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ObjectiveVasomotor symptoms (VMS) may be a marker of cardiovascular risk. We aimed to evaluate the cross-sectional association of VMS presence and severity with hemostatic parameter levels measured at baseline among Women's Health Initiative (WHI) Hormone Therapy trial postmenopausal participants.MethodsThis cross-sectional analysis included 2,148 postmenopausal women with measures of VMS presence and severity reported in the 4 weeks before WHI baseline, who were not using warfarin or hormone therapy and for whom the following baseline hemostatic parameters were measured within the WHI Cardiovascular Disease Biomarker Case-Control Study: antithrombin, plasminogen activator inhibitor-1, protein C antigen, total and free protein S antigen, total and free tissue factor pathway inhibitor, D-dimer, normalized activated protein C sensitivity ratio, and thrombin generation. Using multiple linear regression, we estimated the adjusted average difference in each hemostatic parameter associated with VMS presence and severity. A multiple comparisons-corrected P value was computed using the P-min procedure to determine statistical significance of our smallest observed P value.ResultsWomen were 67 years of age on average and 33% reported VMS presence at baseline. There was some suggestion that VMS presence may be associated with a -0.34 adjusted difference in normalized activated protein C sensitivity ratio compared with no VMS (95% CI, -0.60 to -0.087; P = 0.009), but this association was not significant after correction for multiple comparisons (P = 0.073). VMS presence or severity was not significantly associated with the other hemostatic parameters.ConclusionsWe found no convincing evidence that VMS presence or severity was associated with levels of hemostatic parameters among postmenopausal women.

The emergence of antibiotic-resistant bacterial species, such as vancomycin-resistant enterococci (VRE), necessitates the development of new antimicrobials. Here, we investigate the spectrum of antibacterial activity of three phenylthiazole-substituted aminoguanidines. These compounds possess potent activity against VRE, inhibiting growth of clinical isolates at concentrations as low as 0.5 μg/mL. The compounds exerted a rapid bactericidal effect, targeting cell wall synthesis. Transposon mutagenesis suggested three possible targets: YubA, YubB (undecaprenyl diphosphate phosphatase (UPPP)), and YubD. Both UPPP as well as undecaprenyl diphosphate synthase were inhibited by compound 1. YubA and YubD are annotated as transporters and may also be targets because 1 collapsed the proton motive force in membrane vesicles. Using Caenorhabditis elegans, we demonstrate that two compounds (1, 3, at 20 μg/mL) retain potent activity in vivo, significantly reducing the burden of VRE in infected worms. Taken altogether, the results indicate that compounds 1 and 3 warrant further investigation as novel antibacterial agents against drug-resistant enterococci.

CUORE is a cryogenic detector that will be operated at LNGS to search for neutrinoless double beta decay (0ββ) of 130Te. The detector installation was completed in summer 2016. Before the installation, several cold runs were done to test the cryogenic system performance. In the last cold run the base temperature of 6.3mK was reached in stable condition. CUORE-0, a CUORE prototype, has proven the feasibility of CUORE, demonstrating that the target background of 0.01 counts/keV/kg/y and the energy resolution of 5 keV are within reach.

BackgroundMuch controversy surrounds the association of traditional cardiovascular disease risk factors with venous thromboembolism (VTE).MethodsWe performed an individual level random-effect meta-analysis including 9 prospective studies with measured baseline cardiovascular disease risk factors and validated VTE events. Definitions were harmonized across studies. Traditional cardiovascular disease risk factors were modeled categorically and continuously using restricted cubic splines. Estimates were obtained for overall VTE, provoked VTE (ie, VTE occurring in the presence of 1 or more established VTE risk factors), and unprovoked VTE, pulmonary embolism, and deep-vein thrombosis.ResultsThe studies included 244 865 participants with 4910 VTE events occurring during a mean follow-up of 4.7 to 19.7 years per study. Age, sex, and body mass index-adjusted hazard ratios for overall VTE were 0.98 (95% confidence interval [CI]: 0.89-1.07) for hypertension, 0.97 (95% CI: 0.88-1.08) for hyperlipidemia, 1.01 (95% CI: 0.89-1.15) for diabetes mellitus, and 1.19 (95% CI: 1.08-1.32) for current smoking. After full adjustment, these estimates were numerically similar. When modeled continuously, an inverse association was observed for systolic blood pressure (hazard ratio=0.79 [95% CI: 0.68-0.92] at systolic blood pressure 160 vs 110 mm Hg) but not for diastolic blood pressure or lipid measures with VTE. An important finding from VTE subtype analyses was that cigarette smoking was associated with provoked but not unprovoked VTE. Fully adjusted hazard ratios for the associations of current smoking with provoked and unprovoked VTE were 1.36 (95% CI: 1.22-1.52) and 1.08 (95% CI: 0.90-1.29), respectively.ConclusionsExcept for the association between cigarette smoking and provoked VTE, which is potentially mediated through comorbid conditions such as cancer, the modifiable traditional cardiovascular disease risk factors are not associated with increased VTE risk. Higher systolic blood pressure showed an inverse association with VTE.

