"the other side of the coin": What do business schools teach the typical business undergraduate student about the nonprofit sector? A case study from the Netherlands

This article focuses on the exposure of the typical undergraduate business student to the nonprofit sector and management, as opposed to focusing on learning opportunities available to interested students in particular, as is typically reviewed in research on nonprofit management education. To address this novel question, the authors employed a multimethod research strategy to investigate the coverage of the nonprofit sector in the undergraduate business degree program of a leading international business school: the Rotterdam School of Management, Erasmus University in the Netherlands. Based on an exhaustive review of course syllabi, interviews with faculty members, systematic analysis of course lecture notes, and a student discussion group, the results show rather tepid attention to the nonprofit sector and management in the undergraduate curriculum. The article concludes with a discussion of the implications of these findings for instruction of business administration undergraduate students to prepare them for interaction with the nonprofit sector

The Effectiveness of Minimally Invasive Techniques in the Treatment of Patellar Tendinopathy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

The aim was to determine the effectiveness of minimally invasive techniques (MIT) in patients with patellar tendinopathy. Database searches were performed for randomized controlled trials (RCTs) in electronic databases (WOS, Cochrane Central, SportDiscus, and Medline via PubMed and PEDro). The inclusion criteria used were published in English or Spanish and involving adults with patellar tendinopathy (pain on the inferior pole of the patella for a minimum of 3 months), with at least one group receiving MIT. The quality of the relevant RCTs was evaluated using the PEDro scale. The primary outcome was functionality using the VISA-p questionnaire. Secondary outcome was focused on pain. A total of 1164 studies were screened for possible inclusion in our systematic review. Finally, 10 RCTs were included with a total of 326 individuals. Five RCTs were included in the meta-analysis. The quality assessment revealed that all the studies included were considered to possess high methodological quality. All studies analyzing MIT such as platelet-rich plasma (PRP), dry needling, or skin-derived tenocyte-like cells, when combined with exercise, proved to be effective for patellar tendinopathy. Moreover, the PRP technique with doses greater than 4 mL together and combined with an exercise program lasting over 6 weeks obtained better results in functionality and pain than other treatments in the short term. However, in the long term, dry needling and skin-derived tenocyte-like cells are more effective than PRP. Although the infiltration of drugs was effective at posttreatment, these improvements were not maintained over time and may have secondary effects. Although there are no RCTs analyzing the effectiveness of MIT like percutaneous needle electrolysis, there has been an increasing number of publications achieving excellent results in the last years. However, it is necessary to develop RCTs analyzing not only the effect but also comparing the effectiveness between different MIT such as dry needling and percutaneous needle electrolysis

Abacavir-Reactive memory T Cells are present in drug naïve individuals

Background Fifty-five percent of individuals with HLA-B*57:01 exposed to the antiretroviral drug abacavir develop a hypersensitivity reaction (HSR) that has been attributed to naïve T-cell responses to neo-antigen generated by the drug. Immunologically confirmed abacavir HSR can manifest clinically in less than 48 hours following first exposure suggesting that, at least in some cases, abacavir HSR is due to re-stimulation of a pre-existing memory T-cell population rather than priming of a high frequency naïve T-cell population. Methods To determine whether a pre-existing abacavir reactive memory T-cell population contributes to early abacavir HSR symptoms, we studied the abacavir specific naïve or memory T-cell response using HLA-B*57:01 positive HSR patients or healthy controls using ELISpot assay, intra-cellular cytokine staining and tetramer labelling. Results Abacavir reactive CD8+ T-cell responses were detected in vitro in one hundred percent of abacavir unexposed HLA-B*57:01 positive healthy donors. Abacavir-specific CD8+ T cells from such donors can be expanded from sorted memory, and sorted naïve, CD8+ T cells without need for autologous CD4+ T cells. Conclusions We propose that these pre-existing abacavir-reactive memory CD8+ T-cell responses must have been primed by earlier exposure to another foreign antigen and that these T cells cross-react with an abacavir-HLA-B*57:01-endogenous peptide ligand complex, in keeping with the model of heterologous immunity proposed in transplant rejection

The quest for successful Atlantic salmon restoration: perspectives, priorities, and maxims

