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Background: Spinal muscular atrophy (SMA) is a children’s neuromuscular disorder. Although motor neuron loss is a major feature of the disease, we have identified fatty acid abnormalities in SMA patients and in preclinical animal models, suggesting metabolic perturbation is also an important component of SMA. Methods: Biochemical, histological, proteomic, and high resolution respirometry were used. Results: SMA patients are more susceptible to dyslipidemia than the average population as determined by a standard lipid profile in a cohort of 72 pediatric patients. As well, we observed a non-alcoholic liver disease phenotype in apreclinical mouse model. Denervation alone was not sufficient to induce liver steatosis, as a mouse model of ALS, did not develop fatty liver. Hyperglucagonemia in Smn2B/-mice could explain the hepatic steatosis by increasing plasma substrate availability via glycogen depletion and peripheral lipolysis. Proteomic analysis identified mitochondrion and lipid metabolism as major clusters. Alterations in mitochondrial function were revealed by high-resolution respirometry. Finally, low-fat diets led to increased survival in Smn2B/-mice. Conclusions: These results provide strong evidence for lipid metabolism defects in SMA. Further investigation will be required to establish the primary mechanism of these alterations and understand how they lead to additional co-morbidities in SMA patients.
The History, Electrocardiogram (ECG), Age, Risk Factors, and Troponin (HEART) score is a decision aid designed to risk stratify emergency department (ED) patients with acute chest pain. It has been validated for ED use, but it has yet to be evaluated in a prehospital setting.
A prehospital modified HEART score can predict major adverse cardiac events (MACE) among undifferentiated chest pain patients transported to the ED.
A retrospective cohort study of patients with chest pain transported by two county-based Emergency Medical Service (EMS) agencies to a tertiary care center was conducted. Adults without ST-elevation myocardial infarction (STEMI) were included. Inter-facility transfers and those without a prehospital 12-lead ECG or an ED troponin measurement were excluded. Modified HEART scores were calculated by study investigators using a standardized data collection tool for each patient. All MACE (death, myocardial infarction [MI], or coronary revascularization) were determined by record review at 30 days. The sensitivity and negative predictive values (NPVs) for MACE at 30 days were calculated.
Over the study period, 794 patients met inclusion criteria. A MACE at 30 days was present in 10.7% (85/794) of patients with 12 deaths (1.5%), 66 MIs (8.3%), and 12 coronary revascularizations without MI (1.5%). The modified HEART score identified 33.2% (264/794) of patients as low risk. Among low-risk patients, 1.9% (5/264) had MACE (two MIs and three revascularizations without MI). The sensitivity and NPV for 30-day MACE was 94.1% (95% CI, 86.8-98.1) and 98.1% (95% CI, 95.6-99.4), respectively.
Prehospital modified HEART scores have a high NPV for MACE at 30 days. A study in which prehospital providers prospectively apply this decision aid is warranted.
The discovery of the first electromagnetic counterpart to a gravitational wave signal has generated follow-up observations by over 50 facilities world-wide, ushering in the new era of multi-messenger astronomy. In this paper, we present follow-up observations of the gravitational wave event GW170817 and its electromagnetic counterpart SSS17a/DLT17ck (IAU label AT2017gfo) by 14 Australian telescopes and partner observatories as part of Australian-based and Australian-led research programs. We report early- to late-time multi-wavelength observations, including optical imaging and spectroscopy, mid-infrared imaging, radio imaging, and searches for fast radio bursts. Our optical spectra reveal that the transient source emission cooled from approximately 6 400 K to 2 100 K over a 7-d period and produced no significant optical emission lines. The spectral profiles, cooling rate, and photometric light curves are consistent with the expected outburst and subsequent processes of a binary neutron star merger. Star formation in the host galaxy probably ceased at least a Gyr ago, although there is evidence for a galaxy merger. Binary pulsars with short (100 Myr) decay times are therefore unlikely progenitors, but pulsars like PSR B1534+12 with its 2.7 Gyr coalescence time could produce such a merger. The displacement (~2.2 kpc) of the binary star system from the centre of the main galaxy is not unusual for stars in the host galaxy or stars originating in the merging galaxy, and therefore any constraints on the kick velocity imparted to the progenitor are poor.
We present new far-IR and submillimeter broad-band and spectroscopic results on the dense and very luminous cores of massive star formation regions. The best-studied region, W51, contains one core around the source IRS2 and another around W51 MAIN. Our earlier submillimeter continuum mapping has shown that these two cores are very massive (2-4 × 104 M⊙) and have average densities of nH2 ∼ 105 over their inner parsec. New far-IR maps show that both cores are very luminous (L(MAIN) ∼2 × 106 L⊙; L(IRS2) ∼4x106 L⊙). Observations of the (1,1) and (2,1) transitions of NH3, indicate high kinetic temperatures (200-400 K) for the quiescent gas in the inner several arc seconds (0.1 pc) of both cores. Spectroscopy of the 370 μm J = 7 → 6 and 163 μm J = 16 → 15 transitions of CO toward the cores allows us to characterize the hot high velocity material seen previously on the H2O maser transitions and not readily visible in the low J transitions of CO. The high velocity flow in IRS2 is ∼ 60 times more massive than the very similar outflow in the ∼ 30 times less luminous Orion/KL core. The mass loss rate is ∼ 30 times greater than in Orion. Additional observations of W49 allow us to draw a few general conclusions about the most luminous star formation regions in our galaxy: (1) The luminous cores are 102-103 more massive than the Orion core with the same density. (2) Outflows and warm regions in these cores have physical conditions similar to those in their less luminous counterparts but far more mass is involved in the flows.
