Contrasting prefrontal cortex contributions to episodic memory dysfunction in behavioural variant frontotemporal dementia and alzheimer's disease

Recent evidence has questioned the integrity of episodic memory in behavioural variant frontotemporal dementia (bvFTD), where recall performance is impaired to the same extent as in Alzheimer's disease (AD). While these deficits appear to be mediated by divergent patterns of brain atrophy, there is evidence to suggest that certain prefrontal regions are implicated across both patient groups. In this study we sought to further elucidate the dorsolateral (DLPFC) and ventromedial (VMPFC) prefrontal contributions to episodic memory impairment in bvFTD and AD. Performance on episodic memory tasks and neuropsychological measures typically tapping into either DLPFC or VMPFC functions was assessed in 22 bvFTD, 32 AD patients and 35 age- and education-matched controls. Behaviourally, patient groups did not differ on measures of episodic memory recall or DLPFC-mediated executive functions. BvFTD patients were significantly more impaired on measures of VMPFC-mediated executive functions. Composite measures of the recall, DLPFC and VMPFC task scores were covaried against the T1 MRI scans of all participants to identify regions of atrophy correlating with performance on these tasks. Imaging analysis showed that impaired recall performance is associated with divergent patterns of PFC atrophy in bvFTD and AD. Whereas in bvFTD, PFC atrophy covariates for recall encompassed both DLPFC and VMPFC regions, only the DLPFC was implicated in AD. Our results suggest that episodic memory deficits in bvFTD and AD are underpinned by divergent prefrontal mechanisms. Moreover, we argue that these differences are not adequately captured by existing neuropsychological measures

Effectiveness, cost-effectiveness and cost-benefit of a single annual professional intervention for the prevention of childhood dental caries in a remote rural Indigenous community

Background The aim of the study is to reduce the high prevalence of tooth decay in children in a remote, rural Indigenous community in Australia, by application of a single annual dental preventive intervention. The study seeks to (1) assess the effectiveness of an annual oral health preventive intervention in slowing the incidence of dental caries in children in this community, (2) identify the mediating role of known risk factors for dental caries and (3) assess the cost-effectiveness and cost-benefit of the intervention. Methods/design The intervention is novel in that most dental preventive interventions require regular re-application, which is not possible in resource constrained communities. While tooth decay is preventable, self-care and healthy habits are lacking in these communities, placing more emphasis on health services to deliver an effective dental preventive intervention. Importantly, the study will assess cost-benefit and cost-effectiveness for broader implementation across similar communities in Australia and internationally. Discussion There is an urgent need to reduce the burden of dental decay in these communities, by implementing effective, cost-effective, feasible and sustainable dental prevention programs. Expected outcomes of this study include improved oral and general health of children within the community; an understanding of the costs associated with the intervention provided, and its comparison with the costs of allowing new lesions to develop, with associated treatment costs. Findings should be generalisable to similar communities around the world. The research is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR), registration number ACTRN12615000693527; date of registration: 3rd July 2015

Bacterial morphotype grading for periodontal disease assessment

BACKGROUND: Listgarten and Hellden (1978) used darkfield microscopy of wet mounts to differentiate between healthy and periodontally diseased sites in the mouth by expressing the different bacterial morphotypes observed as a percentage of the total number of bacteria counted. This method of periodontal disease assessment gained favour as a diagnostic tool but presented with the limitation of immediate examination to determine the number of motile rods present and an inability to distinguish between gingivitis and periodontitis. Grading of bacterial morphotypes into several distinct categories of health or disease (Ison and Hay, 2002), simplified the scoring system of Gram-stained smears for the diagnosis of bacterial vaginosis (Nugent et al. 1991). The application of a similar grading system using stained smears rather than wet mounts could be advantageous to the diagnosis of periodontal disease. OBJECTIVES/AIMS: This study tested the hypothesis that stained smears of dental plaque collected from the gingival crevice of individuals with varying probing pocket depths (PD) may provide a grading system for periodontal disease assessment. MATERIALS AND METHODS: Subgingival plaque samples were collected from 49 patients, stained with a silver stain and the proportions of each bacterial morphotype graded relative to their respective PD measurements. RESULTS: This technique allowed for a grading system of I–IV, with grade I indicating health and grade IV indicating severe periodontal disease. DISCUSSION: Stained smear examination eliminates the time restriction for motile rod enumeration and allows for storage of smears for future reference. CONCLUSION: Standardization of the microscopic areas to be evaluated or examined will facilitate the agreement of cut-off values for the diagnosis of periodontal disease.This material is based on work partially supported financially by the National Research Foundation (NRF) of South Africa

