Weight management for overweight and obese men delivered through professional football clubs : a pilot randomized trial

Peer reviewedPublisher PD

Matrix factorisation and the interpretation of geodesic distance

Given a graph or similarity matrix, we consider the problem of recovering a notion of true distance between the nodes, and so their true positions. We show that this can be accomplished in two steps: matrix factorisation, followed by nonlinear dimension reduction. This combination is effective because the point cloud obtained in the first step lives close to a manifold in which latent distance is encoded as geodesic distance. Hence, a nonlinear dimension reduction tool, approximating geodesic distance, can recover the latent positions, up to a simple transformation. We give a detailed account of the case where spectral embedding is used, followed by Isomap, and provide encouraging experimental evidence for other combinations of techniques

Dissolved organic carbon concentration and character in northern hardwood-dominated headwater catchments: A paired-catchment investigation of legacy harvesting impacts

The water quality of forested source water regions can be degraded by natural and anthropogenic landscape disturbances such as wildfires and forest harvesting, the latter an economically important primary industry in Canada and a proposed wildfire mitigation strategy. Harvesting practices can alter the chemistry and hydrologic connectivity of hillslope solute pools, thereby enhancing hillslope-stream transport and the downstream propagation of sediments and solutes, including those relevant to drinking water treatment operations such as dissolved organic carbon (DOC). Although many studies have evaluated the sub-decadal impacts of forest harvesting on the concentration, export, and character of stream DOC, less is known about the legacy (decadal-scale) impacts. The purpose of this thesis was to evaluate the legacy impacts of clearcut harvesting on the variability of stream DOC concentrations, export, and character at the Turkey Lakes experimental Watershed (TLW). Using a paired-catchment approach (unharvested reference vs. legacy (24 years post-) clearcut), inter- and intra-catchment variability in stream DOC concentrations and export was evaluated under a range of flow conditions. Stream DOC variability was related to the concentrations, spatial distribution, and hydrologic connectivity of hillslope solute pool DOC. Additionally, a subset of event-scale stream and hillslope solute pool samples were analyzed for DOC character using Liquid-Chromatography Organic Carbon Detection (LC-OCD). DOC character was expressed in terms of the specific UV absorbance at 254 nm (SUVA) and the relative contributions of LC-OCD-defined DOC fractions. Whereas stream DOC concentrations in the legacy clearcut catchment exceeded (+1.21 mg L-1) and differed significantly (p ≤ 0.05) from the unharvested reference catchment, inter-catchment differences in stream DOC export were inconsistent. No inter-catchment differences were observed in the DOC concentrations or hydrologic connectivity of the hillslope solute pools, despite the common association of these mechanisms with post-harvest increases in stream DOC concentrations. Significant (p ≤ 0.05) inter-catchment differences in the fractional composition of stream DOC were observed at the event-scale but may be related to the presence of a wetland near the outlet of the unharvested reference catchment, rather than a harvesting impact. Wetland position was identified as a key factor in the variability of both DOC concentration and character in the unharvested reference catchment. Overall, the results of this thesis suggest that while forest harvesting practices may result in long-term increases in stream DOC concentration in northern hardwood-dominated headwater catchments, the effects may be limited at decadal-scales and likely do not pose a reasonable threat to downstream drinking water treatment operations

Hierarchical clustering with dot products recovers hidden tree structure

In this paper we offer a new perspective on the well established agglomerative clustering algorithm, focusing on recovery of hierarchical structure. We recommend a simple variant of the standard algorithm, in which clusters are merged by maximum average dot product and not, for example, by minimum distance or within-cluster variance. We demonstrate that the tree output by this algorithm provides a bona fide estimate of generative hierarchical structure in data, under a generic probabilistic graphical model. The key technical innovations are to understand how hierarchical information in this model translates into tree geometry which can be recovered from data, and to characterise the benefits of simultaneously growing sample size and data dimension. We demonstrate superior tree recovery performance with real data over existing approaches such as UPGMA, Ward's method, and HDBSCAN

Words matter: A qualitative investigation of which weight status terms are acceptable and motivate weight loss when used by health professionals

