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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.
Lebanon has a need for innovative approaches to increase access to mental health care to meet the country's current high demand. E-mental health has been included in its national mental health strategy while in parallel the World Health Organization has produced an online intervention called ‘Step-by-Step’ to treat symptoms of depression that is being tested in Lebanon over the coming years.
The primary aim of this study is to conduct bottom-up, community-driven qualitative cognitive interviewing from a multi-stakeholder perspective to inform the cultural adaptation of an Internet-delivered mental health intervention based on behavioural activation in Lebanon.
National Mental Health Programme staff conducted a total of 11 key informant interviews with three mental health professionals, six front-line workers in primary health care centres (PHCCs) and two community members. Also, eight focus group discussions, one with seven front-line workers and seven others with a total of 66 community members (Lebanese, Syrians and Palestinians) were conducted in several PHCCs to inform the adaptation of Step-by-Step. Results were transcribed and analysed thematically by the project coordinator and two research assistants.
Feedback generated from the cognitive interviewing mainly revolved around amending the story, illustrations and the delivery methods to ensure relevance and sensitivity to the local context. The results obtained have informed major edits to the content of Step-by-Step and also to the model of provision. Notably, the intervention was made approximately 30% shorter; it includes additional videos of content alongside the originally proposed comic book-style delivery; there is less emphasis on total inactivity as a symptom of low mood and more focus on enjoyable activities to lift mood; the story and ways to contact participants to provide support were updated in line with local gender norms; and many of the suggested or featured activities have been revised in line with suggestions from community members.
These findings promote and advocate the use of community-driven adaptation of evidence-based psychological interventions. Some of the phenomena recorded mirror findings from other research about barriers to care seeking in the region and so changes made to the intervention should be useful in improving utility and uptake of ‘Step-by-Step’.
To assess variability in antimicrobial use and associations with infection testing in pediatric ventilator-associated events (VAEs).
Descriptive retrospective cohort with nested case-control study.
Pediatric intensive care units (PICUs), cardiac intensive care units (CICUs), and neonatal intensive care units (NICUs) in 6 US hospitals.
Children≤18 years ventilated for≥1 calendar day.
We identified patients with pediatric ventilator-associated conditions (VACs), pediatric VACs with antimicrobial use for≥4 days (AVACs), and possible ventilator-associated pneumonia (PVAP, defined as pediatric AVAC with a positive respiratory diagnostic test) according to previously proposed criteria.
Among 9,025 ventilated children, we identified 192 VAC cases, 43 in CICUs, 70 in PICUs, and 79 in NICUs. AVAC criteria were met in 79 VAC cases (41%) (58% CICU; 51% PICU; and 23% NICU), and varied by hospital (CICU, 20–67%; PICU, 0–70%; and NICU, 0–43%). Type and duration of AVAC antimicrobials varied by ICU type. AVAC cases in CICUs and PICUs received broad-spectrum antimicrobials more often than those in NICUs. Among AVAC cases, 39% had respiratory infection diagnostic testing performed; PVAP was identified in 15 VAC cases. Also, among AVAC cases, 73% had no associated positive respiratory or nonrespiratory diagnostic test.
Antimicrobial use is common in pediatric VAC, with variability in spectrum and duration of antimicrobials within hospitals and across ICU types, while PVAP is uncommon. Prolonged antimicrobial use despite low rates of PVAP or positive laboratory testing for infection suggests that AVAC may provide a lever for antimicrobial stewardship programs to improve utilization.
