Observation of inverse Compton emission from a long γ-ray burst.

Long-duration γ-ray bursts (GRBs) originate from ultra-relativistic jets launched from the collapsing cores of dying massive stars. They are characterized by an initial phase of bright and highly variable radiation in the kiloelectronvolt-to-megaelectronvolt band, which is probably produced within the jet and lasts from milliseconds to minutes, known as the prompt emission1,2. Subsequently, the interaction of the jet with the surrounding medium generates shock waves that are responsible for the afterglow emission, which lasts from days to months and occurs over a broad energy range from the radio to the gigaelectronvolt bands1-6. The afterglow emission is generally well explained as synchrotron radiation emitted by electrons accelerated by the external shock7-9. Recently, intense long-lasting emission between 0.2 and 1 teraelectronvolts was observed from GRB 190114C10,11. Here we report multi-frequency observations of GRB 190114C, and study the evolution in time of the GRB emission across 17 orders of magnitude in energy, from 5 × 10-6 to 1012 electronvolts. We find that the broadband spectral energy distribution is double-peaked, with the teraelectronvolt emission constituting a distinct spectral component with power comparable to the synchrotron component. This component is associated with the afterglow and is satisfactorily explained by inverse Compton up-scattering of synchrotron photons by high-energy electrons. We find that the conditions required to account for the observed teraelectronvolt component are typical for GRBs, supporting the possibility that inverse Compton emission is commonly produced in GRBs.

Evidence for changing intimate partner violence safety planning needs as a result of COVID-19: results from phase I of a rapid intervention.

OBJECTIVES: The aim of the study was to examine the need for modified safety planning strategies in response to COVID-19-related increases in intimate partner violence (IPV) as the initial phase of adapting an IPV safety planning intervention in Toronto, Ontario. METHODS: A rapid, systematic review was conducted to elucidate existing safety planning strategies used during public health emergencies. These were supplemented with strategies from an expert panel. A survey of IPV survivors and service providers gauged the helpfulness of each strategy during COVID-19. RESULTS: Together, the systematic review and expert panel yielded 26 conceptually distinct strategies, which were evaluated by 111 IPV survivors and providers. Of these, 19 (69%) were 'highly recommended', 3 (12%) were 'somewhat recommended' and 6 (23%) were not recommended for use during the COVID-19 pandemic because they might make the violence worse. CONCLUSIONS: Safety planning needs have changed owing to the effect of COVID-19 on IPV incidence, service provision and risk factors, as well as policies restricting freedom of movement. These results will be used to modify an existing IPV safety planning mobile application for use during COVID-19 and future public health emergencies.

Asymmetries in core-collapse supernovae from maps of radioactive 44Ti in Cassiopeia A.

Asymmetry is required by most numerical simulations of stellar core-collapse explosions, but the form it takes differs significantly among models. The spatial distribution of radioactive (44)Ti, synthesized in an exploding star near the boundary between material falling back onto the collapsing core and that ejected into the surrounding medium, directly probes the explosion asymmetries. Cassiopeia A is a young, nearby, core-collapse remnant from which (44)Ti emission has previously been detected but not imaged. Asymmetries in the explosion have been indirectly inferred from a high ratio of observed (44)Ti emission to estimated (56)Ni emission, from optical light echoes, and from jet-like features seen in the X-ray and optical ejecta. Here we report spatial maps and spectral properties of the (44)Ti in Cassiopeia A. This may explain the unexpected lack of correlation between the (44)Ti and iron X-ray emission, the latter being visible only in shock-heated material. The observed spatial distribution rules out symmetric explosions even with a high level of convective mixing, as well as highly asymmetric bipolar explosions resulting from a fast-rotating progenitor. Instead, these observations provide strong evidence for the development of low-mode convective instabilities in core-collapse supernovae.

Transmission of infection to liver transplant recipients from donors with infective endocarditis: lessons learned.

Donors not meeting standard criteria, such as those with bacteremia, are now being used in response to the increasing need for organs for transplantation. Recommended strategies to prevent the occurrence of donor-derived bacteremia include the use of directed antibiotic prophylaxis. However, this approach does not eliminate the risk of infection transmission. Similarly, the management of organ recipients from donors with infective endocarditis (IE) remains uncharacterized. We report 2 cases of donor-derived bacterial infections in liver transplant recipients despite pathogen-specific antibiotic prophylaxis. In both instances, the donors had documented IE treated with appropriate antimicrobial therapy and clearance of bacteremia. Recipients had very distinctive clinical outcomes likely related to pathogen virulence and the extent of donor infection. Persistent infection in the transplanted liver should be suspected in organ recipients of a liver from donors with IE, despite the absence of bacteremia at the time of death and organ procurement. For eradication, recipients may require prolonged pathogen-directed antimicrobial therapy, such as is used for endovascular infections. Prompt recognition of donors with IE, appropriate notification, and prolonged antibiotic prophylaxis are key to reducing the risk of such donor-derived infections.

