planning efforts to conserve regional habitat connectivity. ©2011 Society for Conservation Biology.

A second generation genetic linkage map of Japanese flounder (Paralichthys olivaceus)

PubMed Central

2010-01-01

Background Japanese flounder (Paralichthys olivaceus) is one of the most economically important marine species in Northeast Asia. Information on genetic markers associated with quantitative trait loci (QTL) can be used in breeding programs to identify and select individuals carrying desired traits. Commercial production of Japanese flounder could be increased by developing disease-resistant fish and improving commercially important traits. Previous maps have been constructed with AFLP markers and a limited number of microsatellite markers. In this study, improved genetic linkage maps are presented. In contrast with previous studies, these maps were built mainly with a large number of codominant markers so they can potentially be used to analyze different families and populations. Results Sex-specific genetic linkage maps were constructed for the Japanese flounder including a total of 1,375 markers [1,268 microsatellites, 105 single nucleotide polymorphisms (SNPs) and two genes]; 1,167 markers are linked to the male map and 1,067 markers are linked to the female map. The lengths of the male and female maps are 1,147.7 cM and 833.8 cM, respectively. Based on estimations of map lengths, the female and male maps covered 79 and 82% of the genome, respectively. Recombination ratio in the new maps revealed F:M of 1:0.7. All linkage groups in the maps presented large differences in the location of sex-specific recombination hot-spots. Conclusions The improved genetic linkage maps are very useful for QTL analyses and marker-assisted selection (MAS) breeding programs for economically important traits in Japanese flounder. In addition, SNP flanking sequences were blasted against Tetraodon nigroviridis (puffer fish) and Danio rerio (zebrafish), and synteny analysis has been carried out. The ability to detect synteny among species or genera based on homology analysis of SNP flanking sequences may provide opportunities to complement initial QTL experiments with candidate gene approaches from homologous chromosomal locations identified in related model organisms. PMID:20937088

Modified Alternan: A Novel Microbial Gum with Potential as a Low-Viscosity Bulking Agent

USDA-ARS?s Scientific Manuscript database

Alternan is a microbial gum produced by rare strains of the GRAS lactic acid bacterium, Leuconostoc mesenteroides. The unique alternating alpha-(1,6) and alpha-(1,3) linkage pattern of this glucan imparts high solubility and resistance to most digestive enzymes. Previously, we invented a bioconver...

Participatory Systems Modeling to Explore Sustainable Solutions: Triple Value Simulation Modeling Cases Tackle Nutrient and Watershed Management from a Socio-Ecological Systems (SES) perspective

EPA Science Inventory

Decision makers often need assistance in understanding dynamic interactions and linkages among economic, environmental and social systems in coastal watersheds. They also need scientific input to better evaluate potential costs and benefits of alternative policy interventions. Th...

Hydrodynamic Versus Size-Exclusion Chromatography Characterization of Alternan and Comparison to Off-Line MALS

USDA-ARS?s Scientific Manuscript database

Alternan is an ultra-high molar mass polysaccharide composed of two different types of glycosidic linkages and which also possesses long-chain branching. It has great potential in a number of areas, including as a possible domestic replacement for gum Arabic. The high molar mass and large size of ...

Dimensionally Stable Ether-Containing Polyimide Copolymers

NASA Technical Reports Server (NTRS)

Fay, Catharine C. (Inventor); St.Clair, Anne K. (Inventor)

1999-01-01

Novel polyimide copolymers containing ether linkages were prepared by the reaction of an equimolar amount of dianhydride and a combination of diamines. The polyimide copolymers described herein possess the unique features of low moisture uptake, dimensional stability, good mechanical properties, and moderate glass transition temperatures. These materials have potential application as encapsulants and interlayer dielectrics.

Decade of wildlife tracking in the Sky Islands

Treesearch

Jessica A. Lamberton-Moreno; Sergio Avila-Villegas

2013-01-01

In 2001 Sky Island Alliance developed a citizen science program that uses track and sign identification and count surveys to monitor potential wildlife corridors throughout southeastern Arizona and southwestern New Mexico. The goal of the Wildlife Linkages Program is to protect and advocate for an interconnected landscape where wildlife, based on their ecological needs...

The Quality of Sustainability: Agroecological Partnerships and the Geographic Branding of California Winegrapes

ERIC Educational Resources Information Center

Warner, Keith Douglass

2007-01-01

Quality and sustainability are both socially constructed, ambiguous terms, but they have not been heretofore linked in the rural studies literature. The "quality turn" has received particular attention from researchers for its potential to organize linkages among various forces in agrofood systems, providing more income to producers by…

Ties with Potential: Social Network Structure and Innovative Climate in Dutch Schools

ERIC Educational Resources Information Center

Moolenaar, Nienke M.; Daly, Alan J.; Sleegers, Peter J. C.

2011-01-01

Background/Context: Similar to the United States, government efforts to improve education in the Netherlands are focused on innovation and the development of collaborative structures to support the generation of new knowledge. However, empirical evidence of the relationship between social linkages and innovation in education is scarce. Objective:…

Purification, characterization and antioxidant activity of polysaccharides from Flammulina velutipes residue.

PubMed

Liu, Ying; Zhang, Bin; Ibrahim, S A; Gao, Shuang-Shuang; Yang, Hong; Huang, Wen

2016-07-10

In this study, we isolated polysaccharides from Flammulina velutipes residue (FVRP) using microwave-assisted extraction and then purified the polysaccharides by column chromatography to yield FVRP-1, FVRP-2 and FVRP-3. The structural characteristics of FVRP-1, FVRP-2 and FVRP-3 were investigated, and their antioxidant activities against ABTS(+), DPPH and hydroxyl radicals were also analyzed in vitro. FVRP-1 was found to be neutral and rich in galactose. However, FVRP-2 and FVRP-3 were acidic polysaccharides and were rich in glucose. The average molecular weight of FVRP-1, FVRP-2 and FVRP-3 were 29,930, 62,290, and 36,310Da, respectively. The glycosyl residue of FVRP-1 was an α-type glycosidic linkage, whereas FVRP-2 and FVRP-3 were β-type glycosidic linkages. We found FVRP-1, FVRP-2 and FVRP-3 had strong potential antioxidant activities in the order of FVRP-1

Oligosaccharides from land plants and algae: production and applications in therapeutics and biotechnology.

PubMed

Courtois, Josiane

2009-06-01

Since the past decades, oligosaccharides are considered for their potential biological activities. To exploit them, it was essential to obtain pure molecules in large amounts. Several strategies were developed to produce specific sugar sequences with specific substitution patterns from land plants and algae polysaccharides. Then, pure oligosaccharides were analyzed for their potential biological activities and relations between oligomers structure and function were tackled. First they can be health beneficial molecules when they are added to the diet to enhance the growth of probiotic bacteria, in that case, oligomers that resist to the digestive process are used as specific substrate for the growth of health beneficial bacteria. In other cases, oligomers have to interact with receptors on cells. In this instance, a specific conformation is needed to allow the sugar sequence to establish specific linkages with the receptor. So, to be adapted to the receptor, the oligosaccharides have to present specific groups to the receptor, there, the polymerization degree of oligosaccharides as well as the flexibility of the glycosidic linkages has to be considered.

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.

The Effect of Pinyin Input Experience on the Link Between Semantic and Phonology of Chinese Character in Digital Writing.

PubMed

Chen, Jingjun; Luo, Rong; Liu, Huashan

2017-08-01

With the development of ICT, digital writing is becoming much more common in people's life. Differently from keyboarding alphabets directly to input English words, keyboarding Chinese character is always through typing phonetic alphabets and then identify the glyph provided by Pinyin input-method software while in this process which do not need users to produce orthography spelling, thus it is different from traditional written language production model based on handwriting process. Much of the research in this domain has found that using Pinyin input method is beneficial to Chinese characters recognition, but only a small part explored the effects of individual's Pinyin input experience on the Chinese characters production process. We ask whether using Pinyin input-method will strengthen the semantic-phonology linkage or semantic-orthography linkage in Chinese character mental lexicon. Through recording the RT and accuracy of participants completing semantic-syllable and semantic-glyph consistency judgments, the results found the accuracy of semantic-syllable consistency judgments in high Pinyin input experienced group was higher than that in low-experienced group, and RT was reversed. There were no significant differences on semantic-glyph consistency judgments between the two groups. We conclude that using Pinyin input method in Chinese digital writing can strengthen the semantic-phonology linkage while do not weakening the semantic-orthography linkage in mental lexicon at the same time, which means that Pinyin input method is beneficial to lexical processing involving Chinese cognition.

Dynamic genetic linkage of intermediate blood pressure phenotypes during postural adaptations in a founder population

PubMed Central

Arenas, I. A.; Tremblay, J.; Deslauriers, B.; Sandoval, J.; Šeda, O.; Gaudet, D.; Merlo, E.; Kotchen, T.; Cowley, A. W.

