Does involvement in a cohort study improve health and affect health inequalities? A natural experiment

Abstract Background Evidence suggests that the process of taking part in health research can improve participants\u2019 health, independent of any intended intervention. However, no research has yet explored whether these effects differ across socioeconomic groups. If the effect of mere participation in health research also has a social gradient this could increase health inequalities and bias research results. This study used the Born in Bradford family cohort (BIB) to explore whether simply taking part in BIB had improved participants\u2019 health and, if so, whether this effect was mediated by socioeconomic status. Methods Survey data on self-reported health behaviours were collected between 2007 and 2010 as part of BIB. These were augmented by clinical data on birth weight. Pregnant women on their second pregnancy, joining BIB for the first time formed the control group. Their health was compared to women on their second pregnancy who had both pregnancies within the study, who formed the exposed group. In order to limit the inherent bias in a non-randomised study, propensity score analysis was used, matching on age, ethnicity, education and date of questionnaire. The results were then compared according to mothers' education. Results Of six outcomes tested, only alcohol consumption showed a statistically significant reduction with exposure to BIB (OR: 0.35, 95% CIs 0.13, 0.92). Although effect estimates were larger for women with higher education compared to lower education, these effects were not statistically significant. Conclusions Despite one significant finding, these results overall are insufficient to conclude that simply taking part in BIB affected participants\u2019 health. We recommend that socioeconomic status is considered in future studies testing effects of research participation, and that randomised studies with larger sample sizes are conducted

Recent progress in understanding and projecting regional and global mean sea-level change

Considerable progress has been made in understanding the present and future regional and global sea level in the 2 years since the publication of the Fifth Assessment Report (AR5) of the Intergovernmental Panel on Climate Change. Here, we evaluate how the new results affect the AR5’s assessment of (i) historical sea level rise, including attribution of that rise and implications for the sea level budget, (ii) projections of the components and of total global mean sea level (GMSL), and (iii) projections of regional variability and emergence of the anthropogenic signal. In each of these cases, new work largely provides additional evidence in support of the AR5 assessment, providing greater confidence in those findings. Recent analyses confirm the twentieth century sea level rise, with some analyses showing a slightly smaller rate before 1990 and some a slightly larger value than reported in the AR5. There is now more evidence of an acceleration in the rate of rise. Ongoing ocean heat uptake and associated thermal expansion have continued since 2000, and are consistent with ocean thermal expansion reported in the AR5. A significant amount of heat is being stored deeper in the water column, with a larger rate of heat uptake since 2000 compared to the previous decades and with the largest storage in the Southern Ocean. The first formal detection studies for ocean thermal expansion and glacier mass loss since the AR5 have confirmed the AR5 finding of a significant anthropogenic contribution to sea level rise over the last 50 years. New projections of glacier loss from two regions suggest smaller contributions to GMSL rise from these regions than in studies assessed by the AR5; additional regional studies are required to further assess whether there are broader implications of these results. Mass loss from the Greenland Ice Sheet, primarily as a result of increased surface melting, and from the Antarctic Ice Sheet, primarily as a result of increased ice discharge, has accelerated. The largest estimates of acceleration in mass loss from the two ice sheets for 2003–2013 equal or exceed the acceleration of GMSL rise calculated from the satellite altimeter sea level record over the longer period of 1993–2014. However, when increased mass gain in land water storage and parts of East Antarctica, and decreased mass loss from glaciers in Alaska and some other regions are taken into account, the net acceleration in the ocean mass gain is consistent with the satellite altimeter record. New studies suggest that a marine ice sheet instability (MISI) may have been initiated in parts of the West Antarctic Ice Sheet (WAIS), but that it will affect only a limited number of ice streams in the twenty-first century. New projections of mass loss from the Greenland and Antarctic Ice Sheets by 2100, including a contribution from parts of WAIS undergoing unstable retreat, suggest a contribution that falls largely within the likely range (i.e., two thirds probability) of the AR5. These new results increase confidence in the AR5 likely range, indicating that there is a greater probability that sea level rise by 2100 will lie in this range with a corresponding decrease in the likelihood of an additional contribution of several tens of centimeters above the likely range. In view of the comparatively limited state of knowledge and understanding of rapid ice sheet dynamics, we continue to think that it is not yet possible to make reliable quantitative estimates of future GMSL rise outside the likely range. Projections of twenty-first century GMSL rise published since the AR5 depend on results from expert elicitation, but we have low confidence in conclusions based on these approaches. New work on regional projections and emergence of the anthropogenic signal suggests that the two commonly predicted features of future regional sea level change (the increasing tilt across the Antarctic Circumpolar Current and the dipole in the North Atlantic) are related to regional changes in wind stress and surface heat flux. Moreover, it is expected that sea level change in response to anthropogenic forcing, particularly in regions of relatively low unforced variability such as the low-latitude Atlantic, will be detectable over most of the ocean by 2040. The east-west contrast of sea level trends in the Pacific observed since the early 1990s cannot be satisfactorily accounted for by climate models, nor yet definitively attributed either to unforced variability or forced climate change

