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Aims Restrictions to alcohol availability during the first and second waves of the COVID-19 pandemic in Australia included closures of businesses where alcohol is sold for on-premises consumption (pubs, bars, restaurants and cafes), but not where alcohol is sold for off-premises consumption (take-away and home delivery) This study aimed to compare beer consumption before and after restrictions to alcohol availability during the first and second waves of COVID-19 in Australia Design Interrupted time-series analysis Setting Australia Participants Estimated resident population aged 15+ years Measurements Seasonally adjusted estimates of beer per capita consumption measured in litres of alcohol (LALs) per week, disaggregated by on- and off-premises sales Findings First-wave restrictions (week beginning 23 March 2020) were associated with a significant immediate reduction in on-premises beer per capita consumption [-0 013 LALs, 95% confidence interval (CI) = -0 013 to -0 012, P = < 0 001], but no significant change in off-premises beer per capita consumption Partial removal of first-wave restrictions (week beginning 18 May 2020) was associated with a significant immediate increase in on-premises beer per capita consumption (+0 003 LALs, 95% CI = 0 001 to 0 004, P = 0 006), but no significant change in off-premises beer per capita consumption Second-wave restrictions (week beginning 06 July 2020) were associated with a significant immediate reduction in on-premises beer per capita consumption (-0 004 LALs, 95% CI = -0 006 to -0 002, P = 0 001) but, again, no significant change in off-premises beer per capita consumption Conclusion Restricting the availability of on-premises alcohol during the first and second waves of the COVID-19 pandemic in Australia was associated with significant reductions in on-premises beer consumption, but no significant changes in off-premises beer consumption (PsycInfo Database Record (c) 2021 APA, all rights reserved)

This cross-sectional study evaluates the association between sleep disorders and burnout symptoms among faculty and staff at a large teaching hospital.

Ophiogomphus howei Bromley is a rare North American dragonfly, given a global conservation rank of Vulnerable by NatureServe. This species inhabits localized stretches of a limited number of typically undisturbed, high-quality, forested rivers in two disjunct regions in North America. We describe a new population in between the known ranges from an impaired river in a largely urban watershed in southern Michigan, United States. We also report a previously overlooked specimen from a new location in Pennsylvania, United States, and provide current occurrence and conservation status of the species in North America.

INTRODUCTIONTransmembrane signaling of heterotrimeric guanine nucleotide–binding protein (G protein)–coupled receptors (GPCRs) is mediated by ligand-dependent conformational changes that are transmitted from the extracellular ligand binding site to the intracellular side of the receptor to allow coupling with transducers. One hallmark of GPCR activation is the outward movement of the cytoplasmic end of transmembrane domain 6 (TM6) that opens up an intracellular cavity to accommodate the Gα subunit, leading to nucleotide exchange and activation of the G protein. Comparison of family A and family B receptor-Gs protein complex structures has revealed substantial differences in the conformational changes of TM6 upon activation. In family B GPCRs, TM6 shows a disruption of the helical fold and the formation of a sharp kink. This differs from the gradual bending in TM6 observed in family A GPCRs.RATIONALEDespite the recent surge of determined GPCR–G protein complex structures, the activation mechanism of family B receptors remains poorly understood. The missing conserved structural motifs found in family A GPCRs together with the marked differences in the conformation of TM6 in the active state suggest distinct activation mechanisms between family B and family A GPCRs. In particular, the disruption of the helical fold and the unraveling of the extracellular end of TM6 suggest that the energy required to produce the fully active-state of family B GPCRs is higher than for family A GPCRs. We investigated the functional impact of these structural differences by comparing the structure and function of a prototypical family B receptor, the glucagon receptor (GCGR), with the β2 adrenergic receptor (β2AR), a family A GPCR.RESULTSWe present the cryo–electron microscopy structure of the GCGR-Gs complex bound to an engineered soluble glucagon derivative. The structure shows that full activation of GCGR leads to a disruption in the α-helix of TM6 typical for family B GPCRs. Analysis of the functional consequence of this helix break on receptor-mediated G protein dissociation and guanosine triphosphate (GTP) turnover reveals that GCGR exhibits a substantially lower guanine nucleotide exchange factor (GEF) activity in comparison with the family A receptor β2AR. Characterization of G protein association, guanosine diphosphate (GDP) release, and GTP binding kinetics shows that the receptor-mediated GDP dissociation and GTP binding of Gs are slower for GCGR than for β2AR. Measurements of ligand-dependent conformational alterations of GCGR by means of fluorescence and double electron-electron resonance spectroscopy show that agonist binding alone is insufficient to promote TM6 opening, in contrast to previously studied family A GPCRs, including β2AR. The outward movement of TM6 of GCGR is only observed upon interaction with Gs, suggesting that TM6 activation is only triggered by the engagement of the α5 helix of Gαs. Furthermore, TM6 of GCGR remains in the active state for a prolonged time after disengagement of Gs, which might contribute to the persistent and sustained cyclic adenosine monophosphate (cAMP) signaling previously observed for this receptor. A comprehensive comparison of the G protein activation kinetics for a number of other family A and family B GPCRs shows that family B receptors are in general less efficient than family A GPCRs in triggering G protein signaling.CONCLUSIONOur findings provide evidence for distinct activation mechanisms between family A and family B GPCRs. We propose that formation of the helix break and the sharp kink in TM6 of GCGR requires overcoming a higher energy barrier than the bending and outward movement of TM6 in family A receptors. Because of this kinetic barrier, ligand binding alone is not sufficient to stabilize the outward movement of TM6 but promotes the initial formation of the receptor–G protein complex and subsequent full engagement of the G protein at a slower time scale. Once activated by the insertion of the α5 helix of Gαs into the receptor core, as seen in the nucleotide-free complex structure, TM6 stays in the active conformation long after full disengagement of the G protein. This may be responsible for the previously described sustained and prolonged signaling of GCGR. Our comprehensive comparison of the G protein activation kinetics of family A and family B receptors suggests that the activation mechanism described for GCGR is generalizable to other family B GPCRs.

Medical shops in Nepal are a main point of treatment for many diseases including ophthalmic conditions. We sought to evaluate pharmaceutical shop worker knowledge of corneal ulcers and abrasions. A pharmaceutical shop worker from each of 117 different pharmacies surrounding Bharatpur, Nepal, was presented four different eye photographs (i.e., corneal ulcer, corneal abrasion, conjunctivitis, and a normal eye) and asked about diagnosis and management. Of 117 participants, 86 (74%) identified conjunctivitis correctly but few were able to identify corneal abrasion (50/117; 43%) or corneal infection (47/117; 40%). When presented with an illustrated diagram of potential medications to dispense, 15 (13%) participants chose a topical medication containing a corticosteroid for the corneal abrasion and 25 (21%) did so for the corneal ulcer. The appropriate use of corticosteroids for external eye infections is an important topic for additional training, given the potential for these medications to worsen corneal abrasions and ulcers.

