Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a novel evolutionary divergent RNA virus, is responsible for the present devastating COVID-19 pandemic. To explore the genomic ...signatures, we comprehensively analyzed 2,492 complete and/or near-complete genome sequences of SARS-CoV-2 strains reported from across the globe to the GISAID database up to 30 March 2020. Genome-wide annotations revealed 1,516 nucleotide-level variations at different positions throughout the entire genome of SARS-CoV-2. Moreover, nucleotide (nt) deletion analysis found twelve deletion sites throughout the genome other than previously reported deletions at coding sequence of the ORF8 (open reading frame), spike, and ORF7a proteins, specifically in polyprotein ORF1ab (n = 9), ORF10 (n = 1), and 3´-UTR (n = 2). Evidence from the systematic gene-level mutational and protein profile analyses revealed a large number of amino acid (aa) substitutions (n = 744), demonstrating the viral proteins heterogeneous. Notably, residues of receptor-binding domain (RBD) showing crucial interactions with angiotensin-converting enzyme 2 (ACE2) and cross-reacting neutralizing antibody were found to be conserved among the analyzed virus strains, except for replacement of lysine with arginine at 378th position of the cryptic epitope of a Shanghai isolate, hCoV-19/Shanghai/SH0007/2020 (EPI_ISL_416320). Furthermore, our results of the preliminary epidemiological data on SARS-CoV-2 infections revealed that frequency of aa mutations were relatively higher in the SARS-CoV-2 genome sequences of Europe (43.07%) followed by Asia (38.09%), and North America (29.64%) while case fatality rates remained higher in the European temperate countries, such as Italy, Spain, Netherlands, France, England and Belgium. Thus, the present method of genome annotation employed at this early pandemic stage could be a promising tool for monitoring and tracking the continuously evolving pandemic situation, the associated genetic variants, and their implications for the development of effective control and prophylaxis strategies.
Parental environmental factors, including diet, body composition, metabolism, and stress, affect the health and chronic disease risk of people throughout their lives, as captured in the Developmental ...Origins of Health and Disease concept. Research across the epidemiological, clinical, and basic science fields has identified the period around conception as being crucial for the processes mediating parental influences on the health of the next generation. During this time, from the maturation of gametes through to early embryonic development, parental lifestyle can adversely influence long-term risks of offspring cardiovascular, metabolic, immune, and neurological morbidities, often termed developmental programming. We review periconceptional induction of disease risk from four broad exposures: maternal overnutrition and obesity; maternal undernutrition; related paternal factors; and the use of assisted reproductive treatment. Studies in both humans and animal models have demonstrated the underlying biological mechanisms, including epigenetic, cellular, physiological, and metabolic processes. We also present a meta-analysis of mouse paternal and maternal protein undernutrition that suggests distinct parental periconceptional contributions to postnatal outcomes. We propose that the evidence for periconceptional effects on lifetime health is now so compelling that it calls for new guidance on parental preparation for pregnancy, beginning before conception, to protect the health of offspring.
Abstract Background For acute myocardial infarction (AMI) without heart failure (HF), it is unclear if β-blockers are associated with reduced mortality. Objectives The goal of this study was to ...determine the association between β-blocker use and mortality in patients with AMI without HF or left ventricular systolic dysfunction (LVSD). Methods This cohort study used national English and Welsh registry data from the Myocardial Ischaemia National Audit Project. A total of 179,810 survivors of hospitalization with AMI without HF or LVSD, between January 1, 2007, and June 30, 2013 (final follow-up: December 31, 2013), were assessed. Survival-time inverse probability weighting propensity scores and instrumental variable analyses were used to investigate the association between the use of β-blockers and 1-year mortality. Results Of 91,895 patients with ST-segment elevation myocardial infarction and 87,915 patients with non–ST-segment elevation myocardial infarction, 88,542 (96.4%) and 81,933 (93.2%) received β-blockers, respectively. For the entire cohort, with >163,772 person-years of observation, there were 9,373 deaths (5.2%). Unadjusted 1-year mortality was lower for patients who received β-blockers compared with those who did not (4.9% vs. 11.2%; p < 0.001). However, after weighting and adjustment, there was no significant difference in mortality between those with and without β-blocker use (average treatment effect ATE coefficient: 0.07; 95% confidence interval CI: −0.60 to 0.75; p = 0.827). Findings were similar for ST-segment elevation myocardial infarction (ATE coefficient: 0.30; 95% CI: −0.98 to 1.58; p = 0.637) and non–ST-segment elevation myocardial infarction (ATE coefficient: −0.07; 95% CI: −0.68 to 0.54; p = 0.819). Conclusions Among survivors of hospitalization with AMI who did not have HF or LVSD as recorded in the hospital, the use of β-blockers was not associated with a lower risk of death at any time point up to 1 year. (β-Blocker Use and Mortality in Hospital Survivors of Acute Myocardial Infarction Without Heart Failure; NCT02786654 )
Soils are subject to varying degrees of direct or indirect human disturbance, constituting a major global change driver. Factoring out natural from direct and indirect human influence is not always ...straightforward, but some human activities have clear impacts. These include land‐use change, land management and land degradation (erosion, compaction, sealing and salinization). The intensity of land use also exerts a great impact on soils, and soils are also subject to indirect impacts arising from human activity, such as acid deposition (sulphur and nitrogen) and heavy metal pollution. In this critical review, we report the state‐of‐the‐art understanding of these global change pressures on soils, identify knowledge gaps and research challenges and highlight actions and policies to minimize adverse environmental impacts arising from these global change drivers. Soils are central to considerations of what constitutes sustainable intensification. Therefore, ensuring that vulnerable and high environmental value soils are considered when protecting important habitats and ecosystems, will help to reduce the pressure on land from global change drivers. To ensure that soils are protected as part of wider environmental efforts, a global soil resilience programme should be considered, to monitor, recover or sustain soil fertility and function, and to enhance the ecosystem services provided by soils. Soils cannot, and should not, be considered in isolation of the ecosystems that they underpin and vice versa. The role of soils in supporting ecosystems and natural capital needs greater recognition. The lasting legacy of the International Year of Soils in 2015 should be to put soils at the centre of policy supporting environmental protection and sustainable development.