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

CMV Infection Attenuates the Disease Course in a Murine Model of Multiple Sclerosis

Recent evidence in multiple sclerosis (MS) suggests that active CMV infection may result in more benign clinical disease. The goal of this pilot study was to determine whether underlying murine CMV (MCMV) infection affects the course of the Theiler's murine encephalitis virus (TMEV) induced murine model of MS. A group of eight TMEV-infected mice were co-infected with MCMV at 2 weeks prior to TMEV infection while a second group of TMEV-infected mice received MCMV two weeks post TMEV. We also used 2 control groups, where at the above time points MCMV was replaced with PBS. Outcome measures included (1) monthly monitoring of disability via rotarod for 8 months; (2) in vivo MRI for brain atrophy studies and (3) FACS analysis of brain infiltrating lymphocytes at 8 months post TMEV infection. Co-infection with MCMV influenced the disease course in mice infected prior to TMEV infection. In this group, rotarod detectable motor performance was significantly improved starting 3 months post-infection and beyond (p≤0.024). In addition, their brain atrophy was close to 30% reduced at 8 months, but this was only present as a trend due to low power (p = 0.19). A significant reduction in the proportion of brain infiltrating CD3+ cells was detected in this group (p = 0.026), while the proportion of CD45+ Mac1+ cells significantly increased (p = 0.003). There was also a strong trend for a reduced proportion of CD4+ cells (p = 0.17) while CD8 and B220+ cell proportion did not change. These findings support an immunomodulatory effect of MCMV infection in this MS model. Future studies in this co-infection model will provide insight into mechanisms which modulate the development of demyelination and may be utilized for the development of novel therapeutic strategies

Analyses of zebrafish and Xenopus oocyte maturation reveal conserved and diverged features of translational regulation of maternal cyclin B1 mRNA

<p>Abstract</p> <p>Background</p> <p>Vertebrate development relies on the regulated translation of stored maternal mRNAs, but how these regulatory mechanisms may have evolved to control translational efficiency of individual mRNAs is poorly understood. We compared the translational regulation and polyadenylation of the cyclin B1 mRNA during zebrafish and <it>Xenopus </it>oocyte maturation. Polyadenylation and translational activation of cyclin B1 mRNA is well characterized during <it>Xenopus </it>oocyte maturation. Specifically, <it>Xenopus </it>cyclin B1 mRNA is polyadenylated and translationally activated during oocyte maturation by proteins that recognize the conserved AAUAAA hexanucleotide and U-rich Cytoplasmic Polyadenylation Elements (CPEs) within cyclin B1 mRNA's 3'<b>U</b>n<b>T</b>ranslated <b>R</b>egion (3'<b>UTR</b>).</p> <p>Results</p> <p>The zebrafish cyclin B1 mRNA was polyadenylated during zebrafish oocyte maturation. Furthermore, the zebrafish cyclin B1 mRNA's 3'UTR was sufficient to stimulate translation of a reporter mRNA during zebrafish oocyte maturation. This stimulation required both AAUAAA and U-rich CPE-like sequences. However, in contrast to AAUAAA, the positions and sequences of the functionally defined CPEs were poorly conserved between <it>Xenopus </it>and zebrafish cyclin B1 mRNA 3'UTRs. To determine whether these differences were relevant to translation efficiency, we analyzed the translational activity of reporter mRNAs containing either the zebrafish or <it>Xenopus </it>cyclin B1 mRNA 3'UTRs during both zebrafish and <it>Xenopus </it>oocyte maturation. The zebrafish cyclin B1 3'UTR was quantitatively less effective at stimulating polyadenylation and translation compared to the <it>Xenopus </it>cyclin B1 3'UTR during both zebrafish and <it>Xenopus </it>oocyte maturation.</p> <p>Conclusion</p> <p>Although the factors that regulate translation of maternal mRNAs are highly conserved, the target sequences and overall sequence architecture within the 3'UTR of the cyclin B1 mRNA have diverged to affect translational efficiency, perhaps to optimize levels of cyclin B1 protein required by these different species during their earliest embryonic cell divisions.</p

Using Entropy Maximization to Understand the Determinants of Structural Dynamics beyond Native Contact Topology