High angular resolution observations at optical wavelengths provide valuable insights in stellar astrophysics, directly measuring fundamental stellar parameters, and probing stellar atmospheres, circumstellar disks, elongation of rapidly rotating stars, and pulsations of Cepheid variable stars. The angular size of most stars are of order one milli-arcsecond or less, and to spatially resolve stellar disks and features at this scale requires an optical interferometer using an array of telescopes with baselines on the order of hundreds of meters. We report on the successful implementation of a stellar intensity interferometry system developed for the four VERITAS imaging atmospheric-Cherenkov telescopes. The system was used to measure the angular diameter of the two sub-mas stars $\beta$ Canis Majoris and $\epsilon$ Orionis with a precision better than 5%. The system utilizes an off-line approach where starlight intensity fluctuations recorded at each telescope are correlated post-observation. The technique can be readily scaled onto tens to hundreds of telescopes, providing a capability that has proven technically challenging to current generation optical amplitude interferometry observatories. This work demonstrates the feasibility of performing astrophysical measurements with imaging atmospheric-Cherenkov telescope arrays as intensity interferometers and the promise for integrating an intensity interferometry system within future observatories such as the Cherenkov Telescope Array., Comment: Accepted for publication in Nature Astronomy (2020)

BACKGROUND: The effects on patient safety of eliminating extended-duration work shifts for resident physicians remain controversial. METHODS: We conducted a multicenter, cluster-randomized, crossover trial comparing two schedules for pediatric resident physicians during their intensive care unit (ICU) rotations: extended-duration work schedules that included shifts of 24 hours or more (control schedules) and schedules that eliminated extended shifts and cycled resident physicians through day and night shifts of 16 hours or less (intervention schedules). The primary outcome was serious medical errors made by resident physicians, assessed by intensive surveillance, including direct observation and chart review. RESULTS: The characteristics of ICU patients during the two work schedules were similar, but resident physician workload, described as the mean (±SD) number of ICU patients per resident physician, was higher during the intervention schedules than during the control schedules (8.8±2.8 vs. 6.7±2.2). Resident physicians made more serious errors during the intervention schedules than during the control schedules (97.1 vs. 79.0 per 1000 patient-days; relative risk, 1.53; 95% confidence interval [CI], 1.37 to 1.72; P

Nucleic acid amplification tests are increasingly used to detect ocular chlamydia infection in trachoma research and programs. To evaluate the reliability of Chlamydia trachomatis detection by the Abbott RealTime CT/NG assay (Abbott Molecular, Inc., Des Plaines, IL) on the m2000 platform, three conjunctival samples were collected from each of 200 children aged 0-9 years in Ethiopia: two from the right eye and one from the left eye. Four aliquots were processed for each child: two from the first right eye sample, one from the second right eye sample, and one from the left eye sample. Sixty-nine swabs were processed in a U.S. laboratory and 131 in an Ethiopian laboratory. Intra-class correlation coefficients (ICCs) were high when comparing two aliquots from the same swab (ICC ranged from 0.96 to 0.99), two separate swabs from the right eye (0.89-0.91), and one right and one left eye swab (0.87-0.89), indicating reliable chlamydial load assessment across different samples and laboratory settings.

Background The coronavirus disease 2019 pandemic has had an impact on healthcare systems around the world with 3 million people contracting the disease and 208,000 cases resulting in death as of this writing. Information regarding coronavirus infection in pregnancy is still limited. Objective This study aimed to describe the clinical course of severe and critical coronavirus disease 2019 in hospitalized pregnant women with positive laboratory testing for severe acute respiratory syndrome coronavirus 2. Study Design This is a cohort study of pregnant women with severe or critical coronavirus disease 2019 hospitalized at 12 US institutions between March 5, 2020, and April 20, 2020. Severe disease was defined according to published criteria as patient-reported dyspnea, respiratory rate >30 per minute, blood oxygen saturation ≤93% on room air, ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen 50% within 24–48 hours on chest imaging. Critical disease was defined as respiratory failure, septic shock, or multiple organ dysfunction or failure. Women were excluded from the study if they had presumed coronavirus disease 2019, but laboratory testing was negative. The primary outcome was median duration from hospital admission to discharge. Secondary outcomes included need for supplemental oxygen, intubation, cardiomyopathy, cardiac arrest, death, and timing of delivery. The clinical courses are described by the median disease day on which these outcomes occurred after the onset of symptoms. Treatment and neonatal outcomes are also reported. Results Of 64 hospitalized pregnant women with coronavirus disease 2019, 44 (69%) had severe disease, and 20 (31%) had critical disease. The following preexisting comorbidities were observed: 25% had a pulmonary condition, 17% had cardiac disease, and the mean body mass index was 34 kg/m2. Gestational age was at a mean of 29±6 weeks at symptom onset and a mean of 30±6 weeks at hospital admission, with a median disease day 7 since first symptoms. Most women (81%) were treated with hydroxychloroquine; 7% of women with severe disease and 65% of women with critical disease received remdesivir. All women with critical disease received either prophylactic or therapeutic anticoagulation during their admission. The median duration of hospital stay was 6 days (6 days [severe group] and 10.5 days [critical group]; P=.01). Intubation was usually performed around day 9 on patients who required it, and peak respiratory support for women with severe disease was performed on day 8. In women with critical disease, prone positioning was required in 20% of cases, the rate of acute respiratory distress syndrome was 70%, and reintubation was necessary in 20%. There was 1 case of maternal cardiac arrest, but there were no cases of cardiomyopathy or maternal death. Thirty-two of 64 (50%) women with coronavirus disease 2019 in this cohort delivered during their hospitalization (34% [severe group] and 85% [critical group]). Furthermore, 15 of 17 (88%) pregnant women with critical coronavirus disease 2019 delivered preterm during their disease course, with 16 of 17 (94%) pregnant women giving birth through cesarean delivery; overall, 15 of 20 (75%) women with critical disease delivered preterm. There were no stillbirths or neonatal deaths or cases of vertical transmission. Conclusion In pregnant women with severe or critical coronavirus disease 2019, admission into the hospital typically occurred about 7 days after symptom onset, and the duration of hospitalization was 6 days (6 [severe group] vs 12 [critical group]). Women with critical disease had a high rate of acute respiratory distress syndrome, and there was 1 case of cardiac arrest, but there were no cases of cardiomyopathy or maternal mortality. Hospitalization of pregnant women with severe or critical coronavirus disease 2019 resulted in delivery during the clinical course of the disease in 50% of this cohort, usually in the third trimester. There were no perinatal deaths in this cohort.

The internal motions of integral membrane proteins have largely eluded comprehensive experimental characterization. Here the fast side‐chain dynamics of the α‐helical sensory rhodopsin II and the β‐barrel outer membrane protein W have been investigated in lipid bilayers and detergent micelles by solution NMR relaxation techniques. Despite their differing topologies, both proteins have a similar distribution of methyl‐bearing side‐chain motion that is largely independent of membrane mimetic. The methyl‐bearing side chains of both proteins are, on average, more dynamic in the ps–ns timescale than any soluble protein characterized to date. Accordingly, both proteins retain an extraordinary residual conformational entropy in the folded state, which provides a counterbalance to the absence of the hydrophobic effect. Furthermore, the high conformational entropy could greatly influence the thermodynamics underlying membrane‐protein functions, including ligand binding, allostery, and signaling., Two membrane proteins (one α‐helical and one β‐barrel) have been found, using solution NMR relaxation techniques, to have extraordinary side‐chain motion on the ps–ns timescale in both detergent micelles and lipid bilayers. The extensive side‐chain motion about a highly rigid backbone scaffold is consistent with a high residual conformational entropy and helps explain the stability of the folded state in the absence of the hydrophobic effect.

