Beyond EDI: An Agent’s Role in the Cloud

This year has garnered ample conversation and controversy regarding new cloud‐based ILS systems and their value to libraries. The emphasis of these discussions has been on integrating cloud‐based systems with database services/aggregators and libraries, but there has been very little mention of the Agent or Information Solutions Provider (ISP). Is there a role for the ISP in this new medium? If so, what is it? The presenters, librarian and vendors both, will highlight thoughts and theories on an integrated approach among ILS vendors, ISPs and librarians. Experienced in working with web‐based e‐procurement systems for corporate libraries, ISPs are in a unique position to offer streamlined, real‐time integration with cloud‐based services. These services (the silver linings) go beyond EDI to include exchanging licensing information, pricing, purchase orders and renewals, just to name a few. Information Solution Providers are already comfortable in the cloud and are dedicated to playing a vital role in the supply of information

Progesterone significantly enhances the mobility of boar spermatozoa

Progesterone released from the cumulus cells of the oocyte causes a number of physiological responses in human sperm cells including hyperactivation, acrosome reaction and chemotaxis. We employed a validated sperm mobility assay, which involves measuring the ability of sperm to penetrate an inert cell separation solution over time, to assess the ability of progesterone to enhance the mobility of boar spermatozoa. Cells maximally penetrate the solution over 50 minutes. 100nM progesterone significantly (P = 0.01) increased the mobility of non-capacitated sperm cells causing a doubling in the rate at which the cells penetrated through the cell separation solution (control half maximal penetration rate [Km] = 18.0±2.2; +100nM progesterone Km = 8.8±0.8min). Similarly, capacitated cells penetrated at a rate (Km = 19.2±3.0 min) not significantly different from non-capacitated cells and 100nM progesterone also significantly increased the rate of penetration of capacitated cells (Km = 9.5±1.0 min, P<0.05). The T-type voltage gated calcium channel blocker mibefradil (30mM) significantly inhibited both the control and progesterone enhanced mobility in non-capacitated and capacitated sperm. Only capacitated cells showed a significant increase in the acrosome reaction in response to 100nM progesterone (control non-reacted = 75±4%, +100nM progesterone non-reacted = 47±10%). Western blot analysis confirmed that there was an increase in the total protein tyrosine phosphorylation levels in capacitated cells. In conclusion, we have demonstrated that 100nM progesterone accelerates the mobility of boar sperm cells through an inert cell separation solution in an extracellular calcium dependent manner

Physical ACtivity facilitation for Elders (PACE):Study protocol for a randomised controlled trial

BACKGROUND: As people live longer, their risk of disability increases. Disability affects quality of life and increases health and social care costs. Preventing or delaying disability is therefore an important objective, and identifying an effective intervention could improve the lives of many older people. Observational and interventional evidence suggests that physical activity may reduce the risk of age-related disability, as assessed by physical performance measures. However it is unclear what approach is the most cost-effective intervention in changing long-term physical activity behaviour in older adults. A new theory-driven behavioural intervention has been developed, with the aim of increasing physical activity in the everyday lives of older adults at risk of disability. This pilot study tests the feasibility and acceptability of delivering this intervention to older adults. METHODS/DESIGN: A randomised controlled trial (RCT) design will be used in the pilot study. Sixty patients aged 65 years and older will be recruited from primary care practices. Patients will be eligible to participate if they are inactive, not disabled at baseline, are at risk of developing disability in the future (Short Physical Performance Battery score <10/12), and have no contraindications to physical activity. Following baseline measures, participants will be randomised in a 2:1 ratio to the intervention or to a control arm and all participants will be followed-up after 6 months. Those randomised to the intervention arm will receive sessions with a trained Physical Activity Facilitator, delivering an intervention based on self-determination theory. Control participants receive a booklet on healthy ageing. The main outcomes of interest are recruitment, adherence, retention and acceptability. Data will also be collected on: self-report and accelerometer-recorded physical activity; physical performance; depression; wellbeing; cognitive function; social support; quality of life, healthcare use, and attitudes to physical activity. A mixed-methods process evaluation will run alongside the RCT. DISCUSSION: The intervention, if effective, has the potential to reduce disability and improve quality of life in older adults. Before proceeding to a full-scale trial a pilot trial is necessary to ensure intervention feasibility and acceptability, and that the intervention shows evidence of promise. TRIAL REGISTRATION: Current Controlled Trials ISRCTN80470273. Registered 25 October 2013

Investigation of spinal posture signatures and ground reaction forces during landing in elite female gymnasts

