Assessing Statistical Significance in Microarray Experiments Using the Distance Between Microarrays

We propose permutation tests based on the pairwise distances between microarrays to compare location, variability, or equivalence of gene expression between two populations. For these tests the entire microarray or some pre-specified subset of genes is the unit of analysis. The pairwise distances only have to be computed once so the procedure is not computationally intensive despite the high dimensionality of the data. An R software package, permtest, implementing the method is freely available from the Comprehensive R Archive Network at http://cran.r-project.org

US Veterinarians' Knowledge, Experience, and Perception Regarding the Use of Cannabidiol for Canine Medical Conditions

Due to the myriad of laws concerning cannabis, there is little empirical research regarding the veterinary use of cannabidiol (CBD). This study used the Veterinary Information Network (VIN) to gauge US veterinarians' knowledge level, views and experiences related to the use of cannabinoids in the medical treatment of dogs. Participants (n = 2130) completed an anonymous, online survey. Results were analyzed based on legal status of recreational marijuana in the participants' state of practice, and year of graduation from veterinary school. Participants felt comfortable in their knowledge of the differences between Δ9-tetrahydrocannabinol (THC) and marijuana, as well as the toxic effects of marijuana in dogs. Most veterinarians (61.5%) felt comfortable discussing the use of CBD with their colleagues, but only 45.5% felt comfortable discussing this topic with clients. No differences were found based on state of practice, but recent graduates were less comfortable discussing the topic. Veterinarians and clients in states with legalized recreational marijuana were more likely to talk about the use of CBD products to treat canine ailments than those in other states. Overall, CBD was most frequently discussed as a potential treatment for pain management, anxiety and seizures. Veterinarians practicing in states with legalized recreational marijuana were more likely to advise their clients and recommend the use of CBD, while there was no difference in the likelihood of prescribing CBD products. Recent veterinary graduates were less likely to recommend or prescribe CBD. The most commonly used CBD formulations were oil/extract and edibles. These were most helpful in providing analgesia for chronic and acute pain, relieving anxiety and decreasing seizure frequency/severity. The most commonly reported side-effect was sedation. Participants felt their state veterinary associations and veterinary boards did not provide sufficient guidance for them to practice within applicable laws. Recent graduates and those practicing in states with legalized recreational marijuana were more likely to agree that research regarding the use of CBD in dogs is needed. These same groups also felt that marijuana and CBD should not remain classified as Schedule I drugs. Most participants agreed that both marijuana and CBD products offer benefits for humans and expressed support for use of CBD products for animals

Association of Patient and Visit Characteristics With Rate and Timing of Urologic Procedures for Patients Discharged From the Emergency Department With Renal Colic

Importance: Little is known about the timing of urologic interventions in patients with renal colic discharged from the emergency department. Understanding patients\u27 likelihood of a subsequent urologic intervention could inform decision-making in this population. Objectives: To examine the rate and timing of urologic procedures performed after an emergency department visit for renal colic and the factors associated with receipt of an intervention. Design, Setting, and Participants: This retrospective cohort study used the Massachusetts All Payers Claims Database to identify patients 18 to 64 years of age who were seen in a Massachusetts emergency department for renal colic from January 1, 2011, to October 31, 2014, Patients were identified via International Classification of Diseases, Ninth Revision codes, and all medical care was linked, enabling identification of subsequent health care use. Data analysis was performed from January 1, 2017, to December 31, 2018. Main Outcomes and Measures: The main outcome was receipt of urologic procedure within 60 days. Secondary outcomes included rates of return emergency department visit and urologic and primary care follow-up. Results: A total of 66218 unique index visits by 55314 patients (mean [SD] age, 42.6 [12.4] years; 33 590 [50.7%] female; 25 411 [38.4%] Medicaid insured) were included in the study. A total of 5851 patients (8.8%) had visits resulting in admission at the index encounter, and 1774 (2.7%) had visits resulting in a urologic procedure during that admission. Of the 60367 patient visits resulting in discharge from the emergency department, 3018 (5.0%) led to a urologic procedure within 7 days, 4407 (7.3%) within 14 days, 5916 (9.8%) within 28 days, and 7667 (12.7%) within 60 days. A total of 3226 visits (5.3%) led to a subsequent emergency department visit within 7 days and 6792 (11.3%) within 60 days. For the entire cohort (admitted and discharged patients), 39 189 (59.2%) had contact with a urologist or primary care practitioner within 60 days. Having Medicaid-only insurance was associated with lower rates of urologic procedures (odds ratio, 0.70; 95% CI, 0.66-0.74) and urologic follow-up (5.6% vs 8.8%; P \u3c .001) and higher rates of primary care follow-up (59.2% vs 47.2%; P \u3c .001) compared with patients with all other insurance types. Conclusions and Relevance: In this cohort study, most adult patients younger than 65 years who were discharged from the emergency department with a diagnosis of renal colic did not undergo a procedure or see a urologist within 60 days. This finding has implications for both the emergency department and outpatient treatment of these patients