Diffractions are a useful aspect of the seismic wavefield and are often underutilised. By separating the diffractions from the rest of the wavefield they can be used for various applications such as velocity analysis, structural imaging, and wavefront tomography. However, separating the diffractions is a challenging task due to the comparatively low amplitudes of diffractions as well as the overlap between reflection and diffraction energy. Whilst there are existing analytical methods for separation, these act to remove reflections, leaving a volume which contains diffractions and noise. On top of this, analytical separation techniques can be costly computationally as well as requiring manual parameterisation. To alleviate these issues, a deep neural network has been trained to automatically identify and separate diffractions from reflections and noise on pre-migration data.Here, a Generative Adversarial Network (GAN) has been trained for the automated separation. This is a type of deep neural network architecture which contains two neural networks which compete against one another. One neural network acts as a generator, creating new data which appears visually similar to the real data, while a second neural network acts as a discriminator, trying to identify whether the given data is real or fake. As the generator improves, so too does the discriminator, giving a deeper understanding of the data. To avoid overfitting to a specific dataset as well as to improve the cross-data applicability of the network, data from several different seismic datasets from geologically distinct locations has been used in training. When comparing a network trained on a single dataset compared to one trained on several datasets, it is seen that providing additional data improves the separation on both the original and new datasets.The automatic separation technique is then compared with a conventional, analytical, separation technique; plane-wave destruction (PWD). The computational cost of the GAN separation is vastly superior to that of PWD, performing a separation in minutes on a 3-D dataset in comparison to hours. Although in some complex areas the GAN separation is of a higher quality than the PWD separation, as it does not rely on the dip, there are also areas where the PWD outperforms the GAN separation. The GAN may be enhanced by adding more training data as well as by improving the initial separation used to create the training data, which is based around PWD and thus is imperfect and can introduce bias into the network. A potential for this is training the GAN entirely using synthetic data, which allows for a perfect separation as the points are known, however, it must be of sufficient volume for training and sufficient quality for real data applicability.

Water is a critical resource that can range from being either available in short supply or excess, causing floods. In many locations the majority of this supply is underground. In some geological terrains such as karst these underground systems transport water primarily through crack or conduit flow. Determining the subsurface locations of the dominant flowing structures and their flow rates in such karst systems is a significant challenge. The details of these complex flow networks can, for example, have a first-order control on water supply, surface floods and the locations of seasonal lakes. Current geophysical methods focus on active geophysical imaging of karst structures but usually fail in determining if such structures are flowing. In this work, we take a different approach locating flowing conduits in Irish karst via a multi-method analysis of ground vibrations from temporary deployments of passive seismic sensors. We start by testing the methodology on surface rivers. Hydrological processes including turbulent water flow and sediment transport create ground vibrations that can be detected on seismic stations. In the initial test, we deployed two small aperture arrays of 4 and 6 three-component (3C) short-period seismometers and a short linear array beside a river with a typical flow rate of 25 m3/second. We see clear spectral peaks associated with water flow at frequencies of 10 to 40 Hz. We locate the sources for these frequency bands using both conventional beamforming array analysis and an Amplitude Source Location Method (ASLM). Before ASLM, we constrain the velocity based on array analysis. Both methodologies perform well in determining the known locations of rapid flow in the river. We then move to a test karst location where the subsurface pathways of large conduits are known through cave dives. We deploy 3C short period seismometers for a few hours. Again we see clear peaks in the seismic spectra which, using ASLM and Frequency-Dependent Polarization Analysis (FDPA), located close to the known conduits. In the station close to a known conduit, we see sustained very high-frequency signals which are in agreement with numerical simulation of crack dominated flow for secondary short narrow cracks. This work is the prelude to a larger seismic nodal deployment that will take place in the winter/spring of 2020 in the same location. Initial results from that experiment will also be presented.

Sensory systems are tuned by selection to maximize organismal fitness in particular environments. This tuning has implications for intraspecies communication, the maintenance of species boundaries, and speciation. Tuning of color vision largely depends on the sequence of the expressed opsin proteins. To improve tuning of visual sensitivities to shifts in habitat or foraging ecology over the course of development, many organisms change which opsins are expressed. Changes in this developmental sequence (heterochronic shifts) can create differences in visual sensitivity among closely related species. The genetic mechanisms by which these developmental shifts occur are poorly understood. Here, we use quantitative trait locus analyses, genome sequencing, and gene expression studies in African cichlid fishes to identify a role for the transcription factor Tbx2a in driving a switch between long wavelength sensitive (LWS) and Rhodopsin-like (RH2) opsin expression. We identify binding sites for Tbx2a in the LWS promoter and the highly conserved locus control region of RH2 which concurrently promote LWS expression while repressing RH2 expression. We also present evidence that a single change in Tbx2a regulatory sequence has led to a species difference in visual tuning, providing the first mechanistic model for the evolution of rapid switches in sensory tuning. This difference in visual tuning likely has important roles in evolution as it corresponds to differences in diet, microhabitat choice, and male nuptial coloration.

Gambling advertising has become ubiquitous in westernised countries in the last two decades, yet there is little understanding of the relationship between exposure to gambling advertising and gambling attitudes, intentions and behaviour. We conduct a critical and meta-analytic review of the past two decades of empirical research. The research suggests a positive association between exposure to gambling advertising and gambling-related attitudes, intentions and behaviour. The association is greatest for gambling behaviour. There is some evidence for a dose-response relationship. The quality and breadth of research on gambling advertising are weaker than those in comparable areas (e.g., alcohol, tobacco), with an absence of longitudinal and experimental studies. Gaps in, and methodological problems with, the field are discussed, and research directions recommended.

The relationship between malaria and malnutrition is complicated, and existence of one may predispose or exacerbate the other. We evaluated the relationship between malaria parasitemia and nutritional status in children living in communities participating in a cluster-randomized trial of biannual azithromycin compared with placebo for prevention of childhood mortality. Data were collected during the low malaria transmission and low food insecurity season. Parasitemia was not associated with weight-for-height Z-score (24 months: P = 0.11 azithromycin communities, P = 0.75 placebo communities), weight-for-age Z-score (24 months: P = 0.83 azithromycin, P = 0.78 placebo), height-for-age Z-score (24 months: P = 0.30 azithromycin, P = 0.87 placebo), or mid-upper arm circumference (24 months: P = 0.12 azithromycin, P = 0.56 placebo). There was no statistically significant evidence of a difference in the relationship in communities receiving azithromycin or placebo. During the low transmission season, there was no evidence that malaria parasitemia and impaired nutritional status co-occur in children.

