Dynamical downscaling of tropical cyclones from CCSM4 simulations of the Last Glacial Maximum

Dynamical downscaling of simulations of the Last Glacial Maximum (LGM) and late twentieth century (20C) were conducted using the Weather Research and Forecasting (WRF) model with the aim of (1) understanding how the downscaled kinematic and thermodynamic variables influence simulated tropical cyclone (TC) activity over the western North Pacific during the LGM and the 20C periods and (2) to test the relevance of TC genesis factors for the colder LGM climate. The results show that, despite the lower temperatures during the LGM, the downscaled TC climatology over the western North Pacific in the LGM simulation does not differ significantly from that in the 20C simulation. Among the TC environmental factors, the TC potential intensity, mid‐tropospheric entropy deficit, and vertical wind shear during the LGM were consistent with previous analyses of TC genesis factors in LGM global climate model simulations. Changes in TC genesis density between the LGM and the 20C simulations seem to be well represented by the ventilation index, a nondimensional measure of the combined effects of vertical wind shear, and thermodynamic properties, suggesting the potential applicability of those factors for TC activity evaluation during the LGM and possibly other climates

From little things, big things grow: trends and fads in 110 years of Australian ornithology

Publishing histories can reveal changes in ornithological effort, focus or direction through time. This study presents a bibliometric content analysis of Emu (1901–2011) which revealed 115 trends (long-term changes in publication over time) and 18 fads (temporary increases in publication activity) from the classification of 9,039 articles using 128 codes organised into eight categories (author gender, author affiliation, article type, subject, main focus, main method, geographical scale and geographical location). Across 110 years, private authorship declined, while publications involving universities and multiple institutions increased; from 1960, female authorship increased. Over time, question-driven studies and incidental observations increased and decreased in frequency, respectively. Single species and ‘taxonomic group’ subjects increased while studies of birds at specific places decreased. The focus of articles shifted from species distribution and activities of the host organisation to breeding, foraging and other biological/ecological topics. Site- and Australian-continental-scales slightly decreased over time; non-Australian studies increased from the 1970s. A wide variety of fads occurred (e.g. articles on bird distribution, 1942–1951, and using museum specimens, 1906–1913) though the occurrence of fads decreased over time. Changes over time are correlated with technological, theoretical, social and institutional changes, and suggest ornithological priorities, like those of other scientific disciplines, are temporally labil

Pharmacokinetic-Pharmacodynamic Modeling in Pediatric Drug Development, and the Importance of Standardized Scaling of Clearance.

Pharmacokinetic/pharmacodynamic (PKPD) modeling is important in the design and conduct of clinical pharmacology research in children. During drug development, PKPD modeling and simulation should underpin rational trial design and facilitate extrapolation to investigate efficacy and safety. The application of PKPD modeling to optimize dosing recommendations and therapeutic drug monitoring is also increasing, and PKPD model-based dose individualization will become a core feature of personalized medicine. Following extensive progress on pediatric PK modeling, a greater emphasis now needs to be placed on PD modeling to understand age-related changes in drug effects. This paper discusses the principles of PKPD modeling in the context of pediatric drug development, summarizing how important PK parameters, such as clearance (CL), are scaled with size and age, and highlights a standardized method for CL scaling in children. One standard scaling method would facilitate comparison of PK parameters across multiple studies, thus increasing the utility of existing PK models and facilitating optimal design of new studies

Physical activity and exercise: Strategies to manage frailty

Frailty, a consequence of the interaction of the aging process and certain chronic diseases, compromises functional outcomes in the elderly and substantially increases their risk for developing disabilities and other adverse outcomes. Frailty follows from the combination of several impaired physiological mechanisms affecting multiple organs and systems. And, though frailty and sarcopenia are related, they are two different conditions. Thus, strategies to preserve or improve functional status should consider systemic function in addition to muscle conditioning. Physical activity/exercise is considered one of the main strategies to counteract frailty-related physical impairment in the elderly. Exercise reduces age-related oxidative damage and chronic inflammation, increases autophagy, and improves mitochondrial function, myokine profile, insulin-like growth factor-1 (IGF-1) signaling pathway, and insulin sensitivity. Exercise interventions target resistance (strength and power), aerobic, balance, and flexibility work. Each type improves different aspects of physical functioning, though they could be combined according to need and prescribed as a multicomponent intervention. Therefore, exercise intervention programs should be prescribed based on an individual's physical functioning and adapted to the ensuing response.pre-print2.493 K

Hitomi (ASTRO-H) X-ray Astronomy Satellite

The Hitomi (ASTRO-H) mission is the sixth Japanese x-ray astronomy satellite developed by a large international collaboration, including Japan, USA, Canada, and Europe. The mission aimed to provide the highest energy resolution ever achieved at E  >  2  keV, using a microcalorimeter instrument, and to cover a wide energy range spanning four decades in energy from soft x-rays to gamma rays. After a successful launch on February 17, 2016, the spacecraft lost its function on March 26, 2016, but the commissioning phase for about a month provided valuable information on the onboard instruments and the spacecraft system, including astrophysical results obtained from first light observations. The paper describes the Hitomi (ASTRO-H) mission, its capabilities, the initial operation, and the instruments/spacecraft performances confirmed during the commissioning operations for about a month

