Re: Response to Request for Relevant Information on Bisphenol A Dear Ms. Oshita,

Authoritative Bodies Mechanism: Bisphenol-A). The Polycarbonate