Nitrous oxide and methane in the Atlantic Ocean between 50 degrees North and 52 degrees South: Latitudinal distribution and sea-to-air flux

We discuss nitrous oxide (N2O) and methane (CH4) distributions in 49 vertical profiles covering the upper 300 m of the water column along two 13,500 km transects between 50°N and 52°S during the Atlantic Meridional Transect (AMT) programme (AMT cruises 12 and 13). Vertical N2O profiles were amenable to analysis on the basis of common features coincident with Longhurst provinces. In contrast, CH4 showed no such pattern. The most striking feature of the latitudinal depth distributions was a well-defined “plume” of exceptionally high N2O concentrations coincident with very low levels of CH4, located between 23.5°N and 23.5°S; this feature reflects the upwelling of deep waters containing N2O derived from nitrification, as identified by an analysis of N2O, apparent oxygen utilization (AOU) and NO3-, and presumably depleted in CH4 by bacterial oxidation. Sea-to-air emissions fluxes for a region equivalent to 42% of the Atlantic Ocean surface area were in the range 0.40–0.68 Tg N2O yr-1 and 0.81–1.43 Tg CH4 yr-1. Based on contemporary estimates of the global ocean source strengths of atmospheric N2O and CH4, the Atlantic Ocean could account for 6–15% and 4–13%, respectively, of these source totals. Given that the Atlantic Ocean accounts for around 20% of the global ocean surface, on unit area basis it appears that the Atlantic may be a slightly weaker source of atmospheric N2O than other ocean regions but it could make a somewhat larger contribution to marine-derived atmospheric CH4 than previously thought