Prior research suggests that negligent harms are punished because of the resulting negative outcomes. Under thisaccount, negligent but completely harmless acts should not be punished. An alternative possibility is that negligence is punishedas a way of modifying future thought and behavior. Across three studies we find support for this second proposal. Study 1demonstrates that punishment is assigned to negligent agents, irrespective of whether or not a harm actually occurs. Study 2demonstrates that non-negligent agents who cause harm are punished less than negligent agents who do not cause harm. Study3 shows that the punishment of harmful negligent actions is only judged to be successful when it results in the agent ceasing toact negligently, and not when it results in the harm ceasing to occur. Together, these results suggest that a primary function ofpunishment in cases of negligence is modify future thought.

© Copyright owned by the author(s). CUORE is a ton-scale experiment approaching the data taking phase in Gran Sasso National Laboratory. Its primary goal is to search for the neutrinoless double-beta decay in130Te using 988 crystals of tellurim dioxide. The crystals are operated as bolometers at about 10 mK taking advantage of one of the largest dilution cryostat ever built. Concluded in March 2016, the cryostat commissioning consisted in a sequence of cool down runs each one integrating new parts of the apparatus. The last run was performed with the fully configured cryostat and the thermal load at 4 K reached the impressive mass of about 14 tons. During that run the base temperature of 6.3 mK was reached and maintained for more than 70 days. An array of 8 crystals, called mini-tower, was used to check bolometers operation, readout electronics and DAQ. Results will be presented in terms of cooling power, electronic noise, energy resolution and preliminary background measurements.

CUORE is the first bolometric tonne-scale experiment aiming at the investigation of neutrinoless double-beta (0ν2β) decay of 130Te. The cryogenic commissioning followed by the detector installation and cool down took place during 2016. After the optimisation of all the detectors, the data-taking started in spring 2017. We report about the results of the first dataset acquired in May, which led to a limit on the 0ν2β half-life of 130Te of 6.6×1024 yr. An upgrade of CUORE, named CUPID, is planned to improve the 0ν2β-decay sensitivity via passive and active background reduction and crystal enrichment. Some technologies for CUPID are currently under study and two of them are presented here, involving the detection of Cherenkov and scintillation light emitted by enriched 130TeO2 and Li1002MoO4 crystals respectively. This will allow us to reject the currently dominant α background.

Neutrino oscillation experiments proved that neutrinos have mass and this enhanced the interest in neutrinoless double-beta decay (0vββ). The observation of this very rare hypothetical decay would prove the leptonic number violation and would give us indications about neutrinos mass hierarchy and absolute mass scale. CUORE (Cryogenic Underground Observatory for Rare Events) is an array of 988 crystals of TeO2, for a total sensitive mass of 741 kg. Its goal is the observation of 0vββ of 130Te. The crystals, placed into the a dilution cryostat, are operated as bolometers at a temperature close to 10 mK. CUORE commissioning phase has been concluded recently in Gran Sasso National Laboratory, Italy, and data taking is expected to start in spring 2017. If target background rate is reached (0.01counts/day/keV/kg), the sensibility of CUORE will be, in five years of data taking, T1/21026years (1θ CL). In order to test the quality of materials and optimize the construction procedures, the collaboration realized CUORE-0, that took data from spring of 2013 to summer 2015. Here, after a brief description of CUORE, I report its commissioning status and CUORE-0 results.

We report on the measurement of the two-neutrino double-beta decay half-life of 130Te with the CUORE-0 detector. From an exposure of 33.4 kg year of TeO2, the half-life is determined to be T1/22ν = [8.2 ± 0.2 (stat.) ± 0.6 (syst.)] × 1020 year. This result is obtained after a detailed reconstruction of the sources responsible for the CUORE-0 counting rate, with a specific study of those contributing to the 130Te neutrinoless double-beta decay region of interest.

We report on the measurement of the two-neutrino double-beta decay half-life of 130Te with the CUORE-0 detector. From an exposure of 33.4 kg year of TeO2, the half-life is determined to be T1/22ν = [8.2 ± 0.2 (stat.) ± 0.6 (syst.)] × 1020 year. This result is obtained after a detailed reconstruction of the sources responsible for the CUORE-0 counting rate, with a specific study of those contributing to the 130Te neutrinoless double-beta decay region of interest.

