The Nonprofit Quarterly Study on Nonprofit and Philanthropic Infrastructure

Examines trends in the nonprofit sector's support network and financing system and their capacity to address the impact of the financial crisis on small and midsize nonprofits, share organizational survival strategies, and connect them to resources

Vibrational properties of a loaded string

In this paper we discuss our study of a string–mass chain and its anology to quantum mechanical systems. Theoretical predictions are made based upon the numerical solution to the wave equation. These predictions are tested experimentally using both normal mode analysis and pulse analysis. The frequency band structures for periodic and disordered string mass chains are studied as well as their corresponding eigenfunctions. The theoretical and experimental results are in accord. This experiment, suitable for advanced physics majors, demonstrates many important features of quantum mechanics: eigenvalues, superposition principle, band structure, gap modes, and Anderson localization

Phononic band structure in a mass chain

The vibrational properties of a finite one‐dimensional string‐mass chain are studied experimentally and theoretically. In the experiment both normal mode analysis and pulse analysis are used to obtain the eigenfrequencies of the string‐mass chain. The theoretical predictions are made based upon the numerical solution to the wave equation. The phononic band structure for a periodically massed string as well as Anderson localized gap modes for a disordered system are found. The theoretical and experimental results match satisfactorily well

The ARIA trial protocol: a randomised controlled trial to assess the clinical, technical, and cost-effectiveness of a cloud-based, ARtificially Intelligent image fusion system in comparison to standard treatment to guide endovascular Aortic aneurysm repair

BackgroundEndovascular repair of aortic aneurysmal disease is established due to perceived advantages in patient survival, reduced postoperative complications, and shorter hospital lengths of stay. High spatial and contrast resolution 3D CT angiography images are used to plan the procedures and inform device selection and manufacture, but in standard care, the surgery is performed using image-guidance from 2D X-ray fluoroscopy with injection of nephrotoxic contrast material to visualise the blood vessels. This study aims to assess the benefit to patients, practitioners, and the health service of a novel image fusion medical device (Cydar EV), which allows this high-resolution 3D information to be available to operators at the time of surgery.MethodsThe trial is a multi-centre, open label, two-armed randomised controlled clinical trial of 340 patient, randomised 1:1 to either standard treatment in endovascular aneurysm repair or treatment using Cydar EV, a CE-marked medical device comprising of cloud computing, augmented intelligence, and computer vision. The primary outcome is procedural time, with secondary outcomes of procedural efficiency, technical effectiveness, patient outcomes, and cost-effectiveness. Patients with a clinical diagnosis of AAA or TAAA suitable for endovascular repair and able to provide written informed consent will be invited to participate.DiscussionThis trial is the first randomised controlled trial evaluating advanced image fusion technology in endovascular aortic surgery and is well placed to evaluate the effect of this technology on patient outcomes and cost to the NHS.Trial registrationISRCTN13832085. Dec. 3, 202

Cyclin-dependent kinase 9 as a potential target for anti-TNF resistant inflammatory bowel disease

BACKGROUND AND AIMS: Resistance to single cytokine blockade, namely anti-TNF therapy, is a growing concern for patients with inflammatory bowel disease (IBD). The transcription factor T-bet is a critical regulator of intestinal homeostasis, is genetically linked to mucosal inflammation and controls the expression of multiples genes such as the pro-inflammatory cytokines IFN-γ and TNF. Inhibiting T-bet may therefore offer a more attractive prospect for treating IBD but remains challenging to target therapeutically. In this study, we evaluate the effect of targeting the transactivation function of T-bet using inhibitors of P-TEFb (CDK9-cyclin T), a transcriptional elongation factor downstream of T-bet. METHODS: Using an adaptive immune-mediated colitis model, human colonic lymphocytes from IBD patients and multiple large clinical datasets, we investigate the effect of CDK9 inhibitors on cytokine production and gene expression in colonic CD4+ T cells and link these genetic modules to clinical response in patients with IBD. RESULTS: Systemic CDK9 inhibition led to histological improvement of immune-mediated colitis and was associated with targeted suppression of colonic CD4+ T cell-derived IFN-γ and IL-17A. In colonic lymphocytes from IBD patients, CDK9 inhibition potently repressed genes responsible for pro-inflammatory signalling, and in particular genes regulated by T-bet. Remarkably, CDK9 inhibition targeted genes that were highly expressed in anti-TNF resistant IBD and that predicted non-response to anti-TNF therapy. CONCLUSION: Collectively, our findings reveal CDK9 as a potential target for anti-TNF resistant IBD, which has the potential for rapid translation to the clinic

Effective and specific in planta RNAi in cyst nematodes: expression interference of four parasitism genes reduces parasitic success

