A systematic review of the discriminating biomechanical parameters during the single leg squat

Objective: To determine whether there are common biomechanical parameters when analysing the single leg squat movement to compare pathological and non-pathological groups and whether these parameters are able to effectively distinguish between groups. Methods: Five electronic databases were searched using MESH terms, keywords and phrases across four constructs: squat, biomechanical measures, region of interest, study design. Studies were selected based on inclusion of a quantitative biomechanical measure, compared between a pathological and a non-pathological group, and participants performed a single leg squat movement. Results: Fifteen studies were included and reviewed, where the majority of studies investigated patellofemoral pain. There was considerable variation in the biomechanical outcome measure used to compare between groups. The frontal plane projection angle was the most commonly reported measure. There was considerable variation in the manner in which the single leg squat was performed. Conclusion: Due to variation in how the single leg squat was performed, it was not possible to determine specific biomechanical parameters that distinguish between pathological and non-pathological groups. Frontal plane projection angle appeared to be a parameter that could be effectively utilised. Standardisation of the single leg squat movement is needed to allow comparison between studies of pathological and non-pathological groups

Cost-effectiveness of insulin pumps compared with multiple daily injections, both provided with structured education, for adults with type 1 diabetes:a health economic analysis of the Relative Effectiveness of Pumps over Structured Education (REPOSE) randomised controlled trial

Objectives To assess the long-term cost-effectiveness of insulin pumps and Dose Adjustment for Normal Eating (pumps+DAFNE) compared with multiple daily insulin injections and DAFNE (MDI+DAFNE) for adults with type 1 diabetes mellitus (T1DM) in the UK. Methods We undertook a cost–utility analysis using the Sheffield Type 1 Diabetes Policy Model and data from the Relative Effectiveness of Pumps over Structured Education (REPOSE) trial to estimate the lifetime incidence of diabetic complications, intervention-based resource use and associated effects on costs and quality-adjusted life years (QALYs). All economic analyses took a National Health Service and personal social services perspective and discounted costs and QALYs at 3.5% per annum. A probabilistic sensitivity analysis was performed on the base case. Further uncertainties in the cost of pumps and the evidence used to inform the model were explored using scenario analyses. Setting Eight diabetes centres in England and Scotland. Participants Adults with T1DM who were eligible to receive a structured education course and did not have a strong clinical indication or a preference for a pump. Intervention Pumps+DAFNE. Comparator MDI+DAFNE. Main outcome measures Incremental costs, incremental QALYs gained and incremental cost-effectiveness ratios (ICERs). Results Compared with MDI+DAFNE, pumps+DAFNE was associated with an incremental discounted lifetime cost of +£18 853 (95% CI £6175 to £31 645) and a gain in discounted lifetime QALYs of +0.13 (95% CI -0.70 to +0.96). The base case mean ICER was £142 195 per QALY gained. The probability of pump+DAFNE being cost-effective using a cost-effectiveness threshold of £20 000 per QALY gained was 14.0%. All scenario and subgroup analyses examined indicated that the ICER was unlikely to fall below £30 000 per QALY gained. Conclusions Our analysis of the REPOSE data suggests that routine use of pumps in adults without an immediate clinical need for a pump, as identified by National Institute for Health and Care Excellence, would not be cost-effective. Trial registration number ISRCTN61215213

Delivering the diabetes education and self management for ongoing and newly diagnosed (DESMOND) programme for people with newly diagnosed type 2 diabetes: cost effectiveness analysis

Objectives To assess the long term clinical and cost effectiveness of the diabetes education and self management for ongoing and newly diagnosed (DESMOND) intervention compared with usual care in people with newly diagnosed type 2 diabetes

Biochemical autoregulatory gene therapy for focal epilepsy.