2013-01-01

Blood pressure (BP) is a dynamic phenotype that varies rapidly to adjust to changing environmental conditions. Standing upright is a recent evolutionary trait, and genetic factors that influence postural adaptations may contribute to BP variability. We studied the effect of posture on the genetics of BP and intermediate BP phenotypes. We included 384 sib-pairs in 64 sib-ships from families ascertained by early-onset hypertension and dyslipidemia. Blood pressure, three hemodynamic and seven neuroendocrine intermediate BP phenotypes were measured with subjects lying supine and standing upright. The effect of posture on estimates of heritability and genetic covariance was investigated in full pedigrees. Linkage was conducted on 196 candidate genes by sib-pair analyses, and empirical estimates of significance were obtained. A permutation algorithm was implemented to study the postural effect on linkage. ADRA1A, APO, CAST, CORIN, CRHR1, EDNRB, FGF2, GC, GJA1, KCNB2, MMP3, NPY, NR3C2, PLN, TGFBR2, TNFRSF6, and TRHR showed evidence of linkage with any phenotype in the supine position and not upon standing, whereas AKR1B1, CD36, EDNRA, F5, MMP9, PKD2, PON1, PPARG, PPARGC1A, PRKCA, and RET were specifically linked to standing phenotypes. Genetic profiling was undertaken to show genetic interactions among intermediate BP phenotypes and genes specific to each posture. When investigators perform genetic studies exclusively on a single posture, important genetic components of BP are missed. Supine and standing BPs have distinct genetic signatures. Standardized maneuvers influence the results of genetic investigations into BP, thus reflecting its dynamic regulation. PMID:23269701

Expression of a DNA Replication Gene Cluster in Bacteriophage T4: Genetic Linkage and the Control of Gene Product Interactions

PubMed Central

Gerald, W. L.; Karam, J. D.

1984-01-01

The results of this study bear on the relationship between genetic linkage and control of interactions between the protein products of different cistrons. In T4 bacteriophage, genes 45 and 44 encode essential components of the phage DNA replication multiprotein complex. T4 gene 45 maps directly upstream of gene 44 relative to the overall direction of reading of this region of the phage chromosome, but it is not known whether these two genes are cotranscribed. It has been shown that a nonsense lesion of T4 gene 45 exerts a cis-dominant inhibitory effect on growth of a missense mutant of gene 44 but not on growth of phage carrying the wild-type gene 44 allele. In previous work, we confirmed these observations on polarity of the gene 45 mutation but detected no polar effects by this lesion on synthesis of either mutant or wild-type gene 44 protein. In the present study, we demonstrate that mRNA for gene 44 protein is separable by gel electrophoresis from gene 45-protein-encoding mRNA. That is, the two proteins are not synthesized from one polycistronic message, and the cis-dominant inhibitory effect of the gene 45 mutation on gene 44 function is probably expressed at a posttranslational stage. We propose that close genetic linkage, whether or not it provides shared transcriptional and translational regulatory signals for certain clusters of functionally related cistrons, may determine the intracellular compartmentalization for synthesis of proteins encoded by these clusters. In prokaryotes, such linkage-dependent compartmentation may minimize the diffusion distances between gene products that are synthesized at low levels and are destined to interact. PMID:6745641

Soil fungal effects on floral signals, rewards, and aboveground interactions in an alpine pollination web.

PubMed

Becklin, Katie M; Gamez, Guadalupe; Uelk, Bryan; Raguso, Robert A; Galen, Candace

2011-08-01

Plants interact with above- and belowground organisms; the combined effects of these interactions determine plant fitness and trait evolution. To better understand the ecological and evolutionary implications of multispecies interactions, we explored linkages between soil fungi, pollinators, and floral larcenists in Polemonium viscosum (Polemoniaceae). Using a fungicide, we experimentally reduced fungal colonization of krummholz and tundra P. viscosum in 2008-2009. We monitored floral signals and rewards, interactions with pollinators and larcenists, and seed set for fungicide-treated and control plants. Fungicide effects varied among traits, between interactions, and with environmental context. Treatment effects were negligible in 2008, but stronger in 2009, especially in the less-fertile krummholz habitat. There, fungicide increased nectar sugar content and damage by larcenist ants, but did not affect pollination. Surprisingly, fungicide also enhanced seed set, suggesting that direct resource costs of soil fungi exceed indirect benefits from reduced larceny. In the tundra, fungicide effects were negligible in both years. However, pooled across treatments, colonization by mycorrhizal fungi in 2009 correlated negatively with the intensity and diversity of floral volatile organic compounds, suggesting integrated above- and belowground signaling pathways. Fungicide effects on floral rewards in P. viscosum link soil fungi to ecological costs of pollinator attraction. Trait-specific linkages to soil fungi should decouple expression of sensitive and buffered floral phenotypes in P. viscosum. Overall, this study demonstrates how multitrophic linkages may lead to shifting selection pressures on interaction traits, restricting the evolution of specialization.

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.

Global Sources and Pathways of Mercury in the Context of Human Health.

PubMed

Sundseth, Kyrre; Pacyna, Jozef M; Pacyna, Elisabeth G; Pirrone, Nicola; Thorne, Rebecca J

2017-01-22

This paper reviews information from the existing literature and the EU GMOS (Global Mercury Observation System) project to assess the current scientific knowledge on global mercury releases into the atmosphere, on global atmospheric transport and deposition, and on the linkage between environmental contamination and potential impacts on human health. The review concludes that assessment of global sources and pathways of mercury in the context of human health is important for being able to monitor the effects from implementation of the Minamata Convention targets, although new research is needed on the improvement of emission inventory data, the chemical and physical behaviour of mercury in the atmosphere, the improvement of monitoring network data, predictions of future emissions and speciation, and on the subsequent effects on the environment, human health, as well as the economic costs and benefits of reducing these aspects.

Detecting the unexpected: a research framework for ocean acidification.

PubMed

Pfister, Catherine A; Esbaugh, Andrew J; Frieder, Christina A; Baumann, Hannes; Bockmon, Emily E; White, Meredith M; Carter, Brendan R; Benway, Heather M; Blanchette, Carol A; Carrington, Emily; McClintock, James B; McCorkle, Daniel C; McGillis, Wade R; Mooney, T Aran; Ziveri, Patrizia

2014-09-02

The threat that ocean acidification (OA) poses to marine ecosystems is now recognized and U.S. funding agencies have designated specific funding for the study of OA. We present a research framework for studying OA that describes it as a biogeochemical event that impacts individual species and ecosystems in potentially unexpected ways. We draw upon specific lessons learned about ecosystem responses from research on acid rain, carbon dioxide enrichment in terrestrial plant communities, and nitrogen deposition. We further characterize the links between carbon chemistry changes and effects on individuals and ecosystems, and enumerate key hypotheses for testing. Finally, we quantify how U.S. research funding has been distributed among these linkages, concluding that there is an urgent need for research programs designed to anticipate how the effects of OA will reverberate throughout assemblages of species.

Cost-effectiveness of community-based strategies to strengthen the continuum of HIV care in rural South Africa: a health economic modelling analysis.

PubMed

Smith, Jennifer A; Sharma, Monisha; Levin, Carol; Baeten, Jared M; van Rooyen, Heidi; Celum, Connie; Hallett, Timothy B; Barnabas, Ruanne V

2015-04-01

Home HIV counselling and testing (HTC) achieves high coverage of testing and linkage to care compared with existing facility-based approaches, particularly among asymptomatic individuals. In a modelling analysis we aimed to assess the effect on population-level health and cost-effectiveness of a community-based package of home HTC in KwaZulu-Natal, South Africa. We parameterised an individual-based model with data from home HTC and linkage field studies that achieved high coverage (91%) and linkage to antiretroviral therapy (80%) in rural KwaZulu-Natal, South Africa. Costs were derived from a linked microcosting study. The model simulated 10,000 individuals over 10 years and incremental cost-effectiveness ratios were calculated for the intervention relative to the existing status quo of facility-based testing, with costs discounted at 3% annually. The model predicted implementation of home HTC in addition to current practice to decrease HIV-associated morbidity by 10–22% and HIV infections by 9–48% with increasing CD4 cell count thresholds for antiretroviral therapy initiation. Incremental programme costs were US$2·7 million to $4·4 million higher in the intervention scenarios than at baseline, and costs increased with higher CD4 cell count thresholds for antiretroviral therapy initiation; antiretroviral therapy accounted for 48–87% of total costs. Incremental cost-effectiveness ratios per disability-adjusted life-year averted were $1340 at an antiretroviral therapy threshold of CD4 count lower than 200 cells per μL, $1090 at lower than 350 cells per μL, $1150 at lower than 500 cells per μL, and $1360 at universal access to antiretroviral therapy. Community-based HTC with enhanced linkage to care can result in increased HIV testing coverage and treatment uptake, decreasing the population burden of HIV-associated morbidity and mortality. The incremental cost-effectiveness ratios are less than 20% of South Africa's gross domestic product per person, and are therefore classed as very cost effective. Home HTC can be a viable means to achieve UNAIDS' ambitious new targets for HIV treatment coverage. National Institutes of Health, Bill & Melinda Gates Foundation, Wellcome Trust.

