Timing of retinal neuronal and axonal loss in MS: a longitudinal OCT study

The objective of the study was to investigate the timing of central nervous system tissue atrophy in MS by evaluating longitudinal retinal volume changes in a broadly representative cohort with disease duration across the entire arc of disease. In this longitudinal study, 135 patients with MS and 16 healthy reference subjects underwent spectral-domain optical coherence tomography (OCT) at baseline and 2 years later. Following OCT quality control, automated segmentation of the peripapillary retinal nerve fiber layer (pRNFL), macular ganglion cell–inner plexiform layer (mGCIPL) and macular inner nuclear layer (mINL) was performed. Generalized estimation equations were used to analyze longitudinal changes and associations with disease duration and clinical measures. Participants had a median disease duration at baseline of 16.4 years (range 0.1–45.4). Nearly half (44 %) of the MS patients had previously experienced MS-related optic neuritis (MSON) more than 6 months prior. The MS patients demonstrated a significant decrease over 2 years of the pRNFL (−1.1 µm, 95 % CI 1.4–0.7, p < 0.001) and mGCIPL (−1.1 µm, 95 % CI −1.4 to −0.8, p < 0.001). This thinning was most pronounced early in the course of disease. These findings were irrespective of previous episodes of MSON. No consistent pattern of change was observed for the mINL (−0.03 µm, 95 % CI −0.2 to 0.2, p = 0.795). This longitudinal study demonstrated that injury of the innermost retinal layers is found in MS and that this damage occurs most rapidly during the early stages of disease. The attenuation of atrophy with longer disease duration is suggestive of a plateau effect. These findings emphasize the importance of early intervention to prevent such injury

An Exact Monte Carlo Method for Continuum Fermion Systems

We offer a new proposal for the Monte Carlo treatment of many-fermion systems in continuous space. It is based upon Diffusion Monte Carlo with significant modifications: correlated pairs of random walkers that carry opposite signs; different functions ``guide'' walkers of different signs; the Gaussians used for members of a pair are correlated; walkers can cancel so as to conserve their expected future contributions. We report results for free-fermion systems and a fermion fluid with 14 $^3$He atoms, where it proves stable and correct. Its computational complexity grows with particle number, but slowly enough to make interesting physics within reach of contemporary computers.Comment: latex source, 3 separated figures (2 in jpg format, 1 in eps format

The Relationship Between Therapist Effects and Therapy Delivery Factors: Therapy Modality, Dosage, and Non-completion.

To consider the relationships between, therapist variability, therapy modality, therapeutic dose and therapy ending type and assess their effects on the variability of patient outcomes. Multilevel modeling was used to analyse a large sample of routinely collected data. Model residuals identified more and less effective therapists, controlling for case-mix. After controlling for case mix, 5.8 % of the variance in outcome was due to therapists. More sessions generally improved outcomes, by about half a point on the PHQ-9 for each additional session, while non-completion of therapy reduced the amount of pre-post change by six points. Therapy modality had little effect on outcome. Patient and service outcomes may be improved by greater focus on the variability between therapists and in keeping patients in therapy to completion

Ashamed and Fused with Body Image and Eating: Binge Eating as an Avoidance Strategy

Binge Eating Disorder (BED) is currently recognized as a severe disorder associated with relevant psychiatric and physical comorbidity, and marked emotional distress. Shame is a specific negative emotion that has been highlighted as central in eating disorders. However, the effect of shame and underlying mechanisms on binge eating symptomatology severity remained unclear. This study examines the role of shame, depressive symptoms, weight and shape concerns and eating concerns, and body image-related cognitive fusion, on binge eating symptomatology severity. Participated in this study 73 patients with the diagnosis of BED, established through a clinical interview-Eating Disorder Examination 17.0D-who completed measures of external shame, body-image related cognitive fusion, depressive symptoms and binge eating symptomatology. Results revealed positive associations between binge eating severity and depressive symptoms, shame, weight and shape concerns, eating concerns and body image-related cognitive fusion. A path analysis showed that, when controlling for the effect of depressive symptoms, external shame has a direct effect on binge eating severity, and an indirect effect mediated by increased eating concern and higher levels of body image-related cognitive fusion. Results confirmed the plausibility of the model, which explained 43% of the severity of binge eating symptoms. The proposed model suggests that, in BED patients, perceiving that others see the self negatively may be associated with an entanglement with body image-related thoughts and concerns about eating, which may, in turn, fuel binge eating symptoms. Findings have important clinical implications supporting the relevance of addressing shame and associated processes in binge eating. Copyright © 2015 John Wiley & Sons, Ltd

A comparison of nefazodone, the cognitive behavioral-analysis system of psychotherapy, and their combination for the treatment of chronic depression