Despite the introduction of more than one dozen new antiepileptic drugs in the past 20 years, approximately one-third of people who develop epilepsy continue to have seizures on mono- or polytherapy1. Viral-vector-mediated gene transfer offers the opportunity to design a rational treatment that builds on mechanistic understanding of seizure generation and that can be targeted to specific neuronal populations in epileptogenic foci2. Several such strategies have shown encouraging results in different animal models, although clinical translation is limited by possible effects on circuits underlying cognitive, mnemonic, sensory or motor function. Here, we describe an autoregulatory antiepileptic gene therapy, which relies on neuronal inhibition in response to elevations in extracellular glutamate. It is effective in a rodent model of focal epilepsy and is well tolerated, thus lowering the barrier to clinical translation

Effect of the stellar spin history on the tidal evolution of close-in planets

We investigate how the evolution of the stellar spin rate affects, and is affected by, planets in close orbits, via star-planet tidal interactions. To do this, we used a standard equilibrium tidal model to compute the orbital evolution of single planets orbiting both Sun-like stars and 0.1 M\odot M-dwarfs. We tested two stellar spin evolution profiles, one with fast initial rotation (P=1.2 day) and one with slow initial rotation (P=8 day). We tested the effect of varying the stellar and planetary dissipation and the planet's mass and initial orbital radius. Conclusions: Tidal evolution allows to differentiate the early behaviors of extremely close-in planets orbiting either a rapidly rotating star or a slowly rotating star. The early spin-up of the star allows the close-in planets around fast rotators to survive the early evolution. For planets around M-dwarfs, surviving the early evolution means surviving on Gyr timescales whereas for Sun-like stars the spin-down brings about late mergers of Jupiter planets. In light of this study, we can say that differentiating between one spin evolution from another given the present position of planets can be very tricky. Unless we can observe some markers of former evolution it is nearly impossible to distinguish the two very different spin profiles, let alone intermediate spin profiles. Though some conclusions can still be drawn from statistical distributions of planets around fully convective M-dwarfs. However, if the tidal evolution brings about a merger late in its history it can also entail a noticeable acceleration of the star in late ages, so that it is possible to have old stars that spin rapidly. This raises the question of better constraining the age of stars

Real-time single-molecule observation of rolling-circle DNA replication

We present a simple technique for visualizing replication of individual DNA molecules in real time. By attaching a rolling-circle substrate to a TIRF microscope-mounted flow chamber, we are able to monitor the progression of single-DNA synthesis events and accurately measure rates and processivities of single T7 and Escherichia coli replisomes as they replicate DNA. This method allows for rapid and precise characterization of the kinetics of DNA synthesis and the effects of replication inhibitors

Caregiver delivered sensory electrical stimulation for post stroke upper limb spasticity: A single blind crossover randomized feasibility study

We developed a 64 channel sensory electrical stimulator which delivers a dynamic and variable ‘Sensory Barrage’ Stimulation (SBS). Our aim was to assess the feasibility of caregivers delivering the stimulation in the community for a clinical trial comparing single channel Transcutaneous Electrical Nerve Stimulation (TENS) with SBS for post stroke upper limb spasticity. We trained caregivers of 16 participants with post stroke upper limb spasticity to sequentially administer SBS and TENS for 60 min daily for four weeks each, with a washout period of two weeks in between. Outcome measures tested were recruitment and retention rates, compliance with interventions and daily recording of Participant -reported Numerical Rating Scale (NRS). We also collected results of Action Research Arm Test (ARAT), Leeds Arm Spasticity Impact Scale (LASIS) and Modified Ashworth Scale (MAS) for spasticity. Out of 21 potential participants, 16 consented and 15 completed the protocol. Ten participants received TENS for 80% (23/28) of the intended hours. Eleven participants completed NRS for at 80% (45/56) of the study days. All participants attended all visits. The MAS reduced by at least one in five participants after SBS and in three after TENS. Minimal Clinically Important Difference (MCID) of four points increase in ARAT was seen in five participants following TENS, and in four following SBS. A MCID of 18% decrease in NRS was reported by eight participants after TENS and three after SBS. This study demonstrated the feasibility of undertaking a trial of sensory electrical stimulation for post-stroke spasticity with caregivers delivering intervention in community. The study was not powered to detect efficacy of the interventions. Trial registration number: NCT02907775.Date 20-9-2016

Aberrant Mucin Assembly in Mice Causes Endoplasmic Reticulum Stress and Spontaneous Inflammation Resembling Ulcerative Colitis

Michael McGuckin and colleagues identify two mutations that cause aberrant mucin oligomerization in mice. The resulting phenotype, including endoplasmic reticulum stress, resembles clinical and pathologic features of human ulcerative colitis