467 research outputs found
P04.06. Complementary and alternative medicine in the treatment of pain in fibromyalgia: a systematic review of randomized controlled trials
How Many Subpopulations is Too Many? Exponential Lower Bounds for Inferring Population Histories
Reconstruction of population histories is a central problem in population
genetics. Existing coalescent-based methods, like the seminal work of Li and
Durbin (Nature, 2011), attempt to solve this problem using sequence data but
have no rigorous guarantees. Determining the amount of data needed to correctly
reconstruct population histories is a major challenge. Using a variety of tools
from information theory, the theory of extremal polynomials, and approximation
theory, we prove new sharp information-theoretic lower bounds on the problem of
reconstructing population structure -- the history of multiple subpopulations
that merge, split and change sizes over time. Our lower bounds are exponential
in the number of subpopulations, even when reconstructing recent histories. We
demonstrate the sharpness of our lower bounds by providing algorithms for
distinguishing and learning population histories with matching dependence on
the number of subpopulations. Along the way and of independent interest, we
essentially determine the optimal number of samples needed to learn an
exponential mixture distribution information-theoretically, proving the upper
bound by analyzing natural (and efficient) algorithms for this problem.Comment: 38 pages, Appeared in RECOMB 201
GENOMICS OF ENDOGLIN PATHWAY IN PREECLAMPSIA
THE GENOMICS OF ENDOGLIN PATHWAY IN PREECLAMPSIA
Mandy J. Bell, PhD, RN
University of Pittsburgh, 2012
Preeclampsia is a pregnancy disorder that greatly impacts maternal and fetal/neonatal health and wellbeing. This case-control candidate gene association study investigated endoglin pathway genetic variation and its association with preeclampsia. Tagging single nucleotide polymorphisms (tSNPs) in ENG, TGFβ1, TGFβR1, ALK1, and TGFβR2 were genotyped with iPLEX® and TaqMan® in maternal/fetal dyads. The Prenatal Exposures and Preeclampsia Prevention study provided maternal DNA extracted from peripherally collected white blood cell pellets, along with umbilical cord serum we used for fetal DNA extraction. Data on 355 white (181 cases/174 controls) and 60 black (30 cases/30 controls) women matched on ancestry, age, and parity were analyzed. Separate subgroup allele/genotype/haplotype tests were conducted with Chi-square or Fisher’s exact tests. Binary logistic regression provided odds ratios for tSNPs with significant genotype tests. Analysis of maternal/fetal dyads was not conducted, because unlike the maternal samples, the fetal samples did not provide a quality template suitable for iPLEX® data collection. In white women, variation in ENG (rs11792480, rs10121110) and TGFβR2 (rs6550005) was associated with preeclampsia. Allelic frequency distributions in rs11792480, rs10121110, and rs6550005 were significantly different among cases and controls while genotype distributions of rs10121110 and rs6550005 were further associated with preeclampsia (p-values < .05). For rs10121110, women with the AA genotype were 2.290 times more likely to develop preeclampsia compared to the GG genotype (99% CI [1.022, 5.133], p = .008). ENG haplotype TACGA, which contains rs11792480 and rs10121110 risk alleles, was also over-represented in cases (p = .022). In black women, variation in TGFβ1 (rs4803455, rs4803457), TGFβR1 (rs10739778), and TGFβR2 (rs6550005, rs1346907, rs877572) was associated with preeclampsia. Allelic frequency distributions in rs10739778, rs6550005, rs1346907, and rs877572 were significantly different among cases and controls while genotype distributions of rs10739778, rs4803455, and rs4803457 were further associated with preeclampsia (p-values < .05). For rs4803457, women with the CT genotype were 7.437 more times likely to develop preeclampsia compared to the CC genotype (99% CI [1.192, 46.408], p = .005). These results demonstrate that variation in ENG pathway genes is associated with preeclampsia, with different genes from the same pathway contributing to preeclampsia in white compared to black women
Clonal expansion of CD4+CD8+ T cells in an adult patient with Mycoplasma pneumoniae-associated Erythema multiforme majus
Background: Erythema multiforme (EM) is an acute, immune-mediated mucocutaneous disease, most often preceded by herpes simplex virus (HSV) infection or reactivation. Mycoplasma pneumoniae (Mp) is considered the second major trigger of EM and is often associated with an atypical and more severe presentation of disease, characterized by prominent mucosal involvement. However, contrary to HSV-associated Erythema multiforme (HAEM), immunological mechanisms of Mp-associated EM remain unclear.