Sizing Up Allometric Scaling Theory

Metabolic rate, heart rate, lifespan, and many other physiological properties vary with body mass in systematic and interrelated ways. Present empirical data suggest that these scaling relationships take the form of power laws with exponents that are simple multiples of one quarter. A compelling explanation of this observation was put forward a decade ago by West, Brown, and Enquist (WBE). Their framework elucidates the link between metabolic rate and body mass by focusing on the dynamics and structure of resource distribution networks—the cardiovascular system in the case of mammals. Within this framework the WBE model is based on eight assumptions from which it derives the well-known observed scaling exponent of 3/4. In this paper we clarify that this result only holds in the limit of infinite network size (body mass) and that the actual exponent predicted by the model depends on the sizes of the organisms being studied. Failure to clarify and to explore the nature of this approximation has led to debates about the WBE model that were at cross purposes. We compute analytical expressions for the finite-size corrections to the 3/4 exponent, resulting in a spectrum of scaling exponents as a function of absolute network size. When accounting for these corrections over a size range spanning the eight orders of magnitude observed in mammals, the WBE model predicts a scaling exponent of 0.81, seemingly at odds with data. We then proceed to study the sensitivity of the scaling exponent with respect to variations in several assumptions that underlie the WBE model, always in the context of finite-size corrections. Here too, the trends we derive from the model seem at odds with trends detectable in empirical data. Our work illustrates the utility of the WBE framework in reasoning about allometric scaling, while at the same time suggesting that the current canonical model may need amendments to bring its predictions fully in line with available datasets

A frequentist framework of inductive reasoning

Reacting against the limitation of statistics to decision procedures, R. A. Fisher proposed for inductive reasoning the use of the fiducial distribution, a parameter-space distribution of epistemological probability transferred directly from limiting relative frequencies rather than computed according to the Bayes update rule. The proposal is developed as follows using the confidence measure of a scalar parameter of interest. (With the restriction to one-dimensional parameter space, a confidence measure is essentially a fiducial probability distribution free of complications involving ancillary statistics.) A betting game establishes a sense in which confidence measures are the only reliable inferential probability distributions. The equality between the probabilities encoded in a confidence measure and the coverage rates of the corresponding confidence intervals ensures that the measure's rule for assigning confidence levels to hypotheses is uniquely minimax in the game. Although a confidence measure can be computed without any prior distribution, previous knowledge can be incorporated into confidence-based reasoning. To adjust a p-value or confidence interval for prior information, the confidence measure from the observed data can be combined with one or more independent confidence measures representing previous agent opinion. (The former confidence measure may correspond to a posterior distribution with frequentist matching of coverage probabilities.) The representation of subjective knowledge in terms of confidence measures rather than prior probability distributions preserves approximate frequentist validity.Comment: major revisio

Assessment of two screening tools to identify psoriatic arthritis in patients with psoriasis