Epidemiological evidence has linked low vitamin D status to a range of mood disorders. However, studies examining whether vitamin D supplementation can improve mood-related outcomes in healthy populations are limited. We investigated whether vitamin D supplementation over winter is beneficial for improving mood-related outcomes in healthy women. A total of 152 healthy women (18–40 years) in Dunedin, New Zealand were randomly assigned to receive 50 000 IU (1·25 mg) of oral vitamin D3 or placebo once per month for 6 months. They completed the Center for Epidemiologic Studies Depression Scale, the anxiety subscale of the Hospital Anxiety and Depression Scale and the Flourishing Scale every month. Additionally, they reported their positive and negative mood each day for three consecutive days every 2 months. Participants provided a blood sample at the beginning and at the end of the study for 25-hydroxyvitamin D3 analysis. ANCOVA was used to compare the outcome measures between the groups, controlling for baseline. We found no evidence of lower depression (P = 0·339), lower anxiety (P = 0·862), higher flourishing (P = 0·453), higher positive moods (P = 0·518) or lower negative moods (P = 0·538) in the treatment group compared with the control group at follow-up. Mood outcomes over the study period were similar for the two groups. We found no evidence of any beneficial effect of monthly vitamin D3 supplementation on mood-related outcomes in healthy premenopausal women over the winter period, so recommendations for supplementations are not warranted in this population for mood-related outcomes.
The use of information technology in healthcare has accelerated progress toward the long-term goal of a learning healthcare system, in which data from prior clinical experience provides an ever-expanding resource to guide continuous improvements in health care. Although still in its early stages, the use of data from clinical experience to supplement data from premarket testing is changing the roles of Food and Drug Administration (FDA) and public and private health insurers in healthcare innovation and technology assessment. It could change who decides what research questions to pursue, whose evidentiary standards decide what counts as actionable knowledge, and who pays the costs of research. The shape and direction of resulting changes will depend on which actors and institutions decide to step forward and claim a larger role in healthcare innovation in response to technological and regulatory change.
Problem Management Plus (PM+) is a brief multicomponent intervention incorporating behavioral strategies delivered by lay health workers. The effectiveness of PM+ has been evaluated in randomized controlled trials in Kenya and Pakistan. When developing interventions for large-scale implementation it is considered essential to evaluate their feasibility and acceptability in addition to their efficacy. This paper discusses a qualitative evaluation of PM+ for women affected by adversity in Kenya.
Qualitative interviews were conducted with 27 key informants from peri-urban Nairobi, Kenya, where PM+ was tested. Interview participants included six women who completed PM+, six community health volunteers (CHVs) who delivered the intervention, seven people with local decision making power, and eight project staff involved in the PM+ trial.
Key informants generally noted positive experiences with PM+. Participants and CHVs reported the positive impact PM+ had made on their lives. Nonetheless, potential structural and psychological barriers to scale up were identified. The sustainability of CHVs as unsalaried, volunteer providers was mentioned by most interviewees as the main barrier to scaling up the intervention.
The findings across diverse stakeholders show that PM+ is largely acceptable in this Kenyan setting. The results indicated that when further implemented, PM+ could be of great value to people in communities exposed to adversities such as interpersonal violence and chronic poverty. Barriers to large-scale implementation were identified, of which the sustainability of the non-specialist health workforce was the most important one.
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.
The SkyMapper Transient survey (SMT) is exploring variability in the southern sky by performing (a) a rolling search to discover and study supernovæ, and (b) a Target of Opportunity programme that uses the robotic SkyMapper Telescope at Siding Spring Observatory. The supernova survey is obtaining a non-targeted sample of Type Ia supernovæ (SNe Ia) at low redshifts, z < 0.1, and studying other interesting transients found with the search strategy. We have a Target of Opportunity programme with an automatic response mechanism to search for optical counterparts to gravitational-wave and fast radio-burst events; it benefits from SkyMapper’s large field of view of 5.7 sq. deg. and a rapid data reduction pipeline.