Case presentation: We present the case of a 50-year-old male patient presenting with community-acquired pneumonia (CAP) and erythema multiforme majus (EMM). Acute Mp infection was diagnosed by seroconversion, with no evidence of HSV infection as a cause of EMM. We performed immune phenotyping of blister fluid (BF) and peripheral blood (PB) T cells and detected a clonally expanded TCRV beta 2(+) T cell population that was double positive for CD4 and CD8, and expressed the cytotoxic markers granulysin and perforin. This CD4(+)CD8(+) population comprised up to 50.7% of BF T cells and 24.9% of PB T cells. Two years prior to the onset of disease, the frequency of PB CD4(+)CD8(+)T cells had been within normal range and it gradually returned to baseline levels with the resolution of symptoms, suggesting an involvement of this population in EMM disease pathophysiology.
Conclusions: This report is the first to provide a phenotypic description of lesional T cells in Mp-associated EMM. Characterizing the local immune response might help to address pathophysiological questions and warrants further systematic research
Tolerance Induction to Cytoplasmic -Galactosidase by Hepatic AAV Gene Transfer — Implications for Antigen Presentation and Immunotoxicity
Background: Hepatic gene transfer, in particular using adeno-associated viral (AAV) vectors, has been shown to induce immune tolerance to several protein antigens. This approach has been exploited in animal models of inherited protein deficiency for systemic delivery of therapeutic proteins. Adequate levels of transgene expression in hepatocytes induce a suppressive T cell response, thereby promoting immune tolerance. This study addresses the question of whether AAV gene transfer can induce tolerance to a cytoplasmic protein. Major Findings: AAV-2 vector-mediated hepatic gene transfer for expression of cytoplasmic -galactosidase (-gal) was performed in immune competent mice, followed by a secondary -gal gene transfer with E1/E3-deleted adenoviral Ad-LacZ vector to provoke a severe immunotoxic response. Transgene expression from the AAV-2 vector in 2% of hepatocytes almost completely protected from inflammatory T cell responses against -gal, eliminated antibody formation, and significantly reduced adenovirus-induced hepatotoxicity. Consequently, 10% of hepatocytes continued to express -gal 45 days after secondary Ad-LacZ gene transfer, a time point when control mice had lost all Ad-LacZ derived expression. Suppression of inflammatory T cell infiltration in the liver and liver damage was linked to specific transgene expression and was not seen for secondary gene transfer with Ad-GFP. A combination of adoptive transfer studies and flow cytometric analyses demonstrated induction of Treg that actively suppressed CD8 T cell responses to -gal and that was amplified in liver and spleen upon secondary Ad-LacZ gene transfer. Conclusions: These data demonstrate that tolerance induction by hepatic AAV gene transfer does not require systemic delivery of the transgene product and that expression of a cytoplasmic neo-antigen in few hepatocytes can induce Treg and provide long-term suppression of inflammatory responses and immunotoxicity
Re-municipalization of public services: trend or hype?
