Influence of nucleosome structure on the three-dimensional folding of idealized minichromosomes

AbstractBackground: The closed circular, multinucleosome-bound DNA comprising a minichromosome provides one of the best known examples of chromatin organization beyond the wrapping of the double helix around the core of histone proteins. This higher level of chain folding is governed by the topology of the constituent nucleosomes and the spatial disposition of the intervening protein-free DNA linkers.Results: By simplifying the protein–DNA assembly to an alternating sequence of virtual bonds, the organization of a string of nucleosomes on the minichromosome can be treated by analogy to conventional chemical depictions of macromolecular folding in terms of the bond lengths, valence angles, and torsions of the chain. If the nucleosomes are evenly spaced and the linkers are sufficiently short, regular minichromosome structures can be identified from analytical expressions that relate the lengths and angles formed by the virtual bonds spanning the nucleosome-linker repeating units to the pitch and radius of the organized quaternary structures that they produce.Conclusions: The resulting models with 4–24 bound nucleosomes illustrate how a minichromosome can adopt the low-writhe folding motifs deduced from biochemical studies, and account for published images of the 30 nm chromatin fiber and the simian virus 40 (SV40) nucleohistone core. The marked sensitivity of global folding to the degree of protein–DNA interactions and the assumed nucleosomal shape suggest potential mechanisms for chromosome rearrangements upon histone modification

A framework for conceptualizing how narratives from health-care consumers might improve or impede the use of information about provider quality

Consumers choosing a health-care provider have access to diverse information including narratives by patients about their prior experiences. However, little research has examined how narratives might improve or impede the use of information about the quality of providers’ performance. This paper describes a conceptual framework for examining mechanisms by which narrative information might influence consumer judgments and decisions about providers. We conducted a conceptual review of risk communication and behavioral decision research. We synthesized the literature to form the foundation of a conceptual framework for assessing how narrative information about provider quality impacts consumer decisions about providers. We identified four key characteristics of narratives (convey emotion; explain logic; provide relational information; and capture naturalistic experience) that may address four consumer needs (avoid surprise and regret; recognize dominant options; motivate to act or not act; and make multi-attribute tradeoff decisions). We also identified three main functions of narratives (provide a simple, powerful cue; imbue quality information with meaning; and stimulate cognition and behavior) in four decision contexts (short-term treatments; external disruptions; chronic illness; problematic experiences). A rigorous research program can be derived from the conceptual framework to generate evidence-based recommendations about whether and how patient narratives might encourage: (1) more reasoned decisions; (2) consistency with a patient’s own values/preferences; and (3) engagement with provider quality information. Research results can be used then to develop robust guidance for health communicators reporting diverse and often incommensurate performance metrics

Racial disparities in the SOFA score among patients hospitalized with COVID-19

BACKGROUND: Sequential Organ Failure Assessment (SOFA) score predicts probability of in-hospital mortality. Many crisis standards of care suggest the use of SOFA scores to allocate medical resources during the COVID-19 pandemic. RESEARCH QUESTION: Are SOFA scores elevated among Non-Hispanic Black and Hispanic patients hospitalized with COVID-19, compared to Non-Hispanic White patients? STUDY DESIGN AND METHODS: Retrospective cohort study conducted in Yale New Haven Health System, including 5 hospitals with total of 2681 beds. Study population drawn from consecutive patients aged ≥18 admitted with COVID-19 from March 29th to August 1st, 2020. Patients excluded from the analysis if not their first admission with COVID-19, if they did not have SOFA score recorded within 24 hours of admission, if race and ethnicity data were not Non-Hispanic Black, Non-Hispanic White, or Hispanic, or if they had other missing data. The primary outcome was SOFA score, with peak score within 24 hours of admission dichotomized as \u3c6 or ≥6. RESULTS: Of 2982 patients admitted with COVID-19, 2320 met inclusion criteria and were analyzed, of whom 1058 (45.6%) were Non-Hispanic White, 645 (27.8%) were Hispanic, and 617 (26.6%) were Non-Hispanic Black. Median age was 65.0 and 1226 (52.8%) were female. In univariate logistic screen and in full multivariate model, Non-Hispanic Black patients but not Hispanic patients had greater odds of an elevated SOFA score ≥6 when compared to Non-Hispanic White patients (OR 1.49, 95%CI 1.11-1.99). INTERPRETATION: Given current unequal patterns in social determinants of health, US crisis standards of care utilizing the SOFA score to allocate medical resources would be more likely to deny these resources to Non-Hispanic Black patients