Summary Background The Macrolides Oraux pour Reduire les Deces avec un Oeil sur la Resistance (MORDOR) trial found that biannual mass distribution of azithromycin to children younger than 5 years in Niger reduced the primary outcome of all-cause mortality by 18%. We aimed to determine the causes of mortality among deceased children using verbal autopsy. Methods In this 2-year cluster-randomised controlled trial, 594 community clusters in Niger were randomly allocated (1:1 ratio) to receive biannual mass distributions of either oral azithromycin (approximately 20 mg per kg of bodyweight) or placebo targeted to children aged 1–59 months. Participants, study investigators, and field workers were masked to treatment allocation. Between Nov 23, 2014, and July 31, 2017, 3615 child deaths were recorded by use of biannual house-to-house censuses, and verbal autopsies were done between May 26, 2015, and May 17, 2018, to identify cause of death. Cause-specific mortality, as assessed by verbal autopsy, was a prespecified secondary outcome. This trial is completed and is registered with ClinicalTrials.gov , NCT02047981 . Findings Between Nov 23, 2014, and July 31, 2017, 303 communities (n=40 375 children at baseline) in Niger received mass azithromycin and 291 communities (n=35 747 children at baseline) received placebo. Treatment coverage was 90·3% (SD 10·6) in the azithromycin group and 90·4% (10·1) in the placebo group. No communities were lost to follow-up. In total, 1727 child deaths in the azithromycin group and 1888 child deaths in the placebo group were reported from the population censuses. Of these, the cause of death for 1566 (90·7%) children in the azithromycin group and 1735 (91·9%) children in the placebo group were ascertained by verbal autopsy interviews. In the azithromycin group, 437 (27·9%) deaths were due to malaria, 252 (16·1%) deaths were due to pneumonia, and 234 (14·9%) deaths were due to diarrhoea. In the placebo group, 493 (28·4%) deaths were due to malaria, 275 (15·9%) deaths were due to pneumonia, and 251 (14·5%) deaths were due to diarrhoea. Relative to communities that received placebo, child mortality in communities that received azithromycin was lower for malaria (incidence rate ratio 0·78, 95% CI 0·66–0·92; p=0·0029), dysentery (0·65, 0·44–0·94; p=0·025), meningitis (0·67, 0·46–0·97; p=0·036), and pneumonia (0·83, 0·68–1·00; p=0·051). The distribution of causes of death did not differ significantly between the two study groups (p=0·98). Interpretation Mass azithromycin distribution resulted in approximately a third fewer deaths in children aged 1–59 months due to meningitis and dysentery, and a fifth fewer deaths due to malaria and pneumonia. The lack of difference in the distribution of causes of death between the azithromycin and placebo groups could be attributable to the broad spectrum of azithromycin activity and the study setting, in which most childhood deaths were due to infections. Funding Bill & Melinda Gates Foundation.

HESS J0632+057 is a gamma-ray binary composed of a compact object orbiting a Be star with a period of about $315$ days. Extensive X-ray and TeV gamma-ray observations have revealed a peculiar light curve containing two peaks, separated by a dip. We present the results of simultaneous observations in hard X-rays with NuSTAR and in TeV gamma-rays with VERITAS, performed in November and December 2017. These observations correspond to the orbital phases $\phi\approx0.22$ and $0.3$, where the fluxes are rising towards the first light-curve peak. A significant variation of the spectral index from 1.77$\pm$0.05 to 1.56$\pm$0.05 is observed in the X-ray data. The multi-wavelength spectral energy distributions (SED) derived from the observations are interpreted in terms of a leptonic model, in which the compact object is assumed to be a pulsar and non-thermal radiation is emitted by high-energy electrons accelerated at the shock formed by the collision between the stellar and pulsar wind. The results of the SED fitting show that our data can be consistently described within this scenario, and allow us to estimate the magnetization of the pulsar wind at the location of the shock formation. The constraints on the pulsar-wind magnetization provided by our results are shown to be consistent with those obtained from other systems., Comment: Accepted for publication in The Astrophysical Journal

Summary Diffraction imaging is a niche imaging technique which aims to directly image discontinuities in the subsurface by separating diffractions from the rest of the wavefield and processing them independently. However, to separate diffractions is a complicated procedure due to their weak amplitudes and the overlap of energies between diffractions and the much stronger reflections. While analytical methods exist to separate diffractions, they require parameterisation, are comparatively computationally expensive, and leave a volume which contains both diffractions and noise. Here, we aim to use a Generative Adversarial Network (GAN) to automatically separate diffractions from reflections on pre-migrated seismic data without the need for parameterisation. We have applied the GAN to two real datasets, one for validation, which comes from the same dataset used in training, and one which is used solely for prediction. This shows good results for both the validation and prediction data when compared to plane-wave destruction, an analytical separation technique, and is applied in a fraction of the time. The prediction dataset is then added to the overall training data, the network retrained and applied to the same validation data. This further improves the separation on the validation data and suggests that additional data may enhance the separation.

Diffuse large B-cell lymphoma (DLBCL) is the commonest type of lymphomas, accounting for 30%-40% of new cases each year. Despite the big improvements achieved in the treatment, still 25–40% of patients still succumb due to refractory or relapsed disease. This highlights the need of new drugs for this cancer. The marine environment has recently been recognized as a source of anti-cancer compounds, as demonstrated by different marine drugs approved by different regulatory agencies (trabectedin, cytarabine, eribulin, plitidepsin) or as components of antibody drug conjugates for lymphoma patients (monomethyl auristatin E in polatuzumab vedotin and brentuximab vedotin). Here, we present a large screening of fractions obtained from different marine invertebrates collected in Ireland and in the Pacific Ocean on DLBCL cell lines

We describe a method of automatic feedback provision for students learning computational science and data science methods in Python. We have implemented, used and refined this system since 2009 for growing student numbers, and summarise the design and experience of using it. The core idea is to use a unit testing framework: the teacher creates a set of unit tests, and the student code is tested by running these tests. With our implementation, students typically submit work for assessment, and receive feedback by email within a few minutes after submission. The choice of tests and the reporting back to the student is chosen to optimise the educational value for the students. The system very significantly reduces the staff time required to establish whether a student’s solution is correct, and shifts the emphasis of computing laboratory student contact time from assessing correctness to providing guidance. The self-paced nature of the automatic feedback provision supports a student-centred learning approach. Students can re-submit their work repeatedly and iteratively improve their solution, and enjoy using the system. We include an evaluation of the system from using it in a class of 425 students.

The astrophysical journal 896(1), 41 - (2020). doi:10.3847/1538-4357/ab910e, The radio source 3C 264, hosted by the giant elliptical galaxy NGC 3862, was observed with VERITAS between February 2017 and May 2019. These deep observations resulted in the discovery of very-high-energy (VHE; E $>100$ GeV) $\gamma$-ray emission from this active galaxy. An analysis of $\sim$57 hours of quality-selected live time yields a detection at the position of the source, corresponding to a statistical significance of 7.8 standard deviations above background. The observed VHE flux is variable on monthly time scales, with an elevated flux seen in 2018 observations. The VHE emission during this elevated state is well-characterized by a power-law spectrum with a photon index $\Gamma = 2.20 \pm 0.27$ and flux F($>315$ GeV) = ($7.6\pm 1.2_{\mathrm stat} \pm 2.3_{\mathrm syst})\times 10^{-13}$ cm$^{-2}$ s$^{-1}$, or approximately 0.7% of the Crab Nebula flux above the same threshold. 3C 264 ($z = 0.0217$) is the most distant radio galaxy detected at VHE, and the elevated state is thought to be similar to that of the famously outbursting jet in M 87. Consequently, extensive contemporaneous multi-wavelength data were acquired in 2018 at the time of the VHE high state. An analysis of these data, including VLBA, VLA, HST, Chandra and Swift observations in addition to the VERITAS data, is presented, along with a discussion of the resulting spectral energy distribution., Published by Univ.8743, Chicago, Ill. [u.a.]

