Support for Same-Sex Marriage at Record High, but Key Segments Remain Opposed

As the Supreme Court prepares to decide a key case involving states' requirements to recognize same-sex marriage, public support for allowing gays and lesbians to marry legally continues its rapid rise: A 57%-majority of Americans now favor allowing same-sex marriage and 39% oppose. As recently as five years ago, more opposed (48%) same-sex marriage than supported it (42%).This is the highest level of support measured for same-sex marriage in nearly 20 years of Pew Research Center polling of the issue. Yet even as support for same-sex marriage has increased among nearly all segments in the public, some groups remain broadly opposed to gay marriage.The Pew Research Center survey, conducted May 12-18 among 2,002 adults, finds that partisans are as divided on this issue as ever: Today, 65% of Democrats and an identical percentage of independents favor gay marriage; only about one third (34%) of Republicans do so. Growing shares of all three groups support same-sex-marriage, yet the differences between Democrats and Republicans are as wide today as they were a decade ago

Speaking rate and articulation rate of native speakers of Irish English

Previous studies have shown apparent difference in speaking rate and/or articulation rate between different dialects of English. In addition, native speakers of Irish English are perceived to be speaking very fast; however, there is very little information in the current literature regarding speech rate of speakers of this variety of English. Establishing regional norms might be needed for various reasons, such as speech intervention, if speakers of Irish English do have a higher speaking and articulation rates than individuals who speaks other English dialects. This study measured the speaking rate and articulation rate of 22 men and 22 women who were native speakers of Irish English. The study compared the speech rates between the male and female speakers, and across different speech tasks â first and second reading the Rainbow Passage and spontaneous speech elicited in a conversation. Overall, the male speakers seemed to speak faster than the females, although significant difference was found only in the articulation rate for the second reading of the passage. The speakers showed significantly higher speaking rate during passage reading than in conversation but the difference in articulation rate between the two tasks was not significant. Finally, the Irish English speakers in this study appeared to have relatively higher speech rates than most of the English dialects reported in previous studies

Teenage motherhood: where you live is also important. A prospective cohort study of 14,000 women

The United Kingdom has among the highest rates of teenage motherhood (TM) in Western Europe. The relationship to individual social and material disadvantage is well established but the influence of area of residence is unclear. We tested for additional TM risks in deprived areas or in cities. The Northern Ireland Longitudinal Study was used to identify 14,055 nulliparous females (15-18). TM risk was measured using multilevel logistic regression, adjusting for health status, religion, family structure, socio-economic status, rurality and employment-based area deprivation. Most variation in TM was driven by individual, household and socioeconomic factors with the greatest proportion of mothers in low value or social rented accommodation. Living in an area with fewer employment opportunities was associated with elevated TM risk (most vs. least deprived, ORadj = 1.98 [1.49, 2.63]), as was urban dwelling (urban vs. intermediate, ORadj = 1.42 [1.13, 1.78]). We conclude that area of residence is a significant independent risk factor for TM. Interventions should be targeted towards the most deprived and urban areas and to those in the lowest value housing

A novel live cell assay to measure diacylglycerol lipase α activity

Diacylglycerol lipase α (DAGLα) hydrolyses DAG to generate the principal endocannabinoid (eCB) 2-arachidonoylglycerol (2-AG) in the central nervous system. DAGLα dependent cannabinoid (CB) signalling has been implicated in numerous processes including axonal growth and guidance, adult neurogenesis and retrograde signalling at the synapse. Recent studies have implicated DAGLα as an emerging drug target for several conditions including pain and obesity. Activity assays are critical to the drug discovery process; however, measurement of diacylglycerol lipase (DAGL) activity using its native substrate generally involves low-throughput MS techniques. Some relatively high-throughput membrane based assays utilizing surrogate substrates have been reported, but these do not take into account the rate-limiting effects often associated with the ability of a drug to cross the cell membrane. In the present study, we report the development of a live cell assay to measure DAGLα activity. Two previously reported DAGLα surrogate substrates, p-nitrophenyl butyrate (PNPB) and 6,8-difluoro-4-methylumbelliferyl octanoate (DiFMUO), were evaluated for their ability to detect DAGLα activity in live cell assays using a human cell line stably expressing the human DAGLα transgene. Following optimization, the small molecule chromogenic substrate PNPB proved to be superior by providing lower background activity along with a larger signal window between transfected and parental cells when compared with the fluorogenic substrate DiFMUO. The assay was further validated using established DAGL inhibitors. In summary, the live cell DAGLα assay reported here offers an economical and convenient format to screen for novel inhibitors as part of drug discovery programmes and compliments previously reported high-throughput membrane based DAGL assays

