Approximation Algorithms for Generalized MST and TSP in Grid Clusters

We consider a special case of the generalized minimum spanning tree problem (GMST) and the generalized travelling salesman problem (GTSP) where we are given a set of points inside the integer grid (in Euclidean plane) where each grid cell is $1 \times 1$. In the MST version of the problem, the goal is to find a minimum tree that contains exactly one point from each non-empty grid cell (cluster). Similarly, in the TSP version of the problem, the goal is to find a minimum weight cycle containing one point from each non-empty grid cell. We give a $(1+4\sqrt{2}+\epsilon)$ and $(1.5+8\sqrt{2}+\epsilon)$-approximation algorithm for these two problems in the described setting, respectively. Our motivation is based on the problem posed in [7] for a constant approximation algorithm. The authors designed a PTAS for the more special case of the GMST where non-empty cells are connected end dense enough. However, their algorithm heavily relies on this connectivity restriction and is unpractical. Our results develop the topic further

Profiles of white matter tract pathology in frontotemporal dementia.

Despite considerable interest in improving clinical and neurobiological characterisation of frontotemporal dementia and in defining the role of brain network disintegration in its pathogenesis, information about white matter pathway alterations in frontotemporal dementia remains limited. Here we investigated white matter tract damage using an unbiased, template-based diffusion tensor imaging (DTI) protocol in a cohort of 27 patients with the behavioral variant of frontotemporal dementia (bvFTD) representing both major genetic and sporadic forms, in relation both to healthy individuals and to patients with Alzheimer's disease. Widespread white matter tract pathology was identified in the bvFTD group compared with both healthy controls and Alzheimer's disease group, with prominent involvement of uncinate fasciculus, cingulum bundle and corpus callosum. Relatively discrete and distinctive white matter profiles were associated with genetic subgroups of bvFTD associated with MAPT and C9ORF72 mutations. Comparing diffusivity metrics, optimal overall separation of the bvFTD group from the healthy control group was signalled using radial diffusivity, whereas optimal overall separation of the bvFTD group from the Alzheimer's disease group was signalled using fractional anisotropy. Comparing white matter changes with regional grey matter atrophy (delineated using voxel based morphometry) in the bvFTD cohort revealed co-localisation between modalities particularly in the anterior temporal lobe, however white matter changes extended widely beyond the zones of grey matter atrophy. Our findings demonstrate a distributed signature of white matter alterations that is likely to be core to the pathophysiology of bvFTD and further suggest that this signature is modulated by underlying molecular pathologies. Hum Brain Mapp, 2014. © 2014 Wiley Periodicals, Inc

Reversible temperature regulation of electrical and thermal conductivity using liquid–solid phase transitions

Reversible temperature tuning of electrical and thermal conductivities of materials is of interest for many applications, including seasonal regulation of building temperature, thermal storage and sensors. Here we introduce a general strategy to achieve large contrasts in electrical and thermal conductivities using first-order phase transitions in percolated composite materials. Internal stress generated during a phase transition modulates the electrical and thermal contact resistances, leading to large contrasts in the electrical and thermal conductivities at the phase transition temperature. With graphite/hexadecane suspensions, the electrical conductivity changes 2 orders of magnitude and the thermal conductivity varies up to 3.2 times near 18 °C. The generality of the approach is also demonstrated in other materials such as graphite/water and carbon nanotube/hexadecane suspensions

A Novel Behavioral Assay for Measuring Cold Sensation in Mice

Behavioral models of cold responses are important tools for exploring the molecular mechanisms of cold sensation. To complement the currently cold behavioral assays and allow further studies of these mechanisms, we have developed a new technique to measure the cold response threshold, the cold plantar assay. In this assay, animals are acclimated on a glass plate and a cold stimulus is applied to the hindpaw through the glass using a pellet of compressed dry ice. The latency to withdrawal from the cooled glass is used as a measure of the cold response threshold of the rodents, and the dry ice pellet provides a ramping cold stimulus on the glass that allows the correlation of withdrawal latency values to rough estimates of the cold response threshold temperature. The assay is highly sensitive to manipulations including morphine-induced analgesia, Complete Freund's Adjuvant-induced inflammatory allodynia, and Spinal Nerve Ligation-induced neuropathic allodynia

Study protocol to investigate the effect of a lifestyle intervention on body weight, psychological health status and risk factors associated with disease recurrence in women recovering from breast cancer treatment

