Miracle-dz/UniFAR-FTUs huggingface dataset:
Sensitive Periods for the Effect of Childhood Adversity on DNA Methylation: Results From a Prospective, Longitudinal Study

Background Exposure to “early life” adversity is known to predict DNA methylation (DNAm) patterns that may be related to prolonged psychiatric risk. However, few studies have investigated whether adversity has time-dependent effects based on the age at exposure. Methods Using a two-stage structured life course modeling approach (SLCMA), we tested the hypothesis that there are sensitive periods when adversity induced greater DNAm changes. We tested this hypothesis in relation to two alternative explanations: an accumulation hypothesis, in which the effect of adversity on DNAm increases with the number of occasions exposed, regardless of timing, and a recency model, in which the effect of adversity is stronger for more proximal events. Data came from the Accessible Resource for Integrated Epigenomics Studies (ARIES), a subsample of mother-child pairs from the Avon Longitudinal Study of Parents and Children (ALSPAC; n=670-776). Results After covariate adjustment and multiple testing correction, we identified 40 CpG sites that were differentially methylated at age 7 following exposure to adversity. Most loci (n=32) were predicted by the timing of adversity, namely exposures during infancy. Neither the accumulation nor recency of the adversity explained considerable variability in DNAm. A standard EWAS of lifetime exposure (vs. no exposure) failed to detect these associations. Conclusions The developmental timing of adversity explains more variability in DNAm than the accumulation or recency of exposure. Infancy appears to be a sensitive period when exposure to adversity predicts differential DNAm patterns. Classification of individuals as exposed vs. unexposed to “early life” adversity may dilute observed effects.
Observational Study of Helmet Use Among Children Skiing and Snowboarding

Objectives: The objectives of this study were to observe the use of helmets among school-age children while skiing and snowboarding and to determine factors that influenced helmet use in children. Methods: This was a prospective observational study. Children estimated to be school age (5-17 years of age) were observed at a Western New York area ski resort as they entered ski areas. Data collected included estimated age, helmet use, sex, sport, and whether the children were accompanied by adults or other children or were alone. Results: During February 2005, a total of 1472 children were observed. Thirty-seven percent wore a helmet. Helmets were worn by 42% of skiers and 32% of snowboarders. Sixty percent of children wore helmets when observed with an adult, compared with 28% when observed with other children. Those children on beginner slopes (47%) were more likely to wear helmets than those on intermediate slopes (34%). There was no difference in helmet use among males and females. Conclusions: Despite recommendations for children to wear helmets while participating in winter sports, about a third of the children observed wore a helmet. Children skiing, younger children, and children on beginner slopes were more likely to wear helmets. Future studies are needed to determine if the use of helmets would decrease the incidence of head injuries while skiing and snowboarding.
Acoustic quantification of /i/-/I/ overlap in children 21 to 33 months

This longitudinal investigation examined the temporal and spectral characteristics of the high front vowels /i/ and /I/ as produced by nine monolingual US English children from 21–33 months. Vowel overlap was quantified in two-dimensional (F1, F2) and three-dimensional (F1, F2, duration) space using Spectral Overlap Assessment Measure (SOAM). These findings were compared with the results from Support Vector Machine (SVM) vowel classification, vowel duration ratios, and measures of effect size, to determine whether a spectral/temporal trading effect existed in the early vowel productions of young children. Children between the ages of 21 and 33 months are highly variable in the way they use spectral and temporal parameters to distinguish between these two adjacent vowels. However, findings pointed to the existence of a spectral/temporal trading effect when spectral overlap values are relatively high (>60%) at 21 and 24 months of age.
Alpha (v) integrins license regulatory T cells to apoptotic cells and self‐associated antigens