A gamma-ray burst at a redshift of z approximately 8.2.

Long-duration gamma-ray bursts (GRBs) are thought to result from the explosions of certain massive stars, and some are bright enough that they should be observable out to redshifts of z > 20 using current technology. Hitherto, the highest redshift measured for any object was z = 6.96, for a Lyman-alpha emitting galaxy. Here we report that GRB 090423 lies at a redshift of z approximately 8.2, implying that massive stars were being produced and dying as GRBs approximately 630 Myr after the Big Bang. The burst also pinpoints the location of its host galaxy.

The Stanford Leisure-Time Activity Categorical Item (L-Cat): a single categorical item sensitive to physical activity changes in overweight/obese women.

BACKGROUND: Physical activity is essential for chronic disease prevention, yet <40% of overweight/obese adults meet the national activity recommendations. For time-efficient counseling, clinicians need a brief, easy-to-use tool that reliably and validly assesses a full range of activity levels, and, most importantly, is sensitive to clinically meaningful changes in activity. The Stanford Leisure-Time Activity Categorical Item (L-Cat) is a single item comprising six descriptive categories ranging from inactive to very active. This novel methodological approach assesses national activity recommendations as well as multiple clinically relevant categories below and above the recommendations, and incorporates critical methodological principles that enhance psychometrics (reliability, validity and sensitivity to change). METHODS: We evaluated the L-Cat's psychometrics among 267 overweight/obese women who were asked to meet the national activity recommendations in a randomized behavioral weight-loss trial. RESULTS: The L-Cat had excellent test-retest reliability (κ=0.64, P<0.001) and adequate concurrent criterion validity; each L-Cat category at 6 months was associated with 1059 more daily pedometer steps (95% CI 712-1407, ß=0.38, P<0.001) and 1.9% greater initial weight loss at 6 months (95% CI -2.4 to -1.3, ß=-0.38, P<0.001). Of interest, L-Cat categories differentiated from each other in a dose-response gradient for steps and weight loss (Ps<0.05) with excellent face validity. The L-Cat was sensitive to change in response to the trial's activity component. Women increased one L-Cat category at 6 months (M=1.0±1.4, P<0.001); 55.8% met the recommendations at 6 months whereas 20.6% did at baseline (P<0.001). Even among women not meeting the recommendations at both baseline and 6 months (n=106), women who moved 1 L-Cat categories at 6 months lost more weight than those who did not (M=-4.6%, 95% CI -6.7 to -2.5, P<0.001). CONCLUSIONS: Given strong psychometrics, the L-Cat has timely potential for clinical use such as tracking activity changes via electronic medical records, especially among overweight/obese populations who are unable or unlikely to reach national recommendations.

Combining PARP inhibition and immune checkpoint blockade in ovarian cancer patients: a new perspective on the horizon?

Immune checkpoint inhibitors (ICIs) have completely reshaped the treatment of many malignancies, with remarkable improvements in survival outcomes. In ovarian cancer (OC), however, this emerging class of drugs has not yet found a favorable use due to results from phase I and II studies, which have not suggested a substantial antitumoral activity of these agents when administered as monotherapy. Robust preclinical data seem to suggest that the combination ICIs with poly(ADP-ribose) polymerase (PARP) inhibitors (PARPis) may result in a synergistic activity; furthermore, data from phase II clinical studies, evaluating this combination, have shown encouraging outcomes especially for those OC patients not suitable for platinum retreatment. While waiting for ongoing phase III clinical trial results, which will clarify the role of ICIs in combination with PARPis in the newly diagnosed OC, this review aims to summarize the preclinical data and clinical evidence available to date.

Radioactive synovectomy with Yttrium9° citrate in haemophilic synovitis: Brazilian experience.

