Abstract
Numerous studies have addressed the mesoscale features within extratropical cyclones (ETCs) that are responsible for the most destructive winds, though few have utilized surface observation ...data, and most are based on case studies. By using a 39‐station UK surface observation network, coupled with in‐depth analysis of the causes of extreme gusts during the period 2008–2014, we show that larger‐scale features (warm and cold conveyer belts) are most commonly associated with the top 1% of UK gusts but smaller‐scale features generate the most extreme winds. The cold conveyor belt is far more destructive when joining the momentum of the ETC, rather than earlier in its trajectory, ahead of the approaching warm front. Sting jets and convective lines account for two thirds of severe surface gusts in the UK.
Key Points
A novel way to quantify the relative contributions of mesoscale extratropical cyclone features is introduced
Larger‐scale features are most commonly associated with the top 1% of UK surface gusts but smaller‐scale features generate the most extreme 0.1% of winds
Sting jets and convective lines account for two thirds of severe surface gusts in the UK
To evaluate the efficacy of ropinirole 24-hour prolonged release (ropinirole 24-hour) as an adjunct to levodopa in patients with Parkinson disease (PD) and motor fluctuations.
In a double-blind, ...placebo-controlled, 24-week study, 393 subjects with PD were randomized to ropinirole 24-hour (n = 202) or placebo (n = 191). The primary outcome measure was reduction in hours of daily "off" time.
At week 24, the mean dose of ropinirole 24-hour was 18.8 mg/day with a mean reduction in daily levodopa of 278 mg. There was a mean reduction in daily "off" time of 2.1 hours in the ropinirole 24-hour group and 0.3 hours with placebo. Secondary outcome measures including change in hours and percent of daily "on" time and "on" time without troublesome dyskinesia, Unified PD Rating Scale motor and activities of daily living subscales, Beck Depression Inventory-II, PDQ-39 subscales of mobility, activities of daily living, emotional well-being, stigma and communication, and PD Sleep Scale were significantly improved at week 24 with ropinirole 24-hour. The most common adverse events (AE) with ropinirole 24-hour were dyskinesia, nausea, dizziness, somnolence, hallucinations, and orthostatic hypotension and AEs led to study withdrawal in 5% of both the active and placebo groups.
Ropinirole 24-hour was effective and well tolerated as adjunct therapy in patients with Parkinson disease (PD) not optimally controlled with levodopa. Ropinirole 24-hour demonstrated an improvement in both motor and non-motor PD symptoms, while permitting a reduction in adjunctive levodopa dose.
Rhabdomyosarcoma (RMS), a neoplasm characterised by undifferentiated myoblasts, is the most common soft tissue tumour of childhood. Although aggressive treatment of RMS could provide long-term ...benefit, resistance to current therapies is an ongoing problem. We report here that insulin-like growth factor 2-binding protein 1 (IGF2BP1), an oncofetal protein, is expressed in RMS patient-derived cell lines and in primary tumours where it drives translation of the cellular inhibitor of apoptosis 1 (cIAP1), a key regulator of the nuclear factor-κB signalling pathway and of caspase-8-mediated cell death. We demonstrate that reducing the levels of cIAP1 in RMS, either by IGF2BP1 knockdown or by IAP antagonists, sensitises these cells to tumour necrosis factor-α-mediated cell death. Finally, we show that targeting cIAP1 by IAP antagonists delays RMS tumour growth and improve survival in mice. Our results identify IGF2BP1 as a critical translational regulator of cIAP1-mediated apoptotic resistance in RMS and advocate for the combined use of IAP antagonists and tumour necrosis factor-α as a therapeutic approach for this type of cancer.
This meta-analysis tested the major theoretical assumptions about behavior change by examining the outcomes and mediating mechanisms of different preventive strategies in a sample of 354 ...HIV-prevention interventions and 99 control groups, spanning the past 17 years. There were 2 main conclusions from this extensive review. First, the most effective interventions were those that contained attitudinal arguments, educational information, behavioral skills arguments, and behavioral skills training, whereas the least effective ones were those that attempted to induce fear of HIV. Second, the impact of the interventions and the different strategies behind them was contingent on the gender, age, ethnicity, risk group, and past condom use of the target audience in ways that illuminate the direction of future preventive efforts.