Neutrino oscillation experiments proved that neutrinos have mass and this enhanced the interest in neutrinoless double-beta decay (0vββ). The observation of this very rare hypothetical decay would prove the leptonic number violation and would give us indications about neutrinos mass hierarchy and absolute mass scale. CUORE (Cryogenic Underground Observatory for Rare Events) is an array of 988 crystals of TeO2, for a total sensitive mass of 741 kg. Its goal is the observation of 0vββ of 130Te. The crystals, placed into the a dilution cryostat, are operated as bolometers at a temperature close to 10 mK. CUORE commissioning phase has been concluded recently in Gran Sasso National Laboratory, Italy, and data taking is expected to start in spring 2017. If target background rate is reached (0.01counts/day/keV/kg), the sensibility of CUORE will be, in five years of data taking, T1/21026years (1θ CL). In order to test the quality of materials and optimize the construction procedures, the collaboration realized CUORE-0, that took data from spring of 2013 to summer 2015. Here, after a brief description of CUORE, I report its commissioning status and CUORE-0 results.

Introduction: Older adults frequently return to an emergency department (ED) within 30 days of an initial visit. In this study, we examined the effectiveness of an adapted Care Transitions Intervention (CTI) at reducing risk of ED revisits within 30 days for older adults who live alone. We also explored the interaction between receiving help with healthcare needs and receiving the CTI on the risk of 30-day ED revisits. Methods: We conducted a subgroup analysis of community-dwelling older (age≥60 years) ED patients who reported living alone as part of a randomized controlled trial of CTI effectiveness following discharge home from one of three EDs in two states. The primary outcome (ED revisits within 30 days of discharge) and secondary outcomes (ED revisits within 14 days, outpatient follow-up within 7 and 30 days) were obtained from medical record review and patient surveys. Two-sample t-tests and binomial logistic regression were used to analyze main and interaction effects of the CTI and receiving help with healthcare tasks (self-reported) for each outcome. Results: For participants living alone, key characteristics did not significantly differ across randomization groups (278 intervention, 281 control). Overall, 196 (35.2%) reported receiving help with healthcare needs. The CTI had no direct effect on risk of ED revisits or outpatient follow-up at any time point. The interaction of the CTI and receiving help with healthcare needs did not affect risk of ED revisits but did significantly impact likelihood of outpatient clinic follow-up within 7 days ( p=0.01). Of participants who had help with healthcare needs, those who were assigned to the CTI had decreased odds of outpatient clinic follow-up at 7 days (OR: 0.47, 95%CI 0.86–2.18), compared to those not randomized to the CTI condition. Conclusion: For older adults who live alone being discharged from the ED, assignment to the CTI did not decrease ED revisit risk or increase likelihood of outpatient follow-up. Participants assigned to receive the intervention who reported receiving help with health care needs had a decreased likelihood of outpatient clinic follow-up within 7 days. Further research is needed to explore ways to improve the ED-to-home transition in this population.

Abstract Herbivory by wild and domestic ungulates can influence tree recruitment and understory forest communities throughout the world. Herbivore‐driven declines in tree recruitment have been observed for quaking aspen (Populus tremuloides), a foundation species whose health and management is recognized as a critical priority throughout much of its range. Livestock fencing is commonly used to promote aspen regeneration, but its effectiveness is rarely assessed, especially across large spatial scales. Using a livestock‐reduction experiment, we evaluated the effects of ungulate herbivory on aspen in the Great Basin and southern Cascades, an expansive and environmentally heterogeneous region where aspen faces the interacting threats of climate change, conifer encroachment, and herbivory. We found that livestock fencing only reduced the intensity of herbivore browsing on aspen when wild ungulate abundance was low and did not increase stem densities of aspen recruits. Contrary to expectations, wild ungulate abundance was a strong driver of browsing intensity on juvenile aspen within fenced, but not unfenced, aspen stands, and when the abundance of these herbivores was high, browsing intensity in fenced stands exceeded that in unfenced stands. The density of aspen recruits decreased with browsing intensity on juvenile aspen and with the density of both adult aspen and conifers, suggesting that both herbivory and intra‐ and interspecific competition are important drivers of recruitment. Fire history was also an important driver of recruitment, with stands that burned 10–20 years ago having the greatest density of aspen recruits. Finally, in the stand understory, we found that livestock fencing decreased forb cover, increased shrub species richness, and increased the cover of exotic annual grasses, a group dominated by Bromus tectorum. This latter finding suggests that livestock fencing may not be appropriate in areas where controlling the spread of this invader is a priority. In sum, our findings indicate that aspen recruitment is limited by browsing by both wild and domestic ungulates, is mediated by competition with neighboring trees and fire history, and will require management actions beyond livestock fencing, as this approach does not control browsing by wild ungulates.

