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To evaluate: acceptability and feasibility of trial procedures; distribution of scores on the Roland Morris Disability Questionnaire (RMDQ, planned primary outcome); and efficient working of trial components. A feasibility and external pilot randomised controlled trial (ISRCTN33808269, assigned 10/12/2012) was conducted across 2 UK secondary care outpatient physiotherapy departments associated with regional spinal surgery centres. Consecutive consenting patients aged >18 years; post primary, single level, lumbar discectomy. Participants were randomised to either 1:1 physiotherapy outpatient management including patient leaflet, or patient leaflet alone. Blinded assessments were made at 4 weeks post surgery (baseline) and 12 weeks post baseline (proposed primary end point). Secondary outcomes included: Global Perceived Effect, back/leg pain, straight leg raise, return to work/function, quality of life, fear avoidance, range of movement, medication, re-operation. At discharge, 110 (44%) eligible patients gave consent to be contacted. 59 (54%) patients were recruited. Loss to follow up was 39% at 12 weeks, with one site contributing 83% losses. Mean (SD) RMDQ was 10.07 (5.58) leaflet and 10.52 (5.94) physiotherapy/leaflet at baseline; and 5.37 (4.91) leaflet and 5.53 (4.49) physiotherapy/leaflet at 12 weeks. 5.1% zero scores at 12 weeks illustrated no floor effect. Sensitivity to change was assessed at 12 weeks with mean (SD) change -4.53 (6.41), 95%CI -7.61 to -1.44 for leaflet; and -6.18 (5.59), 95%CI -9.01 to -3.30 for physiotherapy/leaflet. RMDQ mean difference (95%CI) between change from baseline to twelve weeks was 1.65(-2.46 to 5.75). Mean difference (95%CI) between groups at 12 weeks was -0.16 (-3.36 to 3.04). Participant adherence with treatment was good. No adverse events were reported. Both interventions were acceptable, and it is promising that they both demonstrated a trend in reducing disability in this population. A randomised controlled trial, using a different trial design, is needed to ascertain the effectiveness of combining the interventions into a stepped care intervention and comparing to a no intervention arm. Findings will guide design changes for an adequately powered randomised controlled trial, using RMDQ as the primary outcome. ISRCTN registry 33808269.

ObjectiveTo evaluate patients’ and physiotherapists’ perceptions, preferences and feelings about rehabilitation following lumbar discectomy surgery.DesignA qualitative focus group study, informed from the theoretical perspective of phenomenology, of patients’ and physiotherapists’ experiences of rehabilitation following lumbar discectomy was conducted. The focus groups were used to explore patients’ and physiotherapists’ perceptions and their preferences and feelings about different approaches to rehabilitation. The focus groups were facilitated and observed by experienced researchers and were informed by a topic guide that had been piloted previously.SettingThe study was embedded within an external pilot and feasibility trial that randomised patients across two secondary care spinal surgery sites in the UK to receive either 1:1 physiotherapy and leaflet or leaflet-only interventions.ParticipantsFive focus groups took place between April and July 2014. A framework analysis of thematic coding (deductive and inductive components) by two researchers captured identified themes common to both patients and physiotherapists. Data from three focus groups with patients and carers (n=11) and two with physiotherapists (n=15) contributed to the analytic framework.ResultsEmerging themes included: the value of patient leaflets with or without physiotherapy interventions; the importance of self-motivation in the recovery pathway; benefits of group physiotherapy for some patient groups and patient preference influencing rehabilitation.ConclusionPatients and physiotherapists perceived the study patient leaflet and 1:1 physiotherapy interventions as high quality and valuable. Patients’ personal priorities, for example, their need to return to work, influenced their preferences for rehabilitation interventions following surgery.

Using a buried slide technique, hyphal connections are shown to exist between different roots on one plant, Lolium perenne L., and also between two roots of different species L. perenne and Plantago lanceolata L. These two species are commonly found together in permanent pasture.

In six experiments Lolium perenne L. and Plantago lanceolata L. were grown together in pots. Two experiments also included L. perenne alone, P. lanceolata alone, or L. perenne + Trifolium repens L. In five of the experiments prior sterilization of the soil followed by reinoculation was used to obtain two treatments, one having plants infected with vesicular-arbuscular mycorrhiza, the other non-mycorrhizal. The shoots of some plants in each pot ('donors') were injected with32P. After a week these shoots were removed, and after a further week the remaining plants ('receivers') were harvested and their32P content determined. In all experiments and species-combinations there was some32P transfer to the shoots of both mycorrhizal and non-mycorrhizal receiver plants. The amount of transfer in mycorrhizal treatments was 2 to 8-fold greater than in non-mycorrhizal treatments, except in one experiment where mycorrhizal infection was very low. There was no clear difference between the different species combinations in the amount by which phosphorus transfer was enhanced by mycorrhizas. These results show that mycorrhizas can increase phosphorus transport between plants, but do not show whether there is direct transport from one root to another via interconnecting hyphae or whether the phosphorus must leave the donor root before being taken up by mycorrhizal hyphae.