A combination strategy for enhancing linkage to and retention in HIV care among adults newly diagnosed with HIV in Mozambique: study protocol for a site-randomized implementation science study.

PubMed

Elul, Batya; Lahuerta, Maria; Abacassamo, Fatima; Lamb, Matthew R; Ahoua, Laurence; McNairy, Margaret L; Tomo, Maria; Horowitz, Deborah; Sutton, Roberta; Mussa, Antonio; Gurr, Danielle; Jani, Ilesh

2014-10-15

Despite the extraordinary scale up of HIV prevention, care and treatment services in sub-Saharan Africa (SSA) over the past decade, the overall effectiveness of HIV programs has been significantly hindered by high levels of attrition across the HIV care continuum. Data from "real-life" settings are needed on the effectiveness of an easy to deliver package of services that can improve overall performance of the HIV care continuum. We are conducting an implementation science study using a two-arm cluster site-randomized design to determine the effectiveness of a combination intervention strategy (CIS) using feasible, evidence-based, and practical interventions-including (1) point-of-care (POC) CD4 count testing, (2) accelerated antiretroviral therapy initiation for eligible individuals, and (3) SMS reminders for linkage to and retention in care-as compared to the standard of care (SOC) in Mozambique in improving linkage and retention among adults following HIV diagnosis. A pre-post intervention two-sample design is nested within the CIS arm to assess the incremental effectiveness of the CIS plus financial incentives (CIS + FI) compared to the CIS without FI on study outcomes. Randomization is done at the level of the study site, defined as a primary health facility. Five sites are included from the City of Maputo and five from Inhambane Province. Target enrollment is a total of 2,250 adults: 750 in the SOC arm, 750 in the CIS cohort of the intervention arm and 750 in the CIS + FI cohort of the intervention arm (average of 150 participants per site). Participants are followed for 12 months from time of HIV testing to ascertain a combined endpoint of linkage to care within 1 month after testing and retention in care 12 months from HIV test. Cost-effectiveness analyses of CIS compared to SOC and CIS + FI compared to CIS will also be conducted. Study findings will provide evidence on the effectiveness of a CIS and the incremental effectiveness of a CIS + FI in a "real-life" service delivery system in a SSA country severely impacted by HIV. Clinicaltrials.gov, NCT01930084.

Development of a dense SNP-based linkage map of an apple rootstock progeny using the Malus Infinium whole genome genotyping array.

PubMed

Antanaviciute, Laima; Fernández-Fernández, Felicidad; Jansen, Johannes; Banchi, Elisa; Evans, Katherine M; Viola, Roberto; Velasco, Riccardo; Dunwell, Jim M; Troggio, Michela; Sargent, Daniel J

2012-05-25

A whole-genome genotyping array has previously been developed for Malus using SNP data from 28 Malus genotypes. This array offers the prospect of high throughput genotyping and linkage map development for any given Malus progeny. To test the applicability of the array for mapping in diverse Malus genotypes, we applied the array to the construction of a SNP-based linkage map of an apple rootstock progeny. Of the 7,867 Malus SNP markers on the array, 1,823 (23.2%) were heterozygous in one of the two parents of the progeny, 1,007 (12.8%) were heterozygous in both parental genotypes, whilst just 2.8% of the 921 Pyrus SNPs were heterozygous. A linkage map spanning 1,282.2 cM was produced comprising 2,272 SNP markers, 306 SSR markers and the S-locus. The length of the M432 linkage map was increased by 52.7 cM with the addition of the SNP markers, whilst marker density increased from 3.8 cM/marker to 0.5 cM/marker. Just three regions in excess of 10 cM remain where no markers were mapped. We compared the positions of the mapped SNP markers on the M432 map with their predicted positions on the 'Golden Delicious' genome sequence. A total of 311 markers (13.7% of all mapped markers) mapped to positions that conflicted with their predicted positions on the 'Golden Delicious' pseudo-chromosomes, indicating the presence of paralogous genomic regions or mis-assignments of genome sequence contigs during the assembly and anchoring of the genome sequence. We incorporated data for the 2,272 SNP markers onto the map of the M432 progeny and have presented the most complete and saturated map of the full 17 linkage groups of M. pumila to date. The data were generated rapidly in a high-throughput semi-automated pipeline, permitting significant savings in time and cost over linkage map construction using microsatellites. The application of the array will permit linkage maps to be developed for QTL analyses in a cost-effective manner, and the identification of SNPs that have been assigned erroneous positions on the 'Golden Delicious' reference sequence will assist in the continued improvement of the genome sequence assembly for that variety.

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.

Synthesis of N-(β-D-glycuronopyranosyl)alkanamides and 1-(β-D-glycuronopyranosyl)-4-phenyl-[1,2,3]-triazoles as N-glycoprotein linkage region analogs: examination of the effect of C5 substituent on the N-glycosidic torsion (ΦN) based on X-ray crystallography.

PubMed

Mathiselvam, Manoharan; Loganathan, Duraikkannu; Varghese, Babu

2013-10-18

The torsion angle around the N-glycoprotein linkage region (GlcNAc-Asn) is an important factor for presenting sugar on the cell surface which is crucial for many biological processes. Earlier studies using model and analogs showed that this important torsion angle is greatly influenced by substitutions in the sugar part. In the present work, uronic acid alkanamides and triazole derivatives have been designed and synthesized as newer analogs of N-glycoprotein linkage region to understand the influence of the carboxylic group on linkage region torsion as well as on molecular packing. Crystal structure of N-(β-D-galacturonopyranosyl)acetamide is solved with the space group of P22121. Comparison of the torsion angle and molecular packing of this compound with N-(β-D-galactopyranosyl)acetamide showed that changing the C6-hydoxymethyl group to the carboxylic acid group has minimum influence on the N-glycosidic torsion angle, ΦN and significant influence on the molecular packing. Copyright © 2013 Elsevier Ltd. All rights reserved.

Comparative study of lignin characteristics from wheat straw obtained by soda-AQ and kraft pretreatment and effect on the following enzymatic hydrolysis process

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

Yang, Haitao; Xie, Yimin; Zheng, Xing

With this study, to understand the structural changes of lignin after soda-AQ and kraft pretreatment, milled straw lignin, black liquor lignin and residual lignin extracted from wheat straw were characterized by FT-IR, UV, GPC and NMR. The results showed that the main lignin linkages were β-aryl ether substructures (β-O-4'), followed by phenylcoumaran (β-5') and resinol (β-β') substructures, while minor content of spirodienone (β-1'), dibenzodioxocin (5-5') and α,β-diaryl ether linkages were detected as well. After pretreatment, most lignin inter-units and lignin-carbohydrate complex (LCC) linkages were degraded and dissolved in black liquor, with minor amount left in residual pretreated biomass. In addition,more » through quantitative 13C and 2D-HSQC NMR spectral analysis, lignin and LCC were found to be more degraded after kraft pretreatment than soda-AQ pretreatment. Furthermore, the subsequent enzymatic hydrolysis results showed that more cellulose in wheat straw was converted to glucose after kraft pretreatment, indicating that LCC linkages were important in the enzymatic hydrolysis process.« less

Comparative study of lignin characteristics from wheat straw obtained by soda-AQ and kraft pretreatment and effect on the following enzymatic hydrolysis process

DOE PAGES

Yang, Haitao; Xie, Yimin; Zheng, Xing; ...

2016-02-18

With this study, to understand the structural changes of lignin after soda-AQ and kraft pretreatment, milled straw lignin, black liquor lignin and residual lignin extracted from wheat straw were characterized by FT-IR, UV, GPC and NMR. The results showed that the main lignin linkages were β-aryl ether substructures (β-O-4'), followed by phenylcoumaran (β-5') and resinol (β-β') substructures, while minor content of spirodienone (β-1'), dibenzodioxocin (5-5') and α,β-diaryl ether linkages were detected as well. After pretreatment, most lignin inter-units and lignin-carbohydrate complex (LCC) linkages were degraded and dissolved in black liquor, with minor amount left in residual pretreated biomass. In addition,more » through quantitative 13C and 2D-HSQC NMR spectral analysis, lignin and LCC were found to be more degraded after kraft pretreatment than soda-AQ pretreatment. Furthermore, the subsequent enzymatic hydrolysis results showed that more cellulose in wheat straw was converted to glucose after kraft pretreatment, indicating that LCC linkages were important in the enzymatic hydrolysis process.« less

Genomewide significant linkage to recurrent, early-onset major depressive disorder on chromosome 15q.