Background: Many patients with psoriasis have undiagnosed psoriatic arthritis. Low specificity is found with many PsA screening tools. A new instrument, the CONTEST questionnaire, was developed utilizing the most discriminative items from existing instruments. Objective: The aim of this study was to compare the CONTEST and PEST screening tools. Methods: People attending secondary care clinics with psoriasis, but not PsA, completed the questionnaires, were assessed for function and quality of life, and had a physical examination. Patients thought to have PsA were compared to those without. The performance of CONTEST and PEST was compared using area under the receiver operating curve (AUC), and sensitivity and specificity at the previously published cut‐offs. Results: A total of 451 dermatology patients were approached, 35% were reviewed and 27 (17%, 95% CI 12.3–21.7) had unidentified psoriatic arthritis. The sensitivity and specificity (95% CI) of PEST were 0.60 (0.42–0.78)/0.76 (0.69–0.83) and for CONTEST 0.53 (0.34–0.72)/0.71 (0.63–0.79). The confidence limits for the AUC overlapped (AUC for PEST 0.72 (0.61–0.84), for CONTEST 0.66 (0.54–0.77). Conclusions: PEST and CONTEST questionnaires performed equally well, with no superiority of the new CONTEST tool

The Cost of Sex: Quantifying Energetic Investment in Gamete Production by Males and Females

The relative energetic investment in reproduction between the sexes forms the basis of sexual selection and life history theories in evolutionary biology. It is often assumed that males invest considerably less in gametes than females, but quantifying the energetic cost of gamete production in both sexes has remained a difficult challenge. For a broad diversity of species (invertebrates, reptiles, amphibians, fishes, birds, and mammals), we compared the cost of gamete production between the sexes in terms of the investment in gonad tissue and the rate of gamete biomass production. Investment in gonad biomass was nearly proportional to body mass in both sexes, but gamete biomass production rate was approximately two to four orders of magnitude higher in females. In both males and females, gamete biomass production rate increased with organism mass as a power law, much like individual metabolic rate. This suggests that whole-organism energetics may act as a primary constraint on gamete production among species. Residual variation in sperm production rate was positively correlated with relative testes size. Together, these results suggest that understanding the heterogeneity in rates of gamete production among species requires joint consideration of the effects of gonad mass and metabolism

On the thermodynamic origin of metabolic scaling

This work has been funded by projects AYA2013-48623-C2-2, FIS2013-41057-P, CGL2013-46862-C2-1-P and SAF2015-65878-R from the Spanish Ministerio de Economa y Competitividad and PrometeoII/2014/086, PrometeoII/2014/060 and PrometeoII/2014/065 from the Generalitat Valenciana (Spain). BL acknowledges funding from a Salvador de Madariaga fellowship, and L.L. acknowledges funding from EPSRC Early Career fellowship EP/P01660X/1

Explicit and implicit information needs of people with depression: a qualitative investigation of problems reported on an online depression support forum

<p>Abstract</p> <p>Background</p> <p>Health management is impeded when consumers do not possess adequate knowledge about their illness. At a public health level, consumer knowledge about depression is particularly important because depression is highly prevalent and causes substantial disability and burden. However, currently little is known about the information needs of people with depression. This study aimed to investigate the explicit and implicit information needs of users of an online depression support forum.</p> <p>Methods</p> <p>A sample of 2680 posts was systematically selected from three discussion forums on an online depression bulletin board (blueboard.anu.edu.au). Data were examined for evidence of requests for information (reflecting explicit needs) and reports of past or current problems (implicit needs). Thematic analysis was conducted using a data-driven inductive approach with the assistance of NVivo 7, and instances of questions and people reporting particular types of problems were recorded.</p> <p>Results</p> <p>A total of 134 participants with personal experience of depression contributed to the data analysed. Six broad themes represented participant queries and reported problems: Understanding depression; disclosure and stigma; medication; treatment and services; coping with depression; and comorbid health problems. A variety of specific needs were evident within these broad thematic areas. Some people (n = 46) expressed their information needs by asking direct questions (47 queries) but the majority of needs were expressed implicitly (351 problems) by the 134 participants. The most evident need for information related to coping with depression and its consequences, followed by topics associated with medication, treatment and services.</p> <p>Conclusions</p> <p>People with depression have substantial unmet information needs and require strategies to deal with the difficulties they face. They require access to high quality and relevant online resources and professionals; thus, there is a need to rectify current gaps in the provision of information and limitations of dissemination. Greater knowledge about depression and its treatment is also needed at the general community level.</p