Recurrent haemarthroses leading to chronic synovitis and arthropathy remain a major cause of morbidity in patients with haemophilia. Radioactive synovectomy (RS) is considered the first choice of treatment for chronic haemophilic synovitis. The aim of this study was to evaluate the effect of RS with Yttrium(90) citrate (C-Y(90)) in the joints of patients with chronic haemophilic synovitis. From 2003 to 2007, 245 joints (118 knees, 76 elbows, 49 ankles and two shoulders) of 190 patients with haemophilia or von Willebrand disease were submitted to RS with C-Y(90) at Hemocentro de Mato Grosso, Brazil. Forty joints had radiographic Pettersson scores above 8. There were 36 joints of 22 patients with inhibitors to factor VIII. The procedure was safe with low occurrence of adverse events. The main effect was the overall reduction in joint bleeding frequency, from 19.8 to 2.6 per year post-RS. Similar results were obtained in cases with high radiographic scores and in inhibitor patients. Pain reduction was observed in most cases. Average range of motion was maintained or increased 1 year post-RS in most joints. Extension was stable or increased in 88.2% of the knees and 86.5% of the elbows. Ankle plantarflexion was stable or increased in 90.9%, whereas dorsiflexion was maintained or increased in 87.9%. Worsening of the range of motion, when present, ranged from 14 to 17 degrees. We concluded that RS with C-Y(90) represents an important resource for the treatment of chronic haemophilic synovitis, markedly reducing joint bleeding frequency and pain, irrespective of the radiographic stage and inhibitor status.

9°Yttrium-hydroxyapatite: a new therapeutic option for radioactive synovectomy in haemophilic synovitis.

Recurrent haemarthroses often lead to chronic synovitis in patients with haemophilia and von Willebrand disease. Radioactive synovectomy with yttrium-90 (9°Y) citrate is frequently used to treat this complication, usually with good results. Since 2006, the Nuclear Energy Research Institute (IPEN, Sao Paulo, Brazil) has produced hydroxyapatite particles labelled with 9°Y for radioactive synovectomy. The aim of this study was to compare the results achieved by both forms of 9°Y in the treatment of haemophilic synovitis. We included 221 joints from 136 patients (age range: 6-20 years), treated by one of the two radiopharmaceuticals, at the Hemocenter of Mato Grosso, Brazil. The outcomes analysed were the annual frequency of haemarthrosis, articular pain and joint range of motion before and 1 year after RS. Similar results were achieved regardless of whether 9°Y hydroxyapatite or 9°Y citrate was used, and results were independent of the joint type, age, gender, radiologic stage and presence of inhibitors. 9°Y hydroxyapatite appears to be equivalent to the reference product 9°Y citrate in the treatment of chronic synovitis associated with bleeding disorders.

An unexpectedly rapid decline in the X-ray afterglow emission of long gamma-ray bursts.

'Long' gamma-ray bursts (GRBs) are commonly accepted to originate in the explosion of particularly massive stars, which give rise to highly relativistic jets. Inhomogeneities in the expanding flow result in internal shock waves that are believed to produce the gamma-rays we see. As the jet travels further outward into the surrounding circumstellar medium, 'external' shocks create the afterglow emission seen in the X-ray, optical and radio bands. Here we report observations of the early phases of the X-ray emission of five GRBs. Their X-ray light curves are characterised by a surprisingly rapid fall-off for the first few hundred seconds, followed by a less rapid decline lasting several hours. This steep decline, together with detailed spectral properties of two particular bursts, shows that violent shock interactions take place in the early jet outflows.

Influence of all-trans-retinoic acid on oxoglutarate carrier via retinoylation reaction.

All-trans-retinoic acid (atRA), an activated metabolite of vitamin A, is incorporated covalently into proteins both invivo and invitro. AtRA reduced the transport activity of the oxoglutarate carrier (OGC) isolated from testes mitochondria to 58% of control via retinoylation reaction. Labeling of testes mitochondrial proteins with (3)HatRA demonstrated the binding of atRA to a 31.5 KDa protein. This protein was identified as OGC due to the competition for the labeling reaction with 2-oxoglutarate, the specific OGC substrate. The role of retinoylated proteins is currently being explored and here we have the first evidence that retinoic acids bind directly to OGC and inhibit its activity in rat testes mitochondria via retinoylation reaction. This study indicates the evidence of a specific interaction between atRA and OGC and establishes a novel mechanism for atRA action, which could influence the physiological biosynthesis of testosterone in situations such as retinoic acid treatment.

Italian Association of Sleep Medicine (AIMS) position statement and guideline on the treatment of menopausal sleep disorders.