Background Breast cancer survivors often encounter physiological and psychological problems related to their diagnosis and treatment that can influence long-term prognosis. The aim of this research is to investigate the effects of a lifestyle intervention on body weight and psychological well-being in women recovering from breast cancer treatment, and to determine the relationship between changes in these variables and biomarkers associated with disease recurrence and survival. Methods/design Following ethical approval, a total of 100 patients will be randomly assigned to a lifestyle intervention (incorporating dietary energy restriction in conjunction with aerobic exercise training) or normal care control group. Patients randomised to the dietary and exercise intervention will be given individualised healthy eating dietary advice and written information and attend moderate intensity aerobic exercise sessions on three to five days per week for a period of 24 weeks. The aim of this strategy is to induce a steady weight loss of up to 0.5 Kg each week. In addition, the overall quality of the diet will be examined with a view to (i) reducing the dietary intake of fat to ~25% of the total calories, (ii) eating at least 5 portions of fruit and vegetables a day, (iii) increasing the intake of fibre and reducing refined carbohydrates, and (iv) taking moderate amounts of alcohol. Outcome measures will include body weight and body composition, psychological health status (stress and depression), cardiorespiratory fitness and quality of life. In addition, biomarkers associated with disease recurrence, including stress hormones, estrogen status, inflammatory markers and indices of innate and adaptive immune function will be monitored. Discussion This research will provide valuable information on the effectiveness of a practical, easily implemented lifestyle intervention for evoking positive effects on body weight and psychological well-being, two important factors that can influence long-term prognosis in breast cancer survivors. However, the added value of the study is that it will also evaluate the effects of the lifestyle intervention on a range of biomarkers associated with disease recurrence and survival. Considered together, the results should improve our understanding of the potential role that lifestyle-modifiable factors could play in saving or prolonging lives

Low-intensity blue-enriched white light (750 lux) and standard bright light (10 000 lux) are equally effective in treating SAD. A randomized controlled study

<p>Abstract</p> <p>Background</p> <p>Photoreceptor cells containing melanopsin play a role in the phase-shifting effects of short-wavelength light. In a previous study, we compared the standard light treatment (SLT) of SAD with treatment using short-wavelength blue-enriched white light (BLT). Both treatments used the same illuminance (10 000 lux) and were equally highly effective. It is still possible, however, that neither the newly-discovered photoreceptor cells, nor the biological clock play a major role in the therapeutic effects of light on SAD. Alternatively, these effects may at least be partly mediated by these receptor cells, which may have become saturated as a result of the high illuminances used in the therapy. This randomized controlled study compares the effects of low-intensity BLT to those of high-intensity SLT.</p> <p>Method</p> <p>In a 22-day design, 22 patients suffering from a major depression with a seasonal pattern (SAD) were given light treatment (10 000 lux) for two weeks on workdays. Subjects were randomly assigned to either of the two conditions, with gender and age evenly distributed over the groups. Light treatment either consisted of 30 minutes SLT (5000°K) with the EnergyLight^®(Philips, Consumer Lifestyle) with a vertical illuminance of 10 000 lux at eye position or BLT (17 000°K) with a vertical illuminance of 750 lux using a prototype of the EnergyLight^®which emitted a higher proportion of short-wavelengths. All participants completed questionnaires concerning mood, activation and sleep quality on a daily basis. Mood and energy levels were also assessed on a weekly basis by means of the SIGH-SAD and other assessment tools.</p> <p>Results</p> <p>On day 22, SIGH-SAD ratings were significantly lower than on day 1 (SLT 65.2% and BLT 76.4%). On the basis of all assessments no statistically significant differences were found between the two conditions.</p> <p>Conclusion</p> <p>With sample size being small, conclusions can only be preliminary. Both treatment conditions were found to be highly effective. The therapeutic effects of low-intensity blue-enriched light were comparable to those of the standard light treatment. Saturation effects may play a role, even with a light intensity of 750 lux. The therapeutic effects of blue-enriched white light in the treatment of SAD at illuminances as low as 750 lux help bring light treatment for SAD within reach of standard workplace and educational lighting systems.</p

Comparability of Results from Pair and Classical Model Formulations for Different Sexually Transmitted Infections

The “classical model” for sexually transmitted infections treats partnerships as instantaneous events summarized by partner change rates, while individual-based and pair models explicitly account for time within partnerships and gaps between partnerships. We compared predictions from the classical and pair models over a range of partnership and gap combinations. While the former predicted similar or marginally higher prevalence at the shortest partnership lengths, the latter predicted self-sustaining transmission for gonorrhoea (GC) and Chlamydia (CT) over much broader partnership and gap combinations. Predictions on the critical level of condom use (Cc) required to prevent transmission also differed substantially when using the same parameters. When calibrated to give the same disease prevalence as the pair model by adjusting the infectious duration for GC and CT, and by adjusting transmission probabilities for HIV, the classical model then predicted much higher Cc values for GC and CT, while Cc predictions for HIV were fairly close. In conclusion, the two approaches give different predictions over potentially important combinations of partnership and gap lengths. Assuming that it is more correct to explicitly model partnerships and gaps, then pair or individual-based models may be needed for GC and CT since model calibration does not resolve the differences

