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COVID-19 altered research in Clinical and Translational Science Award (CTSA) hubs in an unprecedented manner, leading to adjustments for COVID-19 research.
CTSA members volunteered to conduct a review on the impact of CTSA network on COVID-19 pandemic with the assistance from NIH survey team in October 2020. The survey questions included the involvement of CTSAs in decision-making concerning the prioritization of COVID-19 studies. Descriptive and statistical analyses were conducted to analyze the survey data.
60 of the 64 CTSAs completed the survey. Most CTSAs lacked preparedness but promptly responded to the pandemic. Early disruption of research triggered, enhanced CTSA engagement, creation of dedicated research areas and triage for prioritization of COVID-19 studies. CTSAs involvement in decision-making were 16.75 times more likely to create dedicated diagnostic laboratories (95% confidence interval [CI] = 2.17–129.39; P < 0.01). Likewise, institutions with internal funding were 3.88 times more likely to establish COVID-19 dedicated research (95% CI = 1.12–13.40; P < 0.05). CTSAs were instrumental in securing funds and facilitating establishment of laboratory/clinical spaces for COVID-19 research. Workflow was modified to support contracting and IRB review at most institutions with CTSAs. To mitigate chaos generated by competing clinical trials, central feasibility committees were often formed for orderly review/prioritization.
The lessons learned from the COVID-19 pandemic emphasize the pivotal role of CTSAs in prioritizing studies and establishing the necessary research infrastructure, and the importance of prompt and flexible research leadership with decision-making capacity to manage future pandemics.
We describe here efforts to create and study magnetized electron–positron pair plasmas, the existence of which in astrophysical environments is well-established. Laboratory incarnations of such systems are becoming ever more possible due to novel approaches and techniques in plasma, beam and laser physics. Traditional magnetized plasmas studied to date, both in nature and in the laboratory, exhibit a host of different wave types, many of which are generically unstable and evolve into turbulence or violent instabilities. This complexity and the instability of these waves stem to a large degree from the difference in mass between the positively and the negatively charged species: the ions and the electrons. The mass symmetry of pair plasmas, on the other hand, results in unique behaviour, a topic that has been intensively studied theoretically and numerically for decades, but experimental studies are still in the early stages of development. A levitated dipole device is now under construction to study magnetized low-energy, short-Debye-length electron–positron plasmas; this experiment, as well as a stellarator device that is in the planning stage, will be fuelled by a reactor-based positron source and make use of state-of-the-art positron cooling and storage techniques. Relativistic pair plasmas with very different parameters will be created using pair production resulting from intense laser–matter interactions and will be confined in a high-field mirror configuration. We highlight the differences between and similarities among these approaches, and discuss the unique physics insights that can be gained by these studies.
Although immune-mediated inflammatory diseases (IMID) are associated with multiple mental health conditions, there is a paucity of literature assessing personality disorders (PDs) in these populations. We aimed to estimate and compare the incidence of any PD in IMID and matched cohorts over time, and identify sociodemographic characteristics associated with the incidence of PD.
We used population-based administrative data from Manitoba, Canada to identify persons with incident inflammatory bowel disease (IBD), multiple sclerosis (MS) and rheumatoid arthritis (RA) using validated case definitions. Unaffected controls were matched 5:1 on sex, age and region of residence. PDs were identified using hospitalisation or physician claims. We used unadjusted and covariate-adjusted negative binomial regression to compare the incidence of PDs between the IMID and matched cohorts.
We identified 19 572 incident cases of IMID (IBD n = 6,119, MS n = 3,514, RA n = 10 206) and 97 727 matches overall. After covariate adjustment, the IMID cohort had an increased incidence of PDs (incidence rate ratio [IRR] 1.72; 95%CI: 1.47–2.01) as compared to the matched cohort, which remained consistent over time. The incidence of PDs was similarly elevated in IBD (IRR 2.19; 95%CI: 1.69–2.84), MS (IRR 1.79; 95%CI: 1.29–2.50) and RA (IRR 1.61; 95%CI: 1.29–1.99). Lower socioeconomic status and urban residence were associated with an increased incidence of PDs, whereas mid to older adulthood (age 45–64) was associated with overall decreased incidence. In a restricted sample with 5 years of data before and after IMID diagnosis, the incidence of PDs was also elevated before IMID diagnosis among all IMID groups relative to matched controls.
IMID are associated with an increased incidence of PDs both before and after an IMID diagnosis. These results support the relevance of shared risk factors in the co-occurrence of PDs and IMID conditions.
Shigellosis causes significant morbidity and mortality in developing and developed countries, mostly among infants and young children. The World Health Organization estimates that more than one million people die from Shigellosis every year. In order to evaluate trends in Shigellosis in Israel in the years 2002–2015, we analysed national notifiable disease reporting data. Shigella sonnei was the most commonly identified Shigella species in Israel. Hospitalisation rates due to Shigella flexenri were higher in comparison with other Shigella species. Shigella morbidity was higher among infants and young children (age 0–5 years old). Incidence of Shigella species differed among various ethnic groups, with significantly high rates of S. flexenri among Muslims, in comparison with Jews, Druze and Christians. In order to improve the current Shigellosis clinical diagnosis, we developed machine learning algorithms to predict the Shigella species and whether a patient will be hospitalised or not, based on available demographic and clinical data. The algorithms’ performances yielded an accuracy of 93.2% (Shigella species) and 94.9% (hospitalisation) and may consequently improve the diagnosis and treatment of the disease.