The link between static and dynamic landing lumbar postures, when gymnasts are exposed to large ground reaction forces, has not been established. This investigation aimed to (a) determine if a relationship exists between sagittal static and dynamic landing lumbar spine angles at peak ground reaction force (GRF) and (b) quantify how close to end-range postures the gymnasts were at landing peak GRF. Twenty-one female gymnasts’ upper and lower lumbar spine angles were recorded: statically in sitting and standing, during landing of three gymnastic skills, and during active end-range lumbar flexion. Pearson’s correlations were used to investigate relationships between the angles in different postures. Significant correlations (r = .77–.89, p < .01) were found between all the static/dynamic postures in the lower lumbar spine angle, while fewer and less significant upper lumbar spine correlations were reported. Thirty percent of gymnasts landed a backsault with their lower lumbar spine flexed beyond their active end-range while experiencing GRF 6.8–13.3 times their body weight. These results inform low back pain prevention and management strategies in this population and highlight areas for future research

Synergism of Heat Shock Protein 90 and Histone Deacetylase Inhibitors in Synovial Sarcoma

Current systemic therapies have little curative benefit for synovial sarcoma. Histone deacetylase (HDAC) inhibitors and the heat shock protein 90 (Hsp90) inhibitor 17-AAG have recently been shown to inhibit synovial sarcoma in preclinical models. We tested combinations of 17-AAG with the HDAC inhibitor MS-275 for synergism by proliferation and apoptosis assays. The combination was found to be synergistic at multiple time points in two synovial sarcoma cell lines. Previous studies have shown that HDAC inhibitors not only induce cell death but also activate the survival pathway NF-κB, potentially limiting therapeutic benefit. As 17-AAG inhibits activators of NF-κB, we tested if 17-AAG synergizes with MS-275 through abrogating NF-κB activation. In our assays, adding 17-AAG blocks NF-κB activation by MS-275 and siRNA directed against histone deacetylase 3 (HDAC3) recapitulates the effects of MS-275. Additionally, we find that the NF-κB inhibitor BAY 11-7085 synergizes with MS-275. We conclude that agents inhibiting NF-κB synergize with HDAC inhibitors against synovial sarcoma

Significant reductions in human visual gamma frequency by the GABA reuptake inhibitor tiagabine revealed by robust peak frequency estimation

The frequency of visual gamma oscillations is determined by both the neuronal excitation–inhibition balance and the time constants of GABAergic processes. The gamma peak frequency has been linked to sensory processing, cognitive function, cortical structure, and may have a genetic contribution. To disentangle the intricate relationship among these factors, accurate and reliable estimates of peak frequency are required. Here, a bootstrapping approach that provides estimates of peak frequency reliability, thereby increasing the robustness of the inferences made on this parameter was developed. The method using both simulated data and real data from two previous pharmacological MEG studies of visual gamma with alcohol and tiagabine was validated. In particular, the study by Muthukumaraswamy et al. [2013a] (Neuropsychopharmacology 38(6):1105–1112), in which GABAergic enhancement by tiagabine had previously demonstrated a null effect on visual gamma oscillations, contrasting with strong evidence from both animal models and very recent human studies was re-evaluated. After improved peak frequency estimation and additional exclusion of unreliably measured data, it was found that the GABA reuptake inhibitor tiagabine did produce, as predicted, a marked decrease in visual gamma oscillation frequency. This result demonstrates the potential impact of objective approaches to data quality control, and provides additional translational evidence for the mechanisms of GABAergic transmission generating gamma oscillations in humans

Ataluren treatment of patients with nonsense mutation dystrophinopathy

Introduction: Dystrophinopathy is a rare, severe muscle disorder, and nonsense mutations are found in 13% of cases. Ataluren was developed to enable ribosomal readthrough of premature stop codons in nonsense mutation (nm) genetic disorders. Methods: Randomized, double-blind, placebo-controlled study; males ≥5 years with nm-dystrophinopathy received study drug orally 3 times daily, ataluren 10, 10, 20 mg/kg (N=57); ataluren 20, 20, 40 mg/kg (N=60); or placebo (N=57) for 48 weeks. The primary endpoint was change in 6-Minute Walk Distance (6MWD) at Week 48. Results: Ataluren was generally well tolerated. The primary endpoint favored ataluren 10, 10, 20 mg/kg versus placebo; the week 48 6MWD Δ=31.3 meters, post hoc P=0.056. Secondary endpoints (timed function tests) showed meaningful differences between ataluren 10, 10, 20 mg/kg, and placebo. Conclusions: As the first investigational new drug targeting the underlying cause of nm-dystrophinopathy, ataluren offers promise as a treatment for this orphan genetic disorder with high unmet medical need