Objectives Developing a preclinical training infrastructure for cardiovascular clinician-scientists is an academic workforce priority. The Cardiovascular Research Institute of Vermont developed a cardiovascular summer research fellowship (SRF), wherein medical student awardees were selected by merit-based application and completed mentored research between the first and second years. We aimed to study the impact of the SRF on medical student scholarship and career planning.Design Retrospective survey study.Setting Single academic medical centre.Participants All SRF participants from 2015 to 2020.Interventions Not applicable.Primary and secondary outcome measures Prior SRF participants were surveyed to ascertain current position, research engagement and perspectives regarding SRF experience. Comparisons to American Association of Medical Colleges Graduation Questionnaire data from equivalent years were made using χ2 tests.Results Survey response rate was 87% (20/23), 55% were women. Median time from SRF completion was 2 years (IQR 0.75–2.25), with 75% still enrolled in medical school and 25% in residency. As a result of the first-year summer programme, 45% published a peer-reviewed abstract or manuscript, which was equivalent to the national rate for graduating students (53%, p=0.4). Most respondents (80%) were active in additional research projects during school separate from the SRF, 90% anticipated a career involving research (vs 53% nationally, p

Abstract Background The global rise in the incidence of non-tuberculosis mycobacterial infections is of increasing concern due their high levels of intrinsic antibiotic resistance. Although integrated viral genomes, called prophage, are linked to increased antibiotic resistance in some bacterial species, we know little of their role in mycobacterial drug resistance. Results We present here for the first time, evidence of increased antibiotic resistance and expression of intrinsic antibiotic resistance genes in a strain of Mycobacterium chelonae carrying prophage. Strains carrying the prophage McProf demonstrated increased resistance to amikacin. Resistance in these strains was further enhanced by exposure to sub-inhibitory concentrations of the antibiotic, acivicin, or by the presence of a second prophage, BPs. Increased expression of the virulence gene, whiB7, was observed in strains carrying both prophages, BPs and McProf, relative to strains carrying a single prophage or no prophages. Conclusions This study provides evidence that prophage alter expression of important mycobacterial intrinsic antibiotic resistance genes and additionally offers insight into the role prophage may play in mycobacterial adaptation to stress.

Abstract Background Understanding the genetic mechanisms of local adaptation is an important emerging topic in molecular ecology and evolutionary biology. Results Here, we identify the physiological changes and differential expression of genes among different weeping forsythia populations under drought stress in common garden experiments. Physiological results showed that HBWZ might have higher drought tolerance among four populations. RNA-seq results showed that significant differential expression in the genes responding to the synthesis of flavonoids, aromatic substances, aromatic amino acids, oxidation–reduction process, and transmembrane transport occured among four populations. By further reanalysis of results of previous studies, sequence differentiation was found in the genes related to the synthesis of aromatic substances among different weeping forsythia populations. Conclusions Overall, our study supports the hypothesis that the dual differentiation in gene efficiency and expression increases among populations in response to heterogeneous environments and is an important evolutionary process of local adaptation. Here, we proposed a new working model of local adaptation of weeping forsythia populations under different intensities of drought stress, which provides new insights for understanding the genetic mechanisms of local adaptation for non-model species.

Abstract Southern Iran is a conservation priority area for the endangered Persian onager (Equus hemionus onager), which is threatened by habitat fragmentation and conflict with local communities. To better understand factors that influence onager conservation, we administered a questionnaire in local communities to survey their ecological knowledge, personal experience related to onager, and attitudes toward traditional solutions for reducing crop damage by onager. In addition, we used resistant kernel and factorial least-cost path analyses to identify core areas and corridors for onager movement, and spatial randomization of vehicle collisions and crossing locations to test the predictive ability of resistant kernel and factorial least-cost path predictions of movement. We found that local communities that were knowledgeable about onagers experienced less crop damage from onager compared with those who used traditional methods. Habitat connectivity models revealed that core areas of movement are highly concentrated at the center of protected areas. Some sections of core areas have been cut off by roads where most vehicle collisions with onagers occurred. We propose that effective onager conservation will require integrated landscape-level management to reduce mortality risk, protection of core areas and corridors, development of mitigation strategies to reduce vehicle collisions, and conflict mediation between local communities and onagers.

