Defining Terms for Integrated (Multi-Inter-Trans-Disciplinary) Sustainability Research

This is the published version, also available here: http://dx.doi.org/10.3390/su3081090.Our contemporary social and ecological problems, including climate change, peak oil and food security, necessitate solutions informed by multiple backgrounds that singular disciplines seem unable to provide, and possibly, are even incapable of providing. The increasing occurrence of multi-, inter- and transdisciplinary (MIT) research projects speak to the recognition of that necessity. But as the literature and our own experiences bear out, just calling a project “beyond disciplinary” or integrated does not necessarily yield the intended outcomes or make progress toward alleviating the hurdles of bridging disciplines. Here we examine the distinctions between three categories (multidisciplinary, interdisciplinary and transdisciplinary) of integrated research and offer reflections on how sustainability researchers can categorize their research to improve common understandings

Modelling the Spread of HIV Immune Escape Mutants in a Vaccinated Population

Because cytotoxic T-lymphocytes (CTLs) have been shown to play a role in controlling human immunodeficiency virus (HIV) infection and because CTL-based simian immunodeficiency virus (SIV) vaccines have proved effective in non-human primates, one goal of HIV vaccine design is to elicit effective CTL responses in humans. Such a vaccine could improve viral control in patients who later become infected, thereby reducing onwards transmission and enhancing life expectancy in the absence of treatment. The ability of HIV to evolve mutations that evade CTLs and the ability of these ‘escape mutants’ to spread amongst the population poses a challenge to the development of an effective and robust vaccine. We present a mathematical model of within-host evolution and between-host transmission of CTL escape mutants amongst a population receiving a vaccine that elicits CTL responses to multiple epitopes. Within-host evolution at each epitope is represented by the outgrowth of escape mutants in hosts who restrict the epitope and their reversion in hosts who do not restrict the epitope. We use this model to investigate how the evolution and spread of escape mutants could affect the impact of a vaccine. We show that in the absence of escape, such a vaccine could markedly reduce the prevalence of both infection and disease in the population. However the impact of such a vaccine could be significantly abated by CTL escape mutants, especially if their selection in hosts who restrict the epitope is rapid and their reversion in hosts who do not restrict the epitope is slow. We also use the model to address whether a vaccine should span a broad or narrow range of CTL epitopes and target epitopes restricted by rare or common HLA types. We discuss the implications and limitations of our findings

Computerized clinical decision support systems for acute care management: A decision-maker-researcher partnership systematic review of effects on process of care and patient outcomes

<p>Abstract</p> <p>Background</p> <p>Acute medical care often demands timely, accurate decisions in complex situations. Computerized clinical decision support systems (CCDSSs) have many features that could help. However, as for any medical intervention, claims that CCDSSs improve care processes and patient outcomes need to be rigorously assessed. The objective of this review was to systematically review the effects of CCDSSs on process of care and patient outcomes for acute medical care.</p> <p>Methods</p> <p>We conducted a decision-maker-researcher partnership systematic review. MEDLINE, EMBASE, Evidence-Based Medicine Reviews databases (Cochrane Database of Systematic Reviews, DARE, ACP Journal Club, and others), and the Inspec bibliographic database were searched to January 2010, in all languages, for randomized controlled trials (RCTs) of CCDSSs in all clinical areas. We included RCTs that evaluated the effect on process of care or patient outcomes of a CCDSS used for acute medical care compared with care provided without a CCDSS. A study was considered to have a positive effect (<it>i.e.</it>, CCDSS showed improvement) if at least 50% of the relevant study outcomes were statistically significantly positive.</p> <p>Results</p> <p>Thirty-six studies met our inclusion criteria for acute medical care. The CCDSS improved process of care in 63% (22/35) of studies, including 64% (9/14) of medication dosing assistants, 82% (9/11) of management assistants using alerts/reminders, 38% (3/8) of management assistants using guidelines/algorithms, and 67% (2/3) of diagnostic assistants. Twenty studies evaluated patient outcomes, of which three (15%) reported improvements, all of which were medication dosing assistants.</p> <p>Conclusion</p> <p>The majority of CCDSSs demonstrated improvements in process of care, but patient outcomes were less likely to be evaluated and far less likely to show positive results.</p

Evaluation of variables influencing success and complication rates in canine total hip replacement:Results from the British Veterinary Orthopaedic Association Canine Hip Registry (collation of data: 2010-2012)

