Rapid spectral variability of a giant flare from a magnetar in NGC 253.

Magnetars are neutron stars with extremely strong magnetic fields (1013 to 1015 gauss)1,2, which episodically emit X-ray bursts approximately 100 milliseconds long and with energies of 1040 to 1041 erg. Occasionally, they also produce extremely bright and energetic giant flares, which begin with a short (roughly 0.2 seconds), intense flash, followed by fainter, longer-lasting emission that is modulated by the spin period of the magnetar3,4 (typically 2 to 12 seconds). Over the past 40 years, only three such flares have been observed in our local group of galaxies3-6, and in all cases the extreme intensity of the flares caused the detectors to saturate. It has been proposed that extragalactic giant flares are probably a subset7-11 of short γ-ray bursts, given that the sensitivity of current instrumentation prevents us from detecting the pulsating tail, whereas the initial bright flash is readily observable out to distances of around 10 to 20 million parsecs. Here we report X-ray and γ-ray observations of the γ-ray burst GRB 200415A, which has a rapid onset, very fast time variability, flat spectra and substantial sub-millisecond spectral evolution. These attributes match well with those expected for a giant flare from an extragalactic magnetar12, given that GRB 200415A is directionally associated13 with the galaxy NGC 253 (roughly 3.5 million parsecs away). The detection of three-megaelectronvolt photons provides evidence for the relativistic motion of the emitting plasma. Radiation from such rapidly moving gas around a rotating magnetar may have generated the rapid spectral evolution that we observe.

The 'Pelvic exenteration lexicon': Creating a common language for complex pelvic cancer surgery.

AIM: Pelvic exenteration surgery is an umbrella term for a multitude of operative techniques for locally advanced and recurrent pelvic malignancy. Currently, there is heterogeneity in the operative description that limits the interpretation of patient outcome and collaboration between units through standardized data collection. Our study aims to develop a consensus lexicon to describe the operative components of extended and exenteration pelvic surgery. METHOD: This study adopted a mixed-methods approach using semi-structured interviews, questionnaires, focus groups and validation exercises involving pelvic exenteration experts from centres in the UK. Qualitative data were collected, and descriptive statistics are presented. RESULTS: We identified eight headings with 32 subheadings that encompass all components of the extent of the potential surgery. The lexicon was validated by 15 UK specialists. A 'high-complexity pelvic exenteration' was defined as encompassing 'conventional pelvic exenteration' with the extension of surgery to remove bony structures or the structures in the pelvic sidewall. Pelvic sidewall structures include major vessels, sciatic nerves and/or bone. Bony structures include the sacrum and/or pubic bones. CONCLUSION: This pelvic exenteration lexicon will permit classification of the surgical approach used that will improve data synthesis, allow more accurate activity recording for audit and ultimately improved outcomes for patients.

Search for Invisible Axion Dark Matter in the 3.3-4.2 µeV Mass Range.

We report the results from a haloscope search for axion dark matter in the 3.3-4.2 µeV mass range. This search excludes the axion-photon coupling predicted by one of the benchmark models of "invisible" axion dark matter, the Kim-Shifman-Vainshtein-Zakharov model. This sensitivity is achieved using a large-volume cavity, a superconducting magnet, an ultra low noise Josephson parametric amplifier, and sub-Kelvin temperatures. The validity of our detection procedure is ensured by injecting and detecting blind synthetic axion signals.

Safety and efficacy of subcutaneous alpha-tocopherol in healthy adult horses.