At 40 sites in England and South Wales, mostly in grassland, features of the soil and vegetation were measured. Three Plantago lanceolata individuals were collected from each site, nitrogen, phosphorus and potassium concentrations in the leaves were measured, and the abundance of mycorrhizal infection and of fungi and bacteria on the root surface was determined by microscopic examination of stained root segments. The results were subjected to multiple regression analysis. Mycorrhizal abundance was most significantly related to vascular plant cover (negatively) and Plantago leaf length (positively), bacteria to soil organic matter (positively), fungi to cover of non-grasses (positively) and leaf phosphorus concentration (negatively). The ecological interpretation of these relationships is discussed.

Jeffrey Barrett, Carl Anderson and colleagues report the results of a large genome-wide association study of inflammatory bowel disease. They identify 25 new genome-wide significant loci, 3 of which contain integrin genes, and find that the associated variants at several of these loci are correlated with expression changes in response to immune stimulus. Genetic association studies have identified 215 risk loci for inflammatory bowel disease 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , thereby uncovering fundamental aspects of its molecular biology. We performed a genome-wide association study of 25,305 individuals and conducted a meta-analysis with published summary statistics, yielding a total sample size of 59,957 subjects. We identified 25 new susceptibility loci, 3 of which contain integrin genes that encode proteins in pathways that have been identified as important therapeutic targets in inflammatory bowel disease. The associated variants are correlated with expression changes in response to immune stimulus at two of these genes ( ITGA4 and ITGB8 ) and at previously implicated loci ( ITGAL and ICAM1 ). In all four cases, the expression-increasing allele also increases disease risk. We also identified likely causal missense variants in a gene implicated in primary immune deficiency, PLCG2 , and a negative regulator of inflammation, SLAMF8 . Our results demonstrate that new associations at common variants continue to identify genes relevant to therapeutic target identification and prioritization.

Genome-wide association studies (GWASs) have identified hundreds of loci associated with Crohn’s disease (CD). However, as with all complex diseases, robust identification of the genes dysregulated by noncoding variants typically driving GWAS discoveries has been challenging. Here, to complement GWASs and better define actionable biological targets, we analyzed sequence data from more than 30,000 patients with CD and 80,000 population controls. We directly implicate ten genes in general onset CD for the first time to our knowledge via association to coding variation, four of which lie within established CD GWAS loci. In nine instances, a single coding variant is significantly associated, and in the tenth, ATG4C , we see additionally a significantly increased burden of very rare coding variants in CD cases. In addition to reiterating the central role of innate and adaptive immune cells as well as autophagy in CD pathogenesis, these newly associated genes highlight the emerging role of mesenchymal cells in the development and maintenance of intestinal inflammation. Large-scale sequence-based analyses identify novel risk variants and susceptibility genes for Crohn’s disease, and implicate mesenchymal cell-mediated intestinal homeostasis in disease etiology.

Mutations in glucocerebrosidase (GBA) are the most prevalent genetic risk factor for Lewy body disorders (LBD)—collectively Parkinson’s disease, Parkinson’s disease dementia and dementia with Lewy bodies. Despite this genetic association, it remains unclear how GBA mutations increase susceptibility to develop LBD. We investigated relationships between LBD-specific glucocerebrosidase deficits, GBA-related pathways, and α-synuclein levels in brain tissue from LBD and controls, with and without GBA mutations. We show that LBD is characterised by altered sphingolipid metabolism with prominent elevation of ceramide species, regardless of GBA mutations. Since extracellular vesicles (EV) could be involved in LBD pathogenesis by spreading disease-linked lipids and proteins, we investigated EV derived from post-mortem cerebrospinal fluid (CSF) and brain tissue from GBA mutation carriers and non-carriers. EV purified from LBD CSF and frontal cortex were heavily loaded with ceramides and neurodegeneration-linked proteins including alpha-synuclein and tau. Our in vitro studies demonstrate that LBD EV constitute a “pathological package” capable of inducing aggregation of wild-type alpha-synuclein, mediated through a combination of alpha-synuclein–ceramide interaction and the presence of pathological forms of alpha-synuclein. Together, our findings indicate that abnormalities in ceramide metabolism are a feature of LBD, constituting a promising source of biomarkers, and that GBA mutations likely accelerate the pathological process occurring in sporadic LBD through endolysosomal deficiency.