Background: Health professionals have an important role to play in the management of obesity, but may be unsure how to raise weight issues with patients. The societal stigma associated with excess weight means that weight status terms may be misunderstood, cause offence and risk upsetting patient-professional relationships. This study investigated the views of people who were overweight or obese on the acceptability of weight status terms and their potential to motivate weight loss when used by health professionals. Methods. A qualitative study comprising 34 semi-structured interviews with men and women in their mid-to-late 30s and 50s who were overweight or obese and had recently been informed of their weight status. Thematic framework analysis was conducted to allow the systematic comparison of views by age, gender and apparent motivation to lose weight. Results: Although many people favoured 'Overweight' to describe their weight status, there were doubts about its effectiveness to motivate weight loss. Terms including 'BMI' ('Body Mass Index') or referring to the unhealthy nature of their weight were generally considered acceptable and motivational, although a number of men questioned the validity of BMI as an indicator of excess weight. Participants, particularly women, felt that health professionals should avoid using 'Fat'. Whilst response to 'Obese' was largely negative, people recognised that it could be appropriate in a health consultation. Some younger people, particularly those who appeared motivated to lose weight, felt 'Obese' could encourage weight loss, but it was also clear the term could provoke negative emotions if used insensitively. Conclusions: Although most people who are overweight or obese accept that it is appropriate for health professionals to discuss weight issues with patients, there is great variation in response to the terms commonly used to describe excess weight. There is no one-size-fits-all approach to discussing weight status: some men and younger people may appreciate a direct approach, whilst others need to be treated more sensitively. It is therefore important that health professionals use their knowledge and understanding to select the terms that are most likely to be acceptable, but at the same time have most potential to motivate each individual patient

Differential effect of CLK SR Kinases on HIV-1 gene expression: potential novel targets for therapy

<p>Abstract</p> <p>Background</p> <p>RNA processing plays a critical role in the replication of HIV-1, regulated in part through the action of host SR proteins. To explore the impact of modulating SR protein activity on virus replication, the effect of increasing or inhibiting the activity of the Cdc2-like kinase (CLK) family of SR protein kinases on HIV-1 expression and RNA processing was examined.</p> <p>Results</p> <p>Despite their high homology, increasing individual CLK expression had distinct effects on HIV-1, CLK1 enhancing Gag production while CLK2 inhibited the virus. Parallel studies on the anti-HIV-1 activity of CLK inhibitors revealed a similar discrepant effect on HIV-1 expression. TG003, an inhibitor of CLK1, 2 and 4, had no effect on viral Gag synthesis while chlorhexidine, a CLK2, 3 and 4 inhibitor, blocked virus production. Chlorhexidine treatment altered viral RNA processing, decreasing levels of unspliced and single spliced viral RNAs, and reduced Rev accumulation. Subsequent experiments in the context of HIV-1 replication in PBMCs confirmed the capacity of chlorhexidine to suppress virus replication.</p> <p>Conclusions</p> <p>Together, these findings establish that HIV-1 RNA processing can be targeted to suppress virus replication as demonstrated by manipulating individual CLK function and identified chlorhexidine as a lead compound in the development of novel anti-viral therapies.</p

Activation of conventional protein kinase C (PKC) is critical in the generation of human neutrophil extracellular traps

BACKGROUND: Activation of NADPH oxidase is required for neutrophil extracellular trap (NET) formation. Protein kinase C (PKC) is an upstream mediator of NADPH oxidase activation and thus likely to have a role in NET formation. METHODS: Pharmacological inhibitors were used to block PKC activity in neutrophils harvested from healthy donor blood. RESULTS: Pan PKC inhibition with Ro-31-8220 (p<0.001), conventional PKC inhibition with Go 6976 (p<0.001) and specific PKCβ inhibition with LY333531 (p<0.01) blocked NET formation in response to PMA. Inhibition of novel and atypical PKC had no effect. LY333531 blocked NET induction by the diacylglycerol analogue OAG (conventional PKC activator) (p<0.001). CONCLUSIONS: Conventional PKCs have a prominent role in NET formation. Furthermore PKCβ is the major isoform implicated in NET formation

Crystal Structure of Orthorhombic {bis-[(pyridin-2-yl)methyl](3,5,5,5-tetrachloropentyl)amine-κ\u3csup\u3e3\u3c/sup\u3e\u3cem\u3eN,N\u27,N\u27\u27\u3c/em\u3e}chloridocopper(II) Perchlorate

In the title compound, [CuCl(C17H19Cl4N3)]ClO4, the CuII ion adopts a distorted square-planar geometry defined by one chloride ligand and the three nitro­gen atoms from the bis­[(pyridin-2-yl)meth­yl](3,5,5,5-tetra­chloro­pent­yl)amine ligand. The perchlorate counter-ion is disordered over three sets of sites with refined occupancies 0.0634 (17), 0.221 (16) and 0.145 (7). In addition, the hetero-scorpionate arm of the bis­[(pyridin-2-yl)meth­yl](3,5,5,5-tetra­chloro­pent­yl)amine ligand is disordered over two sets of sites with refined occupancies 0.839 (2) and 0.161 (2). In the crystal, weak Cu⋯Cl inter­actions between symmetry-related mol­ecules create a dimerization with a chloride occupying the apical position of the square-pyramidal geometry typical of many copper(II) chloride hetero-scorpionate complexes