Challenges of Loss to Follow-up in Tuberculosis Research.

In studies evaluating methods for diagnosing tuberculosis (TB), follow-up to verify the presence or absence of active TB is crucial and high dropout rates may significantly affect the validity of the results. In a study assessing the diagnostic performance of the QuantiFERON®-TB Gold In-Tube test in TB suspect children in Tanzania, factors influencing patient adherence to attend follow-up examinations and reasons for not attending were examined. In 160 children who attended and 102 children who did not attend scheduled 2-month follow-up baseline health characteristics, demographic data and risk factors for not attending follow-up were determined. Qualitative interviews were used to understand patient and caretakers reasons for not returning for scheduled follow-up. Being treated for active tb in the dots program (OR: 4.14; 95% CI:1.99-8.62;p-value<0.001) and receiving money for the bus fare (OR:129; 95% CI 16->100;P-value<0.001) were positive predictors for attending follow-up at 2 months, and 21/85(25%) of children not attending scheduled follow-up had died. Interviews revealed that limited financial resources, i.e. lack of money for transportation and poor communication, were related to non-adherence. Patients lost to follow-up is a potential problem for TB research. Receiving money for transportation to the hospital and communication is crucial for adherence to follow-up conducted at a study facility. Strategies to ensure follow-up should be part of any study protocol

Impacts of multiple pollutants on pollinator activity in road verges

Funder: Cornwall Area of Outstanding Natural Beauty unitTo tackle pollinator declines, there is a major need to increase the quantity of flower‐rich habitats. Road verges offer one such opportunity but are exposed to diverse forms of pollution from roads and road traffic. We carried out a broad initial assessment to establish if and how pollution affects the quality of road verges as pollinator foraging environments. We assessed the spatial distribution of pollution, flowers and pollinators in road verges, then used field experiments to simulate and measure the impacts of four ubiquitous and little studied forms of road pollution (noise, turbulence, dust and metals) on pollinator densities and foraging behaviour. We found that pollinators in road verges were exposed to noise, turbulence, dust and metal pollution, which decreased with distance from the road edge but, with the exception of turbulence, extended more than 8 m into road verges. Pollinator densities were lower closer to the road edge—particularly within first 2 m (55% lower than at 7–9 m)—where pollution is greatest. This was despite a similar density and species richness of flowers. Simulated turbulence deterred pollinators by causing intermittent disturbance (reducing visit duration by up to 54%), and some pollinator taxa preferentially avoided concentrations of metals that were more frequently found in flowers within 2 m of roads (resulting in up to 75% fewer visits), while noise and dust had no apparent effect. Synthesis and applications. Pollinators in road verges are exposed to many forms of pollution, and we found impacts of roadside‐realistic levels of turbulence and metals on pollinator densities and foraging behaviour. Although the findings suggest that road verges are largely suitable for pollinator conservation, management enhancements should prioritise areas more than 2 m from the road edge, and verges along roads with relatively lower traffic densities

Sequence variation in the human transcription factor gene POU5F1

<p>Abstract</p> <p>Background</p> <p>POU5F1 expression is required to maintain stem cell pluripotency and for primordial germ cells to retain proliferative capability in embryonic development. Recent evidence suggests that <it>POU5F1 </it>may also be a testicular germ cell carcinoma (TGCC) oncogene, and <it>POU5F1 </it>variation may influence TGCC risk. As an important first step to a genetic association study, we sought to identify all common sequence variants in an 11.3 kb region containing <it>POU5F1</it>, and to describe the linkage disequilibrium patterns, using DNA from individuals of African-descent (AD) and European-descent (ED).</p> <p>Results</p> <p>A higher number of polymorphisms was observed in the AD (n = 102) versus ED (n = 82) population. Among the 41 observed haplotypes, 21 (51%) and 12 (29%) were unique to the AD and ED populations, respectively, while 8 (20%) were observed in both. The number of tagging polymorphisms necessary to explain at least 80% of common variation (minor allele frequency ≥ 0.10) due to the remaining untyped polymorphisms was 17 for an AD and 10 for an ED population, providing a 4.0- and 7.0-fold gain in genotyping efficiency for characterizing nucleotide variation, respectively.</p> <p>Conclusion</p> <p><it>POU5F1 </it>is highly polymorphic, however a smaller subset of polymorphisms can tag the observed genetic variation with little loss of information.</p

An exploratory study to examine intentions to adopt an evidence-based HIV linkage-to-care intervention among state health department AIDS directors in the United States

