Psychiatric morbidity in older people with moderate and severe learning disability (mental retardation). Part I: development and reliability of the patient interview (the PAS-ADD)

This paper describes the development of the PAS-ADD, a semistructured clinical interview for use specifically with patients with learning disabilities, based on items drawn from the PSE. The PAS-ADD includes a number of novel features including: parallel interviewing of patient and informant; a three-tier structure to provide a flexible interview appropriate to the patient's intellectual level; use of a memorable 'anchor event' in the patient's life to improve time focus; and simplified wording, improved organisation and lay out. Inter-rater reliability was investigated using an experimental design in which two raters viewed and re-rated videotaped PAS-ADD interviews which had been conducted by an experienced clinician. Reliability results compared favourably with those obtained in a major study of PSE reliability with a sample drawn from non-learning disabled individuals. Mean kappa for all items was 0.72. Other indexes of reliability were also good. In the current phase of development, the PAS-ADD is to be expanded to include further diagnostic categories, including schizophrenia and autism. The new version will be updated for use with ICD-10 criteria

A phase I, randomized study of combined IL-2 and therapeutic immunisation with antiretroviral therapy

BACKGROUND: Fully functional HIV-1-specific CD8 and CD4 effector T-cell responses are vital to the containment of viral activity and disease progression. These responses are lacking in HIV-1-infected patients with progressive disease. We attempted to augment fully functional HIV-1-specific CD8 and CD4 effector T-cell responses in patients with advanced chronic HIV-1 infection. DESIGN: Chronically infected patients with low CD4 counts T-cell counts who commenced antiretroviral therapy (ART) were subsequently treated with combined interleukin-2 and therapeutic vaccination. METHODS: Thirty six anti-retroviral naive patients were recruited and initiated on combination ART for 17 weeks before randomization to: A) ongoing ART alone; B) ART with IL-2 twice daily for 5 days every four weeks starting at week 17 for 3 cycles; C) ART with IL-2 as in group B and Remune HIV-1 vaccine administered once every 3 months, starting at week 17; and D) ART with Remune vaccine as in group C. Patients were studied for 65 weeks following commencement of ART, with an additional prior 6 week lead-in observation period. CD4 and CD8 T-cell counts, evaluations of HIV-1 RNA levels and proliferative responses to recall and HIV-1 antigens were complemented with assessment of IL-4-secretion alongside quantification of anti-HIV-1 CD8 T-cell responses and neutralizing antibody titres. RESULTS: Neither IL-2 nor Remune™ vaccination induced sustained HIV-1-specific T-cell responses. However, we report an inverse relationship between HIV-1-specific proliferative responses and IL-4 production which continuously increased in patients receiving immunotherapy, but not patients receiving ART alone. CONCLUSION: Induction of HIV-1-specific cell-mediated responses is a major challenge in chronically HIV-1-infected patients even when combining immunisation with IL-2 therapy. An antigen-specific IL-4-associated suppressive response may play a role in attenuating HIV-specific responses

Limits on precursor and afterglow radio emission from a fast radio burst in a star-forming galaxy

We present a new fast radio burst at 920 MHz discovered during commensal observations conducted with the Australian Square Kilometre Array Pathfinder (ASKAP) as part of the Commensal Real-time ASKAP Fast Transients (CRAFT) survey. FRB 191001 was detected at a dispersion measure (DM) of 506.92(4) pc cm$^{-3}$ and its measured fluence of 143(15) Jy ms is the highest of the bursts localized to host galaxies by ASKAP to date. The sub-arcsecond localisation of the FRB provided by ASKAP reveals that the burst originated in the outskirts of a highly star-forming spiral in a galaxy pair at redshift $z=0.2340(1)$. Radio observations show no evidence for a compact persistent radio source associated with the FRB 191001 above a flux density of $15\mu$Jy. However, we detect diffuse synchrotron radio emission from the disk of the host galaxy that we ascribe to ongoing star formation. FRB 191001 was also detected as an image-plane transient in a single 10-s snapshot with a flux density of 19.3 mJy in the low-time-resolution visibilities obtained simultaneously with CRAFT data. The commensal observation facilitated a search for repeating and slowly varying radio emissions 8 hrs before and 1 hr after the burst. We found no variable radio emission on timescales ranging from 1 ms to 1.4 hr. We report our upper limits and briefly review FRB progenitor theories in the literature which predict radio afterglows. Our data are still only weakly constraining of any afterglows at the redshift of the FRB. Future commensal observations of more nearby and bright FRBs will potentially provide stronger constraints.Comment: 12 pages, 6 figures, Accepted for publication in ApJ Letter