High-mobility group box 1 protein, receptor for advanced glycation end products and nucleosomes increases after marathon

Background: Prolonged and strenuous exercise has been linked to potential exercise-induced myocardial damages. One potential key to unmask the discussed underlying mechanisms of this subclinical cardiac damage could be markers of immunogenic cell damage (ICD). We investigated the kinetics of high-mobility group box 1 protein (HMGB1), soluble receptor for advanced glycation end products (sRAGE), nucleosomes, high sensitive troponin T (hs-TnT) and high sensitive C-reactive protein (hs-CRP) before and up to 12 weeks post-race and described associations with routine laboratory markers and physiological covariates. Methods: In our prospective longitudinal study, 51 adults (82% males; 43 ± 9 years) were included. All participants underwent a cardiopulmonary evaluation 10-12 weeks pre-race. HMGB1, sRAGE, nucleosomes, hs-TnT and, hs-CRP were analysed 10-12 weeks prior, 1-2 weeks before, immediately, 24 h, 72 h, and 12 weeks post-race. Results: HMGB1, sRAGE, nucleosomes and hs-TnT increased significantly from pre- to immediately post-race (0.82-2.79 ng/mL; 1132-1388 pg/mL; 9.24-56.65 ng/mL; 6-27 ng/L; p < 0.001) and returned to baseline within 24-72 h. Hs-CRP increased significantly 24 h post-race (0.88-11.5 mg/L; p < 0.001). Change in sRAGE was positively associated with change in hs-TnT (rs = 0.352, p = 0.011). Longer marathon finishing time was significantly associated with decreased levels of sRAGE [-9.2 pg/mL (β = -9.2, SE = 2.2, p < 0.001)]. Conclusion: Prolonged and strenuous exercise increases markers of ICD immediately post-race, followed by a decrease within 72 h. An acute marathon event results in transient alterations of ICD, we assume that this is not solely driven by myocyte damages

Engaging Emergency Department Patients in the Creation of a Shared Decision-­Making Tool Regarding CT Scanning in Kidney Stones: Challenges to Traditional Stakeholder Engagement

Background: Every year approximately 2 million patients are seen in US EDs for suspected renal colic, and the majority receive CT scans. The objective of our study was to develop a stakeholder-informed conversation aid to help clinicians use SDM regarding CT scanning in patients with suspected renal colic. Methods: Using a published decision aid development framework, and under the direction of a multi-disciplinary Steering Committee, we engaged a diverse set of stakeholders via qualitative methods. EM clinicians, urologists, radiologists, researchers, and emergency department patients participated in focus groups and semi-structured interviews. All groups were recorded, transcribed, and analyzed in an iterative process by a four-person coding team. Emergent themes were identified and used to develop a decision aid which was iteratively refined. Results: A total of 8 interviews and 7 focus groups were conducted with 36 stakeholders (including local ED patients) The following three themes emerged: 1. Patient participants reported a desire to be involved in this decision and wanted more information regarding risks and benefits of CT scans. 2. Clinicians were comfortable diagnosing kidney stones without a CT scan, however, some felt that clinical uncertainty was a barrier to SDM. 3. All stakeholders identified strategies to facilitate this conversation such as check-lists and visual aids. Conclusion: Using stakeholder input, we developed a communication tool to facilitate an SDM conversation around the use of CT in suspected renal colic. Further testing will assess whether this tool can safely improve patient engagement and decrease low yield CT usage

Randomized, double-blind, placebo-controlled trial of arimoclomol in rapidly progressive SOD1 ALS