Vitamin E is essential for neuromuscular function. The primary treatment, oral supplementation with natural ('RRR') α-tocopherol, is not effective in all horses. The objectives of this pilot study were to evaluate the safety and efficacy of a subcutaneously administered RRR-α-tocopherol preparation. Horses were randomly assigned in a cross-over design to initially receive RRR-α-tocopherol (5000 IU/450 kg of 600 IU/mL) subcutaneously (n = 3) or orally (n = 3) or were untreated sentinels (n = 2). Tissue reactions following injection in Phase I of the study necessitated adjustment of the preparation with reduction of the RRR-α-tocopherol concentration to 500 IU/mL in Phase 2. Following an 8-week washout period, horses received the reciprocal treatment route with the new preparation (5000 IU/450 kg of 500 IU/mL). Serum, CSF and muscle α-tocopherol concentrations were determined by high-performance liquid chromatography over a 14-day period during each phase. Serum and CSF α-tocopherol concentrations increased significantly postinjection only when the 500 IU/mL product was administered (P<0.0001). There was no significant difference in the muscle concentration of α-tocopherol following either treatment. All eight horses had marked tissue reaction to subcutaneous injection, regardless of product concentration. Whilst we have demonstrated that this route may be a useful alternative to oral supplementation, the marked tissue reaction makes use of such products limited at this time to only the most refractory of cases.

Improving understanding of type 2 diabetes remission: research recommendations from Diabetes UK's 2019 remission workshop.

AIM: To describe the process and outputs of a workshop convened to identify key priorities for future research in the area of remission of type 2 diabetes, and provide recommendations to researchers and research funders on how best to address them. With the ultimate aim of enabling the remission of type 2 diabetes to become a possibility for more people. METHODS: A 1-day research workshop was conducted, bringing together 31 researchers, people living with diabetes, healthcare professionals and members of staff from Diabetes UK to identify and prioritize recommendations for future research into remission of type 2 diabetes. RESULTS: Workshop attendees identified 10 key themes for further research. Four of these themes were prioritized for further focus: (i) understanding how to personalize lifestyle approaches based on biology, patient choice and subtypes; (ii) understanding the biology of remission; (iii) understanding the most effective approaches to implementation of lifestyle interventions; and (iv) understanding the best approaches to combining therapies (gut hormones, other drugs, lifestyle approaches and bariatric surgery). CONCLUSIONS: This paper outlines recommendations to address the current gaps in knowledge related to remission of type 2 diabetes.

An audit of process and outcome for emergency colectomy in England and Wales.

AIM: The aim of this work was to describe process and outcome for patients undergoing emergency colectomy for colitis in England and Wales. METHOD: The National Emergency Laparotomy Audit (NELA) is a national audit including patients undergoing emergency laparotomy and laparoscopic resectional procedures. Data from adult patients under 65 years of age who underwent emergency subtotal colectomy or panproctocolectomy for colitis between 2013 and 2016 were analysed. RESULTS: In total 1204 patients were included. Although approximately a third of patients underwent a colectomy within 5 days of admission [37% (440/1204)], 32% (383/1204) were admitted for more than 10 days prior to surgery. Colorectal surgeons were present at operation in 72% (869/1204) of cases and consultant surgeons attended 94% (1137/1204) of procedures. Laparoscopy was attempted in 32% (390/1204) of operations with wide institutional variation in its use (0-100% of cases). The overall 30-day inpatient mortality was 2.9% (35/1204). On multivariable regression analysis, age > 55 years [OR 3.59 (1.05-12.21), P = 0.041], female gender [OR 2.88 (1.27-6.52), P = 0.011] and American Society of Anesthesiologists grade 5 [OR 37.43 (2.72-514.52), P = 0.007] were associated with increased mortality. CONCLUSION: There is a consultant-driven service that is largely delivered by specialist colorectal surgeons. Laparoscopy rates were high although there was wide variation in use across institutions. Preoperative delays were evident, and further work is necessary to determine the underlying reasons for these.

Implementation of a clinical pathway for the surgical treatment of colorectal cancer during the COVID-19 pandemic.