The Woody Guthrie Centennial Bibliography

This bibliography updates two extensive works designed to include comprehensively all significant works by and about Woody Guthrie. Richard A. Reuss published A Woody Guthrie Bibliography, 1912–1967 in 1968 and Jeffrey N. Gatten\u27s article “Woody Guthrie: A Bibliographic Update, 1968–1986” appeared in 1988. With this current article, researchers need only utilize these three bibliographies to identify all English-language items of relevance related to, or written by, Guthrie

Neurophysiological modeling of bladder afferent activity in the rat overactive bladder model

The overactive bladder (OAB) is a syndrome-based urinary dysfunction characterized by “urgency, with or without urge incontinence, usually with frequency and nocturia”. Earlier we developed a mathematical model of bladder nerve activity during voiding in anesthetized rats and found that the nerve activity in the relaxation phase of voiding contractions was all afferent. In the present study, we applied this mathematical model to an acetic acid (AA) rat model of bladder overactivity to study the sensitivity of afferent fibers in intact nerves to bladder pressure and volume changes. The afferent activity in the filling phase and the slope, i.e., the sensitivity of the afferent fibers to pressure changes in the post-void relaxation phase, were found to be significantly higher in AA than in saline measurements, while the offset (nerve activity at pressure ~0) and maximum pressure were comparable. We have thus shown, for the first time, that the sensitivity of afferent fibers in the OAB can be studied without cutting nerves or preparation of single fibers. We conclude that bladder overactivity induced by AA in rats is neurogenic in origin and is caused by increased sensitivity of afferent sensors in the bladder wall

Precipitation Constrains Amphibian Chytrid Fungus Infection Rates in a Terrestrial Frog Assemblage in Jamaica, West Indies

We model Batrachochytrium dendrobatidis (Bd) infection rates in Jamaican frogs—one of the most threatened amphibian fauna in the world. The majority of species we surveyed were terrestrial direct‐developing frogs or frogs that breed in tank bromeliads, rather than those that use permanent water bodies to breed. Thus, we were able to investigate the climatic correlates of Bd infection in a frog assemblage that does not rely on permanent water bodies. We sampled frogs for Bd across all of the major habitat types on the island, used machine learning algorithms to identify climatic variables that are correlated with infection rates, and extrapolated infection rates across the island. We compared the effectiveness of the machine learning algorithms for species distribution modeling in the context of our study, and found that infection rate rose quickly with precipitation in the driest month. Infection rates also increased with mean temperature in the warmest quarter until 22 °C, and remained relatively level thereafter. Both of these results are in accordance with previous studies of the physiology of Bd . Based on our environmental results, we suggest that frogs occupying high‐precipitation habitats with cool rainy‐season temperatures, though zcurrently experiencing low frequencies of infection, may experience an increase in infection rates as global warming increases temperatures in their habitat.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106115/1/btp12093.pd

A prospective, double-blind, randomized, controlled clinical trial comparing standard wound care with adjunctive hyperbaric oxygen therapy (HBOT) to standard wound care only for the treatment of chronic, non-healing ulcers of the lower limb in patients with diabetes mellitus: a study protocol