Atlantic salmon is often a focal species of restoration efforts throughout the north Atlantic and it is therefore an excellent case study for how best to design programmes to address and mitigate threats and correct population declines. This perspective is written to promote the work that has been accomplished towards restoration of Atlantic salmon populations and synthesize how we believe the lessons can be used effectively to support efforts by management agencies to restore populations. We reviewed where restoration is needed for Atlantic salmon, agreed on definitions for three levels of successful restoration, and then applied these criteria to 49 published papers focused on Atlantic salmon restoration. We identified 16 successful examples of restoration among 49 papers reviewed and discussed what interventions led to success versus failure. We then addressed key questions about when hatchery stocking should be used as part of a restoration measure and whether local restoration efforts are enough when these wide-ranging species encounter broad-scale changes in the north Atlantic, specifically related to issues of climate change and to marine survival. We advise to avoid restoration as much as possible by protecting and managing existing populations and when restoration is necessary, problems should be identified and addressed in partnership with river users. With appropriate resources and research to resolve ongoing mysteries, restoration of lost Atlantic salmon populations is absolutely feasible

Association of Genetic Variation with Keratoconus

Importance: Keratoconus is a condition in which the cornea progressively thins and protrudes in a conical shape, severely affecting refraction and vision. It is a major indication for corneal transplant. To discover new genetic loci associated with keratoconus and better understand the causative mechanism of this disease, we performed a genome-wide association study on patients with keratoconus.Objective: To identify genetic susceptibility regions for keratoconus in the human genome.Design, Setting, and Participants: This study was conducted with data from eye clinics in Australia, the United States, and Northern Ireland. The discovery cohort of individuals with keratoconus and control participants from Australia was genotyped using the Illumina HumanCoreExome single-nucleotide polymorphism array. After quality control and data cleaning, genotypes were imputed against the 1000 Genomes Project reference panel (phase III; version 5), and association analyses were completed using PLINK version 1.90. Single-nucleotide polymorphisms with P -6 were assessed for replication in 3 additional cohorts. Control participants were drawn from the cohorts of the Blue Mountains Eye Study and a previous study of glaucoma. Replication cohorts were from a previous keratoconus genome-wide association study data set from the United States, a cohort of affected and control participants from Australia and Northern Ireland, and a case-control cohort from Victoria, Australia. Data were collected from January 2006 to March 2019.Main Outcomes and Measures: Associations between keratoconus and 6 252 612 genetic variants were estimated using logistic regression after adjusting for ancestry using the first 3 principal components.Results: The discovery cohort included 522 affected individuals and 655 control participants, while the replication cohorts included 818 affected individuals (222 from the United States, 331 from Australia and Northern Ireland, and 265 from Victoria, Australia) and 3858 control participants (2927 from the United States, 229 from Australia and Northern Ireland, and 702 from Victoria, Australia). Two novel loci reached genome-wide significance (defined as P -8), with a P value of 7.46 × 10-9 at rs61876744 in patatin-like phospholipase domain-containing 2 gene (PNPLA2) on chromosome 11 and a P value of 6.35 × 10-12 at rs138380, 2.2 kb upstream of casein kinase I isoform epsilon gene (CSNK1E) on chromosome 22. One additional locus was identified with a P value less than 1.00 × 10-6 in mastermind-like transcriptional coactivator 2 (MAML2) on chromosome 11 (P = 3.91 × 10-7). The novel locus in PNPLA2 reached genome-wide significance in an analysis of all 4 cohorts (P = 2.45 × 10-8).Conclusions and Relevance: In this relatively large keratoconus genome-wide association study, we identified a genome-wide significant locus for keratoconus in the region of PNPLA2 on chromosome 11