The objective of this study was to assess the variables associated with complications of total hip replacement (THR) and report owner-assessed outcomes. Entries into the British Veterinary Orthopaedic Association-Canine Hip Registry (BVOA-CHR) between September 2011 and December 2012 were reviewed separately and in conjunction with previous data (January 2010-August 2011). An outcomes assessment questionnaire was used to collect data from owners. Incidences of surgeon-reported and owner-reported complications were 8.2 per cent and 4.3 per cent, respectively. THR using the BioMedtrix BFX cup/stem prosthesis had a greater incidence of complications compared with THR using the BioMedtrix CFX cup/stem prosthesis (P=0.002); complications were 4.48 times more likely when using the BioMedtrix BFX cup/stem prosthesis versus the BioMedtrix CFX cup/stem prosthesis. THR using the BioMedtrix BFX cup/stem prosthesis had a higher incidence of complications compared with THR using a hybrid prosthesis (BioMedtrix BFX cup/CFX stem, BioMedtrix CFX cup/BFX stem) (P=0.046); complications were 2.85 times more likely when using the BioMedtrix BFX cup/ stem prosthesis versus a hybrid prosthesis. In 95 per cent of cases, owner satisfaction with the outcome of THR was 'very good' or 'good'. Complication rates from the BVOA-CHR are similar to previous studies. The data suggest that prosthesis type is associated with complication rate, with BioMedtrix BFX (circa 2012) having a high short-term complication rate

The status of the world's land and marine mammals: diversity, threat, and knowledge

Knowledge of mammalian diversity is still surprisingly disparate, both regionally and taxonomically. Here, we present a comprehensive assessment of the conservation status and distribution of the world's mammals. Data, compiled by 1700+ experts, cover all 5487 species, including marine mammals. Global macroecological patterns are very different for land and marine species but suggest common mechanisms driving diversity and endemism across systems. Compared with land species, threat levels are higher among marine mammals, driven by different processes (accidental mortality and pollution, rather than habitat loss), and are spatially distinct (peaking in northern oceans, rather than in Southeast Asia). Marine mammals are also disproportionately poorly known. These data are made freely available to support further scientific developments and conservation action

Software for the frontiers of quantum chemistry:An overview of developments in the Q-Chem 5 package

This article summarizes technical advances contained in the fifth major release of the Q-Chem quantum chemistry program package, covering developments since 2015. A comprehensive library of exchange–correlation functionals, along with a suite of correlated many-body methods, continues to be a hallmark of the Q-Chem software. The many-body methods include novel variants of both coupled-cluster and configuration-interaction approaches along with methods based on the algebraic diagrammatic construction and variational reduced density-matrix methods. Methods highlighted in Q-Chem 5 include a suite of tools for modeling core-level spectroscopy, methods for describing metastable resonances, methods for computing vibronic spectra, the nuclear–electronic orbital method, and several different energy decomposition analysis techniques. High-performance capabilities including multithreaded parallelism and support for calculations on graphics processing units are described. Q-Chem boasts a community of well over 100 active academic developers, and the continuing evolution of the software is supported by an “open teamware” model and an increasingly modular design

Abdominal aortic aneurysm is associated with a variant in low-density lipoprotein receptor-related protein 1

Abdominal aortic aneurysm (AAA) is a common cause of morbidity and mortality and has a significant heritability. We carried out a genome-wide association discovery study of 1866 patients with AAA and 5435 controls and replication of promising signals (lead SNP with a p value &lt; 1 × 10-5) in 2871 additional cases and 32,687 controls and performed further follow-up in 1491 AAA and 11,060 controls. In the discovery study, nine loci demonstrated association with AAA (p &lt; 1 × 10-5). In the replication sample, the lead SNP at one of these loci, rs1466535, located within intron 1 of low-density-lipoprotein receptor-related protein 1 (LRP1) demonstrated significant association (p = 0.0042). We confirmed the association of rs1466535 and AAA in our follow-up study (p = 0.035). In a combined analysis (6228 AAA and 49182 controls), rs1466535 had a consistent effect size and direction in all sample sets (combined p = 4.52 × 10-10, odds ratio 1.15 [1.10-1.21]). No associations were seen for either rs1466535 or the 12q13.3 locus in independent association studies of coronary artery disease, blood pressure, diabetes, or hyperlipidaemia, suggesting that this locus is specific to AAA. Gene-expression studies demonstrated a trend toward increased LRP1 expression for the rs1466535 CC genotype in arterial tissues; there was a significant (p = 0.029) 1.19-fold (1.04-1.36) increase in LRP1 expression in CC homozygotes compared to TT homozygotes in aortic adventitia. Functional studies demonstrated that rs1466535 might alter a SREBP-1 binding site and influence enhancer activity at the locus. In conclusion, this study has identified a biologically plausible genetic variant associated specifically with AAA, and we suggest that this variant has a possible functional role in LRP1 expression

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant