Evaluating the neurophysiological evidence for predictive processing as a model of perception

For many years, the dominant theoretical framework guiding research into the neural origins of perceptual experience has been provided by hierarchical feedforward models, in which sensory inputs are passed through a series of increasingly complex feature detectors. However, the long‐standing orthodoxy of these accounts has recently been challenged by a radically different set of theories that contend that perception arises from a purely inferential process supported by two distinct classes of neurons: those that transmit predictions about sensory states and those that signal sensory information that deviates from those predictions. Although these predictive processing (PP) models have become increasingly influential in cognitive neuroscience, they are also criticized for lacking the empirical support to justify their status. This limited evidence base partly reflects the considerable methodological challenges that are presented when trying to test the unique predictions of these models. However, a confluence of technological and theoretical advances has prompted a recent surge in human and nonhuman neurophysiological research seeking to fill this empirical gap. Here, we will review this new research and evaluate the degree to which its findings support the key claims of PP

Reducing dementia risk by targeting modifiable risk factors in mid-life: study protocol for the Innovative midlife intervention for dementia deterrence (In-MINDD) randomised controlled feasibility trial

Background Dementia prevalence is increasing as populations live longer, with no cure and the costs of caring exceeding many other conditions. There is increasing evidence for modifiable risk factors which, if addressed in mid-life, can reduce the risk of developing dementia in later life. These include physical inactivity, low cognitive activity, mid-life obesity, high blood pressure, and high cholesterol. This study aims to assess the acceptability and feasibility and impact of giving those in mid-life, aged between 40 and 60 years, an individualised dementia risk modification score and profile and access to personalised on-line health information and goal setting in order to support the behaviour change required to reduce such dementia risk. A secondary aim is to understand participants’ and practitioners’ views of dementia prevention and explore the acceptability and integration of the Innovative Midlife Intervention for Dementia Deterrence (In-MINDD) intervention into daily life and routine practice. Methods/design In-MINDD is a multi-centre, primary care-based, single-blinded randomised controlled feasibility trial currently being conducted in four European countries (France, Ireland, the Netherlands and the UK). Participants are being recruited from participating general practices. Inclusion criteria will include age between 40 and 60 years; at least one modifiable risk factor for dementia risk (including diabetes, hypertension, obesity, renal dysfunction, current smoker, raised cholesterol, coronary heart disease, current or previous history of depression, self-reported sedentary lifestyle, and self-reported low cognitive activity) access to the Internet. Primary outcome measure will be a change in dementia risk modification score over the timescale of the trial (6 months). A qualitative process evaluation will interview a sample of participants and practitioners about their views on the acceptability and feasibility of the trial and the links between modifiable risk factors and dementia prevention. This work will be underpinned by Normalisation Process Theory. Discussion This study will explore the feasibility and acceptability of a risk profiler and on-line support environment to help individuals in mid-life assess their risk of developing dementia in later life and to take steps to alleviate that risk by tackling health-related behaviour change. Testing the intervention in a robust and theoretically informed manner will inform the development of a future, full-scale randomised controlled trial

Human papillomavirus and survival of patients with oropharyngeal cancer.

BACKGROUND: Oropharyngeal squamous-cell carcinomas caused by human papillomavirus (HPV) are associated with favorable survival, but the independent prognostic significance of tumor HPV status remains unknown. METHODS: We performed a retrospective analysis of the association between tumor HPV status and survival among patients with stage III or IV oropharyngeal squamous-cell carcinoma who were enrolled in a randomized trial comparing accelerated-fractionation radiotherapy (with acceleration by means of concomitant boost radiotherapy) with standard-fractionation radiotherapy, each combined with cisplatin therapy, in patients with squamous-cell carcinoma of the head and neck. Proportional-hazards models were used to compare the risk of death among patients with HPV-positive cancer and those with HPV-negative cancer. RESULTS: The median follow-up period was 4.8 years. The 3-year rate of overall survival was similar in the group receiving accelerated-fractionation radiotherapy and the group receiving standard-fractionation radiotherapy (70.3% vs. 64.3%; P=0.18; hazard ratio for death with accelerated-fractionation radiotherapy, 0.90; 95% confidence interval [CI], 0.72 to 1.13), as were the rates of high-grade acute and late toxic events. A total of 63.8% of patients with oropharyngeal cancer (206 of 323) had HPV-positive tumors; these patients had better 3-year rates of overall survival (82.4%, vs. 57.1% among patients with HPV-negative tumors; P\u3c0.001 by the log-rank test) and, after adjustment for age, race, tumor and nodal stage, tobacco exposure, and treatment assignment, had a 58% reduction in the risk of death (hazard ratio, 0.42; 95% CI, 0.27 to 0.66). The risk of death significantly increased with each additional pack-year of tobacco smoking. Using recursive-partitioning analysis, we classified our patients as having a low, intermediate, or high risk of death on the basis of four factors: HPV status, pack-years of tobacco smoking, tumor stage, and nodal stage. CONCLUSIONS: Tumor HPV status is a strong and independent prognostic factor for survival among patients with oropharyngeal cancer. (ClinicalTrials.gov number, NCT00047008.

Provision of foot health services for people with rheumatoid arthritis in New South Wales: a web-based survey of local podiatrists

Background: It is unclear if podiatric foot care for people with rheumatoid arthritis (RA) in New South Wales (NSW) meets current clinical recommendations. The objective of this study was to survey podiatrists' perceptions of the nature of podiatric foot care provision for people who have RA in NSW.Methods: An anonymous, cross-sectional survey with a web-based questionnaire was conducted. The survey questionnaire was developed according to clinical experience and current foot care recommendations. State registered podiatrists practising in the state of NSW were invited to participate. The survey link was distributed initially via email to members of the Australian Podiatry Association (NSW), and distributed further through snowballing techniques using professional networks. Data was analysed to assess significant associations between adherence to clinical practice guidelines, and private/public podiatry practices.Results: 86 podiatrists participated in the survey (78% from private practice, 22% from public practice). Respondents largely did not adhere to formal guidelines to manage their patients (88%). Only one respondent offered a dedicated service for patients with RA. Respondents indicated that the primary mode of accessing podiatry was by self-referral (68%). Significant variation was observed regarding access to disease and foot specific assessments and treatment strategies. Assessment methods such as administration of patient reported outcome measures, vascular and neurological assessments were not conducted by all respondents. Similarly, routine foot care strategies such as prescription of foot orthoses, foot health advice and footwear were not employed by all respondents.Conclusions: The results identified issues in foot care provision which should be explored through further research. Foot care provision in NSW does not appear to meet the current recommended standards for the management of foot problems in people who have RA. Improvements to foot care could be undertaken in terms of providing better access to examination techniques and treatment strategies that are recommended by evidence based treatment paradigms. © 2013 Hendry et al.; licensee BioMed Central Ltd

Do emotional difficulties and peer problems hew together from childhood to adolescence? The case of children with a history of developmental language disorder (DLD)

Children and adolescents with developmental language disorder (DLD) are, overall, vulnerable to difficulties in emotional adjustment and in peer relations. However, previous research has shown that different subgroups follow different trajectories in respect of quality of peer relations. Less is known of the trajectories of emotional development. We consider here the possibility that development in these two domains is interrelated: that is, the trajectories of emotional and peer problems will proceed in parallel. We conducted longitudinal joint trajectories analyses of emotional and peer relations in a sample of young people identified as having DLD at age 7 years and seen at intervals up to 16 years. Potential influences on joint trajectory group membership were examined. Findings revealed five distinct joint trajectories. Emotional and peer difficulties do hew together from childhood to adolescence for just over half of the sample, but not all. The variables most clearly associated with group membership were pragmatic language ability, prosociality and parental mental health. This is the first study to examine joint longitudinal trajectories of emotional and peer difficulties in individuals with DLD. We demonstrate that development in individuals with DLD is heterogeneous and identify three key variables associated with personal and social adjustment from childhood to adolescence. Theoretical and clinical implications of these findings are discussed

Host-parasite co-metabolic activation of antitrypanosomal aminomethyl-benzoxaboroles

<div><p>Recent development of benzoxaborole-based chemistry gave rise to a collection of compounds with great potential in targeting diverse infectious diseases, including human African Trypanosomiasis (HAT), a devastating neglected tropical disease. However, further medicinal development is largely restricted by a lack of insight into mechanism of action (MoA) in pathogenic kinetoplastids. We adopted a multidisciplinary approach, combining a high-throughput forward genetic screen with functional group focused chemical biological, structural biology and biochemical analyses, to tackle the complex MoAs of benzoxaboroles in <i>Trypanosoma brucei</i>. We describe an oxidative enzymatic pathway composed of host semicarbazide-sensitive amine oxidase and a trypanosomal aldehyde dehydrogenase TbALDH3. Two sequential reactions through this pathway serve as the key underlying mechanism for activating a series of 4-aminomethylphenoxy-benzoxaboroles as potent trypanocides; the methylamine parental compounds as pro-drugs are transformed first into intermediate aldehyde metabolites, and further into the carboxylate metabolites as effective forms. Moreover, comparative biochemical and crystallographic analyses elucidated the catalytic specificity of TbALDH3 towards the benzaldehyde benzoxaborole metabolites as xenogeneic substrates. Overall, this work proposes a novel drug activation mechanism dependent on both host and parasite metabolism of primary amine containing molecules, which contributes a new perspective to our understanding of the benzoxaborole MoA, and could be further exploited to improve the therapeutic index of antimicrobial compounds.</p></div

Medial longitudinal arch development of school children : The College of Podiatry Annual Conference 2015: meeting abstracts

Background Foot structure is often classified into flat foot, neutral and high arch type based on the variability of the Medial Longitudinal Arch (MLA). To date, the literature provided contrasting evidence on the age when MLA development stabilises in children. The influence of footwear on MLA development is also unknown. Aim This study aims to (i) clarify whether the MLA is still changing in children from age 7 to 9 years old and (ii) explore the relationship between footwear usage and MLA development, using a longitudinal approach. Methods We evaluated the MLA of 111 healthy school children [age = 6.9 (0.3) years] using three parameters [arch index (AI), midfoot peak pressure (PP) and maximum force (MF: % of body weight)] extracted from dynamic foot loading measurements at baseline, 10-month and 22-month follow-up. Information on the type of footwear worn was collected using survey question. Linear mixed modelling was used to test for differences in the MLA over time. Results Insignificant changes in all MLA parameters were observed over time [AI: P = .15; PP: P = .84; MF: P = .91]. When gender was considered, the AI of boys decreased with age [P = .02]. Boys also displayed a flatter MLA than girls at age 6.9 years [AI: mean difference = 0.02 (0.01, 0.04); P = .02]. At baseline, subjects who wore close-toe shoes displayed the lowest MLA overall [AI/PP/MF: P < .05]. Subjects who used slippers when commencing footwear use experienced higher PP than those who wore sandals [mean difference = 31.60 (1.44, 61.75) kPa; post-hoc P = .04]. Discussion and conclusion Our findings suggested that the MLA of children remained stable from 7 to 9 years old, while gender and the type of footwear worn during childhood may influence MLA development. Clinicians may choose to commence therapy when a child presents with painful flexible flat foot at age 7 years, and may discourage younger children from wearing slippers when they commence using footwear

BHPR research: qualitative1. Complex reasoning determines patients' perception of outcome following foot surgery in rheumatoid arhtritis

Background: Foot surgery is common in patients with RA but research into surgical outcomes is limited and conceptually flawed as current outcome measures lack face validity: to date no one has asked patients what is important to them. This study aimed to determine which factors are important to patients when evaluating the success of foot surgery in RA Methods: Semi structured interviews of RA patients who had undergone foot surgery were conducted and transcribed verbatim. Thematic analysis of interviews was conducted to explore issues that were important to patients. Results: 11 RA patients (9 ♂, mean age 59, dis dur = 22yrs, mean of 3 yrs post op) with mixed experiences of foot surgery were interviewed. Patients interpreted outcome in respect to a multitude of factors, frequently positive change in one aspect contrasted with negative opinions about another. Overall, four major themes emerged. Function: Functional ability & participation in valued activities were very important to patients. Walking ability was a key concern but patients interpreted levels of activity in light of other aspects of their disease, reflecting on change in functional ability more than overall level. Positive feelings of improved mobility were often moderated by negative self perception ("I mean, I still walk like a waddling duck”). Appearance: Appearance was important to almost all patients but perhaps the most complex theme of all. Physical appearance, foot shape, and footwear were closely interlinked, yet patients saw these as distinct separate concepts. Patients need to legitimize these feelings was clear and they frequently entered into a defensive repertoire ("it's not cosmetic surgery; it's something that's more important than that, you know?”). Clinician opinion: Surgeons' post operative evaluation of the procedure was very influential. The impact of this appraisal continued to affect patients' lasting impression irrespective of how the outcome compared to their initial goals ("when he'd done it ... he said that hasn't worked as good as he'd wanted to ... but the pain has gone”). Pain: Whilst pain was important to almost all patients, it appeared to be less important than the other themes. Pain was predominately raised when it influenced other themes, such as function; many still felt the need to legitimize their foot pain in order for health professionals to take it seriously ("in the end I went to my GP because it had happened a few times and I went to an orthopaedic surgeon who was quite dismissive of it, it was like what are you complaining about”). Conclusions: Patients interpret the outcome of foot surgery using a multitude of interrelated factors, particularly functional ability, appearance and surgeons' appraisal of the procedure. While pain was often noted, this appeared less important than other factors in the overall outcome of the surgery. Future research into foot surgery should incorporate the complexity of how patients determine their outcome Disclosure statement: All authors have declared no conflicts of interes

Constructing “Packages” of Evidence-Based Programs to Prevent Youth Violence: Processes and Illustrative Examples From the CDC’s Youth Violence Prevention Centers

This paper describes the strategic efforts of six National Centers of Excellence in Youth Violence Prevention (YVPC), funded by the U.S. Centers for Disease Control and Prevention, to work in partnership with local communities to create comprehensive evidence-based program packages to prevent youth violence. Key components of a comprehensive evidence-based approach are defined and examples are provided from a variety of community settings (rural and urban) across the nation that illustrate attempts to respond to the unique needs of the communities while maintaining a focus on evidence-based programming and practices. At each YVPC site, the process of selecting prevention and intervention programs addressed the following factors: (1) community capacity, (2) researcher and community roles in selecting programs, (3) use of data in decision-making related to program selection, and (4) reach, resources, and dosage. We describe systemic barriers to these efforts, lessons learned, and opportunities for policy and practice. Although adopting an evidence-based comprehensive approach requires significant upfront resources and investment, it offers great potential for preventing youth violence and promoting the successful development of children, families and communities