ABSTRACT
Deep moist convection (DMC) requires three ingredients: instability, moisture and lift. One measure that incorporates two of these, instability and moisture, is convective available ...potential energy (CAPE). A 10‐year climatology of CAPE over Great Britain is presented covering the period 1 June 2002–31 May 2012, based on a 9‐km grid spacing implementation of the Weather Research and Forecasting (WRF) model, with two‐way interactive nesting. Appropriate tests are carried out to verify model reliability by comparing simulated and observed CAPE. CAPE is found to be highly variable both spatially and temporally, the highest values being produced during Spanish plume events. A strong relationship is confirmed between surface temperature and CAPE magnitude, the highest CAPE across Great Britain during this period locally exceeding 3000 J kg−1. In an average year, 15 days produce CAPE in excess of 500 J kg−1 somewhere in Great Britain, 4 days > 1000 J kg−1 and 1 day > 1500 J kg−1. Three main CAPE seasons are identified: ‘land dominated CAPE’ between April and September, ‘sea dominated CAPE’ between September and January and ‘low CAPE’ from January to April. The southern North Sea witnesses significant CAPE all year round because of a combination of favourable synoptic situations, including warm air plumes in spring/summer and cold air incursions over warmer seas in winter. CAPE is not a direct predictor of thunderstorm incidence, due in part to the confounding effect of convective inhibition (CIN). However, at the annual scale, when comparing against an existing days of thunder climatology, we observe a close correspondence with >500 J kg−1 CAPE frequency.
Background and purpose
OnabotulinumtoxinA was effective and well tolerated for prophylaxis of headache in patients with chronic migraine (CM) in two randomized, double‐blind, placebo‐controlled, ...phase 3 trials. To further assess the safety and tolerability of onabotulinumtoxinA in CM prophylaxis in adults, the pooled safety data from four double‐blind, placebo‐controlled trials were analyzed.
Methods
The pooled analysis included two phase 2 and two phase 3 double‐blind, placebo‐controlled trials. The safety population was 2436 patients, 1997 of whom received ≥1 dose of onabotulinumtoxinA. The studies shared similar dosing intervals (approximately 12 weeks) with doses between 75 and 260 U. Safety assessments included adverse events (AEs), physical examination and clinical laboratory tests.
Results
OnabotulinumtoxinA was safe and well tolerated, with a low discontinuation rate (3.4%) due to AEs. The majority of patients in this pooled analysis received doses between 150 and 200 U, with an average of 163 U per treatment cycle. Of the 1997 patients who received any onabotulinumtoxinA injections, 1455 patients (72.9%) reported at least one AE. Neck pain (12.6%) was the most common onabotulinumtoxinA‐associated AE, followed by muscle weakness (8.0%), musculoskeletal stiffness (6.1%) and eyelid ptosis (4.6%). Serious AEs were infrequent, occurring in 5.4% of patients who received any onabotulinumtoxinA treatment and 3.0% of patients receiving placebo. AEs were consistent with the known tolerability profile of onabotulinumtoxinA.
Conclusions
Multiple treatments with onabotulinumtoxinA at doses of 75–260 U administered every 12 weeks, and up to five treatment cycles, were well tolerated for the prophylaxis of headache in adults with CM.