There is a growing concern about the role of the environment in the dissemination of antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARG). In this systematic review, we summarize evidence for increases of ARG in the natural environment associated with potential sources of ARB and ARG such as agricultural facilities and wastewater treatment plants. A total of 5247 citations were identified, including studies that ascertained both ARG and ARB outcomes. All studies were screened for relevance to the question and methodology. This paper summarizes the evidence only for those studies with ARG outcomes (n = 24). Sixteen studies were at high (n = 3) or at unclear (n = 13) risk of bias in the estimation of source effects due to lack of information or failure to control for confounders. Statistical methods were used in nine studies; three studies assessed the effect of multiple sources using modeling approaches, and none reported effect measures. Most studies reported higher ARG concentration downstream/near the source, but heterogeneous findings hindered making any sound conclusions. To quantify increases of ARG in the environment due to specific point sources, there is a need for studies that emphasize analytic or design control of confounding, and that provide effect measure estimates.
After the diagnosis of immune-mediated inflammatory diseases (IMID) such as inflammatory bowel disease (IBD), multiple sclerosis (MS) and rheumatoid arthritis (RA), the incidence of psychiatric comorbidity is increased relative to the general population. We aimed to determine whether the incidence of psychiatric disorders is increased in the 5 years before the diagnosis of IMID as compared with the general population.
Using population-based administrative health data from the Canadian province of Manitoba, we identified all persons with incident IBD, MS and RA between 1989 and 2012, and cohorts from the general population matched 5 : 1 on year of birth, sex and region to each disease cohort. We identified members of these groups with at least 5 years of residency before and after the IMID diagnosis date. We applied validated algorithms for depression, anxiety disorders, bipolar disorder, schizophrenia, and any psychiatric disorder to determine the annual incidence of these conditions in the 5-year periods before and after the diagnosis year.
We identified 12 141 incident cases of IMID (3766 IBD, 2190 MS, 6350 RA) and 65 424 matched individuals. As early as 5 years before diagnosis, the incidence of depression [incidence rate ratio (IRR) 1.54; 95% CI 1.30–1.84) and anxiety disorders (IRR 1.30; 95% CI 1.12–1.51) were elevated in the IMID cohort as compared with the matched cohort. Similar results were obtained for each of the IBD, MS and RA cohorts. The incidence of bipolar disorder was elevated beginning 3 years before IMID diagnosis (IRR 1.63; 95% CI 1.10–2.40).
The incidence of psychiatric comorbidity is elevated in the IMID population as compared with a matched population as early as 5 years before diagnosis. Future studies should elucidate whether this reflects shared risk factors for psychiatric disorders and IMID, a shared final common inflammatory pathway or other aetiology.
Herein we describe a protocol for a systematic review of the evidence on whether point sources of anthropogenic effluent are associated with an increase in antibiotic resistance in the adjacent environment. The review question was based on the Population, Exposure, Comparator, Outcome, Study Design (PECOS) framework as follows: Is the prevalence or concentration of antibiotic resistant bacteria or resistance genes (O) in soil, water, air or free-living wildlife (P) higher in close proximity to, or downstream from, known or suspected sources of anthropogenic effluent (E) compared to areas more distant from or upstream from these sources (C)? A comprehensive search strategy was created to capture all relevant, published literature. Criteria for two stages of eligibility screening were developed to exclude publications that were not relevant to the question, and determine if the study used a design that permitted estimation of an association between a source and levels of resistance. A decision matrix was created for assessment of risk of bias to internal validity due to sample selection bias, information bias, and confounding. The goal of this protocol is to provide a method for determining the state of knowledge about the effect of point sources on antibiotic resistance in the environment.
Patients treated with intensity-modulated radiation therapy (IMRT) for head-and-neck cancer are often positioned supine on a carbon fibre board to which a thermoplastic mask is attached to immobilise the head and shoulders. For patients unable to tolerate a supine position, we developed a tilting board that accommodates a full-scale head-and-shoulder mask.
Materials and methods
Phantom measurements were obtained to confirm the dosimetric accuracy of our treatment planning system when using this board. A patient was simulated in the flat and tilted positions on the board. The two corresponding treatment plans were evaluated by comparing the target coverage and doses with organs at risk. The patient’s intra-fraction motion was quantified during his tilted treatments.
Phantom measurements confirmed the accuracy of the dosimetric calculations. The tilted plan met dosimetric standards for clinical acceptability. The intra-fraction motion of the patient in the tilted position was >3 mm in any direction.
The tilting board met clinical requirements for IMRT planning and delivery. Full-scale head-and-shoulder immobilisation was achieved in a more tolerable tilted position.