Insomnia, vasomotor symptoms (VMS) and depression often co-occur after the menopause, with consequent health problems and reductions in quality of life. The aim of this position statement is to provide evidence-based advice on the management of postmenopausal sleep disorders derived from a systematic review of the literature. The latter yielded results on VMS, insomnia, circadian rhythm disorders, obstructive sleep apnea (OSA) and restless leg syndrome (RLS). Overall, the studies show that menopausal hormone therapy (MHT) improves VMS, insomnia, and mood. Several antidepressants can improve insomnia, either on their own or in association with MHT; these include selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), and mirtazapine. Long-term benefits for postmenopausal insomnia may also be achieved with non-drug strategies such as cognitive behavioral therapy (CBT) and aerobic exercise. Continuous positive airway pressure (CPAP) and mandibular advancement devices (MADs) both reduce blood pressure and cortisol levels in postmenopausal women suffering from OSA. However, the data regarding MHT on postmenopausal restless legs syndrome are conflicting.

Home and neighbourhood built environment features in family-based treatment for childhood obesity.

BACKGROUND: Family-based behavioural weight loss treatment (FBT) for childhood obesity helps families develop strategies to facilitate healthy choices in their home and other environments (e.g. home neighbourhood). The current study examines how the home food environment, both pre-FBT and post-FBT, and the neighbourhoods in which families live are associated with child weight and weight-related outcomes in FBT. METHODS: Parent-child dyads (n = 181) completed a 16-session FBT programme and completed home environment, anthropometric and child dietary/activity assessments at pre-FBT and post-FBT. Parents reported on availability of food, electronics and physical activity equipment in the home. The neighbourhood food and recreation environments around each dyad's residence was characterized using existing data within a geographic information system. RESULTS: Families successfully made healthy home environment modifications during FBT. Regression models showed reducing RED (e.g. high-energy-dense and low-nutrient-dense) foods and electronics in the home during FBT had positive effects on child weight and weight-related outcomes. No neighbourhood food or recreation environment variables were significantly related to outcomes, although having a larger density of public recreation spaces was associated with increases in physical activity at the trend-level. CONCLUSIONS: Modifying the home environment, specifically reducing RED foods and electronics, may be particularly important for FBT success.

Infective endocarditis caused by USA300 methicillin-resistant Staphylococcus aureus (MRSA).

We report seven cases of infective endocarditis caused by USA300 methicillin-resistant Staphylococcus aureus (MRSA) at an urban, tertiary care, academic institution. Five strains were community associated and two were healthcare associated. All patients were injection drug users. Staphylococcus aureus isolates were characterised as USA300-type MRSA using pulsed-field gel electrophoresis. Five cases were right-sided endocarditis and two cases were left-sided. The mean length of in-hospital antimicrobial therapy was 23 days and the mean length of total antibiotic therapy was 55 days. Complications included heart failure resulting in valve replacement in one patient as well as death in that patient. As USA300 strains of MRSA continue to increase in prevalence, clinicians must be aware of the increasing spectrum of illness in considering management and prevention strategies.

[Development of an objective structured clinical examination (OSCE) for evaluating clinical competence in vascular medicine]. / Développement d'un examen clinique objectif structuré (ECOS) pour évaluer les compétences des étudiants en médecine vasculaire.

OBJECTIVES: Vascular medicine is now a clinical specialty in France. During their studies, students will acquire clinical reasoning in addition to technical skills. An Objective Structured Clinical Examination (OSCE) is considered as the gold standard for evaluating clinical competence. Our main objective was to evaluate the feasibility and acceptability of OSCE for the evaluation of students, secondarily their performance. METHODS: Three representative clinical cases of the specialty were developed. The OSCE consisted of a sequence of clinical situations presented in three stations of 7minutes each. The role of the simulated patient was played by medical students. At the end of the OSCE, observers and students completed the evaluation form. We compared the performances between junior and senior vascular medicine students. Written questionnaires were used to measure OSCE satisfaction. RESULTS: We were able to develop and organize this examination without difficulties. Fifteen students were evaluated. All participants agreed that the clinical situations were representative of vascular medicine practice, the cases were realistic and standardized patients were convincing. The performance of senior students was statistically higher than junior students in one case. DISCUSSION: Our study demonstrates the feasibility and acceptability of the OSCE in students in vascular medicine. The small number of stations and candidates requires further studies on a larger scale to evaluate their performance.

Swift and NuSTAR observations of GW170817: Detection of a blue kilonova.