We present first results of the SMT survey. The SMT pipeline can process and obtain potential candidates within 12 hours of observation. It disentangles real transients from processing artefacts using a machine-learning algorithm. To date, SMT has discovered over 60 spectroscopically confirmed supernovæ, several peculiar objects, and over 40 SNe Ia including one (SNIa 2016hhd) which was found within the first few days of explosion. We have also participated in searches for optical counterparts of gravitational waves, fast radio bursts and other transients, and have published observations of the optical counterpart of the gravitational-wave event GW170817. We also participate in coordinated observations with the Deeper Wider Faster programme, and the Kepler K2 cosmology project.
Adult ventilator-associated event (VAE) definitions include ventilator-associated conditions (VAC) and subcategories for infection-related ventilator-associated complications (IVAC) and possible ventilator-associated pneumonia (PVAP). We explored these definitions for children.
Pediatric, cardiac, or neonatal intensive care units (ICUs) in 6 US hospitals
Patients ≤18 years old ventilated for ≥1 day
We identified patients with pediatric VAC based on previously proposed criteria. We applied adult temperature, white blood cell count, antibiotic, and culture criteria for IVAC and PVAP to these patients. We matched pediatric VAC patients with controls and evaluated associations with adverse outcomes using Cox proportional hazards models.
In total, 233 pediatric VACs (12,167 ventilation episodes) were identified. In the cardiac ICU (CICU), 62.5% of VACs met adult IVAC criteria; in the pediatric ICU (PICU), 54.2% of VACs met adult IVAC criteria; and in the neonatal ICU (NICU), 20.2% of VACs met adult IVAC criteria. Most patients had abnormal white blood cell counts and temperatures; we therefore recommend simplifying surveillance by focusing on “pediatric VAC with antimicrobial use” (pediatric AVAC). Pediatric AVAC with a positive respiratory diagnostic test (“pediatric PVAP”) occurred in 8.9% of VACs in the CICU, 13.3% of VACs in the PICU, and 4.3% of VACs in the NICU. Hospital mortality was increased, and hospital and ICU length of stay and duration of ventilation were prolonged among all pediatric VAE subsets compared with controls.
We propose pediatric AVAC for surveillance related to antimicrobial use, with pediatric PVAP as a subset of AVAC. Studies on generalizability and responsiveness of these metrics to quality improvement initiatives are needed, as are studies to determine whether lower pediatric VAE rates are associated with improvements in other outcomes.
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.
The four years that have elapsed since the last meeting of the International Astronomical Union have witnessed steady progress in the determination of radial velocities, principally at the Mt Wilson Observatory, Pasadena, Cal., the Lick Observatory, Mt Hamilton, Cal., the Yerkes Observatory, Williams Bay, Wis., the Dominion Astrophysical Observatory, Victoria, B.C., the Observatory of the University of Michigan, Ann Arbor, Mich., and the Simeis Observatory in Russia. It will be useful, for the members of the Commission, to give a short summary of the radial velocity work completed and in progress since the last meeting.
The Report as printed was discussed section by section. Section I being only a summary of progress was, with the correction of a typographical error, accepted.
Section III was discussed and, on the motion of Frost and Moore, a sub-committee was appointed by the Chairman consisting of Adams, Moore and Harper, to prepare a suitable list of standard velocity stars for the faint stars and to revise the previous list of standard velocity stars, omitting those now known or suspected to vary slightly in velocity.
During the past three years the measurement of stellar radial velocities has formed an important part of the spectroscopic programme of most observatories possessing large telescopes. As observations are carried to fainter and fainter stars and the number of observable objects increases rapidly, a natural development has been the selection of special groups and types of stars, the radial velocities of which will aid in the solution of certain specific problems. Illustrations are the studies of the O, B and A type stars made at the Dominion Astrophysical, the Lick, and the Simeis Observatories, of the members of the galactic clusters at the Lick Observatory, and of the fainter Cepheid variables and early-type stars with strong interstellar lines at the Mount Wilson Observatory.
In November 1934 the President circulated a letter to the members of the Commission as follows:
Since the 1932 meeting the following projects have been completed, or are nearing completion:
(1)The publication of many lists of trigonometric parallaxes.
