Decadal Salinity Changes in the Oceanic Subtropical Gyres and Connection to Changes in the Global Water Cycle

There is evidence that the global water cycle has been undergoing an intensification over several decades as a response to increasing atmospheric temperatures, particularly in regions with skewed evaporation – precipitation (E-P) patterns such as the oceanic subtropical gyres. However, observational data (rain gauges, etc.) can be quite sparse over such areas due to the inaccessibility of open ocean regions. This study utilizes in situ data, reanalysis, and model outputs to infer interannual to decadal scale trends in surface freshwater forcing within remote, evaporation-dominated subtropical regions of the ocean as they pertain to the past and present state of the global water cycle. Emphasized in this study is the importance of utilizing a wide range of ocean parameters to strengthen and validate the inferences made from any one proxy of a given parameter. A positive trend in sea surface salinity in the subtropical gyres revealed evidence for decadal intensification in the surface forcing of these regions. Zonal drift in the location of the salinity maximum of the south Pacific, north Atlantic, and south Indian regions implies a change in the mean near-surface currents responsible for advecting high salinity waters into the region. Additionally, a comparison of satellite, in situ, and model salinity datasets was conducted to highlight the potential applications of Aquarius and SMOS satellite-derived salinity products over oceanic regions of low observational density. Spatial and temporal salinity trends in the five subtropical gyre regions were also analyzed over the past six decades, with a focus on the subsurface salinity of the upper 1000 m of the ocean. Our results indicate an overall salinity increase within the mixed layer, and a salinity decrease at depths greater than 200m in the global subtropical gyres over 61 years. Our analysis of decadal variability of depth-integrated mixed layer fluxes into and out of the gyres reveals little change in the strength of the mean currents through this region despite an increase in both the annual import and export of salt in the southern hemisphere gyres. This suggests that the salt content of E-P maximum waters advected into the subtropical gyres is increasing over time. Another method of monitoring the marine branch of the global water cycle is through measurement of time variable mass over the Earth. We analyzed interannual freshwater fluxes inferred from the GRACE satellite mission and obtained striking agreement with trends observed through salinity and altimetry. The strengths of the mass concentration (mascon) processing technique relative to spherical harmonics is demonstrated. We suggest that discrepancies between sea level based and gravity based mass flux estimates are due primarily to an undersampling of the subsurface ocean, and not attributed to errors in GRACE measurement or retrieval

Employers Should Owe a Duty of Loyalty to Their Workers

An employee’s overarching legal commitment to his or her employer is commonly known as the “duty of loyalty.” This lopsided duty of loyalty exacerbates the inordinate power that employers possess over their workers. We propose that the duty of loyalty owed by workers to their employers be made reciprocal: employers should also owe a general duty of loyalty and care towards their employees

Changes in CEBPB expression in circulating leukocytes following eccentric elbow-flexion exercise

This is the final version of the article. Available from Springer via the DOI in this record.In mouse models, CCAAT enhancer-binding protein beta (CEBPB) is necessary for M2 macrophage-mediated regeneration after muscle injury. In humans, CEBPB expression in blood was strongly associated with muscle strength. In this study we aimed to test whether CEBPB expression in blood in people is increased 2 days after exercise designed to induce muscle damage and subsequent repair. Sixteen healthy male volunteers undertook elbow flexor exercises designed to induce acute muscle micro-damage. Peripheral blood samples were collected at baseline and days 1, 2, 4 and 7 following exercise. Expression of CEBPB and related genes were analysed by qRT-PCR. Extent of muscle damage was determined by decline in maximal voluntary isometric torque and by plasma creatine kinase activity. Nine subjects had peak (day 4) creatine kinase activity exceeding 10,000 U/l. In this subgroup, CEBPB expression was elevated from baseline to 2 days post exercise (paired-samples t (1,8) = 3.72, p = 0.006). Related expression and selected cytokine changes after exercise did not reach significance. Muscle-damaging exercise in humans can be followed by induction of CEBPB transcript expression in peripheral blood. Associations between CEBPB expression in blood and muscle strength may be consistent with the CEBPB-dependent muscle repair process.Wellcome TrustNational Institute for Health Researc

Treatment of tuberculosis in a region with high drug resistance: Outcomes, drug resistance amplification and re-infection

