726 research outputs found

    Daraprim Specialty Drug Pricing: A Case Study

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    Psychological distress among Plains Indian mothers with children referred to screening for Fetal Alcohol Spectrum Disorders

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    <p>Abstract</p> <p>Background</p> <p>Psychological distress (PD) includes symptoms of depression and anxiety and is associated with considerable emotional suffering, social dysfunction and, often, with problematic alcohol use. The rate of current PD among American Indian women is approximately 2.5 times higher than that of U.S. women in general. Our study aims to fill the current knowledge gap about the prevalence and characteristics of PD and its association with self-reported current drinking problems among American Indian mothers whose children were referred to screening for fetal alcohol spectrum disorders (FASD).</p> <p>Methods</p> <p>Secondary analysis of cross-sectional data was conducted from maternal interviews of referred American Indian mothers (n = 152) and a comparison group of mothers (n = 33) from the same Plains culture tribes who participated in an NIAAA-funded epidemiology study of FASD. Referred women were from one of six Plains Indian reservation communities and one urban area who bore children suspected of having an FASD. A 6-item PD scale (PD-6, Cronbach's alpha = .86) was constructed with a summed score range of 0-12 and a cut-point of 7 indicating serious PD. Multiple statistical tests were used to examine the characteristics of PD and its association with self-reported current drinking problems.</p> <p>Results</p> <p>Referred and comparison mothers had an average age of 31.3 years but differed (respectively) on: education (<high school: 47.4%, 9.1%), PD-6 mean scores (3.57, 1.48), current prevalence of serious PD (19.1%, 0.0%), and a current drinking problem (31.6%, 12.1%). Among referred mothers, those with a current drinking problem had a significantly higher mean PD-6 score. Having PD, serious PD, and 2 specific scale items significantly increased the odds that a referred mother would have a current drinking problem.</p> <p>Conclusions</p> <p>Psychological distress among referred mothers is significantly associated with having a self-reported drinking problem. FASD prevention requires multi-level prevention efforts that provide real opportunities for educational attainment and screening and monitoring of PD and alcohol use during the childbearing years. Mixed methods studies are needed to illuminate the social and cultural determinants at the base of the experience of PD and to identify the strengths and protective factors of unaffected peers who reside within the same communities.</p

    Overview of MPLNET Version 3 Cloud Detection

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    The National Aeronautics and Space Administration Micro Pulse Lidar Network, version 3, cloud detection algorithm is described and differences relative to the previous version are highlighted. Clouds are identified from normalized level 1 signal profiles using two complementary methods. The first method considers vertical signal derivatives for detecting low-level clouds. The second method, which detects high-level clouds like cirrus, is based on signal uncertainties necessitated by the relatively low signal-to-noise ratio exhibited in the upper troposphere by eye-safe network instruments, especially during daytime. Furthermore, a multitemporal averaging scheme is used to improve cloud detection under conditions of a weak signal-to-noise ratio. Diurnal and seasonal cycles of cloud occurrence frequency based on one year of measurements at the Goddard Space Flight Center (Greenbelt, Maryland) site are compared for the new and previous versions. The largest differences, and perceived improvement, in detection occurs for high clouds (above 5 km, above MSL), which increase in occurrence by over 5%. There is also an increase in the detection of multilayered cloud profiles from 9% to 19%. Macrophysical properties and estimates of cloud optical depth are presented for a transparent cirrus dataset. However, the limit to which the cirrus cloud optical depth could be reliably estimated occurs between 0.5 and 0.8. A comparison using collocated CALIPSO measurements at the Goddard Space Flight Center and Singapore Micro Pulse Lidar Network (MPLNET) sites indicates improvements in cloud occurrence frequencies and layer heights

    Human CCAAT-binding proteins have heterologous subunits

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    We have characterized three distinct proteins present in HeLa cell extracts that specifically recognize different subsets of transcriptional elements containing the pentanucleotide sequence CCAAT. One of these CCAAT-binding proteins, CP1, binds with high affinity to CCAAT elements present in the human a-globin promoter and the adenovirus major late promoter (MLP). A second protein, CP2, binds with high affinity to a CCAAT element present in the rat γ-fibrinogen promoter. Finally, the third CCAAT-binding protein is nuclear factor I (NF-I), a cellular DNA-binding protein that binds to the adenovirus origin of replication and is required for the initiation of adenoviral replication. CPi, CP2, and NF-I are distinct activities in that each binds to its own recognition site with an affinity that is at least three orders of magnitude higher than that with which it binds to the recognition sites of the other two proteins. Surprisingly, CP1, CP2, and NF-I each appear to recognize their binding site with highest affinity as a multisubunit complex composed of heterologous subunits. In the case of CP1, two different types of subunits form a stable complex in the absence of a DNA-binding site. Moreover, both subunits are present in the CP1-DNA complex. We thus propose the existence of a family of related multisubunit CCAAT-binding proteins that are composed of heterologous subunits

    Associations between comorbid anxiety and sleep disturbance in people with bipolar disorder: Findings from actigraphy and subjective sleep measures