GenoType® MTBDRsl assay for resistance to second-line anti-tuberculosis drugs

Background Genotype® MTBDRsl (MTBDRsl) is a rapid DNA-based test for detecting specific mutations associated with resistance to fluoroquinolones and second-line injectable drugs (SLIDs) in Mycobacterium tuberculosis complex. MTBDRsl version 2.0 (released in 2015) identifies the mutations detected by version 1.0, as well as additional mutations. The test may be performed on a culture isolate or a patient specimen, which eliminates delays associated with culture. Version 1.0 requires a smear-positive specimen, while version 2.0 may use a smear-positive or -negative specimen. We performed this updated review as part of a World Health Organization process to develop updated guidelines for using MTBDRsl. Objectives To assess and compare the diagnostic accuracy of MTBDRsl for: 1. fluoroquinolone resistance, 2. SLID resistance, and 3. extensively drug-resistant tuberculosis, indirectly on a M. tuberculosis isolate grown from culture or directly on a patient specimen. Participants were people with rifampicin-resistant or multidrug-resistant tuberculosis. The role of MTBDRsl would be as the initial test, replacing culture-based drug susceptibility testing (DST), for detecting second-line drug resistance. Search methods We searched the following databases without language restrictions up to 21 September 2015: the Cochrane Infectious Diseases Group Specialized Register; MEDLINE; Embase OVID; Science Citation Index Expanded, Conference Proceedings Citation Index-Science, and BIOSIS Previews (all three from Web of Science); LILACS; and SCOPUS; registers for ongoing trials; and ProQuest Dissertations & Theses A&I. We reviewed references from included studies and contacted specialists in the field. Selection criteria We included cross-sectional and case-control studies that determined MTBDRsl accuracy against a defined reference standard (culture-based DST, genetic sequencing, or both). Data collection and analysis Two review authors independently extracted data and assessed quality using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. We synthesized data for versions 1.0 and 2.0 separately. We estimated MTBDRsl sensitivity and specificity for fluoroquinolone resistance, SLID resistance, and extensively drug-resistant tuberculosis when the test was performed indirectly or directly (smear-positive specimen for version 1.0, smear-positive or -negative specimen for version 2.0). We explored the influence on accuracy estimates of individual drugs within a drug class and of different reference standards. We performed most analyses using a bivariate random-effects model with culture-based DST as reference standard. Main results We included 27 studies. Twenty-six studies evaluated version 1.0, and one study version 2.0. Of 26 studies stating specimen country origin, 15 studies (58%) evaluated patients from low- or middle-income countries. Overall, we considered the studies to be of high methodological quality. However, only three studies (11%) had low risk of bias for the reference standard; these studies used World Health Organization (WHO)-recommended critical concentrations for all drugs in the culture-based DST reference standard. MTBDRsl version 1.0 Fluoroquinolone resistance: indirect testing, MTBDRsl pooled sensitivity and specificity (95% confidence interval (CI)) were 85.6% (79.2% to 90.4%) and 98.5% (95.7% to 99.5%), (19 studies, 2223 participants); direct testing (smear-positive specimen), pooled sensitivity and specificity were 86.2% (74.6% to 93.0%) and 98.6% (96.9% to 99.4%), (nine studies, 1771 participants, moderate quality evidence). SLID resistance: indirect testing, MTBDRsl pooled sensitivity and specificity were 76.5% (63.3% to 86.0%) and 99.1% (97.3% to 99.7%), (16 studies, 1921 participants); direct testing (smear-positive specimen), pooled sensitivity and specificity were 87.0% (38.1% to 98.6%) and 99.5% (93.6% to 100.0%), (eight studies, 1639 participants, low quality evidence). Extensively drug-resistant tuberculosis: indirect testing, MTBDRsl pooled sensitivity and specificity were 70.9% (42.9% to 88.8%) and 98.8% (96.1% to 99.6%), (eight studies, 880 participants); direct testing (smear-positive specimen), pooled sensitivity and specificity were 69.4% (38.8% to 89.0%) and 99.4% (95.0% to 99.3%), (six studies, 1420 participants, low quality evidence). Similar to the original Cochrane review, we found no evidence of a significant difference in MTBDRsl version 1.0 accuracy between indirect and direct testing for fluoroquinolone resistance, SLID resistance, and extensively drug-resistant tuberculosis. MTBDRsl version 2.0 Fluoroquinolone resistance: direct testing, MTBDRsl sensitivity and specificity were 97% (83% to 100%) and 98% (93% to 100%), smear-positive specimen; 80% (28% to 99%) and 100% (40% to 100%), smear-negative specimen. SLID resistance: direct testing, MTBDRsl sensitivity and specificity were 89% (72% to 98%) and 90% (84% to 95%), smear-positive specimen; 80% (28% to 99%) and 100% (40% to 100%), smear-negative specimen. Extensively drug-resistant tuberculosis: direct testing, MTBDRsl sensitivity and specificity were 79% (49% to 95%) and 97% (93% to 99%), smear-positive specimen; 50% (1% to 99%) and 100% (59% to 100%), smear-negative specimen. We had insufficient data to estimate summary sensitivity and specificity of version 2.0 (smear-positive and -negative specimens) or to compare accuracy of the two versions. A limitation was that most included studies did not consistently use the World Health Organization (WHO)-recommended concentrations for drugs in the culture-based DST reference standard. Authors' conclusions In people with rifampicin-resistant or multidrug-resistant tuberculosis, MTBDRsl performed on a culture isolate or smear-positive specimen may be useful in detecting second-line drug resistance. MTBDRsl (smear-positive specimen) correctly classified around six in seven people as having fluoroquinolone or SLID resistance, although the sensitivity estimates for SLID resistance varied. The test rarely gave a positive result for people without drug resistance. However, when second-line drug resistance is not detected (MTBDRsl result is negative), conventional DST can still be used to evaluate patients for resistance to the fluoroquinolones or SLIDs. We recommend that future work evaluate MTBDRsl version 2.0, in particular on smear-negative specimens and in different settings to account for different resistance-causing mutations that may vary by strain. Researchers should also consider incorporating WHO-recommended critical concentrations into their culture-based reference standards

Automatic Cough Classification for Tuberculosis Screening in a Real-World Environment