Context. In February 2017 the blazar OJ 287, one of the best super-massive binary-black-hole-system candidates, was detected for the first time at very high energies (VHEs; E > 100 GeV) with the ground-based γ-ray observatory VERITAS. Aims. Very high energy γ rays are thought to be produced in the near vicinity of the central engine in active galactic nuclei. For this reason, and with the main goal of providing useful information for the characterization of the physical mechanisms connected with the observed teraelectronvolt flaring event, we investigate the parsec-scale source properties by means of high-resolution very long baseline interferometry observations. Methods. We use 86 GHz Global Millimeter-VLBI Array (GMVA) observations from 2015 to 2017 and combine them with additional multiwavelength radio observations at different frequencies from other monitoring programs. We investigate the source structure by modeling the brightness distribution with two-dimensional Gaussian components in the visibility plane. Results. In the GMVA epoch following the source VHE activity, we find a new jet feature (labeled K) at ∼0.2 mas from the core region and located in between two quasi-stationary components (labeled S1 and S2). Multiple periods of enhanced activity are detected at different radio frequencies before and during the VHE flaring state. Conclusions. Based on the findings of this work, we identify as a possible trigger for the VHE flaring emission during the early months of 2017 the passage of a new jet feature through a recollimation shock (represented by the model-fit component S1) in a region of the jet located at a de-projected distance of ∼10 pc from the radio core. © ESO 2022., This research has made use of data obtained with the Global Millimeter VLBI Array (GMVA), which consists of telescopes operated by the MPIfR, IRAM, Onsala, Metsahovi, Yebes and the VLBA. The Green Bank Observatory is a facility of the National Science Foundation operated under cooperative agreement by Associated Universities, Inc. The data were correlated at the correlator of the MPIfR in Bonn, Germany. R. L., J. L. G., G. Y. Z., A. F., T. T., I. C., I. A. and A. A. acknowledge financial support from the State Agency for Research of the Spanish MCIU through the “Center of Excellence Severo Ochoa” award for the Instituto de Astrofísica de Andalucía (SEV-2017-0709), from the Spanish Ministerio de Economía y Competitividad, and Ministerio de Ciencia e Innovación (grants AYA2016-80889-P, PID2019-108995GB-C21, PID2019-107847RB-C44), the Consejería de Economía, Conocimiento, Empresas y Universidad of the Junta de Andalucía (grant P18-FR-1769), the Consejo Superior de Investigaciones Científicas (grant 2019AEP112). This study makes use of 43 GHz VLBA data from the VLBA-BU Blazar Monitoring Program (BEAM-ME and VLBA-BU-BLAZAR; http://www.bu.edu/blazars/VLBAproject.html), funded by NASA through the Fermi Guest Investigator Program. The research at Boston University was supported in part by NASA Fermi Guest Investigator program grant 80NSSC20K1567. The VLBA is an instrument of the National Radio Astronomy Observatory. The National Radio Astronomy Observatory is a facility of the National Science Foundation operated by Associated Universities, Inc. The POLAMI observations were carried out at the IRAM 30m Telescope. IRAM is supported by INSU/CNRS (France), MPG (Germany) and IGN (Spain). This research has made use of data from the MOJAVE database that is maintained by the MOJAVE team (Lister et al. 2018). This research has made use of data from the OVRO 40-m monitoring program (Richards et al. 2011), supported by private funding from the California Insitute of Technology and the Max Planck Institute for Radio Astronomy, and by NASA grants NNX08AW31G, NNX11A043G, and NNX14AQ89G and NSF grants AST-0808050 and AST- 1109911.

Structural phase transitions run in families of crystalline solids. Perovskites, for example, feature a remarkable number of structural transformations that produce a wealth of exotic behaviors, including ferroelectricity, magnetoresistance, metal–insulator transitions and superconductivity. In superatomic crystals and other such materials assembled from programmable building blocks, phase transitions offer pathways to new properties that are both tunable and switchable. Here we describe [Co6Te8(PEt3)6][C70]2, a novel superatomic crystal with two separate phase transitions that drastically transform the collective material properties. A coupled structural-electronic phase transition triggers the emergence of a new electronic band in the fullerene sublattice of the crystal, increasing its electrical conductivity by 2 orders of magnitude, while narrowing its optical gap and increasing its spin density. Independently, an order–disorder transition transforms [Co6Te8(PEt3)6][C70]2 from a phonon crystal to a ph...

BACKGROUND: Mass distributions of azithromycin for trachoma have been associated with secondary benefits, including reductions in child mortality. METHODS: In the Partnership for the Rapid Elimination of Trachoma cluster-randomized trial in Niger, 24 communities were randomized to annual treatment of everyone and 24 communities were randomized to biannual treatment of children under 12 for 3 years (clinicaltrials.gov, NCT00792922). Treatment was a single dose of directly observed oral azithromycin (20 mg/kg up to 1 g in adults). Vital status was assessed during annual census and monitoring visits. In this prespecified secondary analysis, we compared the mortality rate among children 6 months to less than 5 years of age by treatment arm using negative binomial regression. RESULTS: Among children 6 months to less than 5 years of age, 404 deaths occurred during the study period. The mortality rate was 35.6 deaths per 1000 person-years (231 deaths, 95% CI: 30.9-40.9) in the annual arm and 29.0 deaths per 1000 person-years (173 deaths, 95% CI: 24.8-33.8) in the biannual arm. The mortality rate ratio comparing children in the biannual arm to the annual arm was 0.81 (95% CI: 0.66-1.00, P = 0.07; primary outcome). The mortality rate ratio comparing children who died from infectious causes in the biannual arm to the annual arm was 0.73 (95% CI: 0.57-0.94; P = 0.02). No adverse events were reported. CONCLUSIONS: This secondary analysis of a cluster-randomized trial found a nonsignificant 19% decrease in mortality among children 6 months to less than 5 years of age who received biannual azithromycin compared with children who received annual azithromycin. This study was conducted in a high mortality, trachoma-endemic area; thus, results may be specific to this environment only. In addition, the trial was neither designed nor powered to detect a mortality effect, and we cannot rule out the possibility that mortality differences resulted from bias.

The bombo con platillo, a double-headed bass drum with a mounted cymbal, is a potent icon of murga porteña, a genre of Carnival art from Buenos Aires, Argentina. The instrument also has strong associations with other marginalized popular activities: soccer fandom and Peronist political demonstration. These historical associations alone are not sufficient to account for the drum’s importance, however. This ethnographic account considers the social life of the bombo as an agent with the power to generate effects that are sonic, corporeal, economic, and political in the service of these marginalized popular identities. El bombo con platillo, un tambor grave de dos parches con un platillo montado, es un ícono potente de la murga porteña, un género de arte carnavalesco de Buenos Aires, Argentina. El instrumento también conlleva asociaciones fuertes con otros circuitos populares y marginales: la hinchada de fútbol y la manifestación política peronista. Sin embargo, estas asociaciones históricas no son del todo suficientes para explicar su importancia. Este análisis etnográfico trata la vida social del bombo como actor que tiene el poder de generar efectos sonoros, corporales, económicos, y políticos, en servicio de estas identidades marginales.

Joint neuropathic pain occurs in a subset of arthritis patients, and lysophosphatidic acid (LPA) has been implicated as a mediator of joint neuropathy. The mechanism by which LPA promotes neuropathic pain is unknown but may be related to altered signalling of the voltage-gated sodium channel Nav1.8 located on nociceptors. Because arthritis and neuropathic pain are more prevalent in females, this study aimed to explore potential sex differences in the development of LPA-induced joint neuropathy and whether Nav1.8 played a role in the associated neuropathic pain. Joint neuropathy was induced in male and female Wistar rats (179-284 g) by intra-articular injection of 50-µg LPA. Pain behaviour was assessed over 21 days using von Frey hair algesiometry. On day 21, electrophysiological recordings of joint primary afferents were conducted to measure peripheral sensitisation. Saphenous nerve morphology and expression of the nerve-damage marker ATF3 and Nav1.8 in ipsilateral dorsal root ganglions were compared on the basis of sex. The analgesic properties of the selective Nav1.8 antagonist A-803467 was determined in pain behaviour and electrophysiology experiments. Females developed more severe mechanical allodynia than males after LPA treatment. Lysophosphatidic acid caused more pronounced demyelination of the saphenous nerve in females, but no sex differences were observed in the expression of ATF3 or Nav1.8 in dorsal root ganglion neurones. Blockade of Nav1.8 channels with A-803467 resulted in a decrease in joint mechanosensitivity and secondary allodynia with females exhibiting a greater response. These findings suggest that LPA has sex-specific effects on joint neuropathy and Nav1.8 gating, which should be considered when treating neuropathic arthritis patients.