Introduction: Emerging antituberculosis drug resistance is a serious threat for tuberculosis (TB) control, especially in Eastern European countries. Methods: We combined drug susceptibility results and molecular strain typing data with treatment outcome reports to assess the influence of drug resistance on TB treatment outcomes in a prospective cohort of patients from Abkhazia (Georgia). Patients received individualized treatment regimens based on drug susceptibility testing (DST) results. Definitions for antituberculosis drug resistance and treatment outcomes were in line with current WHO recommendations. First and second line DST, and molecular typing were performed in a supranational laboratory for Mycobacterium tuberculosis (MTB) strains from consecutive sputum smear-positive TB patients at baseline and during treatment. Results: At baseline, MTB strains were fully drug-susceptible in 189/326 (58.0%) of patients. Resistance to at least H or R (PDR-TB) and multidrug-resistance (MDR-TB) were found in 69/326 (21.2%) and 68/326 (20.9%) of strains, respectively. Three MDR-TB strains were also extensively resistant (XDR-TB). During treatment, 3/189 (1.6%) fully susceptible patients at baseline were re-infected with a MDR-TB strain and 2/58 (3.4%) PDR-TB patients became MDR-TB due to resistance amplification. 5/ 47 (10.6%) MDR- patients became XDR-TB during treatment. Treatment success was observed in 161/189 (85.2%), 54/69 (78.3%) and 22/68 (32.3%) of patients with fully drug susceptible, PDR- and MDR-TB, respectively. Development of ofloxacin resistance was significantly associated with a negative treatment outcome. Conclusion: In Abkhazia, a region with high prevalence of drug resistant TB, the use of individualized MDR-TB treatment regimens resulted in poor treatment outcomes and XDR-TB amplification. Nosocomial transmission of MDR-TB emphasizes the importance of infection control in hospitals

Whole-genome sequencing to understand the genetic architecture of common gene expression and biomarker phenotypes.

Initial results from sequencing studies suggest that there are relatively few low-frequency (<5%) variants associated with large effects on common phenotypes. We performed low-pass whole-genome sequencing in 680 individuals from the InCHIANTI study to test two primary hypotheses: (i) that sequencing would detect single low-frequency-large effect variants that explained similar amounts of phenotypic variance as single common variants, and (ii) that some common variant associations could be explained by low-frequency variants. We tested two sets of disease-related common phenotypes for which we had statistical power to detect large numbers of common variant-common phenotype associations-11 132 cis-gene expression traits in 450 individuals and 93 circulating biomarkers in all 680 individuals. From a total of 11 657 229 high-quality variants of which 6 129 221 and 5 528 008 were common and low frequency (<5%), respectively, low frequency-large effect associations comprised 7% of detectable cis-gene expression traits [89 of 1314 cis-eQTLs at P < 1 × 10(-06) (false discovery rate ∼5%)] and one of eight biomarker associations at P < 8 × 10(-10). Very few (30 of 1232; 2%) common variant associations were fully explained by low-frequency variants. Our data show that whole-genome sequencing can identify low-frequency variants undetected by genotyping based approaches when sample sizes are sufficiently large to detect substantial numbers of common variant associations, and that common variant associations are rarely explained by single low-frequency variants of large effect

Body-Mounted Robotic System for MRI-Guided Shoulder Arthrography: Cadaver and Clinical Workflow Studies

This paper presents an intraoperative MRI-guided, patient-mounted robotic system for shoulder arthrography procedures in pediatric patients. The robot is designed to be compact and lightweight and is constructed with nonmagnetic materials for MRI safety. Our goal is to transform the current two-step arthrography procedure (CT/x-ray-guided needle insertion followed by diagnostic MRI) into a streamlined single-step ionizing radiation-free procedure under MRI guidance. The MR-conditional robot was evaluated in a Thiel embalmed cadaver study and healthy volunteer studies. The robot was attached to the shoulder using straps and ten locations in the shoulder joint space were selected as targets. For the first target, contrast agent (saline) was injected to complete the clinical workflow. After each targeting attempt, a confirmation scan was acquired to analyze the needle placement accuracy. During the volunteer studies, a more comfortable and ergonomic shoulder brace was used, and the complete clinical workflow was followed to measure the total procedure time. In the cadaver study, the needle was successfully placed in the shoulder joint space in all the targeting attempts with translational and rotational accuracy of 2.07 ± 1.22mm and 1.46 ± 1.06 degrees, respectively. The total time for the entire procedure was 94 min and the average time for each targeting attempt was 20 min in the cadaver study, while the average time for the entire workflow for the volunteer studies was 36 min. No image quality degradation due to the presence of the robot was detected. This Thiel-embalmed cadaver study along with the clinical workflow studies on human volunteers demonstrated the feasibility of using an MR-conditional, patient-mounted robotic system for MRI-guided shoulder arthrography procedure. Future work will be focused on moving the technology to clinical practice