AIM: This report summarizes the early experience of implementing elective colorectal cancer surgery during the COVID-19 pandemic. METHODS: A pathway to minimize the risk of including COVID-19-positive patients for elective surgery was established. Prioritization and additional safety measures were introduced into clinical practice. Minimal invasive surgery was used where appropriate. RESULTS: Thirty-eight patients were prioritized, and 23 patients underwent surgery (eight colon, 14 rectal and one anal cancer). The minimal invasive surgery rate was 78%. There were no major postoperative complications or patients diagnosed with COVID-19. Histopathological outcomes were similar to normal practice. CONCLUSION: A safe pathway to offer standard high-quality surgery to colorectal cancer patients during the COVID-19 pandemic is feasible.

Abnormal expression of the co-stimulatory molecule B7-H3 in lichen simplex chronicus is associated with expansion of Langerhans cells.

BACKGROUND: The co-stimulatory molecule B7-H3, a cell surface transmembrane glycoprotein, was assessed for its functional and prognostic role in lichen simplex chronicus (LSC). AIM: To investigate if abnormal expression of the co-stimulatory molecule B7-H3 in LSC is associated with Langerhans cell (LC) expansion. METHODS: We used immunohistochemistry to stain LSC skin tissue, and evaluated if the immunostaining of B7-H3 and interleukin (IL)-6 was significantly different. RESULTS: Our results indicated that B7-H3 is abnormally expressed in LSC skin tissue and positively regulates LC expansion. We also found that IL-6 might modulate B7-H3 expression. Moreover, LC expansion in LSC leads to the proliferation of T cells. CONCLUSIONS: Our study indicates the potential value of immunotherapy as a treatment for LSC.

Colorectal cancer patients under the age of 50 experience delays in primary care leading to emergency diagnoses: a population-based study.

AIM: The incidence of colorectal cancer in the under 50s is increasing. In this national population-based study we aim to show that missed opportunities for diagnosis in primary care are leading to referral delays and emergency diagnoses in young patients. METHOD: We compared the interval before diagnosis, presenting symptom(s) and the odds ratio (OR) of an emergency diagnosis for those under the age of 50 with older patients sourced from the cancer registry with linkage to a national database of primary-care records. RESULTS: The study included 7315 patients, of whom 508 (6.9%) were aged under 50 years, 1168 (16.0%) were aged 50-59, 2294 (31.4%) were aged 60-69 and 3345 (45.7%) were aged 70-79 years. Young patients were more likely to present with abdominal pain and via an emergency, and had the lowest percentage of early stage cancer. They experienced a longer interval between referral and diagnosis (12.5 days) than those aged 60-69, reflecting the higher proportion of referrals via the nonurgent pathway (33.3%). The OR of an emergency diagnosis did not differ with age if a red-flag symptom was noted at presentation, but increased significantly for young patients if the symptom was nonspecific. CONCLUSION: Young patients present to primary care with symptoms outside the national referral guidelines, increasing the likelihood of an emergency diagnosis.

Complications after discharge and delays in adjuvant chemotherapy following colonic resection: a cohort study of linked primary and secondary care data.

AIM: By understanding the reasons for delays in adjuvant chemotherapy (AC) after colonic resection, there is the potential to improve patient outcome. The aim of this study is to determine the extent and impact of complications after hospital discharge on delays to AC. METHOD: The study cohort included patients from Hospital Episode Statistics (HES) who had a colorectal cancer resection; linkage to primary care data was provided by the Clinical Practice Research Datalink (CPRD). Complications during the index hospital stay (from HES) and after discharge (from CPRD) were compared. The risk of late AC treatment (8 weeks or later) following a complication, stoma at the index procedure or emergency admission was described after accounting for age and Charlson score. A Cox hazards model determined the association of these factors with overall survival (OS). RESULTS: A total of 1266 patients underwent AC following colon cancer resection, of whom 598 (47.2%) received treatment within 8 weeks. Patients receiving late AC had a significantly higher proportion of re-operations (7.0% vs 3.3% P < 0.005) and wound infections (5.5% vs 3.7% P = 0.042), with 96% of the latter only being noted in CPRD. In multivariate analysis, the risk of AC delay significantly increased following a complication (OR 1.53, 95% CI 1.16-2.03, P = 0.003) or a stoma at the index operation. AC delay was associated with worse OS [hazard ratio (HR) 1.44, 95% CI 1.16-1.79, P = 0.001], as was an emergency admission (HR 1.59, 95% CI 1.21-1.98, P < 0.0005). However, the presence of a complication did not independently reduce OS (HR 1.15, 95%CI 0.89-1.48, P = 0.295). CONCLUSION: The true extent and impact of complications following colonic resection is underestimated when only secondary care data are used.