Biogenic habitat structure, such as that created by foundation macrophytes , shapes the interactions of higher trophic level organisms by creating three-dimensional refuge spaces. In recent decades, many kelp habitats have transformed into turf-dominated communities. This represents a fundamental change in the overall habitat structure in these communities, with an unknown impact on upper trophic level organisms. We investigated how macroalgae morphology affects a common residential mid-trophic level wrasse , Tautogolabrus adspersus (cunner), which utilizes macroalgae for both refuge and foraging. Three studies were conducted: in situ behavioral video observations, a refuge choice experiment, and a foraging efficiency experiment. Video observations revealed that in kelp-dominated and mixed habitat types cunner use macroalgae more often for refuge than for foraging, but in turf-dominated habitats refuge and foraging events were equal. In these habitats, refuge-seeking was more often associated with a tall, morphologically simple kelp. The refuge choice experiment supported our video observations with cunner preferentially seeking refuge beneath taller but less morphologically complex algae instead of shorter filamentous forms. In predation trials, macroalgae complexity did not significantly affect the number of prey the fish captured. Our results provide evidence that the refuge-seeking behavior of this residential mid-trophic level fish may be impacted by the ongoing shifts in macroalgae dominance in the Gulf of Maine. Loss of its preferred refuge (tall, canopy-forming kelps) may force it to use the less-preferred introduced turf algae instead. However, whether turf provides sufficient protection for this species remains unclear. With the ongoing loss of kelp in temperate coastal ecosystems worldwide, it is important to understand the potential indirect effects that changes in habitat structure will have on the trophic interactions of upper level organisms.

Objective To compare oral voriconazole vs placebo in addition to topical antifungals in the treatment of filamentous fungal keratitis. Design Non-prespecified, secondary case-control analysis from a multicenter, double-masked, randomized placebo-controlled clinical trial. Methods Study Participants : Patients with smear-positive filamentous fungal ulcers and visual acuity of 20/400 or worse who eventuated to therapeutic penetrating keratoplasty (TPK). Intervention : Study participants were randomized to oral voriconazole vs oral placebo; all received topical antifungal drops. Main Outcome Measures : TPK button culture positivity. Results A total of 95 of 194 (49.5%) study participants enrolled at Madurai, Coimbatore, or Pondicherry, India eventuated to TPK in an average of 20.9 days (standard deviation 15.2 days, range 2-71 days). TPK button cultures were available for 67 of 95 (71%) of the TPKs performed and were positive for filamentous fungus in 45 of 67 (67%) cases. For each 1-day increase in the time to TPK there was 0.94-fold decreased odds of fungal culture positivity (95% confidence interval [CI] 0.90–0.98, P = .005). Those randomized to oral voriconazole had 1.26-fold increased odds of TPK button culture positivity after controlling for time to TPK and baseline organism, but this was not statistically significant (95% CI 0.32–4.87; P = .74). Those who underwent TPK for lack of response to medical therapy were 10.64-fold more likely to be culture positive than if the indication for surgery was perforation and this was statistically significant (95% CI 2.16–51.70; P = .003). Conclusions There appears to be no benefit to adding oral voriconazole to topical antifungal agents in the treatment of severe filamentous fungal ulcers. Infection rather than inflammation appears to be the reason for the worsening clinical picture in many of these patients.

Cannabis has been used for millennia to treat a multitude of medical conditions including chronic pain. Osteoarthritis (OA) pain is one of the most common types of pain and patients often turn to medical cannabis to manage their symptoms. While the majority of these reports are anecdotal, there is a growing body of scientific evidence which supports the analgesic potential of cannabinoids to treat OA pain. OA pain manifests as a combination of inflammatory, nociceptive, and neuropathic pain, each requiring modality-specific analgesics. The body's innate endocannabinoid system (ECS) has been shown to ameliorate all of these pain subtypes. This review summarizes the components of the ECS and details the latest research pertaining to plant-based and man-made cannabinoids for the treatment of OA pain. Recent pre-clinical evidence supporting a role for the ECS to control OA pain is described as well as current clinical evidence of the efficacy of cannabinoids for treating OA pain in mixed patient populations.

Purpose: We compare results from regression discontinuity (RD) analysis to primary results of a randomized controlled trial (RCT) utilizing data from two contemporaneous RCTs for treatment of fungal corneal ulcers. Methods: Patients were enrolled in the Mycotic Ulcer Treatment Trials I and II (MUTT I & MUTT II) based on baseline visual acuity: patients with acuity ≤ 20/400 (logMAR 1.3) enrolled in MUTT I, and >20/400 in MUTT II. MUTT I investigated the effect of topical natamycin versus voriconazole on best spectacle-corrected visual acuity. MUTT II investigated the effect of topical voriconazole plus placebo versus topical voriconazole plus oral voriconazole. We compared the RD estimate (natamycin arm of MUTT I [N = 162] versus placebo arm of MUTT II [N = 54]) to the RCT estimate from MUTT I (topical natamycin [N = 162] versus topical voriconazole [N = 161]). Results: In the RD, patients receiving natamycin had mean improvement of 4-lines of visual acuity at 3 months (logMAR −0.39, 95% CI: −0.61, −0.17) compared to topical voriconazole plus placebo, and 2-lines in the RCT (logMAR −0.18, 95% CI: −0.30, −0.05) compared to topical voriconazole. Conclusions: The RD and RCT estimates were similar, although the RD design overestimated effects compared to the RCT.

BACKGROUND: Direct-to-adolescent text messaging may be a consideration for vaccine reminders, including human papilloma virus (HPV), but no studies have explored the minimum age at which parents would allow adolescents to receive a text message. METHODS: We distributed a survey to parents of 10–17 year olds during any office visit in two practice based research networks in South Carolina and Oklahoma. We asked about parental preference for receiving vaccine reminders for their adolescent, whether they would allow the healthcare provider to directly message their adolescent, and if so, what would be the acceptable minimum age. RESULTS: In 546 surveys from 11 practices, parents of females were more supportive of direct-to-teen text message reminders than were parents of males, (75% v. 60%, p < .001). The median age at which parents would allow direct text messages from physicians’ offices was 14 in females compared to 15 in males, p = .049. We found a correlation between the child’s age and the youngest age at which parents would allow a direct text message. Of the parents who permitted a text message directly to their adolescent, most reported an allowable age higher than their adolescent’s current age until the age of 15. CONCLUSION: Our study suggests that direct-to-adolescent text messaging would be allowed by parents for older adolescents. This supports an intervention aimed at older adolescents, such as for receipt of MCV4 dose #2, delayed HPV vaccine series completion and annual influenza vaccination.