With the first direct detection of merging black holes in 2015, the era of gravitational wave (GW) astrophysics began. A complete picture of compact object mergers, however, requires the detection of an electromagnetic (EM) counterpart. We report ultraviolet (UV) and x-ray observations by Swift and the Nuclear Spectroscopic Telescope Array of the EM counterpart of the binary neutron star merger GW170817. The bright, rapidly fading UV emission indicates a high mass (≈0.03 solar masses) wind-driven outflow with moderate electron fraction (Ye ≈ 0.27). Combined with the x-ray limits, we favor an observer viewing angle of ≈30° away from the orbital rotation axis, which avoids both obscuration from the heaviest elements in the orbital plane and a direct view of any ultrarelativistic, highly collimated ejecta (a γ-ray burst afterglow).

Strategies for improving maintenance of weight loss. Toward a continuous care model of obesity management.

The management of obesity represents an important objective in the care of many NIDDM patients. In recent years, progress has been made in increasing initial weight reductions, but poor long-term maintenance of weight loss remains a vital clinical concern. This article reviews the challenge of weight-loss maintenance and recommends the adoption of a continuous care model of obesity management. Strategies to improve the long-term maintenance of weight loss are described, and empirical tests of their effectiveness are reviewed. Collectively, the findings suggest that, after treatment for obesity, multifaceted programs comprised of continued professional contact, skills training, social support, and exercise, can enhance the long-term maintenance of weight loss.

Supernovae. 44Ti gamma-ray emission lines from SN1987A reveal an asymmetric explosion.

In core-collapse supernovae, titanium-44 ((44)Ti) is produced in the innermost ejecta, in the layer of material directly on top of the newly formed compact object. As such, it provides a direct probe of the supernova engine. Observations of supernova 1987A (SN1987A) have resolved the 67.87- and 78.32-kilo-electron volt emission lines from decay of (44)Ti produced in the supernova explosion. These lines are narrow and redshifted with a Doppler velocity of ~700 kilometers per second, direct evidence of large-scale asymmetry in the explosion.

(Phosphinyloxy)acyl amino acid inhibitors of angiotensin converting enzyme (ACE). 1. Discovery of (S)-1-[6-amino-2-[[hydroxy(4-phenylbutyl)phosphinyl]oxy]-1-oxohexyl]-L -proline a novel orally active inhibitor of ACE.

The synthesis of a series of orally active, phosphinyloxyacyl proline inhibitors of angiotensin converting enzyme (ACE) is described. The in vitro and in vivo ACE inhibitory activities are reported for each compound. The structure-activity relationship for this series of compounds in relation to the carboxyalkyl dipeptide ACE inhibitors as well as other types of hydroxyphosphinyl-containing ACE inhibitors (e.g., the corresponding nitrogen and carbon isosteres) is discussed. Within an isosteric series of phosphorus-containing inhibitors based on the lysylproline terminal dipeptide sequence, only the phosphonates (oxygen isosteres) show a high level of oral activity. Optimum potency and oral activity in the phosphonate series occurs with the (phenylbutyl)- and n-hexylphosphonate side chains. An aminobutyl side chain in the P1' residue is an absolute requirement for full expression of oral activity. The most potent of these compounds, 8b (SQ 29,852), has intravenous and oral activities superior in potency to those of captopril in the normotensive rat.

Treatment for snoring. Combined weight loss, sleeping on side, and nasal spray.

OBJECTIVE: We sought to find a combination of noninvasive treatments for snoring by adding weight loss to previously studied treatments, including the combination of sleeping on one's side and using a decongestant nasal spray. STUDY POPULATION: Twenty asymptomatic men who snore heavily were studied previously on a control night and on a night when they slept on their side and used a nasal spray. With these two treatments, minor improvements in apnea/hypopnea index (AHI) were seen, but no improvement occurred in snoring frequency. Nineteen of these subjects subsequently completed a 6-month weight loss program, and 12 lost weight. These 19 subjects comprise the study population of this report. STUDY DESIGN: At the conclusion of the weight loss program, a repeated sleep study was done from which the effect of adding weight loss to the two previously studied treatments could be assessed. RESULTS: Those 12 subjects who lost any amount of weight showed a very mild reduction in snores per hour from 328 using two modalities of treatment to 232 per hour with the addition of weight loss (p = 0.15). The nine subjects who lost > or = 3 kg reduced the number of snores per hour from 320 to 176 (p = 0.0496). Three subjects losing an average of only 7.6 kg showed virtual elimination of snoring after weight loss. Subjects who gained weight had no improvement in snoring. Weight loss added to the other two modalities of treatment had no effect on the AHI. CONCLUSION: In most cases, the combination of weight loss, sleeping on one's side, and the administration of a nasal decongestant significantly reduces the frequency of snoring in asymptomatic men who snore heavily. The major effect appears to be related to weight loss.