This study assessed the effect of resistance training (RT) in 60 healthy postpartum women. Participants were randomized to 18 weeks of RT or an active comparison group (flexibility training). RT and ...flexibility training (FT) exercises were completed twice‐weekly based on the American College of Sports Medicine recommendations. Study outcomes included muscular strength, body composition (dual‐energy x‐ray absorptiometry), exercise self‐efficacy, depressive symptoms Center for Epidemiological Studies Depression Scale (CES‐D), and physical activity (accelerometery). For completers (n = 44), the RT group showed greater strength gains than the FT group, respectively (bench press: +36% vs +8%, P < 0.001; leg press: +31% vs +7%, P < 0.01; abdominal curl‐ups: +228% vs +43%, P < 0.01); however, body composition changes were not different. There was a significant group × time interaction for exercise self‐efficacy (F = 5.33, P = 0.026). For CES‐D score, the RT group decreased (F = 4.61, P = 0.016), while the FT group did not; however, the group × time interaction in CES‐D score was not significant (F = 1.33, P = 0.255). Sedentary time decreased (F = 5.27, P = 0.027) and light‐intensity activity time increased (F = 5.55, P = 0.023) more in the RT than FT group. Intent‐to‐treat analyses did not alter the results. Twice‐weekly RT increases strength and may be associated with better exercise self‐efficacy and improved physical activity outcomes compared with FT in postpartum women.
A true physical understanding of the mysteries involved in the recovery process of the wake momentum deficit, downstream of utility-scale wind turbines in the atmosphere, has not been obtained to ...date. Field data are not acquired at sufficient spatial and temporal resolutions to dissect some of the mysteries of wake turbulence. It is here that the actuator line method has evolved to become the technology standard in the wind energy community. This work presents the actuator line method embedded into an Open source Field Operation and Manipulation (OpenFOAM) large-eddy simulation solver and applies it to two small wind farms, the first one consisting of an array of two National Renewable Energy Laboratory 5 Megawatt (NREL 5-MW) turbines separated by seven rotor diameters in neutral and unstable atmospheric boundary-layer flow and the second one consisting of five NREL 5-MW wind turbines in unstable atmospheric conditions arranged in two staggered arrays of two and three turbines, respectively. Detailed statistics involving power spectral density (PSD) of turbine power along with standard deviations reveal the effects of atmospheric turbulence and its space and time scales. High-resolution surface data extracts provide new insight into the complex recovery process of the wake momentum deficit governed by turbulence transport phenomena.
The purpose of this study was to confirm with pathologic verification 2 beliefs related to Alzheimer's disease (AD): (a) the long-standing impression that bilateral temporo-parietal hypometabolism, ...as noted on FDG PET imaging, is the metabolic abnormality associated with Alzheimer's disease (AD) and (b) that the sensitivity, specificity, and diagnostic accuracy of the metabolic pattern of bilateral temporo-parietal hypometabolism allows differentiation between other degenerative causes of dementia.
Twenty two individuals (8 women, 14 men) with difficult-to-characterize memory loss or dementia (using standard clinical criteria), and who eventually received pathologic confirmation of diagnosis, were evaluated. FDG PET brain scans were obtained and visually graded by an experienced nuclear medicine physician as to the presence of classic bilateral temporo-parietal hypometabolism as seen in Alzheimer's type dementia. Sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of the metabolic pattern of bilateral temporo-parietal hypometabolism were determined using pathologic diagnosis as the gold standard.
The clinical diagnosis of possible or probable AD was determined as the primary cause of dementia in 12 patients. The sensitivity and specificity of the clinical diagnosis for probable AD were 63% and 100%, respectively. The sensitivity and specificity of the clinical diagnosis for possible and probable AD were 75% and 100%, respectively. The sensitivity, specificity, and diagnostic accuracy of bilateral temporo-parietal hypometabolism being associated with AD were 93%, 63%, and 82%, respectively.
This study confirms that bilateral temporo-parietal hypometabolism is indeed the classic metabolic abnormality associated with AD. Furthermore, in individuals with dementia whose FDG PET scans indicated a metabolic pattern other than bilateral temporo-parietal hypometabolism, a cause of dementia other than AD should be suspected. These observations may be of clinical importance in differentiating dementia syndromes. The sensitivity, specificity, and diagnostic accuracy of FDG PET are acceptable as tests to be used in the evaluation of dementia and particularly to confirm the clinical suspicion of AD.
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