Objectives: There is no research examining alcohol-related aggression and anti-social behaviour in UK or European sportspeople (athletes), and no research has examined relationships between masculinity, alcohol consumption, and alcohol-related aggression and antisocial behaviour in sportspeople (athletes). This study addresses this gap. Design: Cross-sectional. Methods: A sample (N = 2048; women = 892, 44%) of in season sportspeople enrolled at UK universities (response 83%), completed measures of masculinity, alcohol consumption, within-sport (on-field) violence, and having been the perpetrator and/or victim of alcohol-related violent/aggressive and antisocial behaviour (e.g., hit/assaulted, vandalism, sexual assault). Logistic regressions examined predictors of alcohol-related violence/aggression and anti-social behaviours. Results: Significant bivariate relationships between masculinity, within-sport violence, alcohol consumption, and alcohol-related aggression and anti-social behaviour were found for both men and women (p's < .001). Logistic regression adjusting for all variables showed that higher levels of masculinity and alcohol consumption in men and women were related to an increased odds of having conducted an aggressive, violent and/or anti-social act in the past 12 months when intoxicated. Odds ratios were largest for relationships between masculinity, alcohol consumption, within-sport violence, and interpersonal violence/aggression (p's < .001). A similar pattern of results was found for having been the victim of aggression and anti-social behaviour. Conclusions: Alcohol-related aggression and anti-social behaviour appear to be problematic in UK university sportspeople, and is related to masculinity and excessive drinking. Interventions that reduce excessive alcohol consumption, masculine norms and associated within-sport violence, could be effective in reducing alcohol-related aggression and antisocial behaviour in UK sportspeople. (C) 2017 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

The study conducts an initial examination of the associations between participation and saving in the Promise Indiana Children's Savings Account (CSA) program and school administrative data on attendance and standardized math and reading scores. The primary research questions guiding this analysis are whether or not having a CSA is associated with lower absenteeism and/or higher reading and math scores and, for those who have a CSA, whether being a saver or the amount saved in the account is associated with better academic outcomes. Given the importance of family income to savings behaviors and academic achievement, analyses were conducted for the full sample as well as for the subsample of low-income students, defined by free/reduced lunch status. Among the low-income subsample, having a CSA is positively associated with both reading and math scores; this association is not found in the aggregate sample. The amount contributed to the CSA has a positive association with math and reading scores in the overall sample, but not with the scores of children receiving free/reduced lunch. Being a saver is associated with reading scores for both the overall and free/reduced lunch samples. Student attendance was not associated with any account variables. While more research is needed before policy conclusions can be drawn, these findings suggest that CSA programs may complement schools' academic objectives. Further, this study adds to the literature on children's assets by finding some differences in academic outcomes associated with different engagement with the CSA (e.g. account ownership and saving).

The seismic wavefield arises from interactions of a source wavefield with subsurface heterogeneities as the wavefield propagates through the earth. In a conventional seismic processing workflow, the reflected portion of the wavefield is enhanced at the expense of the rest of the wavefield. While this is useful, considerable information which is contained outside of the reflections is lost. To alleviate this issue, we propose a deep learning technique which aims to separate the wavefield into three of the wavefield components: reflections, diffractions, and noise. This technique involves first performing several data domain transformations on the input and applying these as input classes on a pixel-by-pixel basis to guide the neural network. A simple separation is performed to remove the reflections and noise, allowing the diffractions to be processed independently. This technique, called Multi-domain diffraction identification, gives a high standard classification of the diffractions in a fraction of the time and computational cost of plane-wave destruction. These diffractions have then been removed from the data and compared with separation results from plane-wave destruction, showing similarities in the diffractions and demonstrating the denoising capability of the method.

The recent discovery of electromagnetic signals in coincidence with neutron-star mergers has solidified the importance of multimessenger campaigns in studying the most energetic astrophysical events. Pioneering multimessenger observatories, such as LIGO/Virgo and IceCube, record many candidate signals below the detection significance threshold. These sub-threshold event candidates are promising targets for multimessenger studies, as the information provided by them may, when combined with contemporaneous gamma-ray observations, lead to significant detections. Here we describe a new method that uses such candidates to search for transient events using archival very-high-energy gamma-ray data from imaging atmospheric Cherenkov telescopes (IACTs). We demonstrate the application of this method to sub-threshold binary neutron star (BNS) merger candidates identified in Advanced LIGO's first observing run. We identify eight hours of archival VERITAS observations coincident with seven BNS merger candidates and search them for TeV emission. No gamma-ray emission is detected; we calculate upper limits on the integral flux and compare them to a short gamma-ray burst model. We anticipate this search method to serve as a starting point for IACT searches with future LIGO/Virgo data releases as well as in other sub-threshold studies for multimessenger transients, such as IceCube neutrinos. Furthermore, it can be deployed immediately with other current-generation IACTs, and has the potential for real-time use that places minimal burden on experimental operations. Lastly, this method may serve as a pilot for studies with the Cherenkov Telescope Array, which has the potential to observe even larger fields of view in its divergent pointing mode.

A correction to this paper has been published: https://doi.org/10.1007/s13178-021-00599-2

Objective: To estimate the prevalence of moderate and vigorous physical activity (MVPA), as defined by the World Health Organisation (WHO), and associated factors among teenagers from Barcelona in 2012. Methods: Cross-sectional survey to assess risk factors in a representative sample of secondary school students (aged 13-16 years, International Standard Classification of Education [ISCED]2, n = 2,162; and 17-18 years, ISCED 3, n = 1016) in Barcelona. We estimated MVPA prevalence overall, and for each independent variable and each gender. Poisson regression models with robust variance were fit to examine the factors associated with high-level MVPA, and obtained prevalence ratios (PR) and 95% confidence intervals (95%CI). Results: Only 13% of ISCED 2 and 10% of ISCED 3 students met the WHO physical activity recommendations. This percentage was lower among girls at both academic levels. MVPA was lower among ISCED 3 compared to ISCED 2 students, and among students with a lower socioeconomic status. Physical activity was associated with positive self-perception of the health status (e.g., positive self-perception of health status among ISCED 2 compared to ISCED 3 students: PR = 1.31 [95%CI: 1.22-1.41] and 1.61 [95%CI: 1.44-1.81] for boys and girls, respectively]. Conclusions: The percentage of teenagers who met WHO MVPA recommendations was low. Strategies are needed to increase MVPA levels, particularly in older girls, and students from low socioeconomic backgrounds. (C) 2016 SESPAS. Published by Elsevier Espana, S.L.U.

While membrane technology continues to thrive in seawater desalination, it would defeat the very purpose of saving the environment if toxic solvents are involved in membrane manufacture. As a paradigm of green chemistry, a non-toxic solvent, triethyl phosphate (TEP), was used for the first time to fabricate polyvinylidene fluoride (PVDF) hollow fiber membranes for direct contact membrane distillation (DCMD). The phase inversion kinetics of the PVDF/TEP system was closely investigated and compared with the conventional N-Methyl-2-pyrrolidone (NMP)/PVDF system. The former showed a less abrupt phase inversion rate and produced a more porous sponge-like structure than the latter. The 12/88 wt% PVDF/TEP binary solution produced fibers with promising performance. They not only possessed robust mechanical properties and a liquid entry pressure up to 2.0 bar but also exhibited an average flux of 20 kg/m 2 ·h at 60 °C and a NaCl rejection of 99.99%. In addition, hollow fiber membranes spun from this PVDF/TEP system had porosity of greater than 83% for all conditions studied. Since there were no additives or non-solvents in the dope solutions and no post-treatments involved, the use of TEP as a green solvent could significantly reduce the complexity of membrane fabrication, scale up and commercialization. Clearly, the much safer solvent TEP is able to replace toxic solvents commonly used in membrane manufacture and to produce membranes with highly competitive performance.