Delays in referral from primary care are associated with a worse survival in patients with esophagogastric cancer.

NICE referral guidelines for suspected cancer were introduced to improve prognosis by reducing referral delays. However, over 20% of patients with esophagogastric cancer experience three or more consultations before referral. In this retrospective cohort study, we hypothesize that such a delay is associated with a worse survival compared with patients referred earlier. By utilizing Clinical Practice Research Datalink, a national primary care linked database, the first presentation, referral date, a number of consultations before referral and stage for esophagogastric cancer patients were determined. The risk of a referral after one or two consultations compared with three or more consultations was calculated for age and the presence of symptom fulfilling the NICE criteria. The risk of death according to the number of consultations before referral was determined, while accounting for stage and surgical management. 1307 patients were included. Patients referred after one (HR 0.80 95% CI 0.68-0.93 p = 0.005) or two consultations (HR 0.81 95% CI 0.67-0.98 p = 0.034) demonstrated significantly improved prognosis compared with those referred later. The risk of death was also lower for patients who underwent a resection, were younger or had an earlier stage at diagnosis. Those presenting with a symptom fulfilling the NICE criteria (OR 0.27 95% CI 0.21-0.35 p < 0.0001) were more likely to be referred earlier. This is the first study to demonstrate an association between a delay in referral and worse prognosis in esophagogastric patients. These findings should prompt further research to reduce primary care delays.

Unresolved Gamma-Ray Sky through its Angular Power Spectrum.

The gamma-ray sky has been observed with unprecedented accuracy in the last decade by the Fermi -large area telescope (LAT), allowing us to resolve and understand the high-energy Universe. The nature of the remaining unresolved emission [unresolved gamma-ray background (UGRB)] below the LAT source detection threshold can be uncovered by characterizing the amplitude and angular scale of the UGRB fluctuation field. This Letter presents a measurement of the UGRB autocorrelation angular power spectrum based on eight years of Fermi-LAT Pass 8 data products. The analysis is designed to be robust against contamination from resolved sources and noise systematics. The sensitivity to subthreshold sources is greatly enhanced with respect to previous measurements. We find evidence (with ∼3.7σ significance) that the scenario in which two classes of sources contribute to the UGRB signal is favored over a single class. A double power law with exponential cutoff can explain the anisotropy energy spectrum well, with photon indices of the two populations being 2.55±0.23 and 1.86±0.15.

Restorative surgery after colectomy for ulcerative colitis in England and Sweden: observations from a comparison of nationwide cohorts.

AIM: A longstanding disparity exists between the approaches to restorative surgery after colectomy for patients with ulcerative colitis (UC) in England and Sweden. This study aims to compare rates of colectomy and restorative surgery in comparable national cohorts. METHOD: The English Hospital Episode Statistics (HES) and Swedish National Patient Register (NPR) were interrogated between 2002 and April 2012. Patients with two diagnostic episodes for UC (age ≥ 15 years) were included. Patients were excluded if they had an episode of inflammatory bowel disease or colectomy before 2002. The cumulative incidences of colectomy and restorative surgery were calculated using the Kaplan-Meier method. RESULTS: A total of 98 691 patients were included in the study, 76 129 in England and 22 562 in Sweden. The 5-year cumulative incidence of all restorative surgery after colectomy in England was 33% vs 46% in Sweden (P-value < 0.001). Of the patients undergoing restorative surgery, 92.3% of English patients had a pouch vs 38.8% in Sweden and 7.7% vs 59.1% respectively had an ileorectal anastomosis (IRA). The 5-year cumulative incidence of colectomy in this study cohort was 13% in England and 6% in Sweden (P-value < 0.001). CONCLUSION: Following colectomy for UC only one-third of English patients and half of Swedish patients underwent restorative surgery. In England nearly all these patients underwent pouches, in Sweden a less significant majority underwent IRAs. It is surprising to demonstrate this discrepancy in a comparable cohort of patients from similar healthcare systems. The causes and consequences of this international variation in management are not fully understood and require further investigation.