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    Background Studies show that comorbid anxiety disorders are common in people with bipolar disorder. However, little is known about whether this anxiety is associated with sleep disturbance. We investigated, in individuals with bipolar disorder, whether comorbid anxiety disorder is associated with sleep disturbance. Methods Participants were 101 (64% female) currently euthymic individuals with a history of bipolar disorder. Sleep disturbances were assessed using self-report measures of sleep quality (Pittsburgh Sleep Quality Index, PSQI) and six weeks of sleep monitoring using actigraphy. Bipolar disorder and comorbid anxiety diagnoses were assessed using the Mini International Neuropsychiatric Interview. Multiple regression analyses examined associations between comorbid anxiety and sleep disturbance, whilst controlling for confounding covariates known to impact on sleep. Results A comorbid anxiety disorder was associated with increased sleep disturbance as measured using the PSQI global score (B = 3.58, 95% CI 1.85–5.32, P < 0.001) but was not associated with sleep metrics (total sleep time, sleep onset latency, sleep efficiency, and wake after sleep onset) derived using actigraphy. Limitations Objective measures of sleep were limited to actigraphy, therefore we were not able to examine differences in sleep neurophysiology. Conclusions Clinicians should be aware that comorbid anxiety may increase the risk of experiencing subjective sleep disturbance in people with bipolar disorder. Research should assess for evidence of comorbid anxiety when examining associations between sleep and bipolar disorder. Future research should explore the mechanisms by which comorbid anxiety may contribute to subjective sleep disturbances in bipolar disorder using neurophysiological measures of sleep (i.e., polysomnography)

    Manacled to Identity: Cosmopolitanism, Class, and ‘The Culture Concept’ in Stephen Crane

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    This article begins with a close reading of Stephen Crane’s short story ‘Manacled’ from 1900, which situates this rarely considered short work within the context of contemporary debates about realism. I then proceed to argue that many of the debates raised by the tale have an afterlife in our own era of American literary studies, which has frequently focused on questions of ‘identity’ and ‘culture’ in its reading of realism and naturalism to the exclusion of the importance of cosmopolitan discourses of diffusion and exchange across national borders. I then offer a brief reading of Crane’s novel George’s Mother, which follows Walter Benn Michaels in suggesting that the recent critical attention paid to particularities of cultural difference in American studies have come to conflate ideas of class and social position with ideas of culture in ways that have ultimately obscured the presence of genuine historical inequalities in US society. In order to challenge this critical commonplace, I situate Crane’s work within a history of transatlantic cosmopolitanism associated with the ideas of Franz Boas and Matthew Arnold to demonstrate the ways in which Crane’s narratives sought out an experience of the universal within their treatments of the particular

    Reduction of \u3ci\u3eStabilin-2\u3c/i\u3e Contributes to a Protection Against Atherosclerosis

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    We have previously identified a novel atherosclerosis quantitative trait locus (QTL), Arch atherosclerosis 5 (Aath5), on mouse chromosome 10 by three-way QTL analyses between Apoe−/− mice on a DBA/2J, 129S6 and C57BL/6J background. The DBA/2J haplotype at the Aath5 locus was associated with smaller plaque size. One of the candidate genes underlying Aath5 was Stabilin-2 (Stab2), which encodes a clearance receptor for hyaluronan (HA) predominantly expressed in liver sinusoidal endothelial cells (LSECs). However, the role of Stab2 in atherosclerosis is unknown. A congenic line of Apoe−/− mice carrying Aath5 covering the Stab2DBA allele on a background of 129S6 confirmed the small reductions of atherosclerotic plaque development. To further determine whether Stab2 is an underlying gene for Aath5, we generated Stab2−/−Apoe−/− mice on a C57BL/6J background. When fed with a Western diet for 8 weeks, Stab2−/−Apoe−/− males developed approximately 30% smaller plaques than Stab2+/+Apoe−/− mice. HA was accumulated in circulation but not in major organs in the Stab2 deficient mice. STAB2-binding molecules that are involved in atherosclerosis, including acLDL, apoptotic cells, heparin and vWF were not likely the direct cause of the protection in the Stab2−/−Apoe−/− males. These data indicate that reduction of Stab2 is protective against atherosclerotic plaque development, and that Stab2 is a contributing gene underlying Aath5, although its effect is small. To test whether non-synonymous amino acid changes unique to DBA/2J affect the function of STAB2 protein, we made HEK293 cell lines expressing STAB2129 or STAB2DBA proteins, as well as STAB2129 proteins carrying each of five DBA-unique replacements that have been predicted to be deleterious. These mutant cells were capable of internalizing 125I -HA and DiI-acLDL similarly to the control cells. These results indicate that the amino acid changes unique to DBA/2J are not affecting the function of STAB2 protein, and support our previous observation that the reduced transcription of Stab2 in the liver sinusoid as a consequence of the insertion of a viral-derived sequence, intracisternal A particle, is the primary contributor to the athero-protection conferred by the DBA/2J allele

    Reduction of Stabilin-2 Contributes to a Protection Against AtherosclerosisStabilin

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    We have previously identified a novel atherosclerosis quantitative trait locus (QTL), Arch atherosclerosis 5 (Aath5), on mouse chromosome 10 by three-way QTL analyses between Apoe−/− mice on a DBA/2J, 129S6 and C57BL/6J background. The DBA/2J haplotype at the Aath5 locus was associated with smaller plaque size. One of the candidate genes underlying Aath5 was Stabilin-2 (Stab2), which encodes a clearance receptor for hyaluronan (HA) predominantly expressed in liver sinusoidal endothelial cells (LSECs). However, the role of Stab2 in atherosclerosis is unknown. A congenic line of Apoe−/− mice carrying Aath5 covering the Stab2DBA allele on a background of 129S6 confirmed the small reductions of atherosclerotic plaque development. To further determine whether Stab2 is an underlying gene for Aath5, we generated Stab2−/−Apoe−/− mice on a C57BL/6J background. When fed with a Western diet for 8 weeks, Stab2−/−Apoe−/− males developed approximately 30% smaller plaques than Stab2+/+Apoe−/− mice. HA was accumulated in circulation but not in major organs in the Stab2 deficient mice. STAB2-binding molecules that are involved in atherosclerosis, including acLDL, apoptotic cells, heparin and vWF were not likely the direct cause of the protection in the Stab2−/−Apoe−/− males. These data indicate that reduction of Stab2 is protective against atherosclerotic plaque development, and that Stab2 is a contributing gene underlying Aath5, although its effect is small. To test whether non-synonymous amino acid changes unique to DBA/2J affect the function of STAB2 protein, we made HEK293 cell lines expressing STAB2129 or STAB2DBA proteins, as well as STAB2129 proteins carrying each of five DBA-unique replacements that have been predicted to be deleterious. These mutant cells were capable of internalizing 125I -HA and DiI-acLDL similarly to the control cells. These results indicate that the amino acid changes unique to DBA/2J are not affecting the function of STAB2 protein, and support our previous observation that the reduced transcription of Stab2 in the liver sinusoid as a consequence of the insertion of a viral-derived sequence, intracisternal A particle, is the primary contributor to the athero-protection conferred by the DBA/2J allele

    Does implementation matter if comprehension is lacking? A qualitative investigation into perceptions of advance care planning in people with cancer

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    Purpose: While advance care planning holds promise, uptake is variable and it is unclear how well people engage with or comprehend advance care planning. The objective of this study was to explore how people with cancer comprehended Advance Care Plans and examine how accurately advance care planning documentation represented patient wishes. Methods: This study used a qualitative descriptive design. Data collection comprised interviews and an examination of participants’ existing advance care planning documentation. Participants included those who had any diagnosis of cancer with an advance care plan recorded: Refusal of Treatment Certificate; Statement of Choices; and/or Enduring Power of Attorney (Medical Treatment) at one cancer treatment centre. Results: Fourteen participants were involved in the study. Twelve participants were female (86%). The mean age was 77 (range: 61-91) and participants had completed their advance care planning documentation between 8 and 72 weeks prior to the interview (mean 33 weeks). Three themes were evident from the data: Incomplete advance care planning understanding and confidence; Limited congruence for attitude and documentation; Advance care planning can enable peace of mind. Complete advance care planning understanding was unusual; most participants demonstrated partial comprehension of their own advance care plan, and some indicated very limited understanding. Participants’ attitudes and their written document congruence was limited, but advance care planning was seen as helpful. Conclusions: This study highlighted advance care planning was not a completely accurate representation of patient wishes. There is opportunity to improve how patients comprehend their own advance care planning documentation

    Establishment of vaginal microbiota composition in early pregnancy and its association with subsequent preterm prelabor rupture of the fetal membranes

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    © 2019 The Authors Vaginal bacterial community composition influences pregnancy outcome. Preterm prelabor rupture of the fetal membranes (PPROM), which precedes 30% of all spontaneous preterm births, is associated with high vaginal bacterial diversity prior to rupture. The point at which vaginal bacterial diversity is established before PPROM is unknown. In this study, we use metataxonomics to longitudinally characterize the vaginal bacterial composition from as early as 6 weeks of gestation in women at high (n = 38) and low (n = 22) risk of preterm birth who subsequently experience PPROM and in women delivering at term without complications (n = 36). Reduced Lactobacillus spp. abundance and high diversity was observed prior to PPROM in 20% and 26% of women at low and high risk of preterm births respectively, but in only 3% of women who delivered at term. PPROM was associated with instability of bacterial community structure during pregnancy and a shift toward higher diversity predominately occurring during the second trimester. This was characterized by increased relative abundance of potentially pathogenic species including Prevotella, Peptoniphilus, Streptococcus, and Dialister. This study identifies reduced Lactobacillus spp. abundance and increasing vaginal bacterial diversity as an early risk factor for PPROM and highlights the need for interventional studies designed to assess the impact of modifying vaginal bacterial composition for the prevention of preterm birth
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