XSTREAM: A practical algorithm for identification and architecture modeling of tandem repeats in protein sequences

<p>Abstract</p> <p>Background</p> <p>Biological sequence repeats arranged in tandem patterns are widespread in DNA and proteins. While many software tools have been designed to detect DNA tandem repeats (TRs), useful algorithms for identifying protein TRs with varied levels of degeneracy are still needed.</p> <p>Results</p> <p>To address limitations of current repeat identification methods, and to provide an efficient and flexible algorithm for the detection and analysis of TRs in protein sequences, we designed and implemented a new computational method called XSTREAM. Running time tests confirm the practicality of XSTREAM for analyses of multi-genome datasets. Each of the key capabilities of XSTREAM (e.g., merging, nesting, long-period detection, and TR architecture modeling) are demonstrated using anecdotal examples, and the utility of XSTREAM for identifying TR proteins was validated using data from a recently published paper.</p> <p>Conclusion</p> <p>We show that XSTREAM is a practical and valuable tool for TR detection in protein and nucleotide sequences at the multi-genome scale, and an effective tool for modeling TR domains with diverse architectures and varied levels of degeneracy. Because of these useful features, XSTREAM has significant potential for the discovery of naturally-evolved modular proteins with applications for engineering novel biostructural and biomimetic materials, and identifying new vaccine and diagnostic targets.</p

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

A first look at consistency of documentation across care settings during emergency transitions of long-term care residents

Abstract Background Documentation during resident transitions from long-term care (LTC) to the emergency department (ED) can be inconsistent, leading to inappropriate care. Inconsistent documentation can lead to undertreatment, inefficiencies and adverse patient outcomes. Many individuals residing in LTC have some form of cognitive impairment and may not be able to advocate for themselves, making accurate and consistent documentation vital to ensuring they receive safe care. We examined documentation consistency related to reason for transfer across care settings during these transitions. Methods We included residents of LTC aged 65 or over who experienced an emergency transition from LTC to the ED via emergency medical services. We used a standardized and pilot-tested tracking tool to collect resident chart/patient record data. We collected data from 38 participating LTC facilities to two participating EDs in Western Canadian provinces. Using qualitative directed content analysis, we categorized documentation from LTC to the ED by sufficiency and clinical consistency. Results We included 591 eligible transitions in this analysis. Documentation was coded as consistent, inconsistent, or ambiguous. We identified the most common reasons for transition for consistent cases (falls), ambiguous cases (sudden change in condition) and inconsistent cases (falls). Among inconsistent cases, three subcategories were identified: insufficient reporting, potential progression of a condition during transition and unclear reasons for inconsistency. Conclusions Shared continuing education on documentation across care settings should result in documentation supports geriatric emergency care; on-the-job training needs to support reporting of specific signs and symptoms that warrant an emergent response, and discourage the use of vague descriptors

The Older Persons’ Transitions in Care (OPTIC) study: pilot testing of the transition tracking tool

Background: OPTIC is a mixed method Partnership for Health System Improvement ( http://www.cihr-irsc.gc.ca/e/34348.html ) study focused on improving care for nursing home (NH) residents who are transferred to and from emergency departments (EDs) via emergency medical services (EMS). In the pilot study we tested feasibility of concurrently collecting individual resident data during transitions across settings using the Transition Tracking Tool (T3). Methods The pilot study tracked 54 residents transferred from NHs to one of two EDs in two western Canadian provinces over a three month period. The T3 is an electronic data collection tool developed for this study to record data relevant to describing and determining success of transitions in care. It comprises 800+ data elements including resident characteristics, reasons and precipitating factors for transfer, advance directives, family involvement, healthcare services provided, disposition decisions, and dates/times and timing. Results Residents were elderly (mean age = 87.1 years) and the majority were female (61.8%). Feasibility of collecting data from multiple sources across two research sites was established. We identified resources and requirements to access and retrieve specific data elements in various settings to manage data collection processes and allocate research staff resources. We present preliminary data from NH, EMS, and ED settings. Conclusions While most research in this area has focused on a unidirectional process of patient progression from one care setting to another, this study established feasibility of collecting detailed data from beginning to end of a transition across multiple settings and in multiple directions.Other UBCNon UBCReviewedFacult