<p>Abstract</p> <p>Background</p> <p>Widespread dissemination and implementation of evidence-based human immunodeficiency virus (HIV) linkage-to-care (LTC) interventions is essential for improving HIV-positive patients' health outcomes and reducing transmission to uninfected others. To date, however, little work has focused on identifying factors associated with intentions to adopt LTC interventions among policy makers, including city, state, and territory health department AIDS directors who play a critical role in deciding whether an intervention is endorsed, distributed, and/or funded throughout their region.</p> <p>Methods</p> <p>Between December 2010 and February 2011, we administered an online questionnaire with state, territory, and city health department AIDS directors throughout the United States to identify factors associated with intentions to adopt an LTC intervention. Guided by pertinent theoretical frameworks, including the Diffusion of Innovations and the "push-pull" capacity model, we assessed participants' attitudes towards the intervention, perceived organizational and contextual demand and support for the intervention, likelihood of adoption given endorsement from stakeholder groups (<it>e.g</it>., academic researchers, federal agencies, activist organizations), and likelihood of enabling future dissemination efforts by recommending the intervention to other health departments and community-based organizations.</p> <p>Results</p> <p>Forty-four participants (67% of the eligible sample) completed the online questionnaire. Approximately one-third (34.9%) reported that they intended to adopt the LTC intervention for use in their city, state, or territory in the future. Consistent with prior, related work, these participants were classified as LTC intervention "adopters" and were compared to "nonadopters" for data analysis. Overall, adopters reported more positive attitudes and greater perceived demand and support for the intervention than did nonadopters. Further, participants varied with their intention to adopt the LTC intervention in the future depending on endorsement from different key stakeholder groups. Most participants indicated that they would support the dissemination of the intervention by recommending it to other health departments and community-based organizations.</p> <p>Conclusions</p> <p>Findings from this exploratory study provide initial insight into factors associated with public health policy makers' intentions to adopt an LTC intervention. Implications for future research in this area, as well as potential policy-related strategies for enhancing the adoption of LTC interventions, are discussed.</p

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

Bmp and Nodal Independently Regulate lefty1 Expression to Maintain Unilateral Nodal Activity during Left-Right Axis Specification in Zebrafish

In vertebrates, left-right (LR) axis specification is determined by a ciliated structure in the posterior region of the embryo. Fluid flow in this ciliated structure is responsible for the induction of unilateral left-sided Nodal activity in the lateral plate mesoderm, which in turn regulates organ laterality. Bmp signalling activity has been implied in repressing Nodal expression on the right side, however its mechanism of action has been controversial. In a forward genetic screen for mutations that affect LR patterning, we identified the zebrafish linkspoot (lin) mutant, characterized by cardiac laterality and mild dorsoventral patterning defects. Mapping of the lin mutation revealed an inactivating missense mutation in the Bmp receptor 1aa (bmpr1aa) gene. Embryos with a mutation in lin/bmpr1aa and a novel mutation in its paralogue, bmpr1ab, displayed a variety of dorsoventral and LR patterning defects with increasing severity corresponding with a decrease in bmpr1a dosage. In Bmpr1a-deficient embryos we observed bilateral expression of the Nodal-related gene, spaw, coupled with reduced expression of the Nodal-antagonist lefty1 in the midline. Using genetic models to induce or repress Bmp activity in combination with Nodal inhibition or activation, we found that Bmp and Nodal regulate lefty1 expression in the midline independently of each other. Furthermore, we observed that the regulation of lefty1 by Bmp signalling is required for its observed downregulation of Nodal activity in the LPM providing a novel explanation for this phenomenon. From these results we propose a two-step model in which Bmp regulates LR patterning. Prior to the onset of nodal flow and Nodal activation, Bmp is required to induce lefty1 expression in the midline. When nodal flow has been established and Nodal activity is apparent, both Nodal and Bmp independently are required for lefty1 expression to assure unilateral Nodal activation and correct LR patterning

The Frequency of Dust Lanes in Edge-on Spiral Galaxies Identified by Galaxy Zoo in KiDS Imaging of GAMA Targets