Phenotypic Plasticity in Uveal Melanoma Is Not Restricted to a Tumor Subpopulation and Is Unrelated to Cancer Stem Cell Characteristics

Purpose: Uveal melanoma (UM) is the most common primary intraocular malignancy in adults and approximately half of those diagnosed will die of metastasis. This study investigates whether UM progression is driven by a subpopulation of stem-like cells, termed “cancer stem cells” (CSCs). Methods: Expression of postulated stem cell markers aldehyde dehydrogenase (ALDH), CD44, and CD133 was analyzed in UM cell lines and primary UM short-term cultures (STCs) established from tumor samples. Additionally, the notion of a “cellular hierarchy” within UM was investigated. Finally, the phenomenon of phenotypic plasticity in response to environmental factors was explored. Results: We demonstrate that expression of ALDH, CD44, and CD133 does not select for a subpopulation of stem-like cells in either UM cell lines or UM STCs. Furthermore, there is an absence of a cellular hierarchy in cell lines and all cells in culture are able to drive tumor progression. Last, we show that established UM cell lines and UM STCs are plastic in nature and switch their phenotype in response to environmental stimuli. Conclusions: We hypothesize that this capacity to undergo phenotypic plasticity may be a consequence of neural crest lineage and renders the exploration of the CSC hypothesis extremely challenging in UM

Patient-reported barriers to adherence to antiretroviral therapy : a systematic review and meta-analysis

Maintaining high levels of adherence to antiretroviral therapy (ART) is a challenge across settings and populations. Understanding the relative importance of different barriers to adherence will help inform the targeting of different interventions and future research priorities.; We searched MEDLINE via PubMed, Embase, Web of Science, and PsychINFO from 01 January 1997 to 31 March 2016 for studies reporting barriers to adherence to ART. We calculated pooled proportions of reported barriers to adherence per age group (adults, adolescents, and children). We included data from 125 studies that provided information about adherence barriers for 17,061 adults, 1,099 children, and 856 adolescents. We assessed differences according to geographical location and level of economic development. The most frequently reported individual barriers included forgetting (adults 41.4%, 95% CI 37.3%-45.4%; adolescents 63.1%, 95% CI 46.3%-80.0%; children/caregivers 29.2%, 95% CI 20.1%-38.4%), being away from home (adults 30.4%, 95% CI 25.5%-35.2%; adolescents 40.7%, 95% CI 25.7%-55.6%; children/caregivers 18.5%, 95% CI 10.3%-26.8%), and a change to daily routine (adults 28.0%, 95% CI 20.9%-35.0%; adolescents 32.4%, 95% CI 0%-75.0%; children/caregivers 26.3%, 95% CI 15.3%-37.4%). Depression was reported as a barrier to adherence by more than 15% of patients across all age categories (adults 15.5%, 95% CI 12.8%-18.3%; adolescents 25.7%, 95% CI 17.7%-33.6%; children 15.1%, 95% CI 3.9%-26.3%), while alcohol/substance misuse was commonly reported by adults (12.9%, 95% CI 9.7%-16.1%) and adolescents (28.8%, 95% CI 11.8%-45.8%). Secrecy/stigma was a commonly cited barrier to adherence, reported by more than 10% of adults and children across all regions (adults 13.6%, 95% CI 11.9%-15.3%; children/caregivers 22.3%, 95% CI 10.2%-34.5%). Among adults, feeling sick (15.9%, 95% CI 13.0%-18.8%) was a more commonly cited barrier to adherence than feeling well (9.3%, 95% CI 7.2%-11.4%). Health service-related barriers, including distance to clinic (adults 17.5%, 95% CI 13.0%-21.9%) and stock outs (adults 16.1%, 95% CI 11.7%-20.4%), were also frequently reported. Limitations of this review relate to the fact that included studies differed in approaches to assessing adherence barriers and included variable durations of follow up. Studies that report self-reported adherence will likely underestimate the frequency of non-adherence. For children, barriers were mainly reported by caregivers, which may not correspond to the most important barriers faced by children.; Patients on ART face multiple barriers to adherence, and no single intervention will be sufficient to ensure that high levels of adherence to treatment and virological suppression are sustained. For maximum efficacy, health providers should consider a more triaged approach that first identifies patients at risk of poor adherence and then seeks to establish the support that is needed to overcome the most important barriers to adherence

A Deep Dive Into Party Affiliation: Sharp Differences by Race, Gender, Generation, Education

Democrats hold advantages in party identification among blacks, Asians, Hispanics, well-educated adults and Millennials. Republicans have leads among whites -- particularly white men, those with less education and evangelical Protestants -- as well as members of the Silent Generation.A new analysis of long-term trends in party affiliation among the public provides a detailed portrait of where the parties stand among various groups in the population. It draws on more than 25,000 interviews conducted by the Pew Research Center in 2014, which allows examination of partisan affiliation across even relatively small racial, ethnic, educational and income subgroups

