The Effect of Increasing Age on the Concentric and Eccentric Contractile Properties of Isolated Mouse Soleus and Extensor Digitorum Longus Muscles

There is currently a limited amount of literature investigating the age-related changes in eccentric muscle function in vitro. The present study uniquely uses the work loop technique, to better replicate in vivo muscle function, in the assessment of the age and muscle-specific changes in acute and sustained concentric and eccentric power and recovery. Whole soleus or EDL muscles were isolated from 10-week and 78-week old mice, and acute and sustained concentric and eccentric work loop power assessed. Despite an age-related increase in body and muscle mass, peak absolute power for both muscles was unaffected by age. Peak concentric power normalised to muscle mass declined significantly for each muscle, whilst peak normalised eccentric power declined only for soleus. Fatigue resistance and recovery for the soleus did not differ between age or contraction type. Older EDL was less resistant to concentric fatigue, but was better able to withstand sustained eccentric activity than young EDL. We have shown that age-related changes in muscle quality are more limited for eccentric function than concentric function. A greater bodily inertia is likely to further reduce in vivo locomotor performance in older animals.</p

RESPOND – A patient-centred program to prevent secondary falls in older people presenting to the emergency department with a fall: Protocol for a multi-centre randomised controlled trial

Introduction: Participation in falls prevention activities by older people following presentation to the Emergency Department (ED) with a fall is suboptimal. This randomised controlled trial (RCT) will test the RESPOND program which is designed to improve older persons’ participation in falls prevention activities through delivery of patient-centred education and behaviour change strategies. Design and setting: An RCT at two tertiary referral EDs in Melbourne and Perth, Australia. Participants: Five-hundred and twenty eight community-dwelling people aged 60-90 years presenting to the ED with a fall and discharged home will be recruited. People who: require an interpreter or hands-on assistance to walk; live in residential aged care or >50 kilometres from the trial hospital; have terminal illness, cognitive impairment, documented aggressive behaviour or history of psychosis; are receiving palliative care; or are unable to use a telephone will be excluded. Methods: Participants will be randomly allocated to the RESPOND intervention or standard care control group. RESPOND incorporates: (1) home-based risk factor assessment; (2) education, coaching, goal setting, and follow-up telephone support for management of one or more of four risk factors with evidence of effective intervention; and (3) healthcare provider communication and community linkage delivered over six months. Primary outcomes are falls and fall injuries per-person-year. Discussion: RESPOND builds on prior falls prevention learnings and aims to help individuals make guided decisions about how they will manage their falls risk. Patient-centred models have been successfully trialled in chronic and cardiovascular disease however evidence to support this approach in falls prevention is limited. Trial registration. The protocol for this study is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12614000336684)

Sampling the Faraday rotation sky of TNG50: Imprint of the magnetised circumgalactic medium around Milky Way-like galaxies

Faraday rotation measure (RM) is arguably the most practical observational tracer of magnetic fields in the diffuse circumgalactic medium (CGM). We sample synthetic Faraday rotation skies of Milky Way-like galaxies in TNG50 of the IllustrisTNG project by placing an observer inside the galaxies at a solar circle-like position. Our synthetic RM grids emulate specifications of current and upcoming surveys; the NRAO VLA Sky Survey (NVSS), the Polarisation Sky Survey of the Universe's Magnetism (POSSUM), and a future Square Kilometre Array (SKA1-mid) polarisation survey. It has been suggested that magnetic fields regulate the survival of high-velocity clouds. However, there is only a small number of observational detections of magnetised clouds thus far. In the first part of the paper, we test conditions for the detection of magnetised circumgalactic clouds. Based on the synthetic RM samplings of clouds in the simulations, we predict upcoming polarimetric surveys will open opportunities for the detection of even low-mass and distant clouds. In the second part of the paper, we investigate the imprint of the CGM in the all-sky RM distribution. We test whether the RM variation produced by the CGM is correlated with global galaxy properties, such as distance to a satellite, specific star formation rate, neutral hydrogen covering fraction, and accretion rate to the supermassive black hole. We argue that the observed fluctuation in the RM measurements on scales less than 1 degree, which has been considered an indication of intergalactic magnetic fields, might in fact incorporate a significant contribution of the Milky Way CGM.Comment: 18 pages, 11 figures, Accepted to MNRA

Impact of Locally Suppressed Wave sources on helioseismic travel times

Wave travel-time shifts in the vicinity of sunspots are typically interpreted as arising predominantly from magnetic fields, flows, and local changes in sound speed. We show here that the suppression of granulation related wave sources in a sunspot can also contribute significantly to these travel-time shifts, and in some cases, an asymmetry between in and outgoing wave travel times. The tight connection between the physical interpretation of travel times and source-distribution homogeneity is confirmed. Statistically significant travel-time shifts are recovered upon numerically simulating wave propagation in the presence of a localized decrease in source strength. We also demonstrate that these time shifts are relatively sensitive to the modal damping rates; thus we are only able to place bounds on the magnitude of this effect. We see a systematic reduction of 10-15 seconds in $p$-mode mean travel times at short distances ($\sim 6.2$ Mm) that could be misinterpreted as arising from a shallow (thickness of 1.5 Mm) increase ($\sim$ 4%) in the sound speed. At larger travel distances ($\sim 24$ Mm) a 6-13 s difference between the ingoing and outgoing wave travel times is observed; this could mistakenly be interpreted as being caused by flows.Comment: Revised version. Submitted to Ap

Children's Medicines in Tanzania: A National Survey of Administration Practices and Preferences.