A general description of ablation polygons is given and variations from widely distributed regions are examined. After discussion of the conditions in which they most frequently develop, possible explanations are considered, leading to the conclusion that the polygons result from ablation by turbulence in the surrounding air, and that the dirt fringes to the polygons may be explained by the “normal trajectory” theory.
To facilitate surveillance and describe the burden of healthcare-associated infection (HAI) in nursing homes (NHs), we compared the quality of resident-level data collected by NH personnel and external staff.
A 1-day point-prevalence survey
SETTING AND PARTICIPANTS
Overall, 9 nursing homes among 4 Centers for Disease Control and Prevention (CDC) Emerging Infection Program (EIP) sites were included in this study.
NH personnel collected data on resident characteristics, clinical risk factors for HAIs, and the presence of 3 HAI screening criteria on the day of the survey. Trained EIP surveillance officers collected the same data elements via retrospective medical chart review for comparison; surveillance officers also collected available data to identify HAIs (using revised McGeer definitions). Overall agreement was calculated among residents identified by both teams with selected risk factors and HAI screening criteria. The impact of using NH personnel to collect screening criteria on HAI prevalence was assessed.
The overall prevalence of clinical risk factors among the 1,272 residents was similar between NH personnel and surveillance officers, but the level of positive agreement (residents with factors identified by both teams) varied between 39% and 87%. Surveillance officers identified 253 residents (20%) with ≥1 HAI screening criterion, resulting in 67 residents with an HAI (5.3 per 100 residents). The NH personnel identified 152 (12%) residents with ≥1 HAI screening criterion; 42 residents had an HAI (3.5 per 100 residents).
We identified discrepancies in resident-level data collection between surveillance officers and NH personnel, resulting in varied estimates of the HAI prevalence. These findings have important implications for the design and implementation of future HAI prevalence surveys.
The mechanism responsible for driving the ubiquitous winds of cool giant and supergiant stars remains to be established. To this end, we are constructing semi-empirical models of the extended outer atmospheres (‘chromospheres’) and winds of selected red supergiants. These models are constrained by analyses of the UV line spectra of single stars, and of red supergiants in binaries that eclipse their main-sequence companions: the ζ Aur and VV Cep stars. These detached binaries are well-separated, with no evidence of mass transfer. The C II] 2325 Å line profiles of the binaries are similar to those of comparable single stars, suggesting that the chromospheres remain relatively unperturbed by binarity. However, it is unclear how much binarity disturbs the wind: binary observations suggest a gradual acceleration (β ∼ 3), but line profile analyses of single red supergiants imply a rapid acceleration (β < 1). To date, we have obtained extensive series of HST/GHRS and STIS observations of three eclipsing red supergiant binaries: ζ Aur, HR 2554 and VV Cep. In this paper, we focus on ζ Aur, and present observations and modelling results for this eclipsing binary.
We discuss GHRS spectra of single and binary late-type stars and describe in detail the spectra of α TrA and of ζ Aurigae obtained at ten orbital phases. The wind properties of α TrA are derived using a complete redistribution radiative transfer code, and we describe the properties of a new code, PRISMA, that we are building to fit line profiles using partial redistribution in a spherically-symmetric geometry. The ζ Aur spectra show that the mass loss process is variable on the timescale of several months, the wind density structure does not repeat from orbit to orbit, and the wind ionization structure is complex.
This work is a continuation of our study of the efficiency of two well-known methods for the numerical integration of the equations of motion of planetary satellites together with the variational equations of the system. The methods are the 10th-order Gauss-Jackson backward-difference method described in [4, 6] and the Runge-Kutta-Nyström RKN12(10)17M .
The Center for Astrophysical Research in Antarctica conducts various educational outreach programs as part of its mission as a National Science Foundation Science and Technology Center. The method behind the outreach programs is one of forging partnerships between Center researchers and other educational organisations. The main program serves primary and secondary students in Chicago. The core of the program is called Space Explorers and is targeted at high school students. These students attend a summer residential institute at the University of Chicago’s Yerkes Observatory. The high school Space Explorers then extend the reach of the program during the academic year by teaching in primary schools using a portable planetarium. The Center also pursues many other outreach activities and is in the process of forming an Antarctic Education Alliance.
