Noise Sensitivity and Diminished Health: Testing Moderators and Mediators of the Relationship

The concept of noise sensitivity emerged in public health and psychoacoustic research to help explain individual differences in reactions to noise. Noise sensitivity has been associated with health problems, but the mechanisms underlying this relationship have yet to be fully examined. Participants (n = 1102) were residents of Auckland, New Zealand, who completed questionnaires and returned them through the post. Models of noise sensitivity and health were tested in the analyses using bootstrapping methods to examine indirect effects. Results indicated that gender and noise exposure were not significant moderators in the model. Perceived stress and sleep problems were significant mediators of the relationship between noise sensitivity and subjective health complaints, even after controlling for the influence of neuroticism. However, the relationship between noise sensitivity and mental health complaints (anxiety and depression) was accounted for by the variance explained by neuroticism. Overall, this study provides considerable understanding of the relationship between noise sensitivity and health problems and identifies areas for further research in the field

Motivation to Learn, Quality of Life and Estimated Academic Achievement: Medical Students Studying in New Zealand

The quality of life of medical students and their motivation to learn are critical factors that have an impact on their ability to learn. The aim of this study was to investigate the associations between medical students' perceptions of their quality of life, motivation to learn, and estimated grade at the end of the academic year. Two hundred and seventy-four medical students at years four and five of medical school participated in the study. Students filled in a demographic survey form, and shortened versions of the World Health Organization Quality of Life Questionnaire and the Motivated Strategies for Learning Questionnaire. Significant correlations between quality of life and motivation to learn measures were obtained. Second, students who scored high on aspects of quality of life and motivation to learn also scored significantly higher on estimates of written grade. In conclusion, the results suggest that medical students’ perceptions about quality of life and motivation to learn are linked to estimation of academic achievement. The findings of this study further resonate with a key conceptual model in the motivation literature, which promotes the importance of creating opportunities for mastery learning, engaging task value, producing optimal learning contexts, and creating mechanisms for coping with and managing the inevitable anxiety-provoking learning experiences that medical students face.The quality of life of medical students and their motivation to learn are critical factors that have an impact on their ability to learn. The aim of this study was to investigate the associations between medical students‟ perceptions of their quality of life, motivation to learn, and estimated grade at the end of the academic year. Two hundred and seventy-four medical students at years four and five of medical school participated in the study. Students filled in a demographic survey form, and shortened versions of the World Health Organization Quality of Life Questionnaire and the Motivated Strategies for Learning Questionnaire. Significant correlations between quality of life and motivation to learn measures were obtained. Second, students who scored high on aspects of quality of life and motivation to learn also scored significantly higher on estimates of written grade. In conclusion, the results suggest that medical students‟ perceptions about quality of life and motivation to learn are linked to estimation of academic achievement. The findings of this study further resonate with a key conceptual model in the motivation literature, which promotes the importance of creating opportunities for mastery learning, engaging task value, producing optimal learning contexts, and creating mechanisms for coping with and managing the inevitable anxiety-provoking learning experiences that medical students face

Decreasing prevalence in cerebral palsy: a multi-site European population-based study, 1980 to 2003

Aim: To monitor the trends in prevalence of cerebral palsy (CP) by birthweight in Europe, 1980 to 2003. Method: Data were collated from 20 population-based registers contributing to the Surveillance of Cerebral Palsy in Europe database. Trend analyses were conducted in four birthweight groups: 2499g (normal birthweight [NBW]). Results: The overall prevalence of CP decreased from 1.90 to 1.77 per 1000 live births, p<0.001, with a mean annual fall of 0.7% (95% confidence interval [CI] −0.3% to −1.0%). Prevalence in NBW children showed a non-significant trend from 1.17 to 0.89 per 1000 live births (p=0.22). Prevalence in MLBW children decreased from 8.5 to 6.2 per 1000 live births (p<0.001), but not linearly. Prevalence in VLBW children also declined from 70.9 to 35.9 per 1000 live births (p<0.001) with a mean annual fall of 3.4% (95% CI −2.4% to −4.3%). Prevalence in ELBW children remained stable, at a mean rate of 42.4 per 1000 live births. Interpretation: The decline in prevalence of CP in children of VLBW continues, and confirms that previously reported. For the first time, there is also a significant decline among those of MLBW, resulting in a significant overall decrease in the prevalence of CP

A Robust Kalman Algorithm to Facilitate Human-Computer Interaction for People with Cerebral Palsy, Using a New Interface Based on Inertial Sensors

This work aims to create an advanced human-computer interface called ENLAZA for people with cerebral palsy (CP). Although there are computer-access solutions for disabled people in general, there are few evidences from motor disabled community (e.g., CP) using these alternative interfaces. The proposed interface is based on inertial sensors in order to characterize involuntary motion in terms of time, frequency and range of motion. This characterization is used to design a filtering technique that reduces the effect of involuntary motion on person-computer interaction. This paper presents a robust Kalman filter (RKF) design to facilitate fine motor control based on the previous characterization. The filter increases mouse pointer directivity and the target acquisition time is reduced by a factor of ten. The interface is validated with CP users who were unable to control the computer using other interfaces. The interface ENLAZA and the RKF enabled them to use the computer

Dying neurons in thalamus of asphyxiated term newborns and rats are autophagic.