Older Persons’ Transitions in Care (OPTIC): a study protocol

Abstract Background Changes in health status, triggered by events such as infections, falls, and geriatric syndromes, are common among nursing home (NH) residents and necessitate transitions between NHs and Emergency Departments (EDs). During transitions, residents frequently experience care that is delayed, unnecessary, not evidence-based, potentially unsafe, and fragmented. Furthermore, a high proportion of residents and their family caregivers report substantial unmet needs during transitions. This study is part of a program of research whose overall aim is to improve quality of care for frail older adults who reside in NHs. The purpose of this study is to identify successful transitions from multiple perspectives and to identify organizational and individual factors related to transition success, in order to inform improvements in care for frail elderly NH residents during transitions to and from acute care. Specific objectives are to: 1. define successful and unsuccessful elements of transitions from multiple perspectives; 2. develop and test a practical tool to assess transition success; 3. assess transition processes in a discrete set of transfers in two study sites over a one year period; 4. assess the influence of organizational factors in key practice locations, e.g., NHs, emergency medical services (EMS), and EDs, on transition success; and 5. identify opportunities for evidence-informed management and quality improvement decisions related to the management of NH – ED transitions. Methods/Design This is a mixed-methods observational study incorporating an integrated knowledge translation (IKT) approach. It uses data from multiple levels (facility, care unit, individual) and sources (healthcare providers, residents, health records, and administrative databases). Discussion Key to study success is operationalizing the IKT approach by using a partnership model in which the OPTIC governance structure provides for team decision-makers and researchers to participate equally in developing study goals, design, data collection, analysis and implications of findings. As preliminary and ongoing study findings are developed, their implications for practice and policy in study settings will be discussed by the research team and shared with study site administrators and staff. The study is designed to investigate the complexities of transitions and to enhance the potential for successful and sustained improvement of these transitions.</p

Older Persons’ Transitions in Care (OPTIC): a study protocol

Background: Changes in health status, triggered by events such as infections, falls, and geriatric syndromes, are common among nursing home (NH) residents and necessitate transitions between NHs and Emergency Departments (EDs). During transitions, residents frequently experience care that is delayed, unnecessary, not evidence-based, potentially unsafe, and fragmented. Furthermore, a high proportion of residents and their family caregivers report substantial unmet needs during transitions. This study is part of a program of research whose overall aim is to improve quality of care for frail older adults who reside in NHs. The purpose of this study is to identify successful transitions from multiple perspectives and to identify organizational and individual factors related to transition success, in order to inform improvements in care for frail elderly NH residents during transitions to and from acute care. Specific objectives are to: 1. define successful and unsuccessful elements of transitions from multiple perspectives; 2. develop and test a practical tool to assess transition success; 3. assess transition processes in a discrete set of transfers in two study sites over a one year period; 4. assess the influence of organizational factors in key practice locations, e.g., NHs, emergency medical services (EMS), and EDs, on transition success; and 5. identify opportunities for evidence-informed management and quality improvement decisions related to the management of NH – ED transitions. Methods/Design: This is a mixed-methods observational study incorporating an integrated knowledge translation (IKT) approach. It uses data from multiple levels (facility, care unit, individual) and sources (healthcare providers, residents, health records, and administrative databases). Discussion: Key to study success is operationalizing the IKT approach by using a partnership model in which the OPTIC governance structure provides for team decision-makers and researchers to participate equally in developing study goals, design, data collection, analysis and implications of findings. As preliminary and ongoing study findings are developed, their implications for practice and policy in study settings will be discussed by the research team and shared with study site administrators and staff. The study is designed to investigate the complexities of transitions and to enhance the potential for successful and sustained improvement of these transitions.Other UBCReviewedFacult

Sex hormone levels and risk of breast cancer with estrogen plus progestin.

BackgroundAlthough high endogenous sex hormone levels and estrogen plus progestin (E+P) therapy are associated with increased breast cancer risk, it is unknown whether pretreatment levels of sex hormones modify E+P effect on breast cancer.MethodsWe conducted a nested case-control study within the Women's Health Initiative randomized clinical trial of E+P. The trial enrolled 16608 postmenopausal women aged 50 to 79 years with intact uterus and no breast cancer history. During a mean of 5.6 years of follow-up, 348 incident breast cancer case subjects were identified and matched with 348 control subjects. Case and control subjects had their sex hormone levels measured at baseline (estrogens, testosterone, progesterone, and sex hormone-binding globulin [SHBG]) and year 1 (estrogens and SHBG) using sensitive assays. All statistical tests were two-sided.ResultsStatistically significant elevations in breast cancer risk were seen with greater pretreatment levels of total estradiol (P trend = .04), bioavailable estradiol (P trend = .03), estrone (P trend = .007), and estrone sulfate (P trend = .007). E+P increased all measured estrogens and SHGB at year 1 (all P &lt; .001). The effect of E+P on breast cancer risk was strongest in women whose pretreatment levels of total estradiol, bioavailable estradiol, and estrone were in the lowest quartiles. For example, the odds ratio for E+P relative to placebo was 2.47 (95% confidence interval [CI] = 1.28 to 4.79) in the lowest total estradiol quartile, compared with 0.96 (95% CI = 0.44 to 2.09) in the highest total estradiol quartile; P interaction = .04).ConclusionsWomen with lower pr-treatment endogenous estrogen levels were at greater risk of breast cancer during E+P therapy compared with those with higher levels. Further studies are warranted to confirm these findings

Sex hormone levels and risk of breast cancer with estrogen plus progestin.