Near-infrared images of a sample of red, blue and giant low surface brightness disk galaxies (LSBGs) were combined with optical data with the aim of constraining their star formation histories. Most LSBGs have strong colour gradients consistent with mean stellar age gradients. We find that LSBGs have a large range of ages and metallicities, spanning those observed in normal disk galaxies. In particular, red and blue LSBGs have very different star formation histories and represent two independent routes to low B band surface brightness. Blue LSBGs are well described by models with low, roughly constant star formation rates, whereas red LSBGs are better described by a ‘faded disk’ scenario.
The Center for Astrophysical Research in Antarctica is a new National Science Foundation Science and Technology Center formed to explore and exploit the unique advantages of the Antarctic Plateau for astrophysical observations.
Food- and waterborne disease is thought to be high in some Canadian Indigenous communities; however, the burden of acute gastrointestinal illness (AGI) is not well understood due to limited availability and quality of surveillance data. This study estimated the burden of community-level self-reported AGI in the Inuit communities of Rigolet, Nunatsiavut, and Iqaluit, Nunavut, Canada. Cross-sectional retrospective surveys captured information on AGI and potential environmental risk factors. Multivariable logistic regression models identified potential AGI risk factors. The annual incidence of AGI ranged from 2·9–3·9 cases/person per year in Rigolet and Iqaluit. In Rigolet, increased spending on obtaining country foods, a homeless person in the house, not visiting a cabin recently, exposure to puppies, and alternative sources of drinking water were associated with increased odds of AGI. In Iqaluit, eating country fish often, exposure to cats, employment status of the person responsible for food preparation, not washing the countertop with soap after preparing meat, a homeless person in the house, and overcrowding were associated with increased odds of AGI. The results highlight the need for systematic data collection to better understand and support previously anecdotal indications of high AGI incidence, as well as insights into unique AGI environmental risk factors in Indigenous populations.
Acute gastrointestinal illness (AGI) is an important public health priority worldwide. Few studies have captured the burden of AGI in developing countries, and even fewer have focused on Indigenous populations. This study aimed to estimate the incidence and determinants of AGI within a Batwa Pygmy Indigenous population in southwestern Uganda. A retrospective cross-sectional survey was conducted in January 2013 via a census of 10 Batwa communities (n = 583 participants). The AGI case definition included any self-reported symptoms of diarrhoea or vomiting in the past 2 weeks. The 14-day prevalence of AGI was 6·17% [95% confidence interval (CI) 4·2–8·1], corresponding to an annual incidence rate of 1·66 (95% CI 1·1–2·2) episodes of AGI per person-year. AGI prevalence was greatest in children aged <3 years (11·3%). A multivariable mixed-effects logistic regression model controlling for clustering at the community level indicated that exposure to goats [odds ratio (OR) 2·6, 95% CI 1·0–6·8], being a child aged <3 years (OR 4·8, 95% CI 1·2–18·9), and being a child, adolescent or senior Batwa in the higher median of wealth (OR 7·0, 95% CI 3·9–9·2) were significantly associated with having AGI. This research represents the first Indigenous community-census level study of AGI in Uganda, and highlights the substantial burden of AGI within this population.
The generic assignments of some 200 Ordovician brachiopod species in the Barr and Lower Ardmillan (upper Darriwilian–lower Katian) succession, Girvan are reviewed and, where necessary, modified. This key database on the distribution and occurrence of a Laurentian-marginal brachiopod assemblage has featured in many analyses of global biogeography for the period and has confirmed the position of Girvan at relatively low latitudes. Revision of these taxonomic assignments within a modified stratigraphical framework permits closer comparisons with coeval faunas elsewhere around the palaeocontinent of Laurentia and beyond and allows the definition of a variety of brachiopod biofacies on a fault-controlled basin founded on a dismembered ophiolite.
Treatment options for large subglottic haemangioma include steroids, laser ablation, open excision, tracheostomy and, more recently, propranolol. This article aims to present the Great Ormond Street Hospital guidelines for using propranolol to treat infantile isolated subglottic haemangioma by ENT surgeons.
The vascular malformations multidisciplinary team at Great Ormond Street Hospital has developed guidelines for treating infantile haemangioma with propranolol.
The Great Ormond Street Hospital guidelines for propranolol treatment for infantile subglottic haemangioma include investigation, treatment and follow up. Propranolol is started at 1 mg/kg/day divided into three doses, increasing to 2 mg/kg/day one week later. On starting propranolol and when increasing the dose, the pulse rate and blood pressure must be checked every 30 minutes for the first 2 hours. Lesion response to treatment is assessed via serial endoscopy.
Recent reports of dramatic responses to oral propranolol in children with haemangioma and acute airway obstruction have led to increased use. We advocate caution, and have developed guidelines (including pre-treatment investigation and monitoring) to improve treatment safety. Propranolol may in time prove to be the best medical treatment for subglottic haemangioma, but at present is considered to be still under evaluation.