A multicentre, randomised controlled trial to compare the clinical and cost-effectiveness of Lee Silverman Voice Treatment versus standard NHS Speech and Language Therapy versus control in Parkinson’s disease: a study protocol for a randomised controlled trial

Abstract: Background: Parkinson’s disease (PD) affects approximately 145,519 people in the UK. Speech impairments are common with a reported prevalence of 68%, which increase physical and mental demands during conversation, reliance on family and/or carers, and the likelihood of social withdrawal reducing quality of life. In the UK, two approaches to Speech and Language Therapy (SLT) intervention are commonly available: National Health Service (NHS) SLT or Lee Silverman Voice Treatment (LSVT LOUD®). NHS SLT is tailored to the individuals’ needs per local practice typically consisting of six to eight weekly sessions; LSVT LOUD® comprises 16 sessions of individual treatment with home-based practice over 4 weeks. The evidence-base for their effectiveness is inconclusive. Methods/design: PD COMM is a phase III, multicentre, three-arm, unblinded, randomised controlled trial. Five hundred and forty-six people with idiopathic PD, reporting speech or voice problems will be enrolled. We will exclude those with a diagnosis of dementia, laryngeal pathology or those who have received SLT for speech problems in the previous 2 years. Following informed consent and completion of baseline assessments, participants will be randomised in a 1:1:1 ratio to no-intervention control, NHS SLT or LSVT LOUD® via a central computer-generated programme, using a minimisation procedure with a random element, to ensure allocation concealment. Participants randomised to the intervention groups will start treatment within 4 (NHS SLT) or 7 (LSVT LOUD®) weeks of randomisation. Primary outcome: Voice Handicap Index (VHI) total score at 3 months. Secondary outcomes include: VHI subscales, Parkinson’s Disease Questionnaire-39; Questionnaire on Acquired Speech Disorders; EuroQol-5D-5 L; ICECAP-O; resource utilisation; adverse events and carer quality of life. Mixed-methods process and health economic evaluations will take place alongside the trial. Assessments will be completed before randomisation and at 3, 6 and 12 months after randomisation. The trial started in December 2015 and will run for 77 months. Recruitment will take place in approximately 42 sites around the UK. Discussion: The trial will test the hypothesis that SLT is effective for the treatment of speech or voice problems in people with PD compared to no SLT. It will further test whether NHS SLT or LSVT LOUD® provide greater benefit and determine the cost-effectiveness of both interventions. Trial registration: International Standard Randomised Controlled Trials Number (ISRCTN) Registry, ID: 12421382. Registered on 18 April 2016

A multicentre, randomised controlled trial to compare the clinical and cost-effectiveness of Lee Silverman Voice Treatment versus standard NHS Speech and Language Therapy versus control in Parkinson’s disease: a study protocol for a randomised controlled trial

Abstract: Background: Parkinson’s disease (PD) affects approximately 145,519 people in the UK. Speech impairments are common with a reported prevalence of 68%, which increase physical and mental demands during conversation, reliance on family and/or carers, and the likelihood of social withdrawal reducing quality of life. In the UK, two approaches to Speech and Language Therapy (SLT) intervention are commonly available: National Health Service (NHS) SLT or Lee Silverman Voice Treatment (LSVT LOUD®). NHS SLT is tailored to the individuals’ needs per local practice typically consisting of six to eight weekly sessions; LSVT LOUD® comprises 16 sessions of individual treatment with home-based practice over 4 weeks. The evidence-base for their effectiveness is inconclusive. Methods/design: PD COMM is a phase III, multicentre, three-arm, unblinded, randomised controlled trial. Five hundred and forty-six people with idiopathic PD, reporting speech or voice problems will be enrolled. We will exclude those with a diagnosis of dementia, laryngeal pathology or those who have received SLT for speech problems in the previous 2 years. Following informed consent and completion of baseline assessments, participants will be randomised in a 1:1:1 ratio to no-intervention control, NHS SLT or LSVT LOUD® via a central computer-generated programme, using a minimisation procedure with a random element, to ensure allocation concealment. Participants randomised to the intervention groups will start treatment within 4 (NHS SLT) or 7 (LSVT LOUD®) weeks of randomisation. Primary outcome: Voice Handicap Index (VHI) total score at 3 months. Secondary outcomes include: VHI subscales, Parkinson’s Disease Questionnaire-39; Questionnaire on Acquired Speech Disorders; EuroQol-5D-5 L; ICECAP-O; resource utilisation; adverse events and carer quality of life. Mixed-methods process and health economic evaluations will take place alongside the trial. Assessments will be completed before randomisation and at 3, 6 and 12 months after randomisation. The trial started in December 2015 and will run for 77 months. Recruitment will take place in approximately 42 sites around the UK. Discussion: The trial will test the hypothesis that SLT is effective for the treatment of speech or voice problems in people with PD compared to no SLT. It will further test whether NHS SLT or LSVT LOUD® provide greater benefit and determine the cost-effectiveness of both interventions. Trial registration: International Standard Randomised Controlled Trials Number (ISRCTN) Registry, ID: 12421382. Registered on 18 April 2016