Evidence for a mixed mass composition at the `ankle' in the cosmic-ray spectrum

We report a first measurement for ultra-high energy cosmic rays of the correlation between the depth of shower maximum and the signal in the water Cherenkov stations of air-showers registered simultaneously by the fluorescence and the surface detectors of the Pierre Auger Observatory. Such a correlation measurement is a unique feature of a hybrid air-shower observatory with sensitivity to both the electromagnetic and muonic components. It allows an accurate determination of the spread of primary masses in the cosmic-ray flux. Up till now, constraints on the spread of primary masses have been dominated by systematic uncertainties. The present correlation measurement is not affected by systematics in the measurement of the depth of shower maximum or the signal in the water Cherenkov stations. The analysis relies on general characteristics of air showers and is thus robust also with respect to uncertainties in hadronic event generators. The observed correlation in the energy range around the `ankle' at $\lg(E/{\rm eV})=18.5-19.0$ differs significantly from expectations for pure primary cosmic-ray compositions. A light composition made up of proton and helium only is equally inconsistent with observations. The data are explained well by a mixed composition including nuclei with mass $A > 4$. Scenarios such as the proton dip model, with almost pure compositions, are thus disfavoured as the sole explanation of the ultrahigh-energy cosmic-ray flux at Earth.Comment: Published version. Added journal reference and DOI. Added Report Numbe

Stem cell-derived macrophages as a new platform for studying host-pathogen interactions in livestock

BACKGROUND: Infectious diseases of farmed and wild animals pose a recurrent threat to food security and human health. The macrophage, a key component of the innate immune system, is the first line of defence against many infectious agents and plays a major role in shaping the adaptive immune response. However, this phagocyte is a target and host for many pathogens. Understanding the molecular basis of interactions between macrophages and pathogens is therefore crucial for the development of effective strategies to combat important infectious diseases. RESULTS: We explored how porcine pluripotent stem cells (PSCs) can provide a limitless in vitro supply of genetically and experimentally tractable macrophages. Porcine PSC-derived macrophages (PSCdMs) exhibited molecular and functional characteristics of ex vivo primary macrophages and were productively infected by pig pathogens, including porcine reproductive and respiratory syndrome virus (PRRSV) and African swine fever virus (ASFV), two of the most economically important and devastating viruses in pig farming. Moreover, porcine PSCdMs were readily amenable to genetic modification by CRISPR/Cas9 gene editing applied either in parental stem cells or directly in the macrophages by lentiviral vector transduction. CONCLUSIONS: We show that porcine PSCdMs exhibit key macrophage characteristics, including infection by a range of commercially relevant pig pathogens. In addition, genetic engineering of PSCs and PSCdMs affords new opportunities for functional analysis of macrophage biology in an important livestock species. PSCs and differentiated derivatives should therefore represent a useful and ethical experimental platform to investigate the genetic and molecular basis of host-pathogen interactions in pigs, and also have wider applications in livestock. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12915-021-01217-8

Distribution and outcomes of a phenotype-based approach to guide COPD management: Results from the CHAIN cohort

Rationale: The Spanish guideline for COPD (GesEPOC) recommends COPD treatment according to four clinical phenotypes: non-exacerbator phenotype with either chronic bronchitis or emphysema (NE), asthma-COPD overlap syndrome (ACOS), frequent exacerbator phenotype with emphysema (FEE) or frequent exacerbator phenotype with chronic bronchitis (FECB). However, little is known on the distribution and outcomes of the four suggested phenotypes. Objective: We aimed to determine the distribution of these COPD phenotypes, and their relation with one-year clinical outcomes. Methods: We followed a cohort of well-characterized patients with COPD up to one-year. Baseline characteristics, health status (CAT), BODE index, rate of exacerbations and mortality up to one year of follow-up were compared between the four phenotypes. Results: Overall, 831 stable COPD patients were evaluated. They were distributed as NE, 550 (66.2%); ACOS, 125 (15.0%); FEE, 38 (4.6%); and FECB, 99 (11.9%); additionally 19 (2.3%) COPD patients with frequent exacerbations did not fulfill the criteria for neither FEE nor FECB. At baseline, there were significant differences in symptoms, FEV1 and BODE index (all p<0.05). The FECB phenotype had the highest CAT score (17.1±8.2, p<0.05 compared to the other phenotypes). Frequent exacerbator groups (FEE and FECB) were receiving more pharmacological treatment at baseline, and also experienced more exacerbations the year after (all p<0.05) with no differences in one-year mortality. Most of NE (93%) and half of exacerbators were stable after one year. Conclusions: There is an uneven distribution of COPD phenotypes in stable COPD patients, with significant differences in demographics, patient-centered outcomes and health care resources use