Defects in apoptotic cell clearance are thought to contribute to autoimmunity by failure to induce tolerance, coupled with accumulation of immunogenic material. However, little is known about the contribution of apoptosis to immune responses at mucosal sites, where regulatory T cells (Treg cells) and other immune cells play an essential active role in maintaining tolerance to self‐associated antigens. In recent studies, we have found that αv integrins have an important role in apoptotic cell phagocytosis and induction of Treg cells in the intestine, and deletion of αv from myeloid cells causes colitis associated with failed apoptotic cell removal and loss of Treg cells. Our data show that activation of transforming growth factor (TGF)‐β by αvβ8 on dendritic cells (DCs) is essential for generating Treg cells and inducing mucosal tolerance. These results provide a mechanism by which tolerance to apoptotic cell–derived and –associated antigens is maintained by DC “licensing” at sites of high TGF‐β expression.
Assessment and treatment of musculoskeletal tension in hyperfunctional voice disorders

Poorly regulated activity of the perilaryngeal muscles affects phonatory function and contributes to a class of disorders known as hyperfunctional or musculoskeletal tension voice disorders. Recognizing the signs and symptoms of excess or dysregulated laryngeal muscle activity is critical to proper diagnosis and selection of appropriate treatment(s). Although numerous approaches exist to manage such hyperfunctional syndromes, manual circumlaryngeal techniques have recently received attention as valuable tools in both assessment and treatment. Therefore, the purpose of this article is to: (1) describe common phenomenological features of dysregulated laryngeal muscle tension, thereby facilitating its recognition, (2) highlight the role of manual circumlaryngeal techniques in assessment and management, (3) survey additional treatment approaches for laryngeal hyperfunction, and explore the evidence to support their effectiveness, and (4) identify unresolved issues and controversies surrounding tension-based voice disorders. A series of pre- and post-treatment audio examples are provided on the journal website at www.informaworld. com/ijslp.
G207 Is There a Link Between ADHD and Social Deprivation?

Aim Attention Deficit Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder that affects approximately 4–6% of school-aged children. Research into the aetiology of ADHD has focussed on genetic and biological factors, with much less information on environment and social aspects. There is a general perception that ADHD is linked to deprivation, but there are not enough studies in literature to prove or disprove this assumption. The aim of this study was to investigate the relationship between social deprivation and ADHD. Method We included all patients diagnosed with ADHD by the community paediatric department (only those on medications). Postcodes of these patients were used to produce deprivation scores, which included overall deprivation and sub-scores for income, social and housing factors. Indices of Deprivation 2010 are available for 32,482 small geographical areas (Lower Super Output Areas, LSOAs) in England, ranked from 1 (most deprived) to 32,482 (least deprived). These are further divided into fifths to produce English deprivation quintiles. Each postcode was then allocated to a quintile based on their deprivation score, where quintile 1 represents the most deprived. Results A total of 144 patients diagnosed with ADHD were being treated with medication. The male to female ratio was 4.5:1 (M: F). The deprivation scores were calculated and it showed that 64 patients (44.4%) were in the most deprived quintile (quintile 1), and followed in a relatively linear pattern. A similar pattern was seen for income, crime, employment, education, skills and training domain and health deprivation and disability, where 69, 57, 74, 69 and 59 patients were placed in quintile 1, respectively. Conclusion Our study shows an association between the prevalence of ADHD in children and deprivation index. Also there is clear link between sub scores for income, crime, employment, education, skills and training domain and health deprivation and disability and prevalence of ADHD. Indices of deprivation could be used to predict the expected prevalence of ADHD within the community and thus plan allocation of resources. Ours is a small sample size, but results support further investigation with a larger study.
Depression in Resident Physicians: A Systematic Review

