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

Examining a staging model for anorexia nervosa: empirical exploration of a four stage model of severity.

Background: An illness staging model for anorexia nervosa (AN) has received increasing attention, but assessing the merits of this concept is dependent on empirically examining a model in clinical samples. Building on preliminary findings regarding the reliability and validity of the Clinician Administered Staging Instrument for Anorexia Nervosa (CASIAN), the current study explores operationalising CASIAN severity scores into stages and assesses their relationship with other clinical features. Method: In women with DSM-IV-R AN and sub-threshold AN (all met AN criteria using DSM 5), receiver operating curve (ROC) analysis (n = 67) assessed the relationship between the sensitivity and specificity of each stage of the CASIAN. Thereafter chi-square and post-hoc adjusted residual analysis provided a preliminary assessment of the validity of the stages comparing the relationship between stage and treatment intensity and AN sub-types, and explored movement between stages after six months (Time 3) in a larger cohort (n = 171). Results: The CASIAN significantly distinguished between milder stages of illness (Stage 1 and 2) versus more severe stages of illness (Stages 3 and 4), and approached statistical significance in distinguishing each of the four stages from one other. CASIAN Stages were significantly associated with treatment modality and primary diagnosis, and CASIAN Stage at Time 1 was significantly associated with Stage at 6 month follow-up. Conclusions: Provisional support is provided for a staging model in AN. Larger studies with longer follow-up of cases are now needed to replicate and extend these findings and evaluate the overall utility of staging as well as optimal staging models

What do general practitioners know about ADHD? Attitudes and knowledge among first-contact gatekeepers: systematic narrative review

Background: Attention Deficit Hyperactivity Disorder (ADHD) is a common childhood disorder with international prevalence estimates of 5 % in childhood, yet significant evidence exists that far fewer children receive ADHD services. In many countries, ADHD is assessed and diagnosed in specialist mental health or neuro-developmental paediatric clinics, to which referral by General (Family) Practitioners (GPs) is required. In such ‘gatekeeper’ settings, where GPs act as a filter to diagnosis and treatment, GPs may either not recognise potential ADHD cases, or may be reluctant to refer. This study systematically reviews the literature regarding GPs’ views of ADHD in such settings. Methods: A search of nine major databases was conducted, with wide search parameters; 3776 records were initially retrieved. Studies were included if they were from settings where GPs are typically gatekeepers to ADHD services; if they addressed GPs’ ADHD attitudes and knowledge; if methods were clearly described; and if results for GPs were reported separately from those of other health professionals. Results: Few studies specifically addressed GP attitudes to ADHD. Only 11 papers (10 studies), spanning 2000–2010, met inclusion criteria, predominantly from the UK, Europe and Australia. As studies varied methodologically, findings are reported as a thematic narrative, under the following themes: Recognition rate; ADHD controversy (medicalisation, stigma, labelling); Causes of ADHD; GPs and ADHD diagnosis; GPs and ADHD treatment; GP ADHD training and sources of information; and Age, sex differences in knowledge and attitudes. Conclusions: Across times and settings, GPs practising in first-contact gatekeeper settings had mixed and often unhelpful attitudes regarding the validity of ADHD as a construct, the role of medication and how parenting contributed to presentation. A paucity of training was identified, alongside a reluctance of GPs to become involved in shared care practice. If access to services is to be improved for possible ADHD cases, there needs to be a focused and collaborative approach to training

Cognitive and behavioral predictors of light therapy use

Objective: Although light therapy is effective in the treatment of seasonal affective disorder (SAD) and other mood disorders, only 53-79% of individuals with SAD meet remission criteria after light therapy. Perhaps more importantly, only 12-41% of individuals with SAD continue to use the treatment even after a previous winter of successful treatment. Method: Participants completed surveys regarding (1) social, cognitive, and behavioral variables used to evaluate treatment adherence for other health-related issues, expectations and credibility of light therapy, (2) a depression symptoms scale, and (3) self-reported light therapy use. Results: Individuals age 18 or older responded (n = 40), all reporting having been diagnosed with a mood disorder for which light therapy is indicated. Social support and self-efficacy scores were predictive of light therapy use (p's<.05). Conclusion: The findings suggest that testing social support and self-efficacy in a diagnosed patient population may identify factors related to the decision to use light therapy. Treatments that impact social support and self-efficacy may improve treatment response to light therapy in SAD. © 2012 Roecklein et al

A fresh look at the evolution and diversification of photochemical reaction centers

In this review, I reexamine the origin and diversification of photochemical reaction centers based on the known phylogenetic relations of the core subunits, and with the aid of sequence and structural alignments. I show, for example, that the protein folds at the C-terminus of the D1 and D2 subunits of Photosystem II, which are essential for the coordination of the water-oxidizing complex, were already in place in the most ancestral Type II reaction center subunit. I then evaluate the evolution of reaction centers in the context of the rise and expansion of the different groups of bacteria based on recent large-scale phylogenetic analyses. I find that the Heliobacteriaceae family of Firmicutes appears to be the earliest branching of the known groups of phototrophic bacteria; however, the origin of photochemical reaction centers and chlorophyll synthesis cannot be placed in this group. Moreover, it becomes evident that the Acidobacteria and the Proteobacteria shared a more recent common phototrophic ancestor, and this is also likely for the Chloroflexi and the Cyanobacteria. Finally, I argue that the discrepancies among the phylogenies of the reaction center proteins, chlorophyll synthesis enzymes, and the species tree of bacteria are best explained if both types of photochemical reaction centers evolved before the diversification of the known phyla of phototrophic bacteria. The primordial phototrophic ancestor must have had both Type I and Type II reaction centers