Generation of an equine biobank to be used for Functional Annotation of Animal Genomes project.

The Functional Annotation of Animal Genomes (FAANG) project aims to identify genomic regulatory elements in both sexes across multiple stages of development in domesticated animals. This study represents the first stage of the FAANG project for the horse, Equus caballus. A biobank of 80 tissue samples, two cell lines and six body fluids was created from two adult Thoroughbred mares. Ante-mortem assessments included full physical examinations, lameness, ophthalmologic and neurologic evaluations. Complete blood counts and serum biochemistries were also performed. At necropsy, in addition to tissue samples, aliquots of serum, ethylenediaminetetraacetic acid (EDTA) plasma, heparinized plasma, cerebrospinal fluid, synovial fluid, urine and microbiome samples from all regions of the gastrointestinal and urogenital tracts were collected. Epidermal keratinocytes and dermal fibroblasts were cultured from skin samples. All tissues were grossly and histologically evaluated by a board-certified veterinary pathologist. The results of the clinical and pathological evaluations identified subclinical eosinophilic and lymphocytic infiltration throughout the length of the gastrointestinal tract as well as a mild clinical lameness in both animals. Each sample was cryo-preserved in multiple ways, and nuclei were extracted from selected tissues. These samples represent the first published systemically healthy equine-specific biobank with extensive clinical phenotyping ante- and post-mortem. The tissues in the biobank are intended for community-wide use in the functional annotation of the equine genome. The use of the biobank will improve the quality of the reference annotation and allow all equine researchers to elucidate unknown genomic and epigenomic causes of disease.

Healthy Skin: Cancer Education for School Teachers and Nurses Using a "Train and Equip" Method.

Skin cancer, especially malignant melanoma, continues on the increase. Different interventions are attempting to impact on this problem. The approach used by the Partners in Health Sciences program at the University of Arkansas for Medical Science is to both "train" and, importantly, "equip" classroom teachers and school nurses in a "Healthy Skin" professional development curriculum. Each participant not only received face-to-face interactive content training in a workshop setting that lasted 6 h; each also received a resource kit of supplies, materials, and equipment used in the workshop and designed for the trainee to use with students in a classroom/school setting. This single "hit" professional development event then can be replicated by each trainee annually for the span of her/his teaching/school-nursing career. A total of 588 trainees participated in "Healthy Skin" workshops that were held in 17 communities throughout the state. Participants attended from 188 different towns/cities. Of those in attendance, 511 (87 %) were females, 77 (13 %) males, 81 % Caucasian, 16 % African Americans, and the remaining 3 % self-identified as "other". There were 471 teachers, 85 nurses, and 32 "others" (administrators, school counselors). Trainees completed anonymous pre/post test measures with an increase in knowledge of 28.5 %. A short-term evaluation was conducted at the end of the workshop. After a minimum of 6 months had elapsed, a long-term evaluation was used to capture data on how the workshop experience transferred into new curricular/learning activities for the students of the workshop participants. There was a high level of satisfaction with the workshop experience and use of workshop content and resource kits. Our experiences in this type of professional development outreach provide a model of how institutions of higher education could contribute to the professional development of K-12 teachers and their students in any content area.

The impact of shortened postgraduate surgical training on colorectal cancer outcome.