Between 1950 and 1964, as a result of slight federal policy shifts, Cold War civil defence went from a pro-urban policy dedicated to the preservation of communities to an anti-urban policy focused on social control in the wake of an attack. Civil defence volunteers in Baltimore along with some of the city's civil defence paid staff, who had bought the federal message that they could protect themselves and their communities for nuclear war, allied with anti-nuclear activists against an increasingly militarized programme – one that by 1961 prioritized post-attack policing and de-emphasized the imperative to preserve urban neighbourhoods.
The lifetime performance and reliability of photovoltaic (PV) modules are critical factors in their successful deployment. Interfaces in thin film PV, such as that between the transparent conductive oxide (TCO) electrode and the absorber layer, are frequently an avenue for degradation; this degradation is promoted by exposure to environmental stressors such as irradiance, heat and humidity. Understanding and suppressing TCO degradation is critical to improving stability and extending the lifetime. Commercially available indium tin oxide (ITO), fluorine doped tin oxide (FTO) and aluminum doped zinc oxide (AZO) were exposed to damp heat (DH), ASTM G154 cycle 4, and modified ASTM G154 for up to 1000 hours. The TCOs’ electrical and optical properties and surface energies were determined before and after each exposure and their relative degradation classified. Data demonstrate that AZO degraded most rapidly of all the TCOs, whereas ITO and FTO degraded at lower to non-quantifiable rates. One approach to suppress degradation could be to use interfacial layers (IFLs), including organofunctional silane layers, to modify the TCO. We modified the TCO surfaces using a variety of organofunctional silanes, and determined a range of surface energies could be obtained without affecting the electrical and optical properties of the TCO. Degradation studies of TCOs with a silane layer were also conducted. We found that an inhomogeneous silane layer was able to delay the resistivity increase for ITO in DH.
While it had long been recognized that herbivores are simultaneously influenced by natural enemies (Hairston et al. 1960) and plant defences (Fraenkel 1959), Price et al. (1980) were among the first to argue forcefully that these dual factors must be considered together. They argued that ‘[w]e cannot understand the plant–herbivore interaction without understanding the role of enemies. We cannot understand predator–prey interactions without understanding the role of plants’ (Price et al. 1980, p. 59). This holistic, tritrophic perspective conceptually unites theory from at least three areas of ecological and evolutionary research. First, this tritrophic perspective expands our view on plant defence from one based strictly on the direct defence, to one that also considers the indirect defence of plants by natural enemies (Janzen 1966; Turlings et al. 1990), as well as how natural enemies mediate the efficacy of direct defences (Moran and Hamilton 1980; Clancy and Price 1987; Williams 1999; Gassmann and Hare 2005). Second, this tritrophic perspective advances our understanding of the forces shaping the evolution of herbivore host plant choice and diet breadth by incorporating the interactive effects of host plant quality and risk of attack by natural enemies (Bernays 1998; Singer et al. 2004a, b). And third, this tritrophic perspective provides a mechanistic framework for understanding the ecological and evolutionary factors that determine the strength of the indirect effects natural enemies have on plant growth, i.e., trophic cascades (Mooney et al. 2010).
Tritrophic interactions have received considerable attention in agricultural systems, with numerous studies documenting the effects of crop traits on herbivores and their natural enemies (Hare 1992; Tumlinson et al. 1992; Vet and Dicke 1992; Bottrell et al. 1998; Turlings and Benrey 1998; Cortesaro et al. 2000; Hare 2002; Ode 2006). In contrast, comparatively little is known of the influences of plant traits on herbivore–enemy interactions from natural systems (e.g., Hare 1992, 2002). Our goals in this review are three-fold. First, where past reviews on this topic have focused on agricultural systems (e.g., Hare 1992, 2002), we give special attention to the evidence for plant variation in herbivore–enemy interactions from natural communities. Second, we position this topic within the framework of trait- and density-mediated indirect interactions. Finally, we consider the evolutionary and ecological implications of plant variation in herbivore–enemy interactions, and we do so with specific reference to the different mechanistic pathways by which such plant effects can occur.
Understanding the timing of mountain glacier and paleolake expansion and retraction in the Great Basin region of the western United States has important implications for regional-scale climate change during the last Pleistocene glaciation. The relative timing of mountain glacier maxima and the well-studied Lake Bonneville highstand has been unclear, however, owing to poor chronological limits on glacial deposits. Here, this problem is addressed by applying terrestrial cosmogenic 10Be exposure dating to a classic set of terminal moraines in Little Cottonwood and American Fork Canyons in the western Wasatch Mountains. The exposure ages indicate that the main phase of deglaciation began at 15.7 ± 1.3 ka in both canyons. This update to the glacial chronology of the western Wasatch Mountains can be reconciled with previous stratigraphic observations of glacial and paleolake deposits in this area, and indicates that the start of deglaciation occurred during or at the end of the Lake Bonneville hydrologic maximum. The glacial chronology reported here is consistent with the growing body of data suggesting that mountain glaciers in the western U.S. began retreating as many as 4 ka after the start of northern hemisphere deglaciation (at ca. 19 ka).