Impact of Sleep and Circadian Disruption on Energy Balance and Diabetes: A Summary of Workshop Discussions

A workshop was held at the National Institute for Diabetes and Digestive and Kidney Diseases with a focus on the impact of sleep and circadian disruption on energy balance and diabetes. The workshop identified a number of key principles for research in this area and a number of specific opportunities. Studies in this area would be facilitated by active collaboration between investigators in sleep/circadian research and investigators in metabolism/diabetes. There is a need to translate the elegant findings from basic research into improving the metabolic health of the American public. There is also a need for investigators studying the impact of sleep/circadian disruption in humans to move beyond measurements of insulin and glucose and conduct more in-depth phenotyping. There is also a need for the assessments of sleep and circadian rhythms as well as assessments for sleep-disordered breathing to be incorporated into all ongoing cohort studies related to diabetes risk. Studies in humans need to complement the elegant short-term laboratory-based human studies of simulated short sleep and shift work etc. with studies in subjects in the general population with these disorders. It is conceivable that chronic adaptations occur, and if so, the mechanisms by which they occur needs to be identified and understood. Particular areas of opportunity that are ready for translation are studies to address whether CPAP treatment of patients with pre-diabetes and obstructive sleep apnea (OSA) prevents or delays the onset of diabetes and whether temporal restricted feeding has the same impact on obesity rates in humans as it does in mice

Diamond nano-pillar arrays for quantum microscopy of neuronal signals

Modern neuroscience is currently limited in its capacity to perform long term, wide-field measurements of neuron electromagnetics with nanoscale resolution. Quantum microscopy using the nitrogen vacancy centre (NV) can provide a potential solution to this problem with electric and magnetic field sensing at nano-scale resolution and good biocompatibility. However, the performance of existing NV sensing technology does not allow for studies of small mammalian neurons yet. In this paper, we propose a solution to this problem by engineering NV quantum sensors in diamond nanopillar arrays. The pillars improve light collection efficiency by guiding excitation/emission light, which improves sensitivity. More importantly, they also improve the size of the signal at the NV by removing screening charges as well as coordinating the neuron growth to the tips of the pillars where the NV is located. Here, we provide a growth study to demonstrate coordinated neuron growth as well as the first simulation of nano-scopic neuron electric and magnetic fields to assess the enhancement provided by the nanopillar geometry.Comment: 18 pages including supplementary and references, 12 figure

Snow crab (Chionoecetes opilio) hemocytes and hepatopancreas transcriptomes: identification, validation, and application of immune-relevant biomarkers of exposure to noise

The snow crab (Chionoecetes opilio) fishery off the east coast of Newfoundland and Labrador, Canada, has been impacted by annual seismic oil and gas surveying in recent decades, and commercial crab harvesters are concerned that it could potentially affect this resource. A laboratory study was performed to investigate the effects of chronic noise exposure on the transcriptomes of snow crab hemocytes and hepatopancreas, which are important in immunity, metabolism and response to environmental stress. Snow crab were held in replicate control or experimental tanks; on alternating days, the experimental tanks were exposed to noise from an underwater speaker which played a recording of a seismic airgun firing every 10 sec in a continuous loop for ~ 22 weeks (chronic noise). RNA sequencing was used to identify candidate noise-responsive molecular biomarkers in both hemocytes and hepatopancreas. The quantified transcripts of individuals (i.e. n=10 from each of the four groups) were compared using DESeq2, identifying over 300 noise-responsive transcripts in each cell/tissue type. Real-time quantitative polymerase chain reaction (qPCR) assays were designed and run for 61 of these transcripts with significant BLASTx hits. One transcript (rgs2) was significantly (p < 0.05) higher expressed in both hemocytes and hepatopancreas in response to noise; five and seven other transcripts were either significant or showed a non-significant trend of differential expression (0.05 < p ≤ 0.1) in hemocytes (e.g. cfb upregulated, sacs and myof downregulated) and hepatopancreas (e.g. gpx3 and atf3 upregulated, sult1c4 downregulated), respectively. To further investigate the performance and utility of these candidate biomarkers in the field, expression levels of 25 selected transcripts were then examined in the hepatopancreas of snow crab that had been subjected to 2D and 3D seismic surveying using both qPCR and multivariate statistical analyses. Overall, few of these biomarkers showed consistent results in field-collected snow crab, highlighting the need to combine lab and field-based studies to fully evaluate the utility of biomarkers. Nonetheless, our study still identified noise-responsive biomarkers in both settings (including stress and immune relevant genes), providing valuable information for understanding the impact of ocean noise on snow crab physiology and health