Molecular Dynamics Simulation Study and Hybrid Pharmacophore Model Development in Human LTA4H Inhibitor Design

Human leukotriene A4 hydrolase (hLTA4H) is a bi-functional enzyme catalyzes the hydrolase and aminopeptidase functions upon the fatty acid and peptide substrates, respectively, utilizing the same but overlapping binding site. Particularly the hydrolase function of this enzyme catalyzes the rate-limiting step of the leukotriene (LT) cascade that converts the LTA4 to LTB4. This product is a potent pro-inflammatory activator of inflammatory responses and thus blocking this conversion provides a valuable means to design anti-inflammatory agents. Four structurally very similar chemical compounds with highly different inhibitory profile towards the hydrolase function of hLTA4H were selected from the literature. Molecular dynamics (MD) simulations of the complexes of hLTA4H with these inhibitors were performed and the results have provided valuable information explaining the reasons for the differences in their biological activities. Binding mode analysis revealed that the additional thiophene moiety of most active inhibitor helps the pyrrolidine moiety to interact the most important R563 and K565 residues. The hLTA4H complexes with the most active compound and substrate were utilized in the development of hybrid pharmacophore models. These developed pharmacophore models were used in screening chemical databases in order to identify lead candidates to design potent hLTA4H inhibitors. Final evaluation based on molecular docking and electronic parameters has identified three compounds of diverse chemical scaffolds as potential leads to be used in novel and potent hLTA4H inhibitor design

Behavioural and neuroanatomical correlates of auditory speech analysis in primary progressive aphasias

Background Non-verbal auditory impairment is increasingly recognised in the primary progressive aphasias (PPAs) but its relationship to speech processing and brain substrates has not been defined. Here we addressed these issues in patients representing the non-fluent variant (nfvPPA) and semantic variant (svPPA) syndromes of PPA. Methods We studied 19 patients with PPA in relation to 19 healthy older individuals. We manipulated three key auditory parameters—temporal regularity, phonemic spectral structure and prosodic predictability (an index of fundamental information content, or entropy)—in sequences of spoken syllables. The ability of participants to process these parameters was assessed using two-alternative, forced-choice tasks and neuroanatomical associations of task performance were assessed using voxel-based morphometry of patients’ brain magnetic resonance images. Results Relative to healthy controls, both the nfvPPA and svPPA groups had impaired processing of phonemic spectral structure and signal predictability while the nfvPPA group additionally had impaired processing of temporal regularity in speech signals. Task performance correlated with standard disease severity and neurolinguistic measures. Across the patient cohort, performance on the temporal regularity task was associated with grey matter in the left supplementary motor area and right caudate, performance on the phoneme processing task was associated with grey matter in the left supramarginal gyrus, and performance on the prosodic predictability task was associated with grey matter in the right putamen. Conclusions Our findings suggest that PPA syndromes may be underpinned by more generic deficits of auditory signal analysis, with a distributed cortico-subcortical neuraoanatomical substrate extending beyond the canonical language network. This has implications for syndrome classification and biomarker development

Hepatitis C Virus (HCV) Evades NKG2D-Dependent NK Cell Responses through NS5A-Mediated Imbalance of Inflammatory Cytokines

Understanding how hepatitis C virus (HCV) induces and circumvents the host's natural killer (NK) cell-mediated immunity is of critical importance in efforts to design effective therapeutics. We report here the decreased expression of the NKG2D activating receptor as a novel strategy adopted by HCV to evade NK-cell mediated responses. We show that chronic HCV infection is associated with expression of ligands for NKG2D, the MHC class I-related Chain (MIC) molecules, on hepatocytes. However, NKG2D expression is downmodulated on circulating NK cells, and consequently NK cell-mediated cytotoxic capacity and interferon-γ production are impaired. Using an endotoxin-free recombinant NS5A protein, we show that NS5A stimulation of monocytes through Toll-like Receptor 4 (TLR4) promotes p38- and PI3 kinase-dependent IL-10 production, while inhibiting IL-12 production. In turn, IL-10 triggers secretion of TGFβ which downmodulates NKG2D expression on NK cells, leading to their impaired effector functions. Moreover, culture supernatants of HCV JFH1 replicating Huh-7.5.1 cells reproduce the effect of recombinant NS5A on NKG2D downmodulation. Exogenous IL-15 can antagonize the TGFβ effect and restore normal NKG2D expression on NK cells. We conclude that NKG2D-dependent NK cell functions are modulated during chronic HCV infection, and demonstrate that this alteration can be prevented by exogenous IL-15, which could represent a meaningful adjuvant for therapeutic intervention