BACKGROUND: Shortened postgraduate surgical training reforms, known as Calman, have altered delivery of surgical training in the UK with reduced working hours and training time aiming to produce a more subspecialised workforce. AIMS: This study aims to compare rectal cancer surgical outcomes of Calman-trained consultants in a single institution to published data. Additionally, the study compared colorectal cancer surgical outcome between Calman-trained consultants (CTCs) and non-Calman consultants (NCTCs) in a national dataset. METHODS: Local dataset Clinicopathological outcome of rectal cancer resection undertaken by CTCs in a single institution (2006-2010) were compared against NCTC counterparts. National dataset All elective colorectal cancer resections between 2004 and 2008 in English NHS hospitals were included. CTCs (present from 2004 onwards) were compared to NCTCs (present prior to 2004). Outcome measures included 30-day in-hospital mortality, reoperation and readmission rates. RESULTS: Local dataset One hundred thirteen patients were operated under five CTC. The 30-day in-hospital mortality for CTCs (1%) was favourable compared to published rates (3-5%). Local recurrence rate (4.4%) was comparable to NCTC (3.6%). National dataset Between 2004 and 2008, 44,106 patients underwent elective colorectal resection. Multiple regression demonstrated CTC patients had a reduced length of stay and reduced reoperation rate. No difference in mortality and unplanned readmission rates were seen. CONCLUSION: CTCs have similar safety outcome to NCTCs for colorectal cancer resection procedures. Further work is needed to assess the impact of further training reductions on clinical outcome.

Publicly available Australian hospital data on infant feeding: A review and comparative analysis of outcomes.

BACKGROUND: Breastfeeding is the optimal method of providing infant nutrition. The Baby Friendly Health Initiative (BFHI) is a global strategy to promote breastfeeding. This study aimed to explore infant feeding data in Australian hospitals and compare outcomes between BFHI and non-BFHI accredited hospitals, and between public and private hospitals. METHODS: We targeted publicly available Australian public and private hospital data on breastfeeding outcomes at discharge from 2018 to 2019. We linked the data to the BFHI accredited hospitals and used t tests to compare mean breastfeeding rates and Chi square or Fisher's exact test for categorical variables. FINDINGS: Across all Australian states and territories, only New South Wales (NSW) and Victoria (VIC) provided the publicly available target data. Breastfeeding indicators were defined differently between these states. In NSW, breastfeeding at discharge was reported as a full breastfeeding rate among live born infants (71 %) whereas in VIC, it was reported as exclusive breastfeeding rates among term babies only (79 %). Comparing public with private hospitals, the rates of full breastfeeding at discharge in NSW and exclusive breastfeeding in VIC were significantly lower among private non-BFHI accredited hospitals compared to public non-BFHI accredited hospitals. CONCLUSION: BFHI accreditation can be beneficial in decreasing the rates of commercial milk formula use. Consistent reinforcement of BFHI principles and implementation in both private and public hospitals is required. Regular state monitoring and national dissemination of aggregated data collected using standardised breastfeeding indicators is also essential.

A genetic basis for the variable effect of smoking/nicotine on Parkinson's disease.

Prior studies have established an inverse association between cigarette smoking and the risk of developing Parkinson's disease (PD), and currently, the disease-modifying potential of the nicotine patch is being tested in clinical trials. To identify genes that interact with the effect of smoking/nicotine, we conducted genome-wide interaction studies in humans and in Drosophila. We identified SV2C, which encodes a synaptic-vesicle protein in PD-vulnerable substantia nigra (P=1 × 10(-7) for gene-smoking interaction on PD risk), and CG14691, which is predicted to encode a synaptic-vesicle protein in Drosophila (P=2 × 10(-11) for nicotine-paraquat interaction on gene expression). SV2C is biologically plausible because nicotine enhances the release of dopamine through synaptic vesicles, and PD is caused by the depletion of dopamine. Effect of smoking on PD varied by SV2C genotype from protective to neutral to harmful (P=5 × 10(-10)). Taken together, cross-validating evidence from humans and Drosophila suggests SV2C is involved in PD pathogenesis and it might be a useful marker for pharmacogenomics studies involving nicotine.