Objective: The automatic discrimination between the coughing sounds produced by patients with tuberculosis (TB) and those produced by patients with other lung ailments. Approach: We present experiments based on a dataset of 1358 forced cough recordings obtained in a developing-world clinic from 16 patients with confirmed active pulmonary TB and 35 patients suffering from respiratory conditions suggestive of TB but confirmed to be TB negative. Using nested cross-validation, we have trained and evaluated five machine learning classifiers: logistic regression (LR), support vector machines (SVM), k-nearest neighbour (KNN), multilayer perceptrons (MLP) and convolutional neural networks (CNN). Main Results: Although classification is possible in all cases, the best performance is achieved using LR. In combination with feature selection by sequential forward selection (SFS), our best LR system achieves an area under the ROC curve (AUC) of 0.94 using 23 features selected from a set of 78 high-resolution mel-frequency cepstral coefficients (MFCCs). This system achieves a sensitivity of 93\% at a specificity of 95\% and thus exceeds the 90\% sensitivity at 70\% specificity specification considered by the World Health Organisation (WHO) as a minimal requirement for a community-based TB triage test. Significance: The automatic classification of cough audio sounds, when applied to symptomatic patients requiring investigation for TB, can meet the WHO triage specifications for the identification of patients who should undergo expensive molecular downstream testing. This makes it a promising and viable means of low cost, easily deployable frontline screening for TB, which can benefit especially developing countries with a heavy TB burden.Comment: This paper has been accepted in Physiological Measurement (2021

How can we make the psychiatric workforce more family focused?

[Extract] Initially, the chapter outlines what we mean by family approaches and then overviews our conception of a continuum of family-focused care and expectations for psychiatric agencies and workers. A brief theoretical review of family-focused care is then outlined followed by information about barriers and enablers to family-focused practice. The chapter ends with reflections from multiple countries regarding the current state of family-focused practice and potential ways forward in each country

Development and Content Validity Testing of a Patient-Reported Treatment Acceptance Measure for Use in Patients Receiving Treatment via Subcutaneous Injection

AbstractBackgroundNew therapies in development for lowering low-density lipoprotein cholesterol, such as alirocumab, require administration by subcutaneous injections. There is a need to assess the acceptance of such treatments and their mode of administration.ObjectivesTo develop a novel patient-reported outcome measure, the Injection-Treatment Acceptance Questionnaire (I-TAQ), and assess its content validity using qualitative methods.MethodsConcepts generated from a literature and instrument review informed the initial drafting of 17 items in the I-TAQ, with item wording adapted from three existing instruments. Three rounds of qualitative interviews were conducted with 29 US-English speaking patients at high cardiovascular risk. Concept elicitation questioning was used to explore patients’ treatment experiences followed by cognitive debriefing of the I-TAQ using “think-aloud” methods. Verbatim transcripts were analyzed using thematic analysis.ResultsQualitative analysis of concept elicitation data identified the following relevant concepts: perceived efficacy, side effects, self-efficacy, convenience, and overall acceptance. Seven (24%) patients discussed an initial fear of needles, but described this as subsiding with no impact on adherence. Five items were added after round one interviews, three of which were retained after round two testing in which two further items were added, forming the conceptually comprehensive 22-item I-TAQ. Patients demonstrated good understanding of item wording, instructions, response scales, and recall period.ConclusionsSuccessive rounds of in-depth interviews resulted in a treatment acceptance measure with strong content validity. Pending demonstration of its psychometric properties, the I-TAQ may prove to be a valuable measure of patients’ perspectives toward being treated with low-density lipoprotein cholesterol–lowering therapies requiring subcutaneous injections

The National Falls and Bone Health Audit: Implications for UK emergency care

Introduction: The National Clinical Audit of Falls and Bone Health, coordinated by the Royal College of Physicians, assesses progress in implementing integrated falls services across the UK against national standards and enables benchmarking between service providers. Nationally, falls are a leading contributor towards mortality and morbidity in older people and account for 700 000 visits to emergency departments and 4 million annual bed days in England alone. Methods: Two rounds of national organisational audit in 2005 and 2008 and one national clinical audit in 2006 were carried out based on indicators developed by a multidisciplinary group. Results: These showed that management of falls and bone health in older people remains suboptimal in emergency departments and minor injury units and opportunities are being missed in carrying out evidence-based risk assessment and management. Conclusions: Older people attending emergency departments in the UK following a fall are receiving a poor deal. There is an urgent need to ensure more effective assessment and management to prevent further falls and fractures