PubMed

Holmans, Peter; Zubenko, George S; Crowe, Raymond R; DePaulo, J Raymond; Scheftner, William A; Weissman, Myrna M; Zubenko, Wendy N; Boutelle, Sandra; Murphy-Eberenz, Kathleen; MacKinnon, Dean; McInnis, Melvin G; Marta, Diana H; Adams, Philip; Knowles, James A; Gladis, Madeleine; Thomas, Jo; Chellis, Jennifer; Miller, Erin; Levinson, Douglas F

2004-06-01

A genome scan was performed on the first phase sample of the Genetics of Recurrent Early-Onset Depression (GenRED) project. The sample consisted of 297 informative families containing 415 independent affected sibling pairs (ASPs), or, counting all possible pairs, 685 informative affected relative pairs (555 ASPs and 130 other pair types). Affected cases had recurrent major depressive disorder (MDD) with onset before age 31 years for probands or age 41 years for other affected relatives; the mean age at onset was 18.5 years, and the mean number of depressive episodes was 7.3. The Center for Inherited Disease Research genotyped 389 microsatellite markers (mean spacing of 9.3 cM). The primary linkage analysis considered allele sharing in all possible affected relative pairs with the use of the Z(lr) statistic computed by the ALLEGRO program. A secondary logistic regression analysis considered the effect of the sex of the pair as a covariate. Genomewide significant linkage was observed on chromosome 15q25.3-26.2 (Zlr=4.14, equivalent LOD = 3.73, empirical genomewide P=.023). The linkage was not sex specific. No other suggestive or significant results were observed in the primary analysis. The secondary analysis produced three regions of suggestive linkage, but these results should be interpreted cautiously because they depended primarily on the small subsample of 42 male-male pairs. Chromosome 15q25.3-26.2 deserves further study as a candidate region for susceptibility to MDD.

Synthesis of β-arabinofuranoside glycolipids, studies of their binding to surfactant protein-A and effect on sliding motilities of M. smegmatis.

PubMed

Naresh, Kottari; Avaji, Prakash Gouda; Maiti, Krishnagopal; Bharati, Binod K; Syal, Kirtimaan; Chatterji, Dipankar; Jayaraman, Narayanaswamy

2012-04-01

Surfactant protein A (SP-A), which is a lung innate immune system component, is known to bind glycolipids present at the cell surface of a mycobacterial pathogen. Lipoarabinomannan (LAM), a component of mycobacterial thick, waxy cell wall, is one of the glycolipid ligands for SP-A. In order to assess binding of synthetic glycolipids with SP-A and the glycosidic linkage preferences for the interaction, β-arabinofuranoside trisaccharide glycolipids constituted with β-(1→2), β-(1→3) and β-(1→2), β-(1→5) linkages relevant to LAM were synthesized through chemical glycosylations. The efficacies of synthetic glycolipids to interact with SP-A were assessed by using the surface plasmon resonance (SPR) technique, from which association-dissociation rate constants and equilibrium binding constants were derived. The equilibrium binding constants of the interaction of two constitutionally varying β-arabinofuranoside glycolipids with SP-A were found to be in the millimolar range. A comparison of the results with few α-anomeric arabinofuranoside glycolipids showed that glycolipids with β-anomeric linkages were having relatively lower equilibrium binding constants than those with α-anomeric linkages in binding to the protein, whereas oligosaccharides alone, without lipidic chains, exhibited higher equilibrium binding constants. Further, the synthetic compounds inhibited the growth of mycobacteria and affected sliding motilities of the bacteria, although to an extent relatively lesser than that of synthetic compounds constituted with α-anomeric linkages.

Development of diagnostic markers for use in breeding potatoes resistant to Globodera pallida pathotype Pa2/3 using germplasm derived from Solanum tuberosum ssp. andigena CPC 2802.

PubMed

Moloney, Claire; Griffin, Denis; Jones, Peter W; Bryan, Glenn J; McLean, Karen; Bradshaw, John E; Milbourne, Dan

2010-02-01

Quantitative resistance to Globodera pallida pathotype Pa2/3, originally derived from Solanum tuberosum ssp. andigena Commonwealth Potato Collection (CPC) accession 2802, is present in several potato cultivars and advanced breeding lines. One genetic component of this resistance, a large effect quantitative trait locus (QTL) on linkage group IV (which we have renamed GpaIV(adg)(s)) has previously been mapped in the tetraploid breeding line 12601ab1. In this study, we show that GpaIV(adg)(s) is also present in a breeding line called C1992/31 via genetic mapping in an F(1) population produced by crossing C1992/31 with the G. pallida susceptible cultivar Record. C1992/31 is relatively divergent from 12601ab1, confirming that GpaIV(adg)(s) is an ideal target for marker-assisted selection in currently available germplasm. To generate markers exhibiting diagnostic potential for GpaIV(adg)(s), three bacterial artificial chromosome clones were isolated from the QTL region, sequenced, and used to develop 15 primer sets generating single-copy amplicons, which were examined for polymorphisms exhibiting linkage to GpaIV(adg)(s) in C1992/31. Eight such polymorphisms were found. Subsequently, one insertion/deletion polymorphism, three single nucleotide polymorphisms and a specific allele of the microsatellite marker STM3016 were shown to exhibit diagnostic potential for the QTL in a panel of 37 potato genotypes, 12 with and 25 without accession CPC2082 in their pedigrees. STM3016 and one of the SNP polymorphisms, C237(119), were assayed in 178 potato genotypes, arising from crosses between C1992/31 and 16 G. pallida susceptible genotypes, undergoing selection in a commercial breeding programme. The results suggest that the diagnostic markers would most effectively be employed in MAS-based approaches to pyramid different resistance loci to develop cultivars exhibiting strong, durable resistance to G. pallida pathotype Pa2/3.

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.

Facile and Stabile Linkages through Tyrosine: Bioconjugation Strategies with the Tyrosine-Click Reaction

PubMed Central

Ban, Hitoshi; Nagano, Masanobu; Gavrilyuk, Julia; Hakamata, Wataru; Inokuma, Tsubasa; Barbas, Carlos F.

2013-01-01

The scope, chemoselectivity, and utility of the click-like tyrosine labeling reaction with 4-phenyl-3H-1,2,4-triazoline-3,5(4H)-diones (PTADs) is reported. To study the utility and chemoselectivity of PTAD derivatives in peptide and protein chemistry, we synthesized PTAD derivatives possessing azide, alkyne, and ketone groups and studied their reactions with amino acid derivatives and peptides of increasing complexity. With proteins we studied the compatibility of the tyrosine click reaction with cysteine and lysine-targeted labeling approaches and demonstrate that chemoselective tri-functionalization of proteins is readily achieved. In particular cases, we noted PTAD decomposition resulted in formation of a putative isocyanate by-product that was promiscuous in labeling. This side reaction product, however, was readily scavenged by the addition of a small amount of 2-amino-2-hydroxymethyl-propane-1,3-diol (Tris) to the reaction medium. To study the potential of the tyrosine click reaction to introduce poly(ethylene) glycol chains onto proteins (PEGylation), we demonstrate that this novel reagent provides for the selective PEGylation of chymotrypsinogen whereas traditional succinimide-based PEGylation targeting lysine residues provided a more diverse range of PEGylated products. Finally, we applied the tyrosine click reaction to create a novel antibody drug conjugate. For this purpose, we synthesized a PTAD derivative linked to the HIV entry inhibitor aplaviroc. Labeling of the antibody trastuzumab with this reagent provided a labeled antibody conjugate that demonstrated potent HIV-1 neutralization activity demonstrating the potential of this reaction in creating protein conjugates with small molecules. The tyrosine click linkage demonstrated stability to extremes of pH, temperature and exposure to human blood plasma indicating that this linkage is significantly more robust than maleimide-type linkages that are commonly employed in bioconjugations. These studies support the broad utility of this reaction in the chemoselective modification of small molecules, peptides, and proteins under mild aqueous conditions over a broad pH range using a wide variety of biologically acceptable buffers such as phosphate buffered saline (PBS) and 2-amino-2-hydroxymethyl-propane-1,3-diol (Tris) buffers as well as others and mixed buffered compositions. PMID:23534985

Mature and old-growth riparian forests: structure, dynamics, and effects on Adirondack stream habitats.

