The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

Diverse perspectives on interdisciplinarity from the Members of the College of the Royal Society of Canada

Various multiple-disciplinary terms and concepts (although most commonly “interdisciplinarity”, which is used herein) are used to frame education, scholarship, research, and interactions within and outside academia. In principle, the premise of interdisciplinarity may appear to have many strengths; yet, the extent to which interdisciplinarity is embraced by the current generation of academics, the benefits and risks for doing so, and the barriers and facilitators to achieving interdisciplinarity represent inherent challenges. Much has been written on the topic of interdisciplinarity, but to our knowledge there have been few attempts to consider and present diverse perspectives from scholars, artists, and scientists in a cohesive manner. As a team of 57 members from the Canadian College of New Scholars, Artists, and Scientists of the Royal Society of Canada (the College) who self-identify as being engaged or interested in interdisciplinarity, we provide diverse intellectual, cultural, and social perspectives. The goal of this paper is to share our collective wisdom on this topic with the broader community and to stimulate discourse and debate on the merits and challenges associated with interdisciplinarity. Perhaps the clearest message emerging from this exercise is that working across established boundaries of scholarly communities is rewarding, necessary, and is more likely to result in impact. However, there are barriers that limit the ease with which this can occur (e.g., lack of institutional structures and funding to facilitate cross-disciplinary exploration). Occasionally, there can be significant risk associated with doing interdisciplinary work (e.g., lack of adequate measurement or recognition of work by disciplinary peers). Solving many of the world’s complex and pressing problems (e.g., climate change, sustainable agriculture, the burden of chronic disease, and aging populations) demand thinking and working across long-standing, but in some ways restrictive, academic boundaries. Academic institutions and key support structures, especially funding bodies, will play an important role in helping to realize what is readily apparent to all who contributed to this paper—that interdisciplinarity is essential for solving complex problems; it is the new norm. Failure to empower and encourage those doing this research will serve as a great impediment to training, knowledge, and addressing societal issues

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Genetic and environmental variation and genotype x environment interactions in New Zealand Romney sheep : [microform] a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Animal Science at Massey University

Performance records were kept on New Zealand Romney ewes from birth to 5 years of age. These ewes were maintained in two subflocks at different stocking rates. A proportion of the ewes were eliminated at random at about 16 months of age. From this stage until 5 years all ewes were retained unless they died of natural causes. The data represented 1944 hoggets and 919 older ewes, the progeny of 49 sires. Each of these sires were used for two consecutive years. The records were calculated between 1966 and 1983 and represented seven sire periods. The significance of genotype x environment interactions (GEI) were investigated for a range of hogget and adult traits, including liveweight (LW), greasy fleece weight (GFW), clean fleece weight (CFW), yield (Y) , quality number (QN), mean fibre diameter (MFD) , staple length (SL) , total crimp number (TCN) , crimp frequency (CF) , staple strength (SST), character (CHG), lustre (LUS), tippiness (TIP), cotting (COT), cotted area (CAG), soundness (SOU), handle (HND), greasy midside colour (GCM), secured midside colour (SCM), greasy fleece colour (GCF), number of lambs born per ewe mated (NLB), number of lambs weaned per ewe mated (NLW), weight of lamb weaned (WLW), weight per lamb weaned (WPL) and lamb survival percentage (LSP). The effects of the environmental factors of birth year, age, number of lambs born and weaned, stocking rate and rearing rank and all interactions among them were assessed for ewe liveweight and wool traits. A similar model was developed for hogget traits but included age at weaning rather than reproductive status. Reproductive trait models included ewe liveweight and did not include rearing rank and reproductive status. Sire x stocking rate and sire x birth year interactions were the only genotype x environment interactions that were should occur at the 'commercial' stocking rate. The environment of the stud should be taken into account when selecting rams. Significant GEI will also have important implications in relation to breeding systems used to assist genetic improvement of the sheep population. Group breeding schemes and sire reference programs will be affected. If the GBS nucleus is in a different environment from the base flocks, both closed and open schemes can suffer a considerable loss in overall selection response when GEI exist. Comparison of sires across flocks using sire referencing is currently receiving much attention. If sire x environment interactions are important, inconsistencies are likely to occur in the ranking of sires. Genotype x year interactions appear likely to be a major cause of inconsistencies in the estimation of breeding values and research to identify the causes of these interactions should be carried out