Objective: To complete a systematic review of the literature addressing major depression in resident physicians. Methods: In 2013, the authors completed a systematic review of articles addressing major depression in physicians in United States residency programs. The following keywords were used: anxiety, stress, and mood, medical residents or interns, physician residents, graduate medical education, depression, stress or anxiety, and suicide. Results: The prevalence of depression in resident physicians is higher than that of the general population. Many sociodemographic and residency-associated factors have been studied in their relation to resident physician depression. Only physical health, an unhappy childhood, and stress at work were found to have association with depression, while the amount of call, lifestyle, age, income, and season of the year were not associated with depression. Other factors had an equivocal relationship. Depression in resident physicians is associated with medical errors, decreased ability to handle work-related stress, leaves of absence, discontinuation of medical training, disruption in personal lives, and suicide. Intervention with treatment for depression, using a low-cost, confidential, off-campus program, was successful. However, physicians may hesitate to seek treatment for mental illness because of the professional consequences, such as difficulty with medical licensing, hospital privileges, and malpractice insurance. Conclusions: Major depression is common in resident physicians in the United States. It has a negative impact on the lives of the doctors and the patients whom they treat. There appear to be effective ways of assisting residents with major depression available to training programs.
Speech and nonspeech: What are we talking about?

Abstract Understanding of the behavioural, cognitive and neural underpinnings of speech production is of interest theoretically, and is important for understanding disorders of speech production and how to assess and treat such disorders in the clinic. This paper addresses two claims about the neuromotor control of speech production: (1) speech is subserved by a distinct, specialised motor control system and (2) speech is holistic and cannot be decomposed into smaller primitives. Both claims have gained traction in recent literature, and are central to a task-dependent model of speech motor control. The purpose of this paper is to stimulate thinking about speech production, its disorders and the clinical implications of these claims. The paper poses several conceptual and empirical challenges for these claims – including the critical importance of defining speech. The emerging conclusion is that a task-dependent model is called into question as its two central claims are founded on ill-defined and inconsistently applied concepts. The paper concludes with discussion of methodological and clinical implications, including the potential utility of diadochokinetic (DDK) tasks in assessment of motor speech disorders and the contraindication of nonspeech oral motor exercises to improve speech function.
Antiproliferative effects of AVN944, a novel inosine 5‐monophosphate dehydrogenase inhibitor, in prostate cancer cells

Inosine 5‐monophosphate dehydrogenase II, a key enzyme in the de novo synthesis of purine nucleotides, is expressed in prostate tumors and prostate cancer cells. AVN944 is a new, specific, noncompetitive IMPDH inhibitor. In this study, we investigated the effects of IMPDH inhibitor AVN944 on LNCaP, CWR22Rv1, DU145 and PC‐3 human prostate cancer cells. AVN944 inhibited proliferation of these 4 prostate cancer cell lines and was associated with cell cycle G1 arrest of LNCaP cells and S‐phase block of androgen‐independent CWR22Rv1, DU145 and PC‐3 cells. AVN944 induced caspase‐dependentand caspase‐independent cell death in LNCaP, CWR22Rv1, and DU145 cells. AVN944 induced expression of p53‐target proteins Bok, Bax and Noxa in androgen‐responsive cell lines and suppressed expression of survivin in prostate cancer cells regardless of their androgen sensitivity. AVN944 also induced differentiation of androgen‐independent prostate cancer cells as indicated by morphological changes and increased expression of genes coding for prostasomal proteins, keratins and other proteins, including tumor suppressor genes MIG‐6 and NDRG1. AVN944‐differentiated androgen‐independent DU145 and PC‐3 cells are sensitized to TRAIL‐induced apoptosis as demonstrated by induction of caspases and PARP cleavage. In summary, AVN944 inhibited the growth of human prostate cancer cells by inducing cell cycle arrest, cell death as well as differentiation. AVN944 is a novel, promising therapeutic agent that might be combined with other agents for treatment of human prostate cancer. © 2008 Wiley‐Liss, Inc.
Reference values of maximum performance tests of speech production