The dearth of age-appropriate formulations of many medicines for children poses a major challenge to pediatric therapeutic practice, adherence, and health care delivery worldwide. We provide information on current administration practices of pediatric medicines and describe key stakeholder preferences for new formulation characteristics. We surveyed children aged 6-12 years, parents/caregivers over age 18 with children under age 12, and healthcare workers in 10 regions of Tanzania to determine current pediatric medicine prescription and administration practices as well as preferences for new formulations. Analyses were stratified by setting, pediatric age group, parent/caregiver education, and healthcare worker cadre. Complete data were available for 206 children, 202 parents/caregivers, and 202 healthcare workers. Swallowing oral solid dosage forms whole or crushing/dissolving them and mixing with water were the two most frequently reported methods of administration. Children frequently reported disliking medication taste, and many had vomited doses. Healthcare workers reported medicine availability most significantly influences prescribing practices. Most parents/caregivers and children prefer sweet-tasting medicine. Parents/caregivers and healthcare workers prefer oral liquid dosage forms for young children, and had similar thresholds for the maximum number of oral solid dosage forms children at different ages can take. There are many impediments to acceptable and accurate administration of medicines to children. Current practices are associated with poor tolerability and the potential for under- or over-dosing. Children, parents/caregivers, and healthcare workers in Tanzania have clear preferences for tastes and formulations, which should inform the development, manufacturing, and marketing of pediatric medications for resource-limited settings

The Force-Velocity Relation for Growing Biopolymers

The process of force generation by the growth of biopolymers is simulated via a Langevin-dynamics approach. The interaction forces are taken to have simple forms that favor the growth of straight fibers from solution. The force-velocity relation is obtained from the simulations for two versions of the monomer-monomer force field. It is found that the growth rate drops off more rapidly with applied force than expected from the simplest theories based on thermal motion of the obstacle. The discrepancies amount to a factor of three or more when the applied force exceeds 2.5kT/a, where a is the step size for the polymer growth. These results are explained on the basis of restricted diffusion of monomers near the fiber tip. It is also found that the mobility of the obstacle has little effect on the growth rate, over a broad range.Comment: Latex source, 9 postscript figures, uses psfig.st

Uptake, outcomes, and costs of implementing non-invasive prenatal testing for Down's syndrome into NHS maternity care: prospective cohort study in eight diverse maternity units.

OBJECTIVE:  To investigate the benefits and costs of implementing non-invasive prenatal testing (NIPT) for Down's syndrome into the NHS maternity care pathway. DESIGN:  Prospective cohort study. SETTING:  Eight maternity units across the United Kingdom between 1 November 2013 and 28 February 2015. PARTICIPANTS:  All pregnant women with a current Down's syndrome risk on screening of at least 1/1000. MAIN OUTCOME MEASURES:  Outcomes were uptake of NIPT, number of cases of Down's syndrome detected, invasive tests performed, and miscarriages avoided. Pregnancy outcomes and costs associated with implementation of NIPT, compared with current screening, were determined using study data on NIPT uptake and invasive testing in combination with national datasets. RESULTS:  NIPT was prospectively offered to 3175 pregnant women. In 934 women with a Down's syndrome risk greater than 1/150, 695 (74.4%) chose NIPT, 166 (17.8%) chose invasive testing, and 73 (7.8%) declined further testing. Of 2241 women with risks between 1/151 and 1/1000, 1799 (80.3%) chose NIPT. Of 71 pregnancies with a confirmed diagnosis of Down's syndrome, 13/42 (31%) with the diagnosis after NIPT and 2/29 (7%) after direct invasive testing continued, resulting in 12 live births. In an annual screening population of 698 500, offering NIPT as a contingent test to women with a Down's syndrome screening risk of at least 1/150 would increase detection by 195 (95% uncertainty interval -34 to 480) cases with 3368 (2279 to 4027) fewer invasive tests and 17 (7 to 30) fewer procedure related miscarriages, for a non-significant difference in total costs (£-46 000, £-1 802 000 to £2 661 000). The marginal cost of NIPT testing strategies versus current screening is very sensitive to NIPT costs; at a screening threshold of 1/150, NIPT would be cheaper than current screening if it cost less than £256. Lowering the risk threshold increases the number of Down's syndrome cases detected and overall costs, while maintaining the reduction in invasive tests and procedure related miscarriages. CONCLUSIONS:  Implementation of NIPT as a contingent test within a public sector Down's syndrome screening programme can improve quality of care, choices for women, and overall performance within the current budget. As some women use NIPT for information only, the Down's syndrome live birth rate may not change significantly. Future research should consider NIPT uptake and informed decision making outside of a research setting

Complete Genome Sequences of Paenibacillus Larvae Phages BN12, Dragolir, Kiel007, Leyra, Likha, Pagassa, PBL1c, and Tadhana

We present here the complete genomes of eight phages that infect Paenibacillus larvae, the causative agent of American foulbrood in honeybees. Phage PBL1c was originally isolated in 1984 from a P. larvae lysogen, while the remaining phages were isolated in 2014 from bee debris, honeycomb, and lysogens from three states in the USA