Gas and dust in the star-forming region ρ Oph A ∗, ∗∗, ∗∗∗: The dust opacity exponent β and the gas-to-dust mass ratio g2d

© ESO, 2015. Aims. We aim at determining the spatial distribution of the gas and dust in star-forming regions and address their relative abundances in quantitative terms. We also examine the dust opacity exponent β for spatial and/or temporal variations. Methods. Using mapping observations of the very dense ρ Oph A core, we examined standard 1D and non-standard 3D methods to analyse data of far-infrared and submillimetre (submm) continuum radiation. The resulting dust surface density distribution can be compared to that of the gas. The latter was derived from the analysis of accompanying molecular line emission, observed with Herschel from space and with APEX from the ground. As a gas tracer we used N<inf>2</inf>H⁺, which is believed to be much less sensitive to freeze-out than CO and its isotopologues. Radiative transfer modelling of the N<inf>2</inf>H⁺ (J = 3-2) and (J = 6-5) lines with their hyperfine structure explicitly taken into account provides solutions for the spatial distribution of the column density N(H<inf>2</inf>), hence the surface density distribution of the gas. Results. The gas-to-dust mass ratio is varying across the map, with very low values in the central regions around the core SM 1. The global average, = 88, is not far from the canonical value of 100, however. In ρ Oph A, the exponent β of the power-law description for the dust opacity exhibits a clear dependence on time, with high values of 2 for the envelope-dominated emission in starless Class -1 sources to low values close to 0 for the disk-dominated emission in Class III objects. β assumes intermediate values for evolutionary classes in between. Conclusions. Since β is primarily controlled by grain size, grain growth mostly occurs in circumstellar disks. The spatial segregation of gas and dust, seen in projection toward the core centre, probably implies that, like C¹⁸O, also N<inf>2</inf>H⁺ is frozen onto the grains

A kinesin-based approach for inducing chromosome-specific mis-segregation in human cells

Various cancer types exhibit characteristic and recurrent aneuploidy patterns. The origins of these cancer type-specific karyotypes are still unknown, partly because introducing or eliminating specific chromosomes in human cells still poses a challenge. Here, we describe a novel strategy to induce mis-segregation of specific chromosomes in different human cell types. We employed Tet repressor or nuclease-dead Cas9 to link a microtubule minus-end-directed kinesin (Kinesin14VIb) from Physcomitrella patens to integrated Tet operon repeats and chromosome-specific endogenous repeats, respectively. By live- and fixed-cell imaging, we observed poleward movement of the targeted loci during (pro)metaphase. Kinesin14VIb-mediated pulling forces on the targeted chromosome were counteracted by forces from kinetochore-attached microtubules. This tug-of-war resulted in chromosome-specific segregation errors during anaphase and revealed that spindle forces can heavily stretch chromosomal arms. By single-cell whole-genome sequencing, we established that kinesin-induced targeted mis-segregations predominantly result in chromosomal arm aneuploidies after a single cell division. Our kinesin-based strategy opens the possibility to investigate the immediate cellular responses to specific aneuploidies in different cell types; an important step toward understanding how tissue-specific aneuploidy patterns evolve.</p

A kinesin-based approach for inducing chromosome-specific mis-segregation in human cells

Various cancer types exhibit characteristic and recurrent aneuploidy patterns. The origins of these cancer type-specific karyotypes are still unknown, partly because introducing or eliminating specific chromosomes in human cells still poses a challenge. Here, we describe a novel strategy to induce mis-segregation of specific chromosomes in different human cell types. We employed Tet repressor or nuclease-dead Cas9 to link a microtubule minus-end-directed kinesin (Kinesin14VIb) from Physcomitrella patens to integrated Tet operon repeats and chromosome-specific endogenous repeats, respectively. By live- and fixed-cell imaging, we observed poleward movement of the targeted loci during (pro)metaphase. Kinesin14VIb-mediated pulling forces on the targeted chromosome were counteracted by forces from kinetochore-attached microtubules. This tug-of-war resulted in chromosome-specific segregation errors during anaphase and revealed that spindle forces can heavily stretch chromosomal arms. By single-cell whole-genome sequencing, we established that kinesin-induced targeted mis-segregations predominantly result in chromosomal arm aneuploidies after a single cell division. Our kinesin-based strategy opens the possibility to investigate the immediate cellular responses to specific aneuploidies in different cell types; an important step toward understanding how tissue-specific aneuploidy patterns evolve