Objective: To examine the safety and tolerability as well as the preliminary efficacy of arimoclomol, a heat shock protein co-inducer that promotes nascent protein folding, in patients with rapidly progressive SOD1 amyotrophic lateral sclerosis (ALS). Methods: This was a double-blind, placebo-controlled trial in which patients with rapidly progressive SOD1-mutant ALS were randomized 1:1 to receive arimoclomol 200 mg tid or matching placebo for up to 12 months. Study procedures were performed using a mix of in-person and remote assessments. Primary outcome was safety and tolerability. Secondary outcome was efficacy, with survival as the principal measure. Additional efficacy measures were the rates of decline of the Revised ALS Functional Rating Scale (ALSFRS-R) and percent predicted forced expiratory volume in 6 seconds (FEV6), and the Combined Assessment of Function and Survival (CAFS). Results: Thirty-eight participants were randomized. Thirty-six (19 placebo, 17 arimoclomol) were included in the prespecified intent-to-treat analysis. Apart from respiratory function, groups were generally well-balanced at baseline. Adverse events occurred infrequently, and were usually mild and deemed unlikely or not related to study drug. Adjusting for riluzole and baseline ALSFRS-R, survival favored arimoclomol with a hazard ratio of 0.77 (95% confidence interval [CI] 0.32–1.80). ALSFRS-R and FEV6 declined more slowly in the arimoclomol group, with treatment differences of 0.5 point/month (95% CI −0.63 to 1.63) and 1.24 percent predicted/month (95% CI −2.77 to 5.25), respectively, and the CAFS similarly favored arimoclomol. Conclusions: This study provides Class II evidence that arimoclomol is safe and well-tolerated at a dosage of 200 mg tid for up to 12 months. Although not powered for therapeutic effect, the consistency of results across the range of prespecified efficacy outcome measures suggests a possible therapeutic benefit of arimoclomol. Clinicaltrials.gov identifier NCT00706147. Classification of evidence This study provides Class II evidence that arimoclomol is safe and well-tolerated at a dosage of 200 mg tid for up to 12 months. The study lacked the precision to conclude, or to exclude, an important therapeutic benefit of arimoclomol

Putting it into perspective: Mathematics in the undergraduate science curriculum

Mathematics and science are tightly interwoven, yet they are often treated as distinct disciplines in the educational context. This study details the development, implementation and outcomes of a teaching intervention that highlights the links between mathematics and science, in the form of a first-year interdisciplinary course. A mixed method study using surveys and focus groups was employed to investigate undergraduate science students' perceptions of their experiences. Findings reveal that students bring strong beliefs about the nature of mathematics and science from secondary school, which can impact significanly on the success of interdisciplinary science-mathematics courese at the teritary level. Despite this, a range of beneficial outcomes can arise from such courses when they are delivered within a framework of analysing real-world issues. However, students with weak mathematical skills derived little benefit from an interdisciplinary approach and are likely to disengage from learning, in comparision with students who enter university with a solid foundation in mathematics

Design and feasibility testing of a novel group intervention for young women who binge drink in groups

BackgroundYoung women frequently drink alcohol in groups and binge drinking within these natural drinking groups is common. This study describes the design of a theoretically and empirically based group intervention to reduce binge drinking among young women. It also evaluates their engagement with the intervention and the acceptability of the study methods.MethodsFriendship groups of women aged 18–35 years, who had two or more episodes of binge drinking (>6 UK units on one occasion; 48g of alcohol) in the previous 30 days, were recruited from the community. A face-to-face group intervention, based on the Health Action Process Approach, was delivered over three sessions. Components of the intervention were woven around fun activities, such as making alcohol free cocktails. Women were followed up four months after the intervention was delivered. Results The target of 24 groups (comprising 97 women) was recruited. The common pattern of drinking was infrequent, heavy drinking (mean consumption on the heaviest drinking day was UK 18.1 units). Process evaluation revealed that the intervention was delivered with high fidelity and acceptability of the study methods was high. The women engaged positively with intervention components and made group decisions about cutting down. Twenty two groups set goals to reduce their drinking, and these were translated into action plans. Retention of individuals at follow up was 87%.ConclusionsThis study successfully recruited groups of young women whose patterns of drinking place them at high risk of acute harm. This novel approach to delivering an alcohol intervention has potential to reduce binge drinking among young women. The high levels of engagement with key steps in the behavior change process suggests that the group intervention should be tested in a full randomised controlled trial

The Euratom Safeguards On-site Laboratories at the Reprocessing Plants of La Hague and Sellafield

In the European Union, nuclear material is reprocessed from irradiated power reactor fuel at two sites ¿ La Hague in France and Sellafield in the United Kingdom. These are the largest nuclear sites within the EU, processing many hundreds of tons of nuclear material in a year. Under the Euratom Treaty, the European Commission has the duty to assure that the nuclear material is only used for declared purposes. The Directorate General for Energy (DG ENER), acting for the Commission, assures itself that the terms of Article 77 of Chapter VII of the Treaty have been complied with. In contrast to the Non Proliferation Treaty, the Euratom Treaty requires to safeguard all civil nuclear material in all EU member states ¿ including the nuclear weapons states. The considerable amount of fissile material separated per year (several tonnes) calls for a stringent system of safeguards measures. The aim of safeguards is to deter diversion of nuclear material from peaceful use by maximizing the chance of early detection. At a broader level, it provides assurance to the public that the European nuclear industry, the EU member states and the European Union honour their legal duties under the Euratom Treaty and their commitments to the Non-Proliferation Treaty. Efficient and effective safeguards measures are essential for the public acceptance of nuclear activities.JRC.E.7-Nuclear Safeguards and Forensic