<p>Abstract</p> <p>Background</p> <p>It has been suggested that the use of adjunctive hyperbaric oxygen therapy improves the healing of diabetic foot ulcers, and decreases the risk of lower extremity amputations. A limited number of studies have used a double blind approach to evaluate the efficacy of hyperbaric oxygen therapy in the treatment of diabetic ulcers. The primary aim of this study is to assess the efficacy of hyperbaric oxygen therapy plus standard wound care compared with standard wound care alone in preventing the need for major amputation in patients with diabetes mellitus and chronic ulcers of the lower limb.</p> <p>Methods/Design</p> <p>One hundred and eighteen (59 patients per arm) patients with non-healing diabetic ulcers of the lower limb, referred to the Judy Dan Research and Treatment Centre are being recruited if they are at least 18 years of age, have either Type 1 or 2 diabetes with a Wagner grading of foot lesions 2, 3 or 4 on lower limb not healing for at least 4 weeks. Patients receive hyperbaric oxygen therapy every day for 6 weeks during the treatment phase and are provided ongoing wound care and weekly assessments. Patients are required to return to the study centre every week for an additional 6 weeks of follow-up for wound evaluation and management. The primary outcome is freedom from having, or meeting the criteria for, a major amputation (below knee amputation, or metatarsal level) up to 12 weeks after randomization. The decision to amputate is made by a vascular surgeon. Other outcomes include wound healing, effectiveness, safety, healthcare resource utilization, quality of life, and cost-effectiveness. The study will run for a total of about 3 years.</p> <p>Discussion</p> <p>The results of this study will provide detailed information on the efficacy of hyperbaric oxygen therapy for the treatment of non-healing ulcers of the lower limb. This will be the first double-blind randomized controlled trial for this health technology which evaluates the efficacy of hyperbaric oxygen therapy in prevention of amputations in diabetic patients.</p> <p>Trial registration</p> <p>ClinicalTrials.gov Identifier: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00621608">NCT00621608</a></p

An integrated transcriptomic and computational analysis for biomarker identification in gastric cancer

This report describes an integrated study on identification of potential markers for gastric cancer in patients’ cancer tissues and sera based on: (i) genome-scale transcriptomic analyses of 80 paired gastric cancer/reference tissues and (ii) computational prediction of blood-secretory proteins supported by experimental validation. Our findings show that: (i) 715 and 150 genes exhibit significantly differential expressions in all cancers and early-stage cancers versus reference tissues, respectively; and a substantial percentage of the alteration is found to be influenced by age and/or by gender; (ii) 21 co-expressed gene clusters have been identified, some of which are specific to certain subtypes or stages of the cancer; (iii) the top-ranked gene signatures give better than 94% classification accuracy between cancer and the reference tissues, some of which are gender-specific; and (iv) 136 of the differentially expressed genes were predicted to have their proteins secreted into blood, 81 of which were detected experimentally in the sera of 13 validation samples and 29 found to have differential abundances in the sera of cancer patients versus controls. Overall, the novel information obtained in this study has led to identification of promising diagnostic markers for gastric cancer and can benefit further analyses of the key (early) abnormalities during its development

Sodium Chloride Inhibits the Growth and Infective Capacity of the Amphibian Chytrid Fungus and Increases Host Survival Rates

The amphibian chytrid fungus Batrachochytrium dendrobatidis is a recently emerged pathogen that causes the infectious disease chytridiomycosis and has been implicated as a contributing factor in the global amphibian decline. Since its discovery, research has been focused on developing various methods of mitigating the impact of chytridiomycosis on amphibian hosts but little attention has been given to the role of antifungal agents that could be added to the host's environment. Sodium chloride is a known antifungal agent used routinely in the aquaculture industry and this study investigates its potential for use as a disease management tool in amphibian conservation. The effect of 0–5 ppt NaCl on the growth, motility and survival of the chytrid fungus when grown in culture media and its effect on the growth, infection load and survivorship of infected Peron's tree frogs (Litoria peronii) in captivity, was investigated. The results reveal that these concentrations do not negatively affect the survival of the host or the pathogen. However, concentrations greater than 3 ppt significantly reduced the growth and motility of the chytrid fungus compared to 0 ppt. Concentrations of 1–4 ppt NaCl were also associated with significantly lower host infection loads while infected hosts exposed to 3 and 4 ppt NaCl were found to have significantly higher survival rates. These results support the potential for NaCl to be used as an environmentally distributed antifungal agent for the prevention of chytridiomycosis in susceptible amphibian hosts. However, further research is required to identify any negative effects of salt exposure on both target and non-target organisms prior to implementation