Barriers and facilitators to the uptake of tuberculosis diagnostic and treatment services by hard-to-reach populations in countries of low and medium tuberculosis incidence: a systematic review of qualitative literature

Summary Tuberculosis disproportionately affects hard-to-reach populations, such as homeless people, migrants, refugees, prisoners, or drug users. These people often face challenges in accessing quality health care. We did a systematic review of the qualitative literature to identify barriers and facilitators to the uptake of tuberculosis diagnostic and treatment services by people from hard-to-reach populations in all European Union (EU), European Economic Area, EU candidate, and Organisation for Economic Co-operation and Development countries. The 12 studies included in this review mainly focused on migrants. Views on perceived susceptibility to and severity of tuberculosis varied widely and included many misconceptions. Stigma and challenges regarding access to health care were identified as barriers to tuberculosis diagnosis and treatment uptake, whereas support from nurses, family, and friends was a facilitator for treatment adherence. Further studies are required to identify barriers and facilitators to the improved identification and management of tuberculosis in hard-to-reach populations to inform recommendations for more effective tuberculosis control programmes

Effectiveness of interventions for diagnosis and treatment of tuberculosis in hard-to-reach populations in countries of low and medium tuberculosis incidence: a systematic review

Tuberculosis is over-represented in hard-to-reach (underserved) populations in high-income countries of low tuberculosis incidence. The mainstay of tuberculosis care is early detection of active tuberculosis (case finding), contact tracing, and treatment completion. We did a systematic review with a scoping component of relevant studies published between 1990 and 2015 to update and extend previous National Institute for Health and Care Excellence (NICE) reviews on the effectiveness of interventions for identifying and managing tuberculosis in hard-to-reach populations. The analyses showed that tuberculosis screening by (mobile) chest radiography improved screening coverage and tuberculosis identification, reduced diagnostic delay, and was cost-effective among several hard-to-reach populations. Sputum culture for pre-migration screening and active referral to a tuberculosis clinic improved identification. Furthermore, monetary incentives improved tuberculosis identification and management among drug users and homeless people. Enhanced case management, good cooperation between services, and directly observed therapy improved treatment outcome and compliance. Strong conclusions cannot be drawn because of the heterogeneity of evidence with regard to study population, methodology, and quality

Methylation of Migraine-Related Genes in Different Tissues of the Rat

Abstract 17ß-Estradiol, an epigenetic modulator, is involved in the increased prevalence of migraine in women. Together with the prophylactic efficacy of valproate, which influences DNA methylation and histone modification, this points to the involvement of epigenetic mechanisms. Epigenetic studies are often performed on leukocytes, but it is unclear to what extent methylation is similar in other tissues. Therefore, we investigated methylation of migraine-related genes that might be epigenetically regulated (CGRP-ergic pathway, estrogen receptors, endothelial NOS, as well as MTHFR) in different migraine-related tissues and compared this to methylation in rat as well as human leukocytes. Further, we studied whether 17ß-estradiol has a prominent role in methylation of these genes. Female rats (n = 35) were ovariectomized or shamoperated and treated with 17b-estradiol or placebo. DNA was isolated and methylation was assessed through bisulphite treatment and mass spectrometry. Human methylation data were obtained using the Illumina 450k genome-wide methylation array in 395 female subjects from a population-based cohort study. We showed that methylation of the Crcp, Calcrl, Esr1 and Nos3 genes is tissue-specific and that methylation in leukocytes was not correlated to that in other tissues. Interestingly, the interindividual variation in methylation differed considerably between genes and tissues. Furthermore we showed that methylation in human leukocytes was similar to that in rat leukocytes in our genes of interest, suggesting that rat may be a good model to study human DNA methylation in tissues that are difficult to obtain. In none of the genes a significant effect of estradiol treatment was observed