(2)The determination of the spectroscopic parallaxes of 4179 stars at Mt Wilson Observatory by Adams, Joy and Humason.
(3)A discussion of systematic errors of trigonometric parallaxes by van Maanen and a re-discussion in the Astrophysical Journal of the same material by Mitchell and by Sterne.
(4)The compilation of a second Yale Catalogue to include parallaxes completed before the end of 1934.
(5)Substantial progress on the proper motions of 32,000 stars by Boss and his associates at the Dudley Observatory.
(6)The publication at the Radcliffe Observatory of the proper motions of 32,000 stars from photographs on 115 Selected Areas.
(7)The completion of the dynamical parallaxes of 2000 stars.
(8)The completion of the proper motions of 18,000 stars derived from parallax plates at the Leander McCormick Observatory.
(9)The publication at the Yale Observatory of the proper motions of 40,000 stars with a probable error less than 0”.010 determined from photographs by re-observing in zones the Astronomische Gesellschaft stars.
(10)The determination of the proper motions of 50,000 stars in the Southern Hemisphere by Luyten from Harvard photographs.
The three years that have elapsed since the Harvard meeting of the Union have witnessed steady progress in the determination of radial velocities. While the three large Pacific Coast Observatories have naturally been able to make the greatest additions to radial velocity work, the Yerkes Observatory, the Simeiz Observatory and the Observatory of the University of Michigan have also made valuable contributions. It is a pleasure to report that there will soon be three major accessions to the list of observatories capable of determining radial velocities. The David Dunlap Observatory of the University of Toronto with its 74-inch telescope, which should be in operation soon after the meeting, will have radial velocities as a prominent feature of its programme. The McDonald Observatory of the University of Texas with an 80-inch telescope now under construction should be ready to commence operations in 1936 and will undertake an extensive radial velocity programme. The Radcliffe Observatory at Oxford has now been granted permission by the Courts to remove to Pretoria, South Africa, and will establish there a 74-inch reflecting telescope, which will also be largely employed in the determination of the urgently needed radial velocities of the southern stars fainter than 5.5 visual magnitude. The Commission may, I believe, congratulate itself that substantial assistance in the preliminary steps leading to this permission of removal was provided by our action at the last meeting in presenting a resolution to the Union, duly passed by the General Assembly, pointing out the urgent need for additional radial velocities in the southern sky, and strongly supporting the project of the Radcliffe Observatory to establish a large telescope at Pretoria.
In November 1931 the President circulated a letter to the members of the Commission which in part was as follows:
In view of the fact that it is now over a quarter of a century since Schlesinger by photography began to determine trigonometric parallaxes by a long focus telescope, and fifteen years since Adams and Kohlschütter derived the first spectroscopic parallaxes, it would seem appropriate to take stock of our present position and to make plans for future development.
Will you be good enough, therefore, to furnish such statements concerning the following topics as are appropriate to the work of your observatory?
The purpose of this pilot study was to evaluate a 12-session group-based motivational intervention for substance misusers in a prison setting. The intervention aimed to increase both participants awareness of problem substance use and motivation to change their substance use behaviour.
Participants were recruited for the intervention through active outreach in the prison. Participants of the intervention group completed a structured interview before the group commencing and standardised pre- and post-outcome measures. The results of the intervention group (n=31) were compared with a waiting list control group (n=11).
Non-parametric analysis showed retention rates on this programme at 2, 4 and 6 weeks were 88%, 79% and 76%, respectively. Outcome data were consistent with the predicted direction for the treatment group compared with the wait-list control with significant between-group differences found on ambivalence and taking steps scores.
This group-based intervention demonstrated positive levels of client engagement and retention. The intervention was also successful in reducing participant ambivalence about their drug use. Implications for service provision are discussed and design limitations of the present study are considered. Overall, findings indicate the potential utility of a group-based motivational intervention for substance misusers in forensic settings.