BackgroundAlthough high endogenous sex hormone levels and estrogen plus progestin (E+P) therapy are associated with increased breast cancer risk, it is unknown whether pretreatment levels of sex hormones modify E+P effect on breast cancer.MethodsWe conducted a nested case-control study within the Women's Health Initiative randomized clinical trial of E+P. The trial enrolled 16608 postmenopausal women aged 50 to 79 years with intact uterus and no breast cancer history. During a mean of 5.6 years of follow-up, 348 incident breast cancer case subjects were identified and matched with 348 control subjects. Case and control subjects had their sex hormone levels measured at baseline (estrogens, testosterone, progesterone, and sex hormone-binding globulin [SHBG]) and year 1 (estrogens and SHBG) using sensitive assays. All statistical tests were two-sided.ResultsStatistically significant elevations in breast cancer risk were seen with greater pretreatment levels of total estradiol (P trend = .04), bioavailable estradiol (P trend = .03), estrone (P trend = .007), and estrone sulfate (P trend = .007). E+P increased all measured estrogens and SHGB at year 1 (all P &lt; .001). The effect of E+P on breast cancer risk was strongest in women whose pretreatment levels of total estradiol, bioavailable estradiol, and estrone were in the lowest quartiles. For example, the odds ratio for E+P relative to placebo was 2.47 (95% confidence interval [CI] = 1.28 to 4.79) in the lowest total estradiol quartile, compared with 0.96 (95% CI = 0.44 to 2.09) in the highest total estradiol quartile; P interaction = .04).ConclusionsWomen with lower pr-treatment endogenous estrogen levels were at greater risk of breast cancer during E+P therapy compared with those with higher levels. Further studies are warranted to confirm these findings

Calcium plus vitamin D supplementation and the risk of fractures.

BackgroundThe efficacy of calcium with vitamin D supplementation for preventing hip and other fractures in healthy postmenopausal women remains equivocal.MethodsWe recruited 36,282 postmenopausal women, 50 to 79 years of age, who were already enrolled in a Women's Health Initiative (WHI) clinical trial. We randomly assigned participants to receive 1000 mg of elemental [corrected] calcium as calcium carbonate with 400 IU of vitamin D3 daily or placebo. Fractures were ascertained for an average follow-up period of 7.0 years. Bone density was measured at three WHI centers.ResultsHip bone density was 1.06 percent higher in the calcium plus vitamin D group than in the placebo group (P&lt;0.01). Intention-to-treat analysis indicated that participants receiving calcium plus vitamin D supplementation had a hazard ratio of 0.88 for hip fracture (95 percent confidence interval, 0.72 to 1.08), 0.90 for clinical spine fracture (0.74 to 1.10), and 0.96 for total fractures (0.91 to 1.02). The risk of renal calculi increased with calcium plus vitamin D (hazard ratio, 1.17; 95 percent confidence interval, 1.02 to 1.34). Censoring data from women when they ceased to adhere to the study medication reduced the hazard ratio for hip fracture to 0.71 (95 percent confidence interval, 0.52 to 0.97). Effects did not vary significantly according to prerandomization serum vitamin D levels.ConclusionsAmong healthy postmenopausal women, calcium with vitamin D supplementation resulted in a small but significant improvement in hip bone density, did not significantly reduce hip fracture, and increased the risk of kidney stones. (ClinicalTrials.gov number, NCT00000611.)

Calcium plus vitamin D supplementation and the risk of fractures

BACKGROUND: The efficacy of calcium with vitamin D supplementation for preventing hip and other fractures in healthy postmenopausal women remains equivocal. METHODS: We recruited 36,282 postmenopausal women, 50 to 79 years of age, who were already enrolled in a Women\u27s Health Initiative (WHI) clinical trial. We randomly assigned participants to receive 1000 mg of elemental [corrected] calcium as calcium carbonate with 400 IU of vitamin D3 daily or placebo. Fractures were ascertained for an average follow-up period of 7.0 years. Bone density was measured at three WHI centers. RESULTS: Hip bone density was 1.06 percent higher in the calcium plus vitamin D group than in the placebo group (PCONCLUSIONS: Among healthy postmenopausal women, calcium with vitamin D supplementation resulted in a small but significant improvement in hip bone density, did not significantly reduce hip fracture, and increased the risk of kidney stones. (ClinicalTrials.gov number, NCT00000611.)