Cyst nematodes are highly evolved sedentary plant endoparasites that use parasitism proteins injected through the stylet into host tissues to successfully parasitize plants. These secretory proteins likely are essential for parasitism as they are involved in a variety of parasitic events leading to the establishment of specialized feeding cells required by the nematode to obtain nourishment. With the advent of RNA interference (RNAi) technology and the demonstration of host-induced gene silencing in parasites, a new strategy to control pests and pathogens has become available, particularly in root-knot nematodes. Plant host-induced silencing of cyst nematode genes so far has had only limited success but similarly should disrupt the parasitic cycle and render the host plant resistant. Additional in planta RNAi data for cyst nematodes are being provided by targeting four parasitism genes through host-induced RNAi gene silencing in transgenic Arabidopsis thaliana, which is a host for the sugar beet cyst nematode Heterodera schachtii. Here it is reported that mRNA abundances of targeted nematode genes were specifically reduced in nematodes feeding on plants expressing corresponding RNAi constructs. Furthermore, this host-induced RNAi of all four nematode parasitism genes led to a reduction in the number of mature nematode females. Although no complete resistance was observed, the reduction of developing females ranged from 23% to 64% in different RNAi lines. These observations demonstrate the relevance of the targeted parasitism genes during the nematode life cycle and, potentially more importantly, suggest that a viable level of resistance in crop plants may be accomplished in the future using this technology against cyst nematodes

Reliably predicting pollinator abundance: challenges of calibrating process-based ecological models

1. Pollination is a key ecosystem service for global agriculture but evidence of pollinator population declines is growing. Reliable spatial modelling of pollinator abundance is essential if we are to identify areas at risk of pollination service deficit and effectively target resources to support pollinator populations. Many models exist which predict pollinator abundance but few have been calibrated against observational data from multiple habitats to ensure their predictions are accurate. 2. We selected the most advanced process-based pollinator abundance model available and calibrated it for bumblebees and solitary bees using survey data collected at 239 sites across Great Britain. We compared three versions of the model: one parameterised using estimates based on expert opinion, one where the parameters are calibrated using a purely data-driven approach and one where we allow the expert opinion estimates to inform the calibration process. 3. All three model versions showed significant agreement with the survey data, demonstrating this model's potential to reliably map pollinator abundance. However, there were significant differences between the nesting/floral attractiveness scores obtained by the two calibration methods and from the original expert opinion scores. 4. Our results highlight a key universal challenge of calibrating spatially-explicit, process-based ecological models. Notably, the desire to reliably represent complex ecological processes in finely mapped landscapes necessarily generates a large number of parameters, which are challenging to calibrate with ecological and geographical data that is often noisy, biased, asynchronous and sometimes inaccurate. Purely data-driven calibration can therefore result in unrealistic parameter values, despite appearing to improve model-data agreement over initial expert opinion estimates. We therefore advocate a combined approach where data-driven calibration and expert opinion are integrated into an iterative Delphi-like process, which simultaneously combines model calibration and credibility assessment. This may provide the best opportunity to obtain realistic parameter estimates and reliable model predictions for ecological systems with expert knowledge gaps and patchy ecological data

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Production of very long chain polyunsaturated omega-3 and omega-6 fatty acids in plants

We report the production of two very long chain polyunsaturated fatty acids, arachidonic acid (AA) and eicosapentaenoic acid (EPA), in substantial quantities in a higher plant. This was achieved using genes encoding enzymes participating in the ω3/6 Δ8-desaturation biosynthetic pathways for the formation of C20 polyunsaturated fatty acids. Arabidopsis thaliana was transformed sequentially with genes encoding a Δ9-specific elongating activity from Isochrysis galbana, a Δ8-desaturase from Euglena gracilis and a Δ5-desaturase from Mortierella alpina. Instrumental in the successful reconstitution of these C20 polyunsaturated fatty acid biosynthetic pathways was the I. galbana C18-Δ9-elongating activity, which may bypass rate-limiting steps present in the conventional Δ6-desaturase/elongase pathways. The accumulation of EPA and AA in transgenic plants is a breakthrough in the search for alternative sustainable sources of fish oils.&nbsp

Arctic Energy Technology Development Laboratory

The Arctic Energy Technology Development Laboratory was created by the University of Alaska Fairbanks in response to a congressionally mandated funding opportunity through the U.S. Department of Energy (DOE), specifically to encourage research partnerships between the university, the Alaskan energy industry, and the DOE. The enabling legislation permitted research in a broad variety of topics particularly of interest to Alaska, including providing more efficient and economical electrical power generation in rural villages, as well as research in coal, oil, and gas. The contract was managed as a cooperative research agreement, with active project monitoring and management from the DOE. In the eight years of this partnership, approximately 30 projects were funded and completed. These projects, which were selected using an industry panel of Alaskan energy industry engineers and managers, cover a wide range of topics, such as diesel engine efficiency, fuel cells, coal combustion, methane gas hydrates, heavy oil recovery, and water issues associated with ice road construction in the oil fields of the North Slope. Each project was managed as a separate DOE contract, and the final technical report for each completed project is included with this final report. The intent of this process was to address the energy research needs of Alaska and to develop research capability at the university. As such, the intent from the beginning of this process was to encourage development of partnerships and skills that would permit a transition to direct competitive funding opportunities managed from funding sources. This project has succeeded at both the individual project level and at the institutional development level, as many of the researchers at the university are currently submitting proposals to funding agencies, with some success