Localization of Double-Strand Break Repair Proteins to Viral Replication Compartments following Lytic Reactivation of Kaposi's Sarcoma-Associated Herpesvirus

ABSTRACT Double-strand breaks (DSBs) in DNA are recognized by the Ku70/80 heterodimer and the MRE11-RAD50-NBS1 (MRN) complex and result in activation of the DNA-PK and ATM kinases, which play key roles in regulating the cellular DNA damage response (DDR). DNA tumor viruses such as Kaposi's sarcoma-associated herpesvirus (KSHV) are known to interact extensively with the DDR during the course of their replicative cycles. Here we show that during lytic amplification of KSHV DNA, the Ku70/80 heterodimer and the MRN complex consistently colocalize with viral genomes in replication compartments (RCs), whereas other DSB repair proteins form foci outside RCs. Depletion of MRE11 and abrogation of its exonuclease activity negatively impact viral replication, while in contrast, knockdown of Ku80 and inhibition of the DNA-PK enzyme, which are involved in nonhomologous end joining (NHEJ) repair, enhance amplification of viral DNA. Although the recruitment of DSB-sensing proteins to KSHV RCs is a consistent occurrence across multiple cell types, activation of the ATM-CHK2 pathway during viral replication is a cell line-specific event, indicating that recognition of viral DNA by the DDR does not necessarily result in activation of downstream signaling pathways. We have also observed that newly replicated viral DNA is not associated with cellular histones. Since the presence and modification of these DNA-packaging proteins provide a scaffold for docking of multiple DNA repair factors, the absence of histone deposition may allow the virus to evade localization of DSB repair proteins that would otherwise have a detrimental effect on viral replication. IMPORTANCE Tumor viruses are known to interact with machinery responsible for detection and repair of double-strand breaks (DSBs) in DNA, although detail concerning how Kaposi's sarcoma-associated herpesvirus (KSHV) modulates these cellular pathways during its lytic replication phase was previously lacking. By undertaking a comprehensive assessment of the localization of DSB repair proteins during KSHV replication, we have determined that a DNA damage response (DDR) is directed to viral genomes but is distinct from the response to cellular DNA damage. We also demonstrate that although recruitment of the MRE11-RAD50-NBS1 (MRN) DSB-sensing complex to viral genomes and activation of the ATM kinase can promote KSHV replication, proteins involved in nonhomologous end joining (NHEJ) repair restrict amplification of viral DNA. Overall, this study extends our understanding of the virus-host interactions that occur during lytic replication of KSHV and provides a deeper insight into how the DDR is manipulated during viral infection. </jats:p

Morphology of the gas-rich debris disk around HD 121617 with SPHERE observations in polarized light

Debris disks are the signposts of collisionally eroding planetesimal circumstellar belts, whose study can put important constraints on the structure of extrasolar planetary systems. The best constraints on the morphology of disks are often obtained from spatially resolved observations in scattered light. Here, we investigate the young (~16 Myr) bright gas-rich debris disk around HD121617. We use new scattered-light observations with VLT/SPHERE to characterize the morphology and the dust properties of this disk. From these properties we can then derive constraints on the physical and dynamical environment of this system, for which significant amounts of gas have been detected. The disk morphology is constrained by linear-polarimetric observations in the J band. Based on our modeling results and archival photometry, we also model the SED to put constraints on the total dust mass and the dust size distribution. We explore different scenarios that could explain these new constraints. We present the first resolved image in scattered light of the debris disk HD121617. We fit the morphology of the disk, finding a semi-major axis of 78.3$\pm$0.2 au, an inclination of 43.1$\pm$0.2{\deg} and a position angle of the major axis with respect to north, of 239.8$\pm$0.3{\deg}, compatible with the previous continuum and CO detection with ALMA. Our analysis shows that the disk has a very sharp inner edge, possibly sculpted by a yet-undetected planet or gas drag. While less sharp, its outer edge is steeper than expected for unperturbed disks, which could also be due to a planet or gas drag, but future observations probing the system farther from the main belt would help explore this further. The SED analysis leads to a dust mass of 0.21$\pm$0.02 M$_{\oplus}$ and a minimum grain size of 0.87$\pm$0.12 $\mu$m, smaller than the blowout size by radiation pressure, which is not unexpected for very bright col...Comment: 12 pages, 7 figures. Accepted in A&A (06/02/2023