OBJECTIVE: Neonatal hypoxic-ischemic encephalopathy (HIE) still carries a high burden by its mortality and long-term neurological morbidity in survivors. Apart from hypothermia, there is no acknowledged therapy for HIE, reflecting the lack of mechanistic understanding of its pathophysiology. (Macro)autophagy, a physiological intracellular process of lysosomal degradation, has been proposed to be excessively activated in excitotoxic conditions such as HIE. The present study examines whether neuronal autophagy in the thalamus of asphyxiated human newborns or P7 rats is enhanced and related to neuronal death processes. METHODS: Neuronal autophagy and cell death were evaluated in the thalamus (frequently injured in severe HIE) of both human newborns who died after severe HIE (n = 5) and P7 hypoxic-ischemic rats (Rice-Vannuci model). Autophagic (LC3, p62), lysosomal (LAMP1, cathepsins), and cell death (TUNEL, caspase-3) markers were studied by immunohistochemistry in human and rat brain sections, and by additional methods in rats (immunoblotting, histochemistry, and electron microscopy). RESULTS: Following severe perinatal asphyxia in both humans and rats, thalamic neurons displayed up to 10-fold (p &lt; 0.001) higher numbers of autophagosomes and lysosomes, implying an enhanced autophagic flux. The highly autophagic neurons presented strong features of apoptosis. These findings were confirmed and elucidated in more detail in rats. INTERPRETATION: These results show for the first time that autophagy is enhanced in severe HIE in dying thalamic neurons of human newborns, as in rats. Experimental neuroprotective strategies targeting autophagy could thus be a promising lead to follow for the development of future therapeutic approaches. Ann Neurol 2014;76:695-711

PIK3CA-associated developmental disorders exhibit distinct classes of mutations with variable expression and tissue distribution

Mosaicism is increasingly recognized as a cause of developmental disorders with the advent of next-generation sequencing (NGS). Mosaic mutations of PIK3CA have been associated with the widest spectrum of phenotypes associated with overgrowth and vascular malformations. We performed targeted NGS using 2 independent deep-coverage methods that utilize molecular inversion probes and amplicon sequencing in a cohort of 241 samples from 181 individuals with brain and/or body overgrowth. We identified PIK3CA mutations in 60 individuals. Several other individuals (n = 12) were identified separately to have mutations in PIK3CA by clinical targetedpanel testing (n = 6), whole-exome sequencing (n = 5), or Sanger sequencing (n = 1). Based on the clinical and molecular features, this cohort segregated into three distinct groups: (a) severe focal overgrowth due to low-level but highly activating (hotspot) mutations, (b) predominantly brain overgrowth and less severe somatic overgrowth due to less-activating mutations, and (c) intermediate phenotypes (capillary malformations with overgrowth) with intermediately activating mutations. Sixteen of 29 PIK3CA mutations were novel. We also identified constitutional PIK3CA mutations in 10 patients. Our molecular data, combined with review of the literature, show that PIK3CA-related overgrowth disorders comprise a discontinuous spectrum of disorders that correlate with the severity and distribution of mutations

White matter integrity in dyskinetic cerebral palsy: Relationship with intelligence quotient and executive function

Background: Dyskinetic cerebral palsy (CP) is one of the most disabling motor types of CP and has been classically associated with injury to the basal ganglia and thalamus. Although cognitive dysfunction is common in CP, there is a paucity of published quantitative analyses investigating the relationship between white matter (WM) microstructure and cognition in this CP type. Aims: This study aims (1) to compare brain WM microstructure between people with dyskinetic CP and healthy controls, (2) to identify brain regions where WM microstructure is related to intelligence and (3) to identify brain regions where WM microstructure is related to executive function in people with dyskinetic CP and (4) to identify brain regions where the correlations are different between controls and people with CP in IQ and executive functions. Patients and methods: Thirty-three participants with dyskinetic CP (mean ± SD age: 24.42 ± 12.61, 15 female) were age and sex matched with 33 controls. Participants underwent a comprehensive neuropsychological battery to assess intelligence quotient (IQ) and four executive function domains (attentional control, cognitive flexibility, goal setting and information processing). Diffusion weighted MRI scans were acquired at 3T. Voxel-based whole brain groupwise analyses were used to compare fractional anisotropy (FA) and of the CP group to the matched controls using a general lineal model. Further general linear models were used to identify regions where white matter FA correlated with IQ and each of the executive function domains. Results: White matter FA was significantly reduced in the CP group in all cerebral lobes, predominantly in regions connected with the parietal and to a lesser extent the temporal lobes. There was no significant correlation between IQ or any of the four executive function domains and WM microstructure in the control group. In participants with CP, lower IQ was associated with lower FA in all cerebral lobes, predominantly in locations that also showed reduced FA compared to controls. Attentional control, goal setting and information processing did not correlate with WM microstructure in the CP group. Cognitive flexibility was associated with FA in regions known to contain connections with the frontal lobe (such as the superior longitudinal fasciculus and cingulum) as well as regions not known to contain tracts directly connected with the frontal lobe (such as the posterior corona radiata, posterior thalamic radiation, retrolenticular part of internal capsule, tapetum, body and splenium of corpus callosum). Conclusion:The widespread loss in the integrity of WM tissue is mainly located in the parietal lobe and related to IQ in dyskinetic CP. Unexpectedly, executive functions are only related with WM microstructure in regions containing fronto-cortical and posterior cortico-subcortical pathways, and not being specifically related to the state of fronto-striatal pathways which might be due to brain reorganization. Further studies of this nature may improve our understanding of the neurobiological bases of cognitive impairments after early brain insult