PubMed

Keeton, William S; Kraft, Clifford E; Warren, Dana R

2007-04-01

Riparian forests regulate linkages between terrestrial and aquatic ecosystems, yet relationships among riparian forest development, stand structure, and stream habitats are poorly understood in many temperate deciduous forest systems. Our research has (1) described structural attributes associated with old-growth riparian forests and (2) assessed linkages between these characteristics and in-stream habitat structure. The 19 study sites were located along predominantly first- and second-order streams in northern hardwood-conifer forests in the Adirondack Mountains of New York (U.S.A.). Sites were classified as mature forest (6 sites), mature with remnant old-growth trees (3 sites), and old-growth (10 sites). Forest-structure attributes were measured over stream channels and at varying distances from each bank. In-stream habitat features such as large woody debris (LWD), pools, and boulders were measured in each stream reach. Forest structure was examined in relation to stand age using multivariate techniques, ANOVA, and linear regression. We investigated linkages between forest structure and stream characteristics using similar methods, preceded by information-theoretic modeling (AIC). Old-growth riparian forest structure is more complex than that found in mature forests and exhibits significantly greater accumulations of aboveground tree biomass, both living and dead. In-stream LWD volumes were significantly (alpha = 0.05) greater at old-growth sites (200 m3/ha) compared to mature sites (34 m3/ha) and were strongly related to the basal area of adjacent forests. In-stream large-log densities correlated strongly with debris-dam densities. AIC models that included large-log density, debris-dam density, boulder density, and bankfull width had the most support for predicting pool density. There were higher proportions of LWD-formed pools relative to boulder-formed pools at old-growth sites as compared to mature sites. Old-growth riparian forests provide in-stream habitat features that have not been widely recognized in eastern North America, representing a potential benefit from late-successional riparian forest management and conservation. Riparian management practices (including buffer delineation and restorative silvicultural approaches) that emphasize development and maintenance of late-successional characteristics are recommended where the associated in-stream effects are desired.

Breed relationships facilitate fine-mapping studies: A 7.8-kb deletion cosegregates with Collie eye anomaly across multiple dog breeds

PubMed Central

Parker, Heidi G.; Kukekova, Anna V.; Akey, Dayna T.; Goldstein, Orly; Kirkness, Ewen F.; Baysac, Kathleen C.; Mosher, Dana S.; Aguirre, Gustavo D.; Acland, Gregory M.; Ostrander, Elaine A.

2007-01-01

The features of modern dog breeds that increase the ease of mapping common diseases, such as reduced heterogeneity and extensive linkage disequilibrium, may also increase the difficulty associated with fine mapping and identifying causative mutations. One way to address this problem is by combining data from multiple breeds segregating the same trait after initial linkage has been determined. The multibreed approach increases the number of potentially informative recombination events and reduces the size of the critical haplotype by taking advantage of shortened linkage disequilibrium distances found across breeds. In order to identify breeds that likely share a trait inherited from the same ancestral source, we have used cluster analysis to divide 132 breeds of dog into five primary breed groups. We then use the multibreed approach to fine-map Collie eye anomaly (cea), a complex disorder of ocular development that was initially mapped to a 3.9-cM region on canine chromosome 37. Combined genotypes from affected individuals from four breeds of a single breed group significantly narrowed the candidate gene region to a 103-kb interval spanning only four genes. Sequence analysis revealed that all affected dogs share a homozygous deletion of 7.8 kb in the NHEJ1 gene. This intronic deletion spans a highly conserved binding domain to which several developmentally important proteins bind. This work both establishes that the primary cea mutation arose as a single disease allele in a common ancestor of herding breeds as well as highlights the value of comparative population analysis for refining regions of linkage. PMID:17916641

The sumLINK statistic for genetic linkage analysis in the presence of heterogeneity.

PubMed

Christensen, G B; Knight, S; Camp, N J

2009-11-01

We present the "sumLINK" statistic--the sum of multipoint LOD scores for the subset of pedigrees with nominally significant linkage evidence at a given locus--as an alternative to common methods to identify susceptibility loci in the presence of heterogeneity. We also suggest the "sumLOD" statistic (the sum of positive multipoint LOD scores) as a companion to the sumLINK. sumLINK analysis identifies genetic regions of extreme consistency across pedigrees without regard to negative evidence from unlinked or uninformative pedigrees. Significance is determined by an innovative permutation procedure based on genome shuffling that randomizes linkage information across pedigrees. This procedure for generating the empirical null distribution may be useful for other linkage-based statistics as well. Using 500 genome-wide analyses of simulated null data, we show that the genome shuffling procedure results in the correct type 1 error rates for both the sumLINK and sumLOD. The power of the statistics was tested using 100 sets of simulated genome-wide data from the alternative hypothesis from GAW13. Finally, we illustrate the statistics in an analysis of 190 aggressive prostate cancer pedigrees from the International Consortium for Prostate Cancer Genetics, where we identified a new susceptibility locus. We propose that the sumLINK and sumLOD are ideal for collaborative projects and meta-analyses, as they do not require any sharing of identifiable data between contributing institutions. Further, loci identified with the sumLINK have good potential for gene localization via statistical recombinant mapping, as, by definition, several linked pedigrees contribute to each peak.

Mapping recessive ophthalmic diseases: linkage of the locus for Usher syndrome type II to a DNA marker on chromosome 1q.

PubMed

Lewis, R A; Otterud, B; Stauffer, D; Lalouel, J M; Leppert, M

1990-06-01

Usher syndrome is a heterogeneous group of autosomal recessive disorders that combines variably severe congenital neurosensory hearing impairment with progressive night-blindness and visual loss similar to that in retinitis pigmentosa. Usher syndrome type I is distinguished by profound congenital (preverbal) deafness and retinal disease with onset in the first decade of life. Usher syndrome type II is characterized by partial hearing impairment and retinal dystrophy that occurs in late adolescence or early adulthood. The chromosomal assignment and the regional localization of the genetic mutation(s) causing the Usher syndromes are unknown. We analyzed a panel of polymorphic genomic markers for linkage to the disease gene among six families with Usher syndrome type I and 22 families with Usher syndrome type II. Significant linkage was established between Usher syndrome type II and the DNA marker locus THH33 (D1S81), which maps to chromosome 1q. The most likely location of the disease gene is at a map distance of 9 cM from THH33 (lod score 6.5). The same marker failed to show linkage in families segregating an allele for Usher syndrome type I. These data confirm the provisional assignment of the locus for Usher syndrome type II to the distal end of chromosome 1q and demonstrate that the clinical heterogeneity between Usher types I and II is caused by mutational events at different genetic loci. Regional localization has the potential to improve carrier detection and to provide antenatal diagnosis in families at risk for the disease.

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

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.

Delivering proportionate governance in the era of eHealth

PubMed Central

Sethi, Nayha; Laurie, Graeme T.

2013-01-01

This article advances a principled proportionate governance model (PPGM) that overcomes key impediments to using health records for research. Despite increasing initiatives for maximising benefits of data linkage, significant challenges remain, including a culture of caution around data sharing and linkage, failure to make use of flexibilities within the law and failure to incorporate intelligent iterative design. The article identifies key issues for consideration and posits a flexible and accessible governance model that provides a robust and efficient means of paying due regard to both privacy and the public interests in research. We argue that proportionate governance based on clear guiding principles accurately gauges risks associated with data uses and assigns safeguards accordingly. This requires a clear articulation of roles and responsibilities at all levels of decision-making and effective training for researchers and data custodians. Accordingly, the PPGM encourages and supports defensible judgements about data linkage in the public interest. PMID:24634569

Rim-drive cable-aligned heliostat collector system

DOEpatents

Dolan, J.E.; Sands, T.D.

1982-09-30

Disclosed is a heliostat collector apparatus comprising at least one heliostat suspended from a plurality of longitudinally extending linkage means. An enclosure structure is disposed adjacent the heliostat and provides a means for allowing the heliostat to be substantially protected from weathering. A first drive means is operatively connected to the heliostat to effect steering thereof in at least one of first and second predetermined directions. Finally, a frame member is adapted for supporting the heliostat at an inner portion thereof. The frame includes a plurality of outer expandable portions. Each one of the expandable portions is adapted to slidably engage a corresponding one of the plurality of linkage means. The expandable portions are further adapted to allow the heliostat to be slidably moved along the linkage means in directions away from and towards the enclosure structure and to substantially reduce stress acting on the heliostat during steering.

Rim-drive cable-aligned heliostat collector system

DOEpatents

Dolan, James E.; Sands, Timothy D.

1984-01-01

Disclosed is a heliostat collector apparatus comprising at least one heliostat suspended from a plurality of longitudinally extending linkage means. An enclosure structure is disposed adjacent the heliostat and provides a means for allowing the heliostat to be substantially protected from weathering. A first drive means is operatively connected to the heliostat to effect steering thereof in at least one of first and second predetermined directions. Finally, a frame member is adapted for supporting the heliostat at an inner portion thereof. The frame includes a plurality of outer expandable portions. Each one of the expandable portions is adapted to slidably engage a corresponding one of the plurality of linkage means. The expandable portions are further adapted to allow the heliostat to be slidably moved along the linkage means in directions away from and towards the enclosure structure and to substantially reduce stress acting on the heliostat during steering.