Site selection strategy for environmental monitoring in connection with shale-gas exploration: Vale of Pickering, Yorkshire and Fylde, Lancashire

This report outlines the strategies for site selection adopted as part of a baseline environmental monitoring investigation in connection with shale-gas exploration and development in the Vale of Pickering, North Yorkshire. The project forms an extension to an ongoing baseline investigation being carried out in the Fylde, Lancashire, and the current project incorporates an air-quality monitoring component that was not within the original remit of the Fylde study. The DECC-funded investigation is led by the British Geological Survey, and is being carried out as a collaboration with the Universities of Birmingham, Bristol, Liverpool, Manchester and York (National Centre for Atmospheric Science, NCAS) and Public Health England (PHE). The project incorporates work packages in monitoring of water quality, air quality and greenhouse gases, soil gas, ground motion and seismicity, and air radon and is being carried out over the period September 2015 to March 2016. Site selection is a critical consideration in setting up a monitoring programme as chosen sites need to be representative of conditions to be tested. While sites will necessarily be subject to practical constraints (land access agreements, existing infrastructure, geological conditions, cost implications etc), site selection has a large part to play in ensuring collection of quantifiable, unbiased data. This report sets out the rationale for site selection in each of the work packages and the steps taken to ensure defensible site-selection decisions and to minimise the impact of practical constraints

SXDF-ALMA 2 Arcmin^2 Deep Survey: Resolving and Characterizing the Infrared Extragalactic Background Light Down to 0.5 mJy

We present a multi-wavelength analysis of five submillimeter sources (S_1.1mm = 0.54-2.02 mJy) that were detected during our 1.1-mm-deep continuum survey in the SXDF-UDS-CANDELS field (2 arcmin^2, 1sigma = 0.055 mJy beam^-1) using the Atacama Large Millimeter/submillimeter Array (ALMA). The two brightest sources correspond to a known single-dish (AzTEC) selected bright submillimeter galaxy (SMG), whereas the remaining three are faint SMGs newly uncovered by ALMA. If we exclude the two brightest sources, the contribution of the ALMA-detected faint SMGs to the infrared extragalactic background light is estimated to be ~ 4.1^{+5.4}_{-3.0} Jy deg^{-2}, which corresponds to ~ 16^{+22}_{-12}% of the infrared extragalactic background light. This suggests that their contribution to the infrared extragalactic background light is as large as that of bright SMGs. We identified multi-wavelength counterparts of the five ALMA sources. One of the sources (SXDF-ALMA3) is extremely faint in the optical to near-infrared region despite its infrared luminosity (L_IR ~ 1e12 L_sun or SFR ~ 100 M_sun yr^{-1}). By fitting the spectral energy distributions (SEDs) at the optical-to-near-infrared wavelengths of the remaining four ALMA sources, we obtained the photometric redshifts (z_photo) and stellar masses (M_*): z_photo ~ 1.3-2.5, M_* ~ (3.5-9.5)e10 M_sun. We also derived their star formation rates (SFRs) and specific SFRs (sSFRs) as ~ 30-200 M_sun yr^{-1} and ~ 0.8-2 Gyr^{-1}, respectively. These values imply that they are main-sequence star-forming galaxies.Comment: PASJ accepted, 15 pages, 6 figures, 2 table