Background Patients with chronic forms of major depression are difficult to treat, and the relative efficacy of medications and psychotherapy is uncertain. Methods We randomly assigned 681 adults with a chronic nonpsychotic major depressive disorder to 12 weeks of outpatient treatment with nefazodone (maximal dose, 600 mg per day), the cognitive behavioral-analysis system of psychotherapy (16 to 20 sessions), or both. At base line, all patients had scores of at least 20 on the 24-item Hamilton Rating Scale for Depression (indicating clinically significant depression). Remission was defined as a score of 8 or less at weeks 10 and 12. For patients who did not have remission, a satisfactory response was defined as a reduction in the score by at least 50 percent from base line and a score of 15 or less. Raters were unaware of the patients’ treatment assignments. Results Of the 681 patients, 662 attended at least one treatment session and were included in the analysis of response. The overall rate of response (both remission and satisfactory response) was 48 percent in both the nefazodone group and the psychotherapy group, as compared with 73 percent in the combined-treatment group (P Conclusions Although about half of patients with chronic forms of major depression have a response to short-term treatment with either nefazodone or a cognitive behavioral-analysis system of psychotherapy, the combination of the two is significantly more efficacious than either treatment alone

Modelling ranging behaviour of female orang-utans: a case study in Tuanan, Central Kalimantan, Indonesia

Quantification of the spatial needs of individuals and populations is vitally important for management and conservation. Geographic information systems (GIS) have recently become important analytical tools in wildlife biology, improving our ability to understand animal movement patterns, especially when very large data sets are collected. This study aims at combining the field of GIS with primatology to model and analyse space-use patterns of wild orang-utans. Home ranges of female orang-utans in the Tuanan Mawas forest reserve in Central Kalimantan, Indonesia were modelled with kernel density estimation methods. Kernel results were compared with minimum convex polygon estimates, and were found to perform better, because they were less sensitive to sample size and produced more reliable estimates. Furthermore, daily travel paths were calculated from 970 complete follow days. Annual ranges for the resident females were approximately 200 ha and remained stable over several years; total home range size was estimated to be 275 ha. On average, each female shared a third of her home range with each neighbouring female. Orang-utan females in Tuanan built their night nest on average 414 m away from the morning nest, whereas average daily travel path length was 777 m. A significant effect of fruit availability on day path length was found. Sexually active females covered longer distances per day and may also temporarily expand their ranges

Effectiveness and cost-effectiveness of transmural collaborative care with consultation letter (TCCCL) and duloxetine for major depressive disorder (MDD) and (sub)chronic pain in collaboration with primary care: design of a randomized placebo-controlled multi-Centre trial: TCC:PAINDIP

__Abstract__ Background: The comorbidity of pain and depression is associated with high disease burden for patients in terms of disability, wellbeing, and use of medical care. Patients with major and minor depression often present themselves with pain to a general practitioner and recognition of depression in such cases is low, but evolving. Also, physical symptoms, including pain, in major depressive disorder, predict a poorer response to treatment. A multi-faceted, patient-tailored treatment programme, like collaborative care, is promising. However, treatment of chronic pain conditions in depressive patients has, so far, received limited attention in research. Cost effectiveness of an integrated approach of pain in depressed patients has not been studied. This article describes the aims and design of a study to evaluate effects and costs of collaborative care with the antidepressant duloxetine for patients with pain symptoms and a depressive disorder, compared to collaborative care with placebo and compared to duloxetine alone

Superoxide dismutase A antigens derived from molecular analysis of sarcoidosis granulomas elicit systemic Th-1 immune responses

<p>Abstract</p> <p>Background</p> <p>Sarcoidosis is an idiopathic granulomatous disease with pathologic and immunologic features similar to tuberculosis. Routine histologic staining and culture fail to identify infectious agents. An alternative means for investigating a role of infectious agents in human pathogenesis involves molecular analysis of pathologic tissues for microbial nucleic acids, as well as recognition of microbial antigens by the host immune system. Molecular analysis for superoxide dismutase A (sodA) allows speciation of mycobacteria. SodA is an abundantly secreted virulence factor that generates cellular immune responses in infected hosts. The purpose of this study is to investigate if target antigens of the sarcoidosis immune response can be identified by molecular analysis of sarcoidosis granulomas.</p> <p>Methods</p> <p>We detected sodA amplicons in 12 of 17 sarcoidosis specimens, compared to 2 of 16 controls (p = 0.001, two-tailed Fisher's exact test), and 3 of 3 tuberculosis specimens (p = 0.54). Analysis of the amplicons revealed sequences identical to <it>M. tuberculosis </it>(MTB) complex, as well as sequences which were genetically divergent. Using peripheral blood mononuclear cells (PBMC) from 12 of the 17 sarcoidosis subjects, we performed enzyme-linked immunospot assay (ELISPOT) to assess for immune recognition of MTB sodA peptides, along with PBMC from 26 PPD- healthy volunteers, and 11 latent tuberculosis subjects.</p> <p>Results</p> <p>Six of 12 sarcoidosis subjects recognized the sodA peptides, compared to one of 26 PPD- controls (p = 0.002), and 6/11 PPD+ subjects (p = .68). Overall, 10 of the 12 sarcoidosis subjects from whom we obtained PBMC and archival tissue possessed molecular or immunologic evidence for sodA.</p> <p>Conclusion</p> <p>Dual molecular and immunologic analysis increases the ability to find infectious antigens. The detection of Th-1 immune responses to sodA peptides derived from molecular analysis of sarcoidosis granulomas reveals that these are among the target antigens contributing to sarcoidosis granulomatous inflammation.</p