Linking effects of anthropogenic debris to ecological impacts.

PubMed

Browne, Mark Anthony; Underwood, A J; Chapman, M G; Williams, Rob; Thompson, Richard C; van Franeker, Jan A

2015-05-22

Accelerated contamination of habitats with debris has caused increased effort to determine ecological impacts. Strikingly, most work on organisms focuses on sublethal responses to plastic debris. This is controversial because (i) researchers have ignored medical insights about the mechanisms that link effects of debris across lower levels of biological organization to disease and mortality, and (ii) debris is considered non-hazardous by policy-makers, possibly because individuals can be injured or removed from populations and assemblages without ecological impacts. We reviewed the mechanisms that link effects of debris across lower levels of biological organization to assemblages and populations. Using plastic, we show microplastics reduce the 'health', feeding, growth and survival of ecosystem engineers. Larger debris alters assemblages because fishing-gear and tyres kill animals and damage habitat-forming plants, and because floating bottles facilitate recruitment and survival of novel taxa. Where ecological linkages are not known, we show how to establish hypothetical links by synthesizing studies to assess the likelihood of impacts. We also consider how population models examine ecological linkages and guide management of ecological impacts. We show that by focusing on linkages to ecological impacts rather than the presence of debris and its sublethal impacts, we could reduce threats posed by debris. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

Characterization of Cell Wall Components and Their Modifications during Postharvest Storage of Asparagus officinalis L.: Storage-Related Changes in Dietary Fiber Composition.

PubMed

Schäfer, Judith; Wagner, Steffen; Trierweiler, Bernhard; Bunzel, Mirko

2016-01-20

Changes in cell wall composition during storage of plant foods potentially alter the physiological effects of dietary fiber components. To investigate postharvest cell wall modifications of asparagus and their consequences in terms of insoluble dietary fiber structures, asparagus was stored at 20 and 1 °C for different periods of time. Structural analyses demonstrated postharvest changes in the polysaccharide profile, dominated by decreased portions of galactans. Increasing lignin contents correlated with compositional changes (monolignol ratios and linkage types) of the lignin polymer as demonstrated by chemical and two-dimensional nuclear magnetic resonance (2D-NMR) methods. Depending on the storage time and temperature, syringyl units were preferentially incorporated into the lignin polymer. Furthermore, a drastic increase in the level of ester-linked phenolic monomers (i.e., p-coumaric acid and ferulic acid) and polymer cross-links (di- and triferulic acids) was detected. The attachment of p-coumaric acid to lignin was demonstrated by 2D-NMR experiments. Potential consequences of postharvest modifications on physiological effects of asparagus dietary fiber are discussed.

Pharmacogenetics and target identification in diabetes.

PubMed

Pearson, Ewan R

2018-02-24

In diabetes, pharmacogenetics can be used both to identify patient subgroups who will have most benefit and/or least harm from a particularly treatment, and to gain insights into the molecular mechanisms of drug action and disease aetiology. There is increasing evidence that genetic variation alters response to diabetes treatments-both in terms of glycaemic response and side effects. This can be seen with dramatic impact on clinical care, in patients with genetic forms of diabetes such as Maturity Onset Diabetes of the Young caused by HNF1A mutations, and Neonatal diabetes due to activating mutations in ABCC8 or KCNJ11. Beyond monogenic diabetes, pharmacogenetic variants have yet to impact on clinical practice, yet the effect sizes (e.g. for metformin intolerance and OCT1 variants; or for metformin action and SLC2A2 variants) are potentially of clinical utility, especially if the genotype is already known at the point of prescribing. Over the next few years, increasing cohort sizes and linkage at scale to electronic medical records will provide considerable potential for stratification and novel target identification in diabetes. Copyright © 2018 Elsevier Ltd. All rights reserved.

Inferring Demographic History Using Two-Locus Statistics.

PubMed

Ragsdale, Aaron P; Gutenkunst, Ryan N

2017-06-01

Population demographic history may be learned from contemporary genetic variation data. Methods based on aggregating the statistics of many single loci into an allele frequency spectrum (AFS) have proven powerful, but such methods ignore potentially informative patterns of linkage disequilibrium (LD) between neighboring loci. To leverage such patterns, we developed a composite-likelihood framework for inferring demographic history from aggregated statistics of pairs of loci. Using this framework, we show that two-locus statistics are more sensitive to demographic history than single-locus statistics such as the AFS. In particular, two-locus statistics escape the notorious confounding of depth and duration of a bottleneck, and they provide a means to estimate effective population size based on the recombination rather than mutation rate. We applied our approach to a Zambian population of Drosophila melanogaster Notably, using both single- and two-locus statistics, we inferred a substantially lower ancestral effective population size than previous works and did not infer a bottleneck history. Together, our results demonstrate the broad potential for two-locus statistics to enable powerful population genetic inference. Copyright © 2017 by the Genetics Society of America.

Stress, Behavior and Health: Developing a Model for Predicting Post-Deployment Morbidity, Mortality and Other Adverse Outcomes

DTIC Science & Technology

2001-07-01

line corresponded very closely to media coverage of "mysterious illnesses" among GWE veterans (17). The role of publicity in affecting healthcare ...of deployment related health, and in particular the potential etiologic role of stress in the development of Gulf War Illnesses (GWI). To this end we...have devoted considerable resources to the scrupulous collection and linkage of data with the potential to shed light on the role of stress and other

A microsatellite-based consensus linkage map for species of Eucalyptus and a novel set of 230 microsatellite markers for the genus

PubMed Central

Brondani, Rosana PV; Williams, Emlyn R; Brondani, Claudio; Grattapaglia, Dario

2006-01-01

Background Eucalypts are the most widely planted hardwood trees in the world occupying globally more than 18 million hectares as an important source of carbon neutral renewable energy and raw material for pulp, paper and solid wood. Quantitative Trait Loci (QTLs) in Eucalyptus have been localized on pedigree-specific RAPD or AFLP maps seriously limiting the value of such QTL mapping efforts for molecular breeding. The availability of a genus-wide genetic map with transferable microsatellite markers has become a must for the effective advancement of genomic undertakings. This report describes the development of a novel set of 230 EMBRA microsatellites, the construction of the first comprehensive microsatellite-based consensus linkage map for Eucalyptus and the consolidation of existing linkage information for other microsatellites and candidate genes mapped in other species of the genus. Results The consensus map covers ~90% of the recombining genome of Eucalyptus, involves 234 mapped EMBRA loci on 11 linkage groups, an observed length of 1,568 cM and a mean distance between markers of 8.4 cM. A compilation of all microsatellite linkage information published in Eucalyptus allowed us to establish the homology among linkage groups between this consensus map and other maps published for E. globulus. Comparative mapping analyses also resulted in the linkage group assignment of other 41 microsatellites derived from other Eucalyptus species as well as candidate genes and QTLs for wood and flowering traits published in the literature. This report significantly increases the availability of microsatellite markers and mapping information for species of Eucalyptus and corroborates the high conservation of microsatellite flanking sequences and locus ordering between species of the genus. Conclusion This work represents an important step forward for Eucalyptus comparative genomics, opening stimulating perspectives for evolutionary studies and molecular breeding applications. The generalized use of an increasingly larger set of interspecific transferable markers and consensus mapping information, will allow faster and more detailed investigations of QTL synteny among species, validation of expression-QTL across variable genetic backgrounds and positioning of a growing number of candidate genes co-localized with QTLs, to be tested in association mapping experiments. PMID:16995939

Linkage mapping in sheep and deer identifies a conserved pecora ruminant linkage group orthologous to two regions of HSA16 and a portion of HSA7Q

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

Broom, J.E.; Tate, M.L.; Dodds, K.G.

1996-05-01

Two orthologous linkage groups have been mapped in sheep and deer. Seven loci have been mapped in deer, and 12 in sheep. The sheep linkage group is assigned of ovine chromosome 24. The linkage groups consist of loci from the short arm of human chromosome 16, spanning the region containing the human Batten disease locus, and from human chromosome 7. One locus from the long arm of human chromosome 16 is also present, demonstrating a previously unknown rearrangement between human and ruminant chromosomes. There is no significant difference in marker order and distances between the two linkage groups, implying thatmore » this linkage pattern was present in the genome of the common ancestor of the pecora ruminants. 35 refs., 1 fig., 2 tabs.« less

Invasive European bird cherry disrupts stream-riparian linkages: effects on terrestrial invertebrate prey subsidies for juvenile coho salmon

USGS Publications Warehouse

Roon, David A.; Wipfli, Mark S.; Wurtz, Tricia L.; Blanchard, Arny L.