Dust lanes bisect the plane of a typical edge-on spiral galaxy as a dark optical absorption feature. Their appearance is linked to the gravitational stability of spiral disks; the fraction of edge-on galaxies that displays a dust lane is a direct indicator of the typical vertical balance between gravity and turbulence: a balance struck between the energy input from star formation and the gravitational pull into the plane of the disk. Based on morphological classifications by the Galaxy Zoo project on the Kilo Degree Survey (KiDS) imaging data in the Galaxy and Mass Assembly (GAMA) fields, we explore the relation of dust lanes to the galaxy characteristics, most of which were determined using the Magphys spectral energy distribution fitting tool: stellar mass, total and specific star formation rates, and several parameters describing the cold dust component. We find that the fraction of dust lanes does depend on the stellar mass of the galaxy; they start to appear at M* ~ 109 M ⊙. A dust lane also strongly implies a dust mass of at least 105 M ⊙, but otherwise does not correlate with cold dust mass parameters of the Magphys spectral energy distribution analysis, nor is there a link with the star formation rate, specific or total. Dust lane identification does not depend on disk ellipticity (disk thickness) or Sérsic profile but correlates with bulge morphology; a round bulge favors dust lane votes. The central component along the line of sight that produces the dust lane is not associated with either one of the components fit by Magphys, the cold diffuse component or the localized, heated component in H ii regions, but a mix of these two

Intranasal Delivery of E-Selectin Reduces Atherosclerosis in ApoE−/− Mice

Mucosal tolerance to E-selectin prevents stroke and protects against ischemic brain damage in experimental models of stroke studying healthy animals or spontaneously hypertensive stroke-prone rats. A reduction in inflammation and neural damage was associated with immunomodulatory or “tolerogenic” responses to E-selectin. The purpose of the current study on ApoE deficient mice is to assess the capacity of this stroke prevention innovation to influence atherosclerosis, a major underlying cause for ischemic strokes; human E-selectin is being translated as a potential clinical prevention strategy for secondary stroke. Female ApoE−/− mice received intranasal delivery of E-selectin prior to (pre-tolerization) or simultaneously with initiation of a high-fat diet. After 7 weeks on the high-fat diet, lipid lesions in the aorta, serum triglycerides, and total cholesterol were assessed as markers of atherosclerosis development. We also assessed E-selectin-specific antibodies and cytokine responses, in addition to inflammatory responses that included macrophage infiltration of the aorta and altered gene expression profiles of aortic mRNA. Intranasal delivery of E-selectin prior to initiation of high-fat chow decreased atherosclerosis, serum total cholesterol, and expression of the leucocyte chemoattractant CCL21 that is typically upregulated in atherosclerotic lesions of ApoE−/− mice. This response was associated with the induction of E-selectin specific cells producing the immunomodulatory cytokine IL-10 and immunosuppressive antibody isotypes. Intranasal administration of E-selectin generates E-selectin specific immune responses that are immunosuppressive in nature and can ameliorate atherosclerosis, a major risk factor for ischemic stroke. These results provide additional preclinical support for the potential of induction of mucosal tolerance to E-selectin to prevent stroke

Galaxy And Mass Assembly (GAMA): Panchromatic Data Release (far-UV --- far-IR) and the low-z energy budget

We present the GAMA Panchromatic Data Release (PDR) constituting over 230deg$^2$ of imaging with photometry in 21 bands extending from the far-UV to the far-IR. These data complement our spectroscopic campaign of over 300k galaxies, and are compiled from observations with a variety of facilities including: GALEX, SDSS, VISTA, WISE, and Herschel, with the GAMA regions currently being surveyed by VST and scheduled for observations by ASKAP. These data are processed to a common astrometric solution, from which photometry is derived for 221,373 galaxies with r<19.8 mag. Online tools are provided to access and download data cutouts, or the full mosaics of the GAMA regions in each band. We focus, in particular, on the reduction and analysis of the VISTA VIKING data, and compare to earlier datasets (i.e., 2MASS and UKIDSS) before combining the data and examining its integrity. Having derived the 21-band photometric catalogue we proceed to fit the data using the energy balance code MAGPHYS. These measurements are then used to obtain the first fully empirical measurement of the 0.1-500$\mu$m energy output of the Universe. Exploring the Cosmic Spectral Energy Distribution (CSED) across three time-intervals (0.3-1.1Gyr, 1.1-1.8~Gyr and 1.8---2.4~Gyr), we find that the Universe is currently generating $(1.5 \pm 0.3) \times 10^{35}$ h$_{70}$ W Mpc$^{-3}$, down from $(2.5 \pm 0.2) \times 10^{35}$ h$_{70}$ W Mpc$^{-3}$ 2.3~Gyr ago. More importantly, we identify significant and smooth evolution in the integrated photon escape fraction at all wavelengths, with the UV escape fraction increasing from 27(18)% at z=0.18 in NUV(FUV) to 34(23)% at z=0.06. The GAMA PDR will allow for detailed studies of the energy production and outputs of individual systems, sub-populations, and representative galaxy samples at $z<0.5$. The GAMA PDR can be found at: http://gama-psi.icrar.org