Re-municipalization is part of a broader set of reverse privatization reforms. We argue the term re-municipalization lacks conceptual clarity and often confuses municipal level reversals from national ones, new service delivery from reversals, and mixed market positions (such as corporatization) from full public control. This conceptual confusion makes measurement of re-municipalization difficult. While more case studies are being discovered, studies based on quantitative time series do not show re-municipalization as an increasing trend. Much case study based research argues re-municipalization is politically transformative, but quantitative research generally finds re-municipalization to be part of a pragmatic market management process, a position confirmed by the papers in this special issue
Parental perception of facilitators and barriers to health among young children with down syndrome: a qualitative study
BackgroundDespite high rates of obesity and weight-related conditions observed in children with Down syndrome, little is known about how to prevent these conditions.PurposeThe purpose of this study was to identify parent-perceived facilitators and barriers to health for toddlers (12–36 months old) with Down syndrome.Materials and methodsWe conducted in-depth, semi-structured interviews with the mothers of 25 toddlers with Down syndrome. All interviews were conducted using Zoom Video Technology, audio recorded and transcribed before being coded in NVivo software using a structured protocol. Thematic analysis was used to identify themes in perceived facilitators and barriers to health at the level of the child, family, and community. Data were triangulated using reflective journaling, video review of child meals, and member-checking techniques.ResultsWe identified unique themes for facilitators (on the move and sound sleep) and barriers (co-occurring conditions and eating behaviors) at the level of the child. At the level of the family and community, overarching themes that were viewed as either a facilitator or barrier, depending on the context, were identified (role models matter, time is critical, the importance of place, and social support).ConclusionThese themes can help clinicians and researchers tailor their health promotion interventions to meet the unique needs of children with Down syndrome by using strength-based approaches and providing families with the tools to overcome barriers
Terminal Pleistocene Alaskan genome reveals first founding population of Native Americans
Despite broad agreement that the Americas were initially populated via Beringia, the land bridge that connected far northeast Asia with northwestern North America during the Pleistocene epoch, when and how the peopling of the Americas occurred remains unresolved. Analyses of human remains from Late Pleistocene Alaska are important to resolving the timing and dispersal of these populations. The remains of two infants were recovered at Upward Sun River (USR), and have been dated to around 11.5 thousand years ago (ka). Here, by sequencing the USR1 genome to an average coverage of approximately 17 times, we show that USR1 is most closely related to Native Americans, but falls basal to all previously sequenced contemporary and ancient Native Americans. As such, USR1 represents a distinct Ancient Beringian population. Using demographic modelling, we infer that the Ancient Beringian population and ancestors of other Native Americans descended from a single founding population that initially split from East Asians around 36 ± 1.5 ka, with gene flow persisting until around 25 ± 1.1 ka. Gene flow from ancient north Eurasians into all Native Americans took place 25–20 ka, with Ancient Beringians branching off around 22–18.1 ka. Our findings support a long-term genetic structure in ancestral Native Americans, consistent with the Beringian ‘standstill model’. We show that the basal northern and southern Native American branches, to which all other Native Americans belong, diverged around 17.5–14.6 ka, and that this probably occurred south of the North American ice sheets. We also show that after 11.5 ka, some of the northern Native American populations received gene flow from a Siberian population most closely related to Koryaks, but not Palaeo-Eskimos, Inuits or Kets, and that Native American gene flow into Inuits was through northern and not southern Native American groups. Our findings further suggest that the far-northern North American presence of northern Native Americans is from a back migration that replaced or absorbed the initial founding population of Ancient Beringians
US chiropractors' attitudes, skills and use of evidence-based practice: A cross-sectional national survey
Background: Evidence based practice (EBP) is being increasingly utilized by health care professionals as a means of improving the quality of health care. The introduction of EBP principles into the chiropractic profession is a relatively recent phenomenon. There is currently a lack of information about the EBP literacy level of US chiropractors and the barriers/facilitators to the use of EBP in the chiropractic profession. Methods: A nationwide EBP survey of US chiropractors was administered online (Nov 2012-Mar 2013) utilizing a validated self-report instrument (EBASE) in which three sub-scores are reported: attitudes, skills and use. Means, medians, and frequency distributions for each of the sub-scores were generated. Descriptive statistics were used to analyze the demographic characteristics of the sample. Means and proportions were calculated for all of the responses to each of the questions in the survey. Results: A total of 1,314 US chiropractors completed the EBASE survey; the sample appeared to be representative of the US chiropractic profession. Respondents were predominantly white (94.3%), male (75%), 47 (+/- 11.6) years of age, and in practice for more than 10 years (60%). EBASE sub-score means (possible ranges) were: attitudes, 31.4 (8-40); skills, 44.3 (13-65); and use, 10.3 (0-24). Survey participants generally held favorable attitudes toward EBP, but reported less use of EBP. A minority of participants indicated that EBP coursework (17%) and critical thinking (29%) were a major part of their chiropractic education. The most commonly reported barrier to the use of EBP was "lack of time". Almost 90% of the sample indicated that they were interested in improving their EBP skills. Conclusion: American chiropractors appear similar to chiropractors in other countries, and other health professionals regarding their favorable attitudes towards EBP, while expressing barriers related to EBP skills such as research relevance and lack of time. This suggests that the design of future EBP educational interventions should capitalize on the growing body of EBP implementation research developing in other health disciplines. This will likely include broadening the approach beyond a sole focus on EBP education, and taking a multilevel approach that also targets professional, organizational and health policy domains
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