2016-01-01

The spread of invasive species in riparian forests has the potential to affect both terrestrial and aquatic organisms linked through cross-ecosystem resource subsidies. However, this potential had not been explored in regards to terrestrial prey subsidies for stream fishes. To address this, we examined the effects of an invasive riparian tree, European bird cherry (EBC, Prunus padus), spreading along urban Alaskan salmon streams, by collecting terrestrial invertebrates present on the foliage of riparian trees, their subsidies to streams, and their consumption by juvenile coho salmon (Oncorhynchus kisutch). Riparian EBC supported four to six times less terrestrial invertebrate biomass on its foliage and contributed two to three times lower subsidies relative to native deciduous trees. This reduction in terrestrial invertebrate biomass was consistent between two watersheds over 2 years. In spite of this reduction in terrestrial prey resource input, juvenile coho salmon consumed similar levels of terrestrial invertebrates in stream reaches bordered by EBC. Although we did not see ecological effects extending to stream salmonids, reduced terrestrial prey subsidies to streams are likely to have negative consequences as EBC continues to spread.

On the potential asthenospheric linkage between Apenninic slab rollback and Alpine topographic uplift: insights from P wave tomography and seismic anisotropy analysis

NASA Astrophysics Data System (ADS)

Malusa', Marco Giovanni; Salimbeni, Simone; Zhao, Liang; Guillot, Stéphane; Pondrelli, Silvia; Margheriti, Lucia; Paul, Anne; Solarino, Stefano; Aubert, Coralie; Dumont, Thierry; Schwartz, Stéphane; Wang, Qingchen; Xu, Xiaobing; Zheng, Tianyu; Zhu, Rixiang

2017-04-01

The role of surface and deep-seated processes in controlling the topography of complex plate-boundary areas is a highly debated issue. In the Western Alps, which include the highest summits in Europe, factors controlling topographic uplift still remain poorly understood. In the absence of active convergence, recent works have suggested a potential linkage between slab breakoff and fast uplift, but this hypothesis is ruled out by the down-dip continuity of the Alpine slab documented by recent tomographic images of the upper mantle beneath the Alpine region (Zhao et al. 2016). In order to shed light on this issue, we use a densely spaced array of temporary broadband seismic stations and previously published observations to analyze the seismic anisotropy pattern along the transition zone between the Alps and the Apennines, within the framework of the upper mantle structure unveiled by P wave tomography. Our results show a continuous trend of anisotropy fast axes near-parallel to the western alpine arc, possibly due to an asthenospheric counterflow triggered by the eastward retreat of the Apenninic slab. This trend is located in correspondence of a low velocity anomaly in the European upper mantle, and beneath the Western Alps region characterized by the highest uplift rates, which may suggest a potential impact of mantle dynamics on Alpine topography. We propose that the progressive rollback of the Apenninic slab induced a suction effect and an asthenospheric counterflow at the rear of the unbroken Alpine slab and around its southern tip, as well as an asthenospheric upwelling, mirrored by low P wave velocities, which may have favored the topographic uplift of the Alpine belt from the Mt Blanc to the Ligurian coast. Zhao L. et al., 2016. Continuity of the Alpine slab unraveled by high-resolution P wave tomography. J. Geophys. Res., doi:10.1002/2016JB013310.

Phase-Division-Based Dynamic Optimization of Linkages for Drawing Servo Presses

NASA Astrophysics Data System (ADS)

Zhang, Zhi-Gang; Wang, Li-Ping; Cao, Yan-Ke

2017-11-01

Existing linkage-optimization methods are designed for mechanical presses; few can be directly used for servo presses, so development of the servo press is limited. Based on the complementarity of linkage optimization and motion planning, a phase-division-based linkage-optimization model for a drawing servo press is established. Considering the motion-planning principles of a drawing servo press, and taking account of work rating and efficiency, the constraints of the optimization model are constructed. Linkage is optimized in two modes: use of either constant eccentric speed or constant slide speed in the work segments. The performances of optimized linkages are compared with those of a mature linkage SL4-2000A, which is optimized by a traditional method. The results show that the work rating of a drawing servo press equipped with linkages optimized by this new method improved and the root-mean-square torque of the servo motors is reduced by more than 10%. This research provides a promising method for designing energy-saving drawing servo presses with high work ratings.

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

Hereditary spastic paraplegia: LOD-score considerations for confirmation of linkage in a heterogeneous trait.

PubMed

Dubé, M P; Mlodzienski, M A; Kibar, Z; Farlow, M R; Ebers, G; Harper, P; Kolodny, E H; Rouleau, G A; Figlewicz, D A

1997-03-01

Hereditary spastic paraplegia (HSP) is a degenerative disorder of the motor system, defined by progressive weakness and spasticity of the lower limbs. HSP may be inherited as an autosomal dominant (AD), autosomal recessive, or an X-linked trait. AD HSP is genetically heterogeneous, and three loci have been identified so far: SPG3 maps to chromosome 14q, SPG4 to 2p, and SPG4a to 15q. We have undertaken linkage analysis with 21 uncomplicated AD families to the three AD HSP loci. We report significant linkage for three of our families to the SPG4 locus and exclude several families by multipoint linkage. We used linkage information from several different research teams to evaluate the statistical probability of linkage to the SPG4 locus for uncomplicated AD HSP families and established the critical LOD-score value necessary for confirmation of linkage to the SPG4 locus from Bayesian statistics. In addition, we calculated the empirical P-values for the LOD scores obtained with all families with computer simulation methods. Power to detect significant linkage, as well as type I error probabilities, were evaluated. This combined analytical approach permitted conclusive linkage analyses on small to medium-size families, under the restrictions of genetic heterogeneity.

[Linkage to care among new human immunodeficiency virus diagnoses in Spain].

PubMed

Oliva, Jesús; Malo, Carmen; Fernández, Ana; Izquierdo, Ana; Marcos, Henar; Cevallos, Carlos; Castilla, Jesús; García, Rocio; Díez, Mercedes

2014-03-01

To describe linkage to care among new HIV diagnoses in Spain; and to estimate factors associated to linkage to care within three months after diagnosis. The distribution of the time elapsing between the date of HIV diagnosis and the date of first determination of CD4 (considered to be the date of linkage to care) was calculated among new HIV diagnoses in 2010 in the seven Autonomous Regions participating, where data on date of CD4 count was available. Linkage to care was considered «correct» if done within three months after diagnosis. Factors associated to correct linkage to care were estimated using logistic regression. A total of 1769 new HIV diagnoses were included. Of them, 83.1% had evidence of linkage to care within a year, and 75.7% were linked within three months after diagnosis. Being an injectable drug user (IDU) was the only factor inversely associated with linkage to care within 3 months (OR = 0.3; 95% CI: 0.2-0.6). In Spain linkage to care after HIV diagnosis is good, but there is still room for improvement, especially among IDUs. Copyright © 2013 Elsevier España, S.L. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

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.

Peer-Delivered Linkage Case Management and Same-Day ART Initiation for Men and Young Persons with HIV Infection - Eswatini, 2015-2017.

PubMed

MacKellar, Duncan; Williams, Daniel; Bhembe, Bonsile; Dlamini, Makhosazana; Byrd, Johnita; Dube, Lenhle; Mazibuko, Sikhathele; Ao, Trong; Pathmanathan, Ishani; Auld, Andrew F; Faura, Pamela; Lukhele, Nomthandazo; Ryan, Caroline

2018-06-15

To achieve epidemic control of human immunodeficiency virus (HIV) infection, sub-Saharan African countries are striving to diagnose 90% of HIV infections, initiate and retain 90% of HIV-diagnosed persons on antiretroviral therapy (ART), and achieve viral load suppression* for 90% of ART recipients (90-90-90) (1). In Eswatini (formerly Swaziland), the country with the world's highest estimated HIV prevalence (27.2%), achieving 90-90-90 depends upon improving access to early ART for men and young adults with HIV infection, two groups with low ART coverage (1-3). Although community-based strategies test many men and young adults with HIV infection in Eswatini, fewer than one third of all persons who test positive in community settings enroll in HIV care within 6 months of diagnosis after receiving standard referral services (4,5). To evaluate the effectiveness of peer-delivered linkage case management † in improving early ART initiation for persons with HIV infection diagnosed in community settings in Eswatini, CDC analyzed data on 651 participants in CommLink, a community-based, mobile HIV-testing, point-of-diagnosis HIV care, and peer-delivered linkage case management demonstration project, and found that after diagnosis, 635 (98%) enrolled in care within a median of 5 days (interquartile range [IQR] = 2-8 days), and 541 (83%) initiated ART within a median of 6 days (IQR = 2-14 days), including 402 (74%) on the day of their first clinic visit (same-day ART). After expanding ART eligibility to all persons with HIV infection on October 1, 2016, 96% of 225 CommLink clients initiated ART, including 87% at their first clinic visit. Compared with women and adult clients aged ≥30 years, similar high proportions of men and persons aged 15-29 years enrolled in HIV care and received same-day ART. To help achieve 90-90-90 by 2020, the United States President's Emergency Plan for AIDS Relief (PEPFAR) is supporting the national scale-up of CommLink in Eswatini and recommending peer-delivered linkage case management as a potential strategy for countries to achieve >90% early enrollment in care and ART initiation after diagnosis of HIV infection (6).