Background The lymph node (Ln) status of patients with resectable pancreatic ductal adenocarcinoma is an important predictor of survival. The survival benefit of extended lymphadenectomy during ...pancreatectomy is, however, disputed, and there is no true definition of the optimal extent of the lymphadenectomy. The aim of this study was to formulate a definition for standard lymphadenectomy during pancreatectomy. Methods During a consensus meeting of the International Study Group on Pancreatic Surgery, pancreatic surgeons formulated a consensus statement based on available literature and their experience. Results The nomenclature of the Japanese Pancreas Society was accepted by all participants. Extended lymphadenectomy during pancreatoduodenectomy with resection of Ln's along the left side of the superior mesenteric artery (SMA) and around the celiac trunk, splenic artery, or left gastric artery showed no survival benefit compared with a standard lymphadenectomy. No level I evidence was available on prognostic impact of positive para-aortic Ln's. Consensus was reached on selectively removing suspected Ln's outside the resection area for frozen section. No consensus was reached on continuing or terminating resection in cases where these nodes were positive. Conclusion Extended lymphadenectomy cannot be recommended. Standard lymphadenectomy for pancreatoduodenectomy should strive to resect Ln stations no. 5, 6, 8a, 12b1, 12b2, 12c, 13a, 13b, 14a, 14b, 17a, and 17b. For cancers of the body and tail of the pancreas, removal of stations 10, 11, and 18 is standard. Furthermore, lymphadenectomy is important for adequate nodal staging. Both pancreatic resection in relatively fit patients or nonresectional palliative treatment were accepted as acceptable treatment in cases of positive Ln's outside the resection plane. This consensus statement could serve as a guide for surgeons and researchers in future directives and new clinical studies.
The milk of lactating cows presents a complex ecosystem of interconnected microbial communities which can influence the pathophysiology of mastitis. We hypothesized possible dynamic shifts of ...microbiome composition and genomic features with different pathological conditions of mastitis (Clinical Mastitis; CM, Recurrent CM; RCM, Subclinical Mastitis; SCM). To evaluate this hypothesis, we employed whole metagenome sequencing (WMS) in 20 milk samples (CM, 5; RCM, 6; SCM, 4; H, 5) to unravel the microbiome dynamics, interrelation, and relevant metabolic functions. The WMS data mapped to 442 bacterial, 58 archaeal and 48 viral genomes with distinct variation in microbiome composition (CM > H > RCM > SCM). Furthermore, we identified a number of microbial genomic features, including 333, 304, 183 and 50 virulence factors-associated genes (VFGs) and 48, 31, 11 and 6 antibiotic resistance genes (ARGs) in CM, RCM, SCM, and H-microbiomes, respectively. We also detected different metabolic pathway and functional genes associated with mastitis pathogenesis. Therefore, profiling microbiome dynamics in different conditions of mastitis and associated microbial genomic features contributes to developing microbiome-based diagnostics and therapeutics for bovine mastitis.