Abstract Field measurements demonstrate a carbon sink in the Amazon and Congo basins, but the cause of this sink is uncertain. One possibility is that forest landscapes are experiencing transient recovery from previous disturbance. Attributing the carbon sink to transient recovery or other processes is challenging because we do not understand the sensitivity of conventional remote sensing methods to changes in aboveground carbon density (ACD) caused by disturbance events. Here we use ultra-high-density drone lidar to quantify the impact of a blowdown disturbance on ACD in a lowland rain forest in Costa Rica. We show that the blowdown decreased ACD by at least 17.6%, increased the number of canopy gaps, and altered the gap size-frequency distribution. Analyses of a canopy-height transition matrix indicate departure from steady-state conditions. This event will initiate a transient sink requiring an estimated 24–49 years to recover pre-disturbance ACD. Our results suggest that blowdowns of this magnitude and extent can remain undetected by conventional satellite optical imagery but are likely to alter ACD decades after they occur.

Abstract Climate‐resilient and highly water‐use efficient crops are needed to meet the future food, feed, fiber, and fuel demands of a growing human population. Cactus pear (Opuntia spp.) are highly productive yet have crop water demands that are approximately 20% that of traditional crops due to their ability to perform crassulacean acid metabolism (CAM). In the first long‐term field trial of Opuntia for bioenergy in the United States, the aboveground biomass (cladode and fruit) productivity and response to different water inputs of O. cochenillifera, O. ficus‐indica, and O. streptacantha were evaluated at a planting density of 1418 plants ha−1 under three irrigation levels over a 5‐year period to investigate their response to different water inputs. Mean cladode fresh weight, cladode dry weight, cladode count, fruit fresh weight, and fruit dry weight increased linearly by 1.26‐, 1.88‐, 1.53‐, 1.89‐, and 2.13‐fold, respectively, with increasing irrigation from 300 to 716 mm year−1. Significant differences in irrigation response appeared in years 4 and 5 as the cactus trees grew larger. However, no significant differences were observed among the three Opuntia spp. for all parameters measured. Biomass productivity increased over 5 years by 140.8‐ and 132.5‐fold for cladode fresh and dry weight, respectively. Mean annual total aboveground biomass at 300, 407, and 716 mm year−1 water input resulted in 8.25, 11.16, and 15.52 Mg dry mass ha−1 year−1, respectively, at the sparse planting density used here to separate irrigation blocks, which could have been easily quadrupled. O. ficus‐indica performed better than O. cochenillifera and O. streptacantha in terms of cladode biomass and fruit count and quality. Biomass productivity was consistent with previous studies for Opuntia spp. demonstrating that cactus pear displays very high biomass and food/forage potential using substantially lower rates of supplemental irrigation than conventional crops grown in semi‐arid and arid regions.

Synovial fluid analysis is important in diagnosing prosthetic joint infection (PJI). The rate of culture-positive PJI in patients who have a dry tap of a total hip arthroplasty (THA) is not well described. We reviewed all image-guided THA aspirations, performed from 2014 to 2021 at a single academic institution. Aspirations were categorized as successful (≥ 0.5 mL) or unsuccessful (< 0.5 mL, "dry tap"). We analyzed culture data on all repeat aspirations and revision surgeries performed within 90 days of the initial dry tap. We reviewed 275 consecutive attempted THA aspirations of which 100 (36.4%) resulted in a dry tap. The dry tap cohort had a significantly higher percentage of fluoroscopic-guided aspirations (64%) and fewer ultrasound-guided aspirations (36%) compared to the successful aspiration cohort (48.9% fluoroscopic, 53.1% ultrasound, P =.0061). Of the 100 patients who have dry taps, 48 underwent revision surgery within 90 days of the initial dry tap, and 15 resulted in 2 or more positive cultures. The rate of PJI defined by MusculoSkeletal Infection Society major criteria in the dry tap cohort was 16.0%. Attempted aspiration of a THA resulted in a dry tap 36.4% of the time. Of those patients who had a dry tap, 16.0% were subsequently found to have PJI based on MusculoSkeletal Infection Society major criteria. Therefore, a "dry tap" does not exclude the diagnosis of infection and should not be considered reassuring for the absence of PJI. [ABSTRACT FROM AUTHOR]