Abstract Purpose: Maximum performance tests examine upper limits of speech motor performance, as used by speech-language pathologists in dysarthria assessment protocols. The Radboud Dysarthria Assessment includes maximum repetition rate, maximum phonation time, fundamental frequency range and maximum phonation volume to assist in detecting pathological performance. This study aims to obtain reference values for each of these tests. Method: A group of 224 healthy Dutch adults aged 18–80 years performed the maximum performance tests. Age, sex, body height, smoking habit, and profession were registered. Using multivariable linear regression, a wide range of models was tested to examine the relationship between these person characteristics and speech performance. The likelihood ratio was used to test the goodness of fit to the data. Result: Above 60 years of age, maximum repetition rate, fundamental frequency range and maximum phonation volume were all negatively affected by age. Below 60 years, only women showed effects of age on fundamental frequency range (increase) and maximum phonation volume (decrease). Maximum phonation time was primarily related to body height (increase). Conclusion: This study presents reference values of four maximum performance tests for comparing the performance of dysarthric patients with non-pathological performance. Age was identified as most important factor influencing maximum speech performance.
From individual to global: Human rights and aphasia

Abstract This commentary marks the 70th anniversary of the Universal Declaration of Human Rights by examining Article 19 and its application to people with aphasia. This group of people still face lack of access, stigmatisation, exclusion, disadvantage and social withdrawal as well as poor public awareness of aphasia and inadequate prioritisation of support and resources. Nevertheless, a range of creative initiatives at individual, healthcare, local community, national and global levels have helped to connect and empower people with aphasia. Such initiatives include provision of accessible information in a range of media, inclusion of people with aphasia in decision-making and as research partners, awareness raising campaigns to counter attitudinal barriers, organisation of community aphasia groups, development of guidelines for best practice, national aphasia associations and international collaborations such as Aphasia United. While ongoing work and resourcing is needed to expand these efforts further, they have helped people with aphasia to be heard and to protect their sense of dignity which underlies human rights. A human rights approach can unite, politicise and refocus these efforts, and highlight the essential role of communication in fostering a better quality of life.
Chemoresistant tumor cell lines display altered epidermal growth factor receptor and HER3 signaling and enhanced sensitivity to gefitinib

Deregulated signaling through the epidermal growth factor receptor (EGFR) is involved in chemoresistance. To identify the molecular determinants of sensitivity to the EGFR inhibitor gefitinib (Iressa, ZD1839) in chemoresistance, we compared the response of matched chemosensitive and chemoresistant glioma and ovarian cancer cell lines. We found that chemoresistant cell lines were 2‐ to 3‐fold more sensitive to gefitinib growth‐inhibitory effects, because of decreased proliferation rather than survival. Sensitivity to gefitinib correlated with overexpression and constitutive phosphorylation of HER2 and HER3, but not EGFR, altered HER ligand expression, and enhanced activation of EGF‐triggered EGFR pathway. No activating mutations were found in EGFR. Gefitinib fully inhibited EGF‐induced and constitutive Akt activation only in chemoresistant cells. In parallel, gefitinib downregulated constitutively phosphorylated HER2 and HER3, and activated GSK3β with a concomitant degradation of cyclin D1. Ectopically overexpressed HER2 on its own was insufficient to sensitize chemonaive cells to gefitinib. pHER3 coimmunoprecipitated with p85‐PI3K in chemoresistant cells and gefitinib dissociated these complexes. siRNA‐mediated inhibition of HER3 decreased constitutive activation of Akt and sensitivity to gefitinib in chemoresistant cells. Our study indicates that in chemoresistant cells gefitinib inhibits both an enhanced EGF‐triggered pathway and a constitutive HER3‐mediated Akt activation, indicating that inhibition of HER3 together with that of EGFR could be relevant in chemorefractory tumors. Furthermore, in combination experiments gefitinib enhanced the effects of coadministered drugs more in chemoresistant than chemosensitive ovarian cancer cells. Combined treatment might be therapeutically beneficial in chemoresistant tumors from ovary and likely from other tissues. © 2008 Wiley‐Liss, Inc.
Modeling the evolution of cortico‐cerebellar systems in primates