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ABSTRACT
We report observed and derived timing parameters for three millisecond pulsars (MSPs) from observations collected with the Parkes 64-m telescope, Murriyang. The pulsars were found during ...reprocessing of archival survey data by Mickaliger et al. One of the new pulsars (PSR J1546–5925) has a spin period P = 7.8 ms and is isolated. The other two (PSR J0921–5202 with P = 9.7 ms and PSR J1146–6610 with P = 3.7 ms) are in binary systems around low-mass (${\gt}0.2\, {\rm M}_{\odot }$) companions. Their respective orbital periods are 38.2 and 62.8 d. While PSR J0921–5202 has a low orbital eccentricity e = 1.3 × 10−5, in keeping with many other Galactic MSPs, PSR J1146–6610 has a significantly larger eccentricity, e = 7.4 × 10−3. This makes it a likely member of a group of eccentric MSP–helium white dwarf binary systems in the Galactic disc whose formation is poorly understood. Two of the pulsars are co-located with previously unidentified point sources discovered with the Fermi satellite’s Large Area Telescope, but no γ-ray pulsations have been detected, likely due to their low spin-down powers. We also show that, particularly in terms of orbital diversity, the current sample of MSPs is far from complete and is subject to a number of selection biases.
Abstract
We report the discovery of PSR J1757−1854, a 21.5-ms pulsar in a highly-eccentric, 4.4-h orbit with a neutron star (NS) companion. PSR J1757−1854 exhibits some of the most extreme ...relativistic parameters of any known pulsar, including the strongest relativistic effects due to gravitational-wave damping, with a merger time of 76 Myr. Following a 1.6-yr timing campaign, we have measured five post-Keplerian parameters, yielding the two component masses (mp = 1.3384(9) M⊙ and mc = 1.3946(9) M⊙) plus three tests of general relativity, which the theory passes. The larger mass of the NS companion provides important clues regarding the binary formation of PSR J1757−1854. With simulations suggesting 3-σ measurements of both the contribution of Lense–Thirring precession to the rate of change of the semimajor axis and the relativistic deformation of the orbit within ∼7–9 yr, PSR J1757−1854 stands out as a unique laboratory for new tests of gravitational theories.
Natural capital and ecosystem service concepts are embodied in the ecosystems approach to sustainable development, which is a framework being consistently adopted by decision making bodies ranging ...from national governments to the United Nations. In the Millennium Ecosystem Assessment soils are given the vital role of a supporting service, but many of the other soil goods and services remain obscured. In this review we address this using and earth-system approach, highlighting the final goods and services soils produce, in a stock-fund, fund-service model of the pedosphere. We also argue that focusing on final goods and services will be counterproductive in the long run and emphasize that final goods and services are derived from an ecosystem supply chain that relies on ecological infrastructure. We propose that an appropriate ecosystems framework for soils should incorporate soil stocks (natural capital) showing their contribution to stock-flows and emergent fund-services as part of the supply chain. By so doing, an operational ecosystems concept for soils can draw on much more supporting data on soil stocks as demonstrated in a case study with soils data from England and Wales showing stocks, gaps in monitoring and drivers of change. Although the focus of this review is on soils, we believe the earth-system approach and principles of the ecosystem supply chain are widely applicable to the ecosystems approach and bring clarity in terms of where goods and services are derived from.
► We critically review natural capital and ecosystem service concepts for soil science. ► We present a new soil framework based on the stock-flow, fund-service concepts and the ecosystem supply chain. ► We identify explicit soil provisioning goods and emergent ecosystem services soils provide. ► We present a synthesis of soil data for England and Wales within the soil ecosystem service framework.
Abstract Purpose Short-term outcomes have been well characterized in acute coronary syndromes; however, longer-term follow-up for the entire spectrum of these patients, including ST-segment-elevation ...myocardial infarction, non-ST-segment-elevation myocardial infarction, and unstable angina, is more limited. Therefore, we describe the longer-term outcomes, procedures, and medication use in Global Registry of Acute Coronary Events (GRACE) hospital survivors undergoing 6-month and 2-year follow-up, and the performance of the discharge GRACE risk score in predicting 2-year mortality. Methods Between 1999 and 2007, 70,395 patients with a suspected acute coronary syndrome were enrolled. In 2004, 2-year prospective follow-up was undertaken in those with a discharge acute coronary syndrome diagnosis in 57 sites. Results From 2004 to 2007, 19,122 (87.2%) patients underwent follow-up; by 2 years postdischarge, 14.3% underwent angiography, 8.7% percutaneous coronary intervention, 2.0% coronary bypass surgery, and 24.2% were re-hospitalized. In patients with 2-year follow-up, acetylsalicylic acid (88.7%), beta-blocker (80.4%), renin-angiotensin system inhibitor (69.8%), and statin (80.2%) therapy was used. Heart failure occurred in 6.3%, (re)infarction in 4.4%, and death in 7.1%. Discharge-to-6-month GRACE risk score was highly predictive of all-cause mortality at 2 years (c-statistic 0.80). Conclusion In this large multinational cohort of acute coronary syndrome patients, there were important later adverse consequences, including frequent morbidity and mortality. These findings were seen in the context of additional coronary procedures and despite continued use of evidence-based therapies in a high proportion of patients. The discriminative accuracy of the GRACE risk score in hospital survivors for predicting longer-term mortality was maintained.
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