Genomic selection and scan for major genes for a new lamb survival trait for the New Zealand sheep industry

Lambing percentage is one of the most significant factors affecting profitability on New Zealand sheep farms. Since the early 1990s, lambing percentage has increased at about 1% per year from a relatively stable level of approximately 100%, and top performing sheep farms are now consistently achieving 150% or more. As lambing percentage increases, the proportion of ewes bearing twins and triplets increases accordingly. Lamb mortality rate in these multiples is higher than in singles, with triplets being particularly susceptible. Consequently, lamb survival has become increasingly important to the New Zealand sheep industry. Sheep Improvement Ltd. (SIL, New Zealand’s national sheep genetic evaluation system owned by Beef + Lamb NZ) records lamb survival to weaning but genetic improvement has been limited due to the low heritability of the trait and the current method of recording. To address those issues, we have developed an improved survival to weaning trait for industry implementation, which is more accurate and more heritable than the current SIL trait. This poster will present results of applying genome-enabled prediction procedures to the new trait to obtain molecular breeding values. It will also describe results from a genome wide association study using the new trait

Derivation of a new lamb survival trait for the New Zealand sheep industry

Previous research identified that a review of the current industry New Zealand lamb survival trait was necessary as its recording accuracy was reliant on farmers notifying their Sheep Improvement Limited bureau of lamb deaths. This paper reports the decision rules and genetic parameters for a new lamb survival trait for the New Zealand sheep industry. These rules define the new lamb survival trait (NEWSUR) using lamb birth fate (BFATE) codes and the presence/absence of lamb weight measurements. Six univariate animal models were tested and used to estimate variance or covariance components and the resulting direct and maternal heritabilities for NEWSUR. The models differed in the way they adjust for the effect of day of birth, the exclusion or inclusion of a litter (dam/year of birth) random effect and the application or not of a logit transformation of the phenotypes. For both the linear and logistic methods, models including the random effect of litter provided the best fit for NEWSUR according to log-likelihood values. Log-likelihoods for the linear and logistic models cannot be compared, therefore a cross-validation method was used to assess whether the logit transformation was appropriate by analyzing the predictive ability of the models. The mean square errors were slightly lower for the linear compared to the logistic model and therefore the linear model was recommended for industry use. The heritability attributed to direct effects ranged from 2 to 5.5%. A direct heritability of 5.5% resulted from a linear model without litter effect and omitting the effect of day of birth on survival, whereas a direct heritability of 2% resulted from the logistic model fitting a random litter effect. The heritability attributed to maternal genetic effects ranged from 1.9 to 7.7%. A maternal genetic heritability of 7.7% resulted from the logistic model omitting the litter effect, whereas a maternal genetic heritability of 1.9% resulted from the linear model fitting a random litter effect. The addition of the litter random effect decreased the maternal heritabilities substantially in all cases and was recommended for industry use to avoid overestimation of the maternal genetic variance. SIL has implemented NEWSUR and the associated genetic evaluation model based on information described in this paper. Industry wide implementation will enable sheep breeders to produce more accurate genetic evaluations to their commercial clients

Derivation of a new lamb survival trait for implementation in the New Zealand sheep industry

Lambing percentage is one of the most significant factors affecting profitability on New Zealand sheep farms. Since the early 1990s, lambing percentage has increased at about 1% per year from a relatively stable level of approximately 100%, and top performing sheep farms are now consistently achieving 150% or more. As lambing percentage increases, the proportion of ewes bearing twins and triplets increases accordingly. Lamb mortality rate in these multiples is higher than in singles, with triplets being particularly susceptible. Consequently, lamb survival has become increasingly important to the New Zealand sheep industry. Sheep Improvement Ltd (SIL, New Zealand's national sheep genetic evaluation system provided by Beef & Lamb NZ) records lamb survival to weaning but genetic improvement has been limited due to the low heritability of the trait and the current method of recording