Choice of Antiretroviral Drugs for Postexposure Prophylaxis for Adults and Adolescents: A Systematic Review

Background. The choice of preferred regimens for human immunodeficiency virus postexposure prophylaxis (PEP) has evolved over the last 2 decades as more data have become available regarding the safety and tolerability of newer antiretroviral drugs. We undertook a systematic review to assess the safety and efficacy of antiretroviral options for PEP to inform the World Health Organization guideline revision process. Methods. Four databases were searched up to 1 June 2014 for studies reporting outcomes associated with specific PEP regimens. Data on PEP completion and discontinuation due to adverse events was extracted and pooled estimates were obtained using random-effects meta-analyses. Results. Fifteen studies (1830 PEP initiations) provided evaluable information on 2-drug regimens (zidovudine [ZDV]- or tenofovir [TDF]-based regimens), and 10 studies (1755 initiations) provided evaluable information on the third drug, which was usually a protease inhibitor. The overall quality of the evidence was rated as very low. For the 2-drug regimen, PEP completion rates were 78.4% (95% confidence interval [CI], 66.1%-90.7%) for people receiving a TDF-based regimen and 58.8% (95% CI, 47.2%-70.4%) for a ZDV-based regimen; the rate of PEP discontinuation due to an adverse event was lower among people taking TDF-based PEP (0.3%; 95% CI, 0%-1.1%) vs a ZDV-based regimen (3.2%; 95% CI, 1.5%-4.9%). For the 3-drug comparison, PEP completion rates were highest for the TDF-based regimens (TDF+emtricitabine [FTC]+lopinavir/ritonavir [LPV/r], 71.1%; 95% CI, 43.6%-98.6%; TDF+FTC+raltegravir [RAL], 74.7%; 95% CI, 41.4%-100%; TDF+FTC+ boosted darunavir [DRV/r], 93.9%; 95% CI, 90.2%-97.7%) and lowest for ZDV+ lamivudine [3TC]+LPV/r (59.1%; 95% CI, 36.2%-82.0%). Discontinuations due to adverse drug reactions were lowest for TDF+FTC+RAL (1.9%; 95% CI, 0%-3.8%) and highest for ZDV+3TC+boosted atazanavir (21.2%; 95% CI, 13.5%-30.0%). Conclusions. The findings of this review provide evidence supporting the use of coformulated TDF and 3TC/FTC as preferred backbone drugs for PEP. Choice of third drug will depend on setting; for resource-limited settings, LPV/r is a reasonable choice, pending the improved availability of better-tolerated drugs with less potential for drug-drug interaction

PHLC Environmental Education Improvement Project

Environmental Engagement in the Community projects, fall 2021 A poster titled PHLC Environmental Education Improvement Project for client Prairie Hill Learning Center (Hunter Armstrong)

Clinicopathological and prognostic significance of RECQL5 helicase expression in breast cancers

RECQL5 is a member of the RecQ family of DNA helicases and has key roles in homologous recombination, base excision repair, replication and transcription. The clinicopathological significance of RECQL5 expression in breast cancer is unknown. In the current study we have evaluated RECQL5 mRNA expression in 1977 breast cancers, and RECQL5 protein level in 1902 breast cancers [Nottingham Tenovus series (n=1650) and ER- cohort (n=252)]. Expression levels were correlated to aggressive phenotypes and survival outcomes. High RECQL5 mRNA expression was significantly associated with high histological grade (p=0.007), HER2 overexpression (p=0.032), ER+/HER2-/high proliferation genefu subtype, integrative molecular clusters (intClust 1and 9) and poor breast cancer specific survival (BCSS) (ps<0.0001). In sub-group analysis, high RECQL5 mRNA level remains significantly associated with poor BCSS in ER+ cohort (p<0.0001) but not in ER- cohort (p=0.116). At the protein level, in tumours with low RAD51, high RECQL5 level was significantly associated with high histological grade (p<0.0001), higher mitotic index (p=0.008), de-differentiation (p=0.025), pleomorphism (p=0.027) and poor BCSS (P=0.003). In sub-group analysis, high RECQL5/low RAD51 remains significantly associated with poor BCSS in ER+ cohort (p=0.010), but not in ER- cohort (p=0.628). In multivariate analysis, high RECQL5 mRNA and high RECQL5/low RAD51 nuclear protein co-expression independently influenced BCSS (p=0.022) in whole cohort and in the ER+ sub-group. Pre-clinically, we show that exogenous expression of RECQL5 in MCF10A cells can drive proliferation supporting an oncogenic function for RECQL5 in breast cancer. We conclude that RECQL5 is a promising biomarker in breast cancer