Routine use of patient reported outcome measures (PROMs) for improving treatment of common mental health disorders in adults

BACKGROUND: Routine outcome monitoring of common mental health disorders (CMHDs), using patient reported outcome measures (PROMs), has been promoted across primary care, psychological therapy and multidisciplinary mental health care settings, but is likely to be costly, given the high prevalence of CMHDs. There has been no systematic review of the use of PROMs in routine outcome monitoring of CMHDs across these three settings. OBJECTIVES: To assess the effects of routine measurement and feedback of the results of PROMs during the management of CMHDs in 1) improving the outcome of CMHDs; and 2) in changing the management of CMHDs. SEARCH METHODS: We searched the Cochrane Depression Anxiety and Neurosis group specialised controlled trials register (CCDANCTR-Studies and CCDANCTR-References), the Oxford University PROMS Bibliography (2002-5), Ovid PsycINFO, Web of Science, The Cochrane Library, and International trial registries, initially to 30 May 2014, and updated to 18 May 2015. SELECTION CRITERIA: We selected cluster and individually randomised controlled trials (RCTs) including participants with CMHDs aged 18 years and over, in which the results of PROMs were fed back to treating clinicians, or both clinicians and patients. We excluded RCTs in child and adolescent treatment settings, and those in which more than 10% of participants had diagnoses of eating disorders, psychoses, substance use disorders, learning disorders or dementia. DATA COLLECTION AND ANALYSIS: At least two authors independently identified eligible trials, assessed trial quality, and extracted data. We conducted meta-analysis across studies, pooling outcome measures which were sufficiently similar to each other to justify pooling. MAIN RESULTS: We included 17 studies involving 8787 participants: nine in multidisciplinary mental health care, six in psychological therapy settings, and two in primary care. Pooling of outcome data to provide a summary estimate of effect across studies was possible only for those studies using the compound Outcome Questionnaire (OQ-45) or Outcome Rating System (ORS) PROMs, which were all conducted in multidisciplinary mental health care or psychological therapy settings, because both primary care studies identified used single symptom outcome measures, which were not directly comparable to the OQ-45 or ORS.Meta-analysis of 12 studies including 3696 participants using these PROMs found no evidence of a difference in outcome in terms of symptoms, between feedback and no-feedback groups (standardised mean difference (SMD) -0.07, 95% confidence interval (CI) -0.16 to 0.01; P value = 0.10). The evidence for this comparison was graded as low quality however, as all included studies were considered at high risk of bias, in most cases due to inadequate blinding of assessors and significant attrition at follow-up.Quality of life was reported in only two studies, social functioning in one, and costs in none. Information on adverse events (thoughts of self-harm or suicide) was collected in one study, but differences between arms were not reported.It was not possible to pool data on changes in drug treatment or referrals as only two studies reported these. Meta-analysis of seven studies including 2608 participants found no evidence of a difference in management of CMHDs between feedback and no-feedback groups, in terms of the number of treatment sessions received (mean difference (MD) -0.02 sessions, 95% CI -0.42 to 0.39; P value = 0.93). However, the evidence for this comparison was also graded as low quality. AUTHORS' CONCLUSIONS: We found insufficient evidence to support the use of routine outcome monitoring using PROMs in the treatment of CMHDs, in terms of improving patient outcomes or in improving management. The findings are subject to considerable uncertainty however, due to the high risk of bias in the large majority of trials meeting the inclusion criteria, which means further research is very likely to have an important impact on the estimate of effect and is likely to change the estimate. More research of better quality is therefore required, particularly in primary care where most CMHDs are treated.Future research should address issues of blinding of assessors and attrition, and measure a range of relevant symptom outcomes, as well as possible harmful effects of monitoring, health-related quality of life, social functioning, and costs. Studies should include people treated with drugs as well as psychological therapies, and should follow them up for longer than six months