Quantifying resilience of humans and other animals

All life requires the capacity to recover from challenges that are as inevitable as they are unpredictable. Understanding this resilience is essential for managing the health of humans and their livestock. It has long been difficult to quantify resilience directly, forcing practitioners to rely on indirect static indicators of health. However, measurements from wearable electronics and other sources now allow us to analyze the dynamics of physiology and behavior with unsurpassed resolution. The resulting flood of data coincides with the emergence of novel analytical tools for estimating resilience from the pattern of micro-recoveries observed in natural time series. Such dynamic indicators of resilience (DIORs) may be used to monitor the risk of systemic failure across systems ranging from organs to entire organisms. These tools invite a fundamental rethink of our approach to the adaptive management of health and resilience

Defaunation changes leaf trait composition of recruit communities in tropical forests in French Guiana

Hunting impacts tropical vertebrate populations, causing declines of species that function as seed dispersers and predators, or that browse seedlings and saplings. Whether and how the resulting reductions in seed dispersal, seed predation, and browsing translate to changes in the tree composition is poorly understood. Here, we assess the effect of defaunation on the functional composition of communities of tree recruits in tropical rainforests in French Guiana. We selected eight sites along a gradient of defaunation, caused by differences in hunting pressure, in otherwise intact old-growth forests in French Guiana. We measured shifts in functional composition by comparing leaf and fruit traits and wood density between tree recruits (up to 5 cm diameter at breast height) and adults, and tested whether and how these compositional shifts related to defaunation. We found a positive relationship with defaunation for shifts in specific leaf area, a negative relationship for shifts of leaf toughness and wood density, and a weak relationship for shifts in fruit traits. Our results suggest that the loss of vertebrates affects ecological processes such as seed dispersal and browsing, of which browsing remains understudied. Even though these changes sometimes seem minor, together they result in major shifts in forest composition. These changes have long-term ramifications that may alter forest dynamics for generations

Cost impact of procalcitonin-guided decision making on duration of antibiotic therapy for suspected early-onset sepsis in neonates

Abstract Backgrounds The large, international, randomized controlled NeoPInS trial showed that procalcitonin (PCT)-guided decision making was superior to standard care in reducing the duration of antibiotic therapy and hospitalization in neonates suspected of early-onset sepsis (EOS), without increased adverse events. This study aimed to perform a cost-minimization study of the NeoPInS trial, comparing health care costs of standard care and PCT-guided decision making based on the NeoPInS algorithm, and to analyze subgroups based on country, risk category and gestational age. Methods Data from the NeoPInS trial in neonates born after 34 weeks of gestational age with suspected EOS in the first 72 h of life requiring antibiotic therapy were used. We performed a cost-minimization study of health care costs, comparing standard care to PCT-guided decision making. Results In total, 1489 neonates were included in the study, of which 754 were treated according to PCT-guided decision making and 735 received standard care. Mean health care costs of PCT-guided decision making were not significantly different from costs of standard care (€3649 vs. €3616). Considering subgroups, we found a significant reduction in health care costs of PCT-guided decision making for risk category ‘infection unlikely’ and for gestational age ≥ 37 weeks in the Netherlands, Switzerland and the Czech Republic, and for gestational age < 37 weeks in the Czech Republic. Conclusions Health care costs of PCT-guided decision making of term and late-preterm neonates with suspected EOS are not significantly different from costs of standard care. Significant cost reduction was found for risk category ‘infection unlikely,’ and is affected by both the price of PCT-testing and (prolonged) hospitalization due to SAEs