Defining a staged-based process for economic and financial evaluations of mHealth programs.

PubMed

LeFevre, Amnesty E; Shillcutt, Samuel D; Broomhead, Sean; Labrique, Alain B; Jones, Tom

2017-01-01

Mobile and wireless technology for health (mHealth) has the potential to improve health outcomes by addressing critical health systems constraints that impede coverage, utilization, and effectiveness of health services. To date, few mHealth programs have been implemented at scale and there remains a paucity of evidence on their effectiveness and value for money. This paper aims to improve understanding among mHealth program managers and key stakeholders of how to select methods for economic evaluation (comparative analysis for determining value for money) and financial evaluation (determination of the cost of implementing an intervention, estimation of costs for sustaining or expanding an intervention, and assessment of its affordability). We outline a 6 stage-based process for selecting and integrating economic and financial evaluation methods into the monitoring and evaluation of mHealth solutions including (1) defining the program strategy and linkages with key outcomes, (2) assessment of effectiveness, (3) full economic evaluation or partial evaluation, (4) sub-group analyses, (5) estimating resource requirements for expansion, (6) affordability assessment and identification of models for financial sustainability. While application of these stages optimally occurs linearly, finite resources, limited technical expertise, and the timing of evaluation initiation may impede this. We recommend that analysts prioritize economic and financial evaluation methods based on programmatic linkages with health outcomes; alignment with an mHealth solution's broader stage of maturity and stage of evaluation; overarching monitoring and evaluation activities; stakeholder evidence needs; time point of initiation; and available resources for evaluations.

On-site bundled rapid HIV/HCV testing in substance use disorder treatment programs: study protocol for a hybrid design randomized controlled trial.

PubMed

Frimpong, Jemima A; D'Aunno, Thomas; Perlman, David C; Strauss, Shiela M; Mallow, Alissa; Hernandez, Diana; Schackman, Bruce R; Feaster, Daniel J; Metsch, Lisa R

2016-03-03

More than 1.2 million people in the United States are living with human immunodeficiency virus (HIV), and 3.2 million are living with hepatitis C virus (HCV). An estimated 25 % of persons living with HIV also have HCV. It is therefore of great public health importance to ensure the prompt diagnosis of both HIV and HCV in populations that have the highest prevalence of both infections, including individuals with substance use disorders (SUD). In this theory-driven, efficacy-effectiveness-implementation hybrid study, we will develop and test an on-site bundled rapid HIV/HCV testing intervention for SUD treatment programs. Its aim is to increase the receipt of HIV and HCV test results among SUD treatment patients. Using a rigorous process involving patients, providers, and program managers, we will incorporate rapid HCV testing into evidence-based HIV testing and linkage to care interventions. We will then test, in a randomized controlled trial, the extent to which this bundled rapid HIV/HCV testing approach increases receipt of HIV and HCV test results. Lastly, we will conduct formative research to understand the barriers to, and facilitators of, the adoption, implementation, and sustainability of the bundled rapid testing strategy in SUD treatment programs. Novel approaches that effectively integrate on-site rapid HIV and rapid HCV testing are needed to address both the HIV and HCV epidemics. If feasible and efficacious, bundled rapid HIV/HCV testing may offer a scalable, potentially cost-effective approach to testing high-risk populations, such as patients of SUD treatment programs. It may ultimately lead to improved linkage to care and progress through the HIV and HCV care and treatment cascades. ClinicalTrials.gov: NCT02355080 . (30 January 2015).

Genome-wide association mapping reveals a rich genetic architecture of stripe rust resistance loci in emmer wheat (Triticum turgidum ssp. dicoccum).

PubMed

Liu, Weizhen; Maccaferri, Marco; Chen, Xianming; Laghetti, Gaetano; Pignone, Domenico; Pumphrey, Michael; Tuberosa, Roberto

2017-11-01

SNP-based genome scanning in worldwide domesticated emmer germplasm showed high genetic diversity, rapid linkage disequilibrium decay and 51 loci for stripe rust resistance, a large proportion of which were novel. Cultivated emmer wheat (Triticum turgidum ssp. dicoccum), one of the oldest domesticated crops in the world, is a potentially rich reservoir of variation for improvement of resistance/tolerance to biotic and abiotic stresses in wheat. Resistance to stripe rust (Puccinia striiformis f. sp. tritici) in emmer wheat has been under-investigated. Here, we employed genome-wide association (GWAS) mapping with a mixed linear model to dissect effective stripe rust resistance loci in a worldwide collection of 176 cultivated emmer wheat accessions. Adult plants were tested in six environments and seedlings were evaluated with five races from the United States and one from Italy under greenhouse conditions. Five accessions were resistant across all experiments. The panel was genotyped with the wheat 90,000 Illumina iSelect single nucleotide polymorphism (SNP) array and 5106 polymorphic SNP markers with mapped positions were obtained. A high level of genetic diversity and fast linkage disequilibrium decay were observed. In total, we identified 14 loci associated with field resistance in multiple environments. Thirty-seven loci were significantly associated with all-stage (seedling) resistance and six of them were effective against multiple races. Of the 51 total loci, 29 were mapped distantly from previously reported stripe rust resistance genes or quantitative trait loci and represent newly discovered resistance loci. Our results suggest that GWAS is an effective method for characterizing genes in cultivated emmer wheat and confirm that emmer wheat is a rich source of stripe rust resistance loci that can be used for wheat improvement.

Effects of a Non-Circular Chainring on Sprint Performance During a Cycle Ergometer Test

PubMed Central

Hintzy, Frédérique; Grappe, Frédéric; Belli, Alain

2016-01-01

Non-circular chainrings have been reported to alter the crank angular velocity profile over a pedal revolution so that more time is spent in the effective power phase. The purpose of this study was to determine whether sprint cycling performance could be improved using a non-circular chainring (Osymetric: ellipticity 1.25 and crank lever mounted nearly perpendicular to the major axis), in comparison with a circular chainring. Twenty sprint cyclists performed an 8 s sprint on a cycle ergometer against a 0.5 N/kg-1 friction force in four crossing conditions (non-circular or circular chainring with or without clipless pedal). Instantaneous force, velocity and power were continuously measured during each sprint. Three main characteristic pedal downstrokes were selected: maximal force (in the beginning of the sprint), maximal power (towards the middle), and maximal velocity (at the end of the sprint). Both average and instantaneous force, velocity and power were calculated during the three selected pedal downstrokes. The important finding of this study was that the maximal power output was significantly higher (+ 4.3%, p < 0.05) when using the non-circular chainring independent from the shoe-pedal linkage condition. This improvement is mainly explained by a significantly higher instantaneous external force that occurs during the downstroke. Non-circular chainring can have potential benefits on sprint cycling performance. Key points The Osymetric non-circular chainring significantly maximized crank power by 4.3% during sprint cycling, in comparison with a circular chainring. This maximal power output improvement was due to significant higher force developed when the crank was in the effective power phase. This maximal power output improvement was independent from the shoe-pedal linkage condition. Present benefits provided by the non-circular chainring on pedalling kinetics occurred only at high cadences. PMID:27274658

[MapDraw: a microsoft excel macro for drawing genetic linkage maps based on given genetic linkage data].

PubMed

Liu, Ren-Hu; Meng, Jin-Ling

2003-05-01

MAPMAKER is one of the most widely used computer software package for constructing genetic linkage maps.However, the PC version, MAPMAKER 3.0 for PC, could not draw the genetic linkage maps that its Macintosh version, MAPMAKER 3.0 for Macintosh,was able to do. Especially in recent years, Macintosh computer is much less popular than PC. Most of the geneticists use PC to analyze their genetic linkage data. So a new computer software to draw the same genetic linkage maps on PC as the MAPMAKER for Macintosh to do on Macintosh has been crying for. Microsoft Excel,one component of Microsoft Office package, is one of the most popular software in laboratory data processing. Microsoft Visual Basic for Applications (VBA) is one of the most powerful functions of Microsoft Excel. Using this program language, we can take creative control of Excel, including genetic linkage map construction, automatic data processing and more. In this paper, a Microsoft Excel macro called MapDraw is constructed to draw genetic linkage maps on PC computer based on given genetic linkage data. Use this software,you can freely construct beautiful genetic linkage map in Excel and freely edit and copy it to Word or other application. This software is just an Excel format file. You can freely copy it from ftp://211.69.140.177 or ftp://brassica.hzau.edu.cn and the source code can be found in Excel's Visual Basic Editor.

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.

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.