Abstract Objectives To determine the effect of therapeutic anticoagulation, with low molecular weight heparin (LMWH) or unfractionated heparin (UFH, high dose nomogram), compared to standard care in hospitalized patients admitted for COVID-19 with an elevated D-dimer on the composite outcome of intensive care unit (ICU) admission, non-invasive positive pressure ventilation, invasive mechanical ventilation or death up to 28 days. Trial design Open-label, parallel, 1:1, phase 3, 2-arm randomized controlled trial Participants The study population includes hospitalized adults admitted for COVID-19 prior to the development of critical illness. Excluded individuals are those where the bleeding risk or risk of transfusion would generally be considered unacceptable, those already therapeutically anticoagulated and those who have already have any component of the primary composite outcome. Participants are recruited from hospital sites in Brazil, Canada, Ireland, Saudi Arabia, United Arab Emirates, and the United States of America. The inclusion criteria are: 1) Laboratory confirmed COVID-19 (diagnosis of SARS-CoV-2 via reverse transcriptase polymerase chain reaction as per the World Health Organization protocol or by nucleic acid based isothermal amplification) prior to hospital admission OR within first 5 days (i.e. 120 hours) after hospital admission; 2) Admitted to hospital for COVID-19; 3) One D-dimer value above the upper limit of normal (ULN) (within 5 days (i.e. 120 hours) of hospital admission) AND EITHER: a. D-Dimer ≥2 times ULN OR b. D-Dimer above ULN and Oxygen saturation ≤ 93% on room air; 4) > 18 years of age; 5) Informed consent from the patient (or legally authorized substitute decision maker). The exclusion criteria are: 1) pregnancy; 2) hemoglobin 1.8 (if testing deemed clinically indicated by the treating physician prior to the initiation of anticoagulation); 6) patient already prescribed intermediate dosing of LMWH that cannot be changed (determination of what constitutes an intermediate dose is to be at the discretion of the treating clinician taking the local institutional thromboprophylaxis protocol for high risk patients into consideration); 7) patient already prescribed therapeutic anticoagulation at the time of screening [low or high dose nomogram UFH, LMWH, warfarin, direct oral anticoagulant (any dose of dabigatran, apixaban, rivaroxaban, edoxaban)]; 8) patient prescribed dual antiplatelet therapy, when one of the agents cannot be stopped safely; 9) known bleeding within the last 30 days requiring emergency room presentation or hospitalization; 10) known history of a bleeding disorder of an inherited or active acquired bleeding disorder; 11) known history of heparin-induced thrombocytopenia; 12) known allergy to UFH or LMWH; 13) admitted to the intensive care unit at the time of screening; 14) treated with non-invasive positive pressure ventilation or invasive mechanical ventilation at the time of screening; 15) Imminent death according to the judgement of the most responsible physician; 16) enrollment in another clinical trial of antithrombotic therapy involving hospitalized patients. Intervention and comparator Intervention: Therapeutic dose of LMWH (dalteparin, enoxaparin, tinzaparin) or high dose nomogram of UFH. The choice of LMWH versus UFH will be at the clinician’s discretion and dependent on local institutional supply. Comparator: Standard care [thromboprophylactic doses of LMWH (dalteparin, enoxaparin, tinzaparin, fondaparinux)] or UFH. Administration of LMWH, UFH or fondaparinux at thromboprophylactic doses for acutely ill hospitalized medical patients, in the absence of contraindication, is generally considered standard care. Main outcomes The primary composite outcome of ICU admission, non-invasive positive pressure ventilation, invasive mechanical ventilation or death at 28 days. Secondary outcomes include (evaluated up to day 28): 1. All-cause death 2. Composite of ICU admission or all-cause death 3. Composite of mechanical ventilation or all-cause death 4. Major bleeding as defined by the ISTH Scientific and Standardization Committee (ISTH-SSC) recommendation; 5. Red blood cell transfusion (>1 unit); 6. Transfusion of platelets, frozen plasma, prothrombin complex concentrate, cryoprecipitate and/or fibrinogen concentrate; 7. Renal replacement therapy; 8. Hospital-free days alive; 9. ICU-free days alive; 10. Ventilator-free days alive; 11. Organ support-free days alive; 12. Venous thromboembolism (defined as symptomatic or incidental, suspected or confirmed via diagnostic imaging and/or electrocardiogram where appropriate); 13. Arterial thromboembolism (defined as suspected or confirmed via diagnostic imaging and/or electrocardiogram where appropriate); 14. Heparin induced thrombocytopenia; 15. Trajectories of COVID-19 disease-related coagulation and inflammatory biomarkers. Randomisation Randomisation will be stratified by site and age (>65 versus ≤65 years) using a 1:1 computer-generated random allocation sequence with variable block sizes. Randomization will occur within the first 5 days (i.e. 120 hours) of participant hospital admission. However, it is recommended that randomization occurs as early as possible after hospital admission. Central randomization using an interactive web response system will ensure allocation concealment. Blinding (masking) No blinding involved. This is an open-label trial. Numbers to be randomised (sample size) 462 patients (231 per group) are needed to detect a 15% risk difference, from 50% in the control group to 35% in the experimental group, with power of 90% at a two-sided alpha of 0.05. Trial Status Protocol Version Number 1.4. Recruitment began on May 11th, 2020. Recruitment is expected to be completed March 2022. Recruitment is ongoing. Trial registration ClinicalTrials.gov Identifier: NCT04362085 Date of Trial Registration: April 24, 2020 Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Abstract The molecular basis underlying fetal programming in response to maternal nutrition remains unclear. Herein, we investigated the regulatory relationships between genes in fetal cerebrum, liver, and muscle tissues to shed light on the putative mechanisms that underlie the effects of early maternal nutrient restriction on bovine developmental programming. To this end, cerebrum, liver, and muscle gene expression were measured with RNA-Seq in 14 fetuses collected on day 50 of gestation from dams fed a diet initiated at breeding to either achieve 60% (RES, n = 7) or 100% (CON, n = 7) of energy requirements. To build a tissue-to-tissue gene network, we prioritized tissue-specific genes, transcription factors, and differentially expressed genes. Furthermore, we built condition-specific networks to identify differentially co-expressed or connected genes. Nutrient restriction led to differential tissue regulation between the treatments. Myogenic factors differentially regulated by ZBTB33 and ZNF131 may negatively affect myogenesis. Additionally, nutrient-sensing pathways, such as mTOR and PI3K/Akt, were affected by gene expression changes in response to nutrient restriction. By unveiling the network properties, we identified major regulators driving gene expression. However, further research is still needed to determine the impact of early maternal nutrition and strategic supplementation on pre- and post-natal performance.