Comparison of elastic network model predictions with experimental data has provided important insights on the dominant role of the network of inter-residue contacts in defining the global dynamics of proteins. Most of these studies have focused on interpreting the mean-square fluctuations of residues, or deriving the most collective, or softest, modes of motions that are known to be insensitive to structural and energetic details. However, with increasing structural data, we are in a position to perform a more critical assessment of the structure-dynamics relations in proteins, and gain a deeper understanding of the major determinants of not only the mean-square fluctuations and lowest frequency modes, but the covariance or the cross-correlations between residue fluctuations and the shapes of higher modes. A systematic study of a large set of NMR-determined proteins is analyzed using a novel method based on entropy maximization to demonstrate that the next level of refinement in the elastic network model description of proteins ought to take into consideration properties such as contact order (or sequential separation between contacting residues) and the secondary structure types of the interacting residues, whereas the types of amino acids do not play a critical role. Most importantly, an optimal description of observed cross-correlations requires the inclusion of destabilizing, as opposed to exclusively stabilizing, interactions, stipulating the functional significance of local frustration in imparting native-like dynamics. This study provides us with a deeper understanding of the structural basis of experimentally observed behavior, and opens the way to the development of more accurate models for exploring protein dynamics

Variability of coastal and ocean water temperature in the upper 700 m along the western Iberian Peninsula from 1975 to 2006

Temperature is observed to have different trends at coastal and ocean locations along the western Iberian Peninsula from 1975 to 2006, which corresponds to the last warming period in the area under study. The analysis was carried out by means of the Simple Ocean Data Assimilation (SODA). Reanalysis data are available at monthly scale with a horizontal resolution of 0.5° × 0.5° and a vertical resolution of 40 levels, which allows obtaining information beneath the sea surface. Only the first 21 vertical levels (from 5.0 m to 729.35 m) were considered here, since the most important changes in heat content observed for the world ocean during the last decades, correspond to the upper 700 m. Warming was observed to be considerably higher at ocean locations than at coastal ones. Ocean warming ranged from values on the order of 0.3 °C dec(-1) near surface to less than 0.1 °C dec(-1) at 500 m, while coastal warming showed values close to 0.2 °C dec(-1) near surface, decreasing rapidly below 0.1 °C dec(-1) for depths on the order of 50 m. The heat content anomaly for the upper 700 m, showed a sharp increase from coast (0.46 Wm(-2)) to ocean (1.59 Wm(-2)). The difference between coastal and ocean values was related to the presence of coastal upwelling, which partially inhibits the warming from surface of near shore water.publishe

The potential benefits of low-molecular-weight heparins in cancer patients

Cancer patients are at increased risk of venous thromboembolism due to a range of factors directly related to their disease and its treatment. Given the high incidence of post-surgical venous thromboembolism in cancer patients and the poor outcomes associated with its development, thromboprophylaxis is warranted. A number of evidence-based guidelines delineate anticoagulation regimens for venous thromboembolism treatment, primary and secondary prophylaxis, and long-term anticoagulation in cancer patients. However, many give equal weight to several different drugs and do not make specific recommendations regarding duration of therapy. In terms of their efficacy and safety profiles, practicality of use, and cost-effectiveness the low-molecular-weight heparins are at least comparable to, and offer several advantages over, other available antithrombotics in cancer patients. In addition, data are emerging that the antithrombotics, and particularly low-molecular-weight heparins, may exert an antitumor effect which could contribute to improved survival in cancer patients when given for long-term prophylaxis. Such findings reinforce the importance of thromboprophylaxis with low-molecular-weight heparin in cancer patients

Climate simulations for 1880-2003 with GISS modelE

We carry out climate simulations for 1880-2003 with GISS modelE driven by ten measured or estimated climate forcings. An ensemble of climate model runs is carried out for each forcing acting individually and for all forcing mechanisms acting together. We compare side-by-side simulated climate change for each forcing, all forcings, observations, unforced variability among model ensemble members, and, if available, observed variability. Discrepancies between observations and simulations with all forcings are due to model deficiencies, inaccurate or incomplete forcings, and imperfect observations. Although there are notable discrepancies between model and observations, the fidelity is sufficient to encourage use of the model for simulations of future climate change. By using a fixed well-documented model and accurately defining the 1880-2003 forcings, we aim to provide a benchmark against which the effect of improvements in the model, climate forcings, and observations can be tested. Principal model deficiencies include unrealistically weak tropical El Nino-like variability and a poor distribution of sea ice, with too much sea ice in the Northern Hemisphere and too little in the Southern Hemisphere. The greatest uncertainties in the forcings are the temporal and spatial variations of anthropogenic aerosols and their indirect effects on clouds.Comment: 44 pages; 19 figures; Final text accepted by Climate Dynamic