The Escape of High-Energy Photons from Gamma-Ray Bursts

Eleven bright gamma-ray bursts (GRBs) detected by BATSE have also been seen at much higher energies by EGRET, six at energies above 10 MeV. Such observations imply that these bursts are optically thin to photon-photon pair production at all observed energies. For bursts more than about 30pc away, internal transparency can be achieved only if the source is moving with a relativistic bulk Lorentz factor $\Gamma\gg 1$, or if the radiation is highly beamed. Early calculations of $\gamma\gamma\to e^+e^-$ considerations for GRBs were limited to cases of a beam with opening half-angle \Thetab\sim 1/\Gamma, or expansions of infinitely thin spherical shells. This paper presents our extension of pair production optical depth calculations in relativistically expanding sources to more general geometries, including shells of finite thickness and arbitrary opening angle. The problem is reduced analytically to a single integral in the broadly applicable case of observing photons along the axis of the expansion. We find that the minimum bulk Lorentz factor for the EGRET sources to be optically thin is only moderately dependent on the shell thickness and virtually independent of its opening solid angle if \Thetab\gtrsim 1/\Gamma. This insensitivity to \Thetab relieves the commonly-perceived number problem for non-repeating sources at cosmological distances, i.e. it is not necessary to invoke small \Thetab to effect photon escape.Comment: 51 pages, including 8 eps figures, to appear in ApJ, December 20 199

Determinants of multimorbidity in low‐ and middle‐income countries: A systematic review of longitudinal studies and discovery of evidence gaps

Summary: Multimorbidity—the coexistence of at least two chronic health conditions within the same individual—is an important global health challenge. In high‐income countries (HICs), multimorbidity is dominated by non‐communicable diseases (NCDs); whereas, the situation may be different in low‐ and middle‐income countries (LMICs), where chronic communicable diseases remain prominent. The aim of this systematic review was to identify determinants (including risk and protective factors) and potential mechanisms underlying multimorbidity from published longitudinal studies across diverse population‐based or community‐dwelling populations in LMICs. We systematically searched three electronic databases (Medline, Embase, and Global Health) using pre‐defined search terms and selection criteria, complemented by hand‐searching. All titles, abstracts, and full texts were independently screened by two reviewers from a pool of four researchers. Data extraction and reporting were according to Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines. Methodological quality and risk of bias assessment was performed using the Newcastle‐Ottawa Scale for cohort studies. Data were summarized using narrative synthesis. The search yielded 1782 records. Of the 52 full‐text articles included for review, 8 longitudinal population‐based studies were included for final data synthesis. Almost all studies were conducted in Asia, with only one from South America and none from Africa. All studies were published in the last decade, with half published in the year 2021. The definitions used for multimorbidity were heterogeneous, including 3–16 chronic conditions per study. The leading chronic conditions were heart disease, stroke, and diabetes, and there was a lack of consideration of mental health conditions (MHCs), infectious diseases, and undernutrition. Prospectively evaluated determinants included socio‐economic status, markers of social inequities, childhood adversity, lifestyle behaviors, obesity, dyslipidemia, and disability. This review revealed a paucity of evidence from LMICs and a geographical bias in the distribution of multimorbidity research. Longitudinal research into epidemiological aspects of multimorbidity is warranted to build up scientific evidence in regions beyond Asia. Such evidence can provide a detailed picture of disease development, with important implications for community, clinical, and interventions in LMICs. The heterogeneity in study designs, exposures, outcomes, and statistical methods observed in the present review calls for greater methodological standardisation while conducting epidemiological studies on multimorbidity. The limited evidence for MHCs, infectious diseases, and undernutrition as components of multimorbidity calls for a more comprehensive definition of multimorbidity globally

Complete Genome Sequences of Cluster A Mycobacteriophages BobSwaget, Fred313, KADY, Lokk, MyraDee, Stagni, and StepMih

Seven mycobacteriophages from distinct geographical locations were isolated, using Mycobacterium smegmatis mc2155 as the host, and then purified and sequenced. All of the genomes are related to cluster A mycobacteriophages, BobSwaget and Lokk in subcluster A2; Fred313, KADY, Stagni, and StepMih in subcluster A3; and MyraDee in subcluster A18, the first phage to be assigned to that subcluster