How robust are the natural history parameters used in chlamydia transmission dynamic models? A systematic review

Transmission dynamic models linked to economic analyses often form part of the decision making process when introducing new chlamydia screening interventions. Outputs from these transmission dynamic models can vary depending on the values of the parameters used to describe the infection. Therefore these values can have an important influence on policy and resource allocation. The risk of progression from infection to pelvic inflammatory disease has been extensively studied but the parameters which govern the transmission dynamics are frequently neglected. We conducted a systematic review of transmission dynamic models linked to economic analyses of chlamydia screening interventions to critically assess the source and variability of the proportion of infections that are asymptomatic, the duration of infection and the transmission probability. We identified nine relevant studies in Pubmed, Embase and the Cochrane database. We found that there is a wide variation in their natural history parameters, including an absolute difference in the proportion of asymptomatic infections of 25% in women and 75% in men, a six-fold difference in the duration of asymptomatic infection and a four-fold difference in the per act transmission probability. We consider that much of this variation can be explained by a lack of consensus in the literature. We found that a significant proportion of parameter values were referenced back to the early chlamydia literature, before the introduction of nucleic acid modes of diagnosis and the widespread testing of asymptomatic individuals. In conclusion, authors should use high quality contemporary evidence to inform their parameter values, clearly document their assumptions and make appropriate use of sensitivity analysis. This will help to make models more transparent and increase their utility to policy makers

Type 2 diabetes, depressive symptoms and trajectories of cognitive decline in a national sample of community-dwellers: a prospective cohort study

We examined the individual and synergistic effects of type 2 diabetes and elevated depressive symptoms on memory and executive function trajectories over 10 and eight years of follow-up, respectively. Our sample comprised 10,524 community-dwellers aged ≥50 years in 2002±03 from the English Longitudinal Study of Ageing. With respect to memory (word recall), participants with either diabetes or elevated depressive symptoms recalled significantly fewer words compared with those free of these conditions (reference category), but more words compared with those with both conditions. There was a significant acceleration in the rate of memory decline in participants aged ≤50±64 years with both conditions (-0.27, 95% CI, -0.45 to -0.08, per study wave), which was not observed in those with either condition or aged ≥65 years. With respect to executive function (animal naming), participants aged 65 years with diabetes or those with elevated depressive symptoms named significantly fewer animals compared with the reference category, while those with both conditions named fewer animals compared with any other category. The rate of executive function decline was significantly greater in participants with both conditions (-0.54, 95% CI, -0.99 to -0.10; and ±0.71, 95% CI, -1.16 to -0.27, per study wave, for those aged 50±64 and ≥65 years, respectively), but not in participants with either condition. Diabetes and elevated depressive symptoms are inversely associated with memory and executive function, but, individually, do not accelerate cognitive decline. The co-occurrence of diabetes and elevated depressive symptoms significantly accelerates cognitive decline over time, especially among those aged 50±64 years

Synergistic Reversal of Intrahepatic HCV-Specific CD8 T Cell Exhaustion by Combined PD-1/CTLA-4 Blockade

Viral persistence is associated with hierarchical antiviral CD8 T cell exhaustion with increased programmed death-1 (PD-1) expression. In HCV persistence, HCV-specific CD8 T cells from the liver (the site of viral replication) display increased PD-1 expression and a profound functional impairment that is not reversed by PD-1 blockade alone. Here, we report that the inhibitory receptor cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is preferentially upregulated in PD-1+ T cells from the liver but not blood of chronically HCV-infected patients. PD-1/CTLA-4 co-expression in intrahepatic T cells was associated with a profound HCV-specific effector dysfunction that was synergistically reversed by combined PD-1/CTLA-4 blockade in vitro, but not by blocking PD-1 or CTLA-4 alone. A similar effect was observed in circulating HCV-specific CD8 T cells with increased PD-1/CTLA-4 co-expression during acute hepatitis C. The functional response to combined blockade was directly associated with CTLA-4 expression, lost with CD28-depletion and CD4-independent (including CD4+FoxP3+ Tregs). We conclude that PD-1 and CTLA-4 pathways both contribute to virus-specific T cell exhaustion at the site of viral replication by a redundant mechanism that requires combined PD-1/CTLA-4 blockade to reverse. These findings provide new insights into the mechanisms of virus-specific T cell dysfunction, and suggest that the synergistic effect by combined inhibitory receptor blockade might have a therapeutic application against chronic viral infection in vivo, provided that it does not induce autoimmunity