Although it is commonly accepted that brains work as functionally distributed systems in which interconnected structures work together in processing particular types of information, few studies have investigated the evolution of functionally specialized neural systems across many different lineages. MR‐related research has provided in‐depth information on connectivity patterns, but because of its focus on particular species, it has given only indicative clues about evolutionary patterns shaping brain organization across primates. Here, we combine depth with breadth of analysis by investigating patterns of covarying size evolution in substructures of the cortico‐cerebellar system across 19 anthropoid species spanning 35 million years of divergent evolution. Results demonstrate two distinct patterns of size covariation in substructures of the cortico‐cerebellar system, suggesting neural systems involving profuse cortico‐cerebellar connections are a major factor in explaining the evolution of anthropoid brain organization. We set out an evolutionary model of relative cortico‐cerebellar expansion and provide a detailed picture of its branch‐specific evolutionary history suggesting the ape radiation is the clade with the strongest and most consistent evolutionary history in relative (frontal) cortico‐cerebellar expansion.
Genetic variation in SIPA1 in relation to breast cancer risk and survival after breast cancer diagnosis

Genetic variation in SIPA1, signal‐induced proliferation‐associated gene 1, has been proposed to be associated with aggressive breast tumor characteristics related to metastasis and worse prognosis in humans and rodents. To test this hypothesis, we genotyped 3 single nucleotide polymorphisms (SNP) located at −3092 (AT, rs3741378), and exon 14 + 14 (C>T, rs746429), and examined them in relation to breast cancer risk and overall survival, stratified by tumor characteristics in 2 independent case–control studies conducted in Poland (1,995 cases, 2,296 controls) and in Britain (2,142 cases, 2,257 controls). Vital status (n = 396 deaths) was available for 911 Polish and 1,919 British breast cancer cases with an average follow‐up time of 5.5 years. Overall, we found no significant associations between genetic variants of SIPA1 SNPs and breast cancer risk (per allele odds ratios, 95% confidence intervals (CI): rs931127–0.99, 0.93–1.06; rs3741378–1.03, 0.94–1.13; and, rs74642–0.98, 0.92–1.04). In both studies, SIPA1 polymorphisms were not related to overall mortality (per allele hazard ratios, 95% CI: 1.02, 0.88–1.17; 0.90, 0.72–1.11; 1.04, 0.90–1.21, respectively). Our results do not support a relationship between SIPA1 polymorphisms and breast cancer risk or subsequent survival. Published 2008 Wiley‐Liss, Inc.
A Simple Case of a Small Elbow Effusion

An 11-month-old child presented with what initially appeared to be 2 simple problems, a small elbow effusion followed 1 week later by croup. This case history is presented to remind emergency medicine physicians of the importance of index of suspicion and recognition of the difference between common events occurring in a normal host versus common events occurring in an abnormal host.
Explaining mirror-touch synesthesia

Mirror-touch synesthesia (MTS) is the conscious experience of tactile sensations induced by seeing someone else touched. This paper considers two different, although not mutually exclusive, theoretical explanations and, in the final section, considers the relation between MTS and other forms of synesthesia and also other kinds of vicarious perception (e.g., contagious yawning). The Threshold Theory explains MTS in terms of hyper-activity within a mirror system for touch and/or pain. This offers a good account for some of the evidence (e.g., from fMRI) but fails to explain the whole pattern (e.g., structural brain differences outside of this system; performance on some tests of social cognition). The Self-Other Theory explains MTS in terms of disturbances in the ability to distinguish the self from others. This can be construed in terms of over-extension of the bodily self in to others, or as difficulties in the control of body-based self-other representations. In this account, MTS is a symptom of a broader cognitive profile. We suggest this meets the criteria for synesthesia, despite the proximal causal mechanisms remaining largely unknown, and that the tendency to localize vicarious sensory experiences distinguishes it from other kinds of seemingly related phenomena (e.g., non-localized affective responses to observing pain).