Reward-Related Dorsal Striatal Activity Differences between Former and Current Cocaine Dependent Individuals during an Interactive Competitive Game

Cocaine addiction is characterized by impulsivity, impaired social relationships, and abnormal mesocorticolimbic reward processing, but their interrelationships relative to stages of cocaine addiction are unclear. We assessed blood-oxygenation-level dependent (BOLD) signal in ventral and dorsal striatum during functional magnetic resonance imaging (fMRI) in current (CCD; n = 30) and former (FCD; n = 28) cocaine dependent subjects as well as healthy control (HC; n = 31) subjects while playing an interactive competitive Domino game involving risk-taking and reward/punishment processing. Out-of-scanner impulsivity-related measures were also collected. Although both FCD and CCD subjects scored significantly higher on impulsivity-related measures than did HC subjects, only FCD subjects had differences in striatal activation, specifically showing hypoactivation during their response to gains versus losses in right dorsal caudate, a brain region linked to habituation, cocaine craving and addiction maintenance. Right caudate activity in FCD subjects also correlated negatively with impulsivity-related measures of self-reported compulsivity and sensitivity to reward. These findings suggest that remitted cocaine dependence is associated with striatal dysfunction during social reward processing in a manner linked to compulsivity and reward sensitivity measures. Future research should investigate the extent to which such differences might reflect underlying vulnerabilities linked to cocaine-using propensities (e.g., relapses)

Do International Health Partnerships contribute to reverse innovation? a mixed methods study of THET-supported partnerships in the UK

Background International health partnerships (IHPs) are changing, with an increased emphasis on mutual accountability and joint agenda setting for both the high- and the low- or middle-income country (LMIC) partners. There is now an important focus on the bi-directionality of learning however for the UK partners, this typically focuses on learning at the individual level, through personal and professional development. We sought to evaluate whether this learning also takes the shape of ‘Reverse Innovation’ –when an idea conceived in a low-income country is subsequently adopted in a higher-income country. Methods This mixed methods study used an initial scoping survey of all the UK-leads of the Tropical Health Education Trust (THET)-supported International Health Partnerships (n = 114) to ascertain the extent to which the IHPs are or have been vehicles for Reverse Innovation. The survey formed the sampling frame for further deep-dive interviews to focus on volunteers’ experiences and attitudes to learning from LMICs. Interviews of IHP leads (n = 12) were audio-recorded and transcribed verbatim. Survey data was analysed descriptively. Interview transcripts were coded thematically, using an inductive approach. Results Survey response rate was 27% (n = 34). The majority (70%) strongly agreed that supporting LMIC partners best described the mission of the partnership but only 13% of respondents strongly agreed that learning about new innovations and models was a primary mission of their partnership. Although more than half of respondents reported having observed innovative practice in the LMIC, only one IHP respondent indicated that this has led to Reverse Innovation. Interviews with a sample of survey respondents revealed themes primarily around how learning is conceptualised, but also a central power imbalance between the UK and LMIC partners. Paternalistic notions of knowledge could be traced to partnership power dynamics and latent attitudes to LMICs. Conclusions Given the global flow of innovation, if High-income countries (HICs) are to benefit from LMIC practices, it is paramount to keep an open mind about where such learning can come from. Making the potential for learning more explicit and facilitating innovation dissemination upon return will ultimately underpin the success of adoption

Search for exotic resonances decaying into WZ/ZZ in pp collisions at √s=7 TeV

Journal of High Energy Physics 2013.2 (2013): 036 reproduced by permission of Scuola Internazionale Superiore di Studi Avanzati (SISSA)Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si le hubiere, y los autores pertenecientes a la UAMA search for new exotic particles decaying to the VZ final state is performed, where V is either a W or a Z boson decaying into two overlapping jets and the Z decays into a pair of electrons, muons or neutrinos. The analysis uses a data sample of pp collisions corresponding to an integrated luminosity of 5 fb-1 collected by the CMS experiment at the LHC at √s=7 TeV in 2011. No significant excess is observed in the mass distribution of the VZ candidates compared with the background expectation from standard model processes. Model-dependent upper limits at the 95% confidence level are set on the product of the cross section times the branching fraction of hypothetical particles decaying to the VZ final state as a function of mass. Sequential standard model W′ bosons with masses between 700 and 940 GeV are excluded. In the Randall-Sundrum model for graviton resonances with a coupling parameter of 0.05, masses between 750 and 880 GeV are also exclude