Mitra Menon et al. study the hybrid zone of two conifer species in New Mexico, and report that adaptation to cooler environments is associated with introgressed variants, whereas drier environments are associated with background genetic variants. These results may indicate how mosaics of allelic variants could show greater resilience to ongoing and future environmental change.

Abstract Background Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus that was first discovered in December 2019 in Wuhan, China. With the growing numbers of community spread cases worldwide, the World Health Organization (WHO) declared the COVID-19 outbreak as a pandemic on March 11, 2020. Like influenza viruses, SARS-CoV-2 is thought to be mainly transmitted by droplets and direct contact, and COVID-19 has a similar disease presentation to influenza. Here we present a case of influenza A and COVID-19 co-infection in a 60-year-old man with end-stage renal disease (ESRD) on hemodialysis. Case presentation A 60-year-old man with ESRD on hemodialysis presented for worsening cough, shortness of breath, and diarrhea. The patient first developed a mild fever (37.8 °C) during hemodialysis 3 days prior to presentation and has been experiencing worsening flu-like symptoms, including fever of up to 38.6 °C, non-productive cough, generalized abdominal pain, nausea, vomiting, and liquid green diarrhea. He lives alone at home with no known sick contacts and denies any recent travel or visits to healthcare facilities other than the local dialysis center. Rapid flu test was positive for influenza A. Procalcitonin was elevated at 5.21 ng/mL with a normal white blood cell (WBC) count. Computed tomography (CT) chest demonstrated multifocal areas of consolidation and extensive mediastinal and hilar adenopathy concerning for pneumonia. He was admitted to the biocontainment unit of Nebraska Medicine for concerns of possible COVID-19 and was started on oseltamivir for influenza and vancomycin/cefepime for the probable bacterial cause of his pneumonia and diarrhea. Gastrointestinal (GI) pathogen panel and Clostridioides difficile toxin assay were negative. On the second day of admission, initial nasopharyngeal swab came back positive for SARS-CoV-2 by real-time reverse-transcriptase polymerase chain reaction (RT-PCR). The patient received supportive care and resumed bedside hemodialysis in strict isolation, and eventually fully recovered from COVID-19. Conclusions We presented a case of co-infection of influenza and SARS-CoV-2 in a hemodialysis patient. The possibility of SARS-CoV-2 co-infection should not be overlooked even when other viruses including influenza can explain the clinical symptoms, especially in high-risk patients.