The nonpsychoactive cannabis-derivative cannabidiol (CBD) reduced nociceptor activity and pain in end-stage osteoarthritis. Prophylactic treatment with CBD prevented joint neuropathy and chronic neuropathic pain., Osteoarthritis (OA) is a multifactorial joint disease, which includes joint degeneration, intermittent inflammation, and peripheral neuropathy. Cannabidiol (CBD) is a noneuphoria producing constituent of cannabis that has the potential to relieve pain. The aim of this study was to determine whether CBD is anti-nociceptive in OA, and whether inhibition of inflammation by CBD could prevent the development of OA pain and joint neuropathy. Osteoarthritis was induced in male Wistar rats (150-175 g) by intra-articular injection of sodium monoiodoacetate (MIA; 3 mg). On day 14 (end-stage OA), joint afferent mechanosensitivity was assessed using in vivo electrophysiology, whereas pain behaviour was measured by von Frey hair algesiometry and dynamic incapacitance. To investigate acute joint inflammation, blood flow and leukocyte trafficking were measured on day 1 after MIA. Joint nerve myelination was calculated by G-ratio analysis. The therapeutic and prophylactic effects of peripheral CBD (100-300 μg) were assessed. In end-stage OA, CBD dose-dependently decreased joint afferent firing rate, and increased withdrawal threshold and weight bearing (P < 0.0001; n = 8). Acute, transient joint inflammation was reduced by local CBD treatment (P < 0.0001; n = 6). Prophylactic administration of CBD prevented the development of MIA-induced joint pain at later time points (P < 0.0001; n = 8), and was also found to be neuroprotective (P < 0.05; n = 6-8). The data presented here indicate that local administration of CBD blocked OA pain. Prophylactic CBD treatment prevented the later development of pain and nerve damage in these OA joints. These findings suggest that CBD may be a safe, useful therapeutic for treating OA joint neuropathic pain.

Multiparametric magnetic resonance imaging (mpMRI) has added to the armamentarium for the diagnosis and surveillance for organ-confined prostate cancer. Atypical small acinar proliferation and high-grade prostatic intraepithelial neoplasia (HGPIN) are premalignant prostatic lesions. The management of such lesions remains contentious, and the addition of mpMRI introduces further uncertainty, given its ability to pick up indolent lesions and its use in targeted biopsy. We aimed to perform a comprehensive review of current evidence regarding atypical small acinar proliferation, high-grade prostatic intraepithelial neoplasia, and mpMRI to ascertain a consensus for a current management algorithm.

The controlled introduction of impurities into the crystal lattice of solid-state compounds is a cornerstone of materials science. Intercalation, the insertion of guest atoms, ions or molecules between the atomic layers of a host structure, can produce novel electronic, magnetic and optical properties in many materials. Here we describe an intercalation compound in which the host [Co6Te8(PnPr3)6][C60]3, formed from the binary assembly of atomically precise molecular clusters, is a superatomic analogue of traditional layered atomic compounds. We find that tetracyanoethylene (TCNE) can be inserted into the superstructure through a single-crystal-to-single-crystal transformation. Using electronic absorption spectroscopy, electrical transport measurements and electronic structure calculations, we demonstrate that the intercalation is driven by the exchange of charge between the host [Co6Te8(PnPr3)6][C60]3 and the intercalant TCNE. These results show that intercalation is a powerful approach to manipulate the material properties of superatomic crystals. Intercalation — a cornerstone of materials science with wide-ranging applications — has now been demonstrated in a superatomic crystal. A redox-active tetracyanoethylene guest was inserted into the lattice of a material consisting of alternate layers of {Co6Te8} clusters and C60 fullerenes, leading to a single-crystal-to-single-crystal transformation that significantly modulates the material's optical and electrical transport properties.

S Sam Lim,1 Alan J Kivitz,2 Doug McKinnell,3 M Edward Pierson,4 Faye S O’Brien4 1Division of Rheumatology, Department of Medicine, Emory University, Atlanta, GA, USA; 2Altoona Center for Clinical Research, Altoona, PA, USA; 3Deloitte Life Sciences Advisory, Basel, Switzerland; 4Clinical Operations, Global Medicines Development, AstraZeneca, Gaithersburg, MD, USA Purpose: We elicited patient experiences from clinical trial simulations to aid in future trial development and to improve patient recruitment and retention.Patients and methods: Two simulations of draft Phase II and Phase III anifrolumab studies for systemic lupus erythematosus (SLE)/lupus nephritis (LN) were performed involving African-American patients from Grady Hospital, an indigent care hospital in Atlanta, GA, USA, and white patients from Altoona Arthritis and Osteoporosis Center in Altoona, PA, USA. The clinical trial simulation included an informed consent procedure, a mock screening visit, a mock dosing visit, and a debriefing period for patients and staff. Patients and staff were interviewed to obtain sentiments and perceptions related to the simulated visits.Results: The Atlanta study involved 6 African-American patients (5 female) aged 27–60years with moderate to severe SLE/LN. The Altoona study involved 12 white females aged 32–75years with mild to moderate SLE/LN. Patient experiences had an impact on four patient-centric care domains: 1) information, communication, and education; 2) responsiveness to needs; 3) access to care; and 4) coordination of care; and continuity and transition. Patients in both studies desired background material, knowledgeable staff, family and friend support, personal results, comfortable settings, shorter wait times, and greater scheduling flexibility. Compared with the Altoona study patients, Atlanta study patients reported greater preferences for information from the Internet, need for strong community and online support, difficulties in discussing SLE, emphasis on transportation and child care help during the visits, and concerns related to financial matters; and they placed greater importance on time commitment, understanding of potential personal benefit, trust, and confidentiality of patient data as factors for participation. Using these results, we present recommendations to improve study procedures to increase retention, recruitment, and compliance for clinical trials.Conclusion: Insights from these two studies can be applied to the development and implementation of future clinical trials to improve patient recruitment, retention, compliance, and advocacy. Keywords: systemic lupus erythematosus, lupus nephritis, clinical trial simulation, patient recruitment, patient retention

Introduction: The Rehabilitation and Exercise Oncology model of care (ActivOnco) was established to optimize cancer survivorship through exercise prescription and active lifestyle promotion, providing a transition of care from hospital to community. Patients having any cancer diagnosis, stage of disease, and treatment were eligible for evaluation and exercise prescription upon deterioration of performance status. The team of professionals included hospital-based physiotherapists proactively screening for rehabilitation needs, loss of functional independence, and exercise eligibility, plus exercise specialists in a community-based Wellness Centre to provide follow-up or direct access for post-treatment or non-complex patients. Methods: From January 2011 to December 2015, the hospital team assessed 1635 patients representing all major cancer sites, and the Wellness Centre team evaluated and prescribed exercise for 1066 participants. Primary interventions provided were education about fatigue management, physical activity promotion, exercise prescription, fracture risk reduction, referral to specialized follow-up services (for example, occupational therapy, lymphedema clinic), and coordination for mobility aids and paratransit services. Results and Conclusions: Implementation of the ActivOnco model of care showed that exercise alone is not a panacea for all functional deterioration associated with the cancer trajectory and its treatment. However, screening to identify rehabilitation needs combined with exercise prescription can effectively improve the quality of survivorship in cancer patients. Program developments are limited by the cost of human resources, lack of hospital-based physical resources, and lack of public funding, all of which significantly limit the scope and development of appropriate services.