Allelic heterogeneity and more detailed analyses of known loci explain additional phenotypic variation and reveal complex patterns of association

The identification of multiple signals at individual loci could explain additional phenotypic variance (‘missing heritability’) of common traits, and help identify causal genes. We examined gene expression levels as a model trait because of the large number of strong genetic effects acting in cis. Using expression profiles from 613 individuals, we performed genome-wide single nucleotide polymorphism (SNP) analyses to identify cis-expression quantitative trait loci (eQTLs), and conditional analysis to identify second signals. We examined patterns of association when accounting for multiple SNPs at a locus and when including additional SNPs from the 1000 Genomes Project. We identified 1298 cis-eQTLs at an approximate false discovery rate 0.01, of which 118 (9%) showed evidence of a second independent signal. For this subset of 118 traits, accounting for two signals resulted in an average 31% increase in phenotypic variance explained (Wilcoxon P< 0.0001). The association of SNPs with cis gene expression could increase, stay similar or decrease in significance when accounting for linkage disequilibrium with second signals at the same locus. Pairs of SNPs increasing in significance tended to have gene expression increasing alleles on opposite haplotypes, whereas pairs of SNPs decreasing in significance tended to have gene expression increasing alleles on the same haplotypes. Adding data from the 1000 Genomes Project showed that apparently independent signals could be potentially explained by a single association signal. Our results show that accounting for multiple variants at a locus will increase the variance explained in a substantial fraction of loci, but that allelic heterogeneity will be difficult to define without resequencing loci and functional work

Does Physical Activity Moderate The Association Between Shorter Leukocyte Telomere Length and Incident Coronary Heart Disease? Data From 54,180 UK Biobank Participants

Telomere shortening is a biological aging hallmark. The effect of short telomere length may be targeted by increased physical activity to reduce the risk of multiple aging-related diseases, including coronary heart disease (CHD). The objective was to assess the moderation effect of accelerometer-based physical activity (aPA) on the association between shorter leukocyte telomere length (LTL) relatively in the population sample and incident CHD. Data were from the UK Biobank participants with well-calibrated accelerometer data for at least 6.5 days (n = 54,180). Relative mean LTL at baseline (5–6 years prior to aPA assessment) was measured in T/S ratio, using a multiplex quantitative polymerase chain reaction (qPCR) technology, by comparing the amount of the telomere amplification product (T) to that of a single-copy gene (S). aPA measures included total number of events (at least 10-s continued physical activity \u3e 32 milligravities [mg]), total volume, mean duration, mean intensity, and peak intensity of all events. LTL, aPA measures, and their interactions were associated with incident CHD (mean follow-up 6.8 years) using Cox proportional hazards models adjusting for covariates. Longer LTL (relative to the sample distribution) was associated with reduced incidence of CHD (adjusted hazard ratio [aHR] = 0.94 per standard deviation [SD] increase in LTL, [95% CI, 0.90 to 0.99], P = .010). Incidence of CHD was reduced by higher total volume of aPA (aHR = 0.82 per SD increase in LTL, [95% CI, 0.71 to 0.95], P = .010) but increased by higher total number of events (aHR = 1.11 per SD increase in LTL, [95% CI, 1.02 to 1.21], P = .020) after controlling for other aPA measures and covariates. However, none of the interactions between LTL and aPA measures was statistically significant (P = .171)

Development and optimisation of in vitro sonodynamic therapy for glioblastoma

Sonodynamic therapy (SDT) is currently on critical path for glioblastoma therapeutics. SDT is a non-invasive approach utilising focused ultrasound to activate photosensitisers like 5-ALA to impede tumour growth. Unfortunately, the molecular mechanisms underlying the therapeutic functions of SDT remain enigmatic. This is primarily due to the lack of intricately optimised instrumentation capable of modulating SDT delivery to glioma cells in vitro. Consequently, very little information is available on the effects of SDT on glioma stem cells which are key drivers of gliomagenesis and recurrence. To address this, the current study has developed and validated an automated in vitro SDT system to allow the application and mapping of focused ultrasound fields under varied exposure conditions and setup configurations. The study optimizes ultrasound frequency, intensity, plate base material, thermal effect, and the integration of live cells. Indeed, in the presence of 5-ALA, focused ultrasound induces apoptotic cell death in primary patient-derived glioma cells with concurrent upregulation of intracellular reactive oxygen species. Intriguingly, primary glioma stem neurospheres also exhibit remarkably reduced 3D growth upon SDT exposure. Taken together, the study reports an in vitro system for SDT applications on tissue culture-based disease models to potentially benchmark the novel approach to the current standard-of-care.</p