Abstract Iran lies at the southernmost range limit of brown bears globally. Therefore, understanding the habitat associations and patterns of population connectivity for brown bears in Iran is relevant for the species’ conservation. We applied species distribution modeling to predict habitat suitability and connectivity modeling to identify population core areas and corridors. Our results showed that forest density, topographical roughness, NDVI and human footprint were the most influential variables in predicting brown bear distribution. The most crucial core areas and corridor networks for brown bear are concentrated in the Alborz and Zagros Mountains. These two core areas were predicted to be fragmented into a total of fifteen isolated patches if dispersal of brown bear across the landscape is limited to 50,000 cost units, and aggregates into two isolated habitat patches if the species is capable of dispersing 400,000 cost units. We found low overlap between corridors, and core habitats with protected areas, suggesting that the existing protected area network may not be adequate for the conservation of brown bear in Iran. Our results suggest that effective conservation of brown bears in Iran requires protection of both core habitats and the corridors between them, especially outside Iran’s network of protected areas.

Peptides and proteins were identified by liquid chromatography with tandem mass spectrometry analysis (LCMS-MS) on an Orbitrap Velos mass spectrometer to further understand biological mechanisms that regulate increased longevity in epididymis compared to ejaculated sperm. Semen from sexually mature bulls were collected and then bulls were slaughtered to collect epididymal samples from the cauda epididymis. All samples were centrifuged to separate spermatozoa from fluids. A high ionic solution was used to remove surface proteins from spermatozoa. Four unique samples were generated: (1) epididymal fluid, (2) seminal plasma (ejaculated fluid), and proteins stripped from (3) epididymal sperm, and (4) ejaculated sperm. Samples were analyzed by LCMS-MS, and data were interpreted with Protein Pilot 5. False discovery rate (FDR) was set at 1%. Unique proteins (n = 458) were identified in ejaculated samples, 178 proteins in seminal plasma and 298 proteins stripped from ejaculated sperm. In epididymal samples, 311 proteins were identified in the fluid, and 334 were identified among proteins stripped from epididymal sperm. This dataset can be useful for further understand of biological mechanisms that control sperm longevity. This dataset is related to the article ‘Proteomic analyses identify differences between bovine epididymal and ejaculated spermatozoa that contribute to longevity’ by (Zoca et al., 2022).

RNA sequencing reads and isobaric tags for a relative and absolute quantification (iTRAQ)-Based Proteomic Data were used to determine the impact of conceptus presence and preovulatory estradiol concentration on function of the d16 uterus in beef cattle. Conceptuses and endometrial biopsies were collected from the uterine horn ipsilateral to the corpus luteum. Total cellular RNA was extracted from endometrium for RNA sequencing across two lanes of a NovaSeq S2, 2 × 50-bp run. Two independent uterine luminal fluid pools (ULF) were made for each group: highE2/conceptus, highE2/noconceptus, lowE2/conceptus, and lowE2/noconceptus. Peptides were labeled with iTRAQ reagents and analyzed using 2-dimensional liquid chromatography mass spectrometry. Transcript abundances were determined using DESeq2 (FDR 2). Scaffold Q+ was used to quantitate peptide and protein identifications in ULF. Datasets include uterine transcript and protein abundances among highE2/conceptus vs highE2/noconceptus and lowE2/conceptus vs lowE2/noconceptus groups. This information can be useful for further investigating the role of specific transcripts and proteins in the maintenance of early pregnancy in beef cattle. This dataset is related to the article ‘Influence of conceptus presence and preovulatory estradiol exposure on uterine gene transcripts and proteins around maternal recognition of pregnancy in beef cattle’ by E.J. Northrop-Albrecht, J.J.J. Rich, R.A. Cushman, R. Yao, X. Ge, G.A. Perry. Molecular and Cellular Endocrinology.

Abstract Illustrated review articles, rooted in scientific rigor, are made up of “capsules” or panels of visuals that together provide an up‐to‐date overview of a topic. Illustrated reviews aim to provide a more accessible format than traditional written reviews to facilitate more effective knowledge translation and dissemination. However, the novelty of this format can dissuade prospective authors due to uncertainty and lack of comfort. To remedy this uncertainty, we have summarized the journey of developing an illustrated review, from identifying an appropriate topic to submitting the final manuscript for peer review. We highlight the importance of approaching an illustrated review from a storytelling perspective, and encouraging authors to keep their audience in mind when picking a theme or characters. We provide storyboard considerations and simplify graphic design principles to develop an outline and line draft for the illustrated review. We list programs available to authors to demystify creating attractive and engaging scientific visuals. Finally, we provide information on choosing colors or fonts and where to find copyright‐free icons, graphics, illustrations, and pictures. This review provides prospective authors with the knowledge, tools, and resources to create an effective illustrated review article. If there is difficulty with the links embedded within the document please download the full PDF.