The Lantern Vol. 47, No. 2, May 1981

• Festival • Ode to Old Tom • Living Room • Writing a Poem • Mission Impossible • The Hinge is Oiled • The Potter\u27s Field at Malvern • Points of Time • Attempted Autonomy • My Love • Love, not War • Death Comes Quickly • You Can\u27t Always Get What You Don\u27t Really Want • You See (Johnny\u27s Tale): An Elegy • Sanguine Hopeshttps://digitalcommons.ursinus.edu/lantern/1118/thumbnail.jp

The Lantern Vol. 47, No. 1, December 1980

• Renewal • She Threw Down Her Diamond • Ragnarok • Cinquains • Euphoria • To the Nahua of the Valley of Mexico • Inamorata • Unspoken Passion • Clouds of Circus Cotton Candy Pink • The First Mate Finds a Captain (Almost) • Dance of Defiance • Concert • Blame • I\u27ve Seen That Movie Too • Greystone • The Philosophers of The Tower • Span • Commando • Cheshire • Summertime, Kryptonite and Falstaf(f) • Experience • Fluid Time • The Plight of Fred in Bed • A Way With Men • Courage to Love - (To A.) • Winter Sleep • Berniehttps://digitalcommons.ursinus.edu/lantern/1117/thumbnail.jp

The Lantern Vol. 47, No. 1, December 1980

• Renewal • She Threw Down Her Diamond • Ragnarok • Cinquains • Euphoria • To the Nahua of the Valley of Mexico • Inamorata • Unspoken Passion • Clouds of Circus Cotton Candy Pink • The First Mate Finds a Captain (Almost) • Dance of Defiance • Concert • Blame • I\u27ve Seen That Movie Too • Greystone • The Philosophers of The Tower • Span • Commando • Cheshire • Summertime, Kryptonite and Falstaf(f) • Experience • Fluid Time • The Plight of Fred in Bed • A Way With Men • Courage to Love - (To A.) • Winter Sleep • Berniehttps://digitalcommons.ursinus.edu/lantern/1117/thumbnail.jp

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Building the nation's body:The contested role of abortion and family planning in post-war South Sudan

: This paper offers an ethnographic analysis of public health policies and interventions targeting unwanted pregnancy (family planning and abortion) in contemporary South Sudan as part of wider 'nation-building' after war, understood as a process of collective identity formation which projects a meaningful future by redefining existing institutions and customs as national characteristics. The paper shows how the expansion of post-conflict family planning and abortion policy and services are particularly poignant sites for the enactment of reproductive identity negotiation, policing and conflict. In addition to customary norms, these processes are shaped by two powerful institutions - ethnic movements and global humanitarian actors - who tend to take opposing stances on reproductive health. Drawing on document review, observations of the media and policy environment and interviews conducted with 54 key informants between 2013 and 2015, the paper shows that during the civil war, the Sudan People's Liberation Army and Movement mobilised customary pro-natalist ideals for military gain by entreating women to amplify reproduction to replace those lost to war and rejecting family planning and abortion. International donors and the Ministry of Health have re-conceptualised such services as among other modern developments denied by war. The tensions between these competing discourses have given rise to a range of societal responses, including disagreements that erupt in legal battles, heated debate and even violence towards women and health workers. In United Nations camps established recently as parts of South Sudan have returned to war, social groups exert a form of reproductive surveillance, policing reproductive health practices and contributing to intra-communal violence when clandestine use of contraception or abortion is discovered. In a context where modern contraceptives and abortion services are largely unfamiliar, conflict around South Sudan's nation-building project is partially manifest through tensions and violence in the domain of reproduction.<br/

Altered structural brain asymmetry in autism spectrum disorder in a study of 54 datasets

Altered structural brain asymmetry in autism spectrum disorder (ASD) has been reported. However, findings have been inconsistent, likely due to limited sample sizes. Here we investigated 1,774 individuals with ASD and 1,809 controls, from 54 independent data sets of the ENIGMA consortium. ASD was significantly associated with alterations of cortical thickness asymmetry in mostly medial frontal, orbitofrontal, cingulate and inferior temporal areas, and also with asymmetry of orbitofrontal surface area. These differences generally involved reduced asymmetry in individuals with ASD compared to controls. Furthermore, putamen volume asymmetry was significantly increased in ASD. The largest case-control effect size was Cohen's d = -0.13, for asymmetry of superior frontal cortical thickness. Most effects did not depend on age, sex, IQ, severity or medication use. Altered lateralized neurodevelopment may therefore be a feature of ASD, affecting widespread brain regions with diverse functions. Large-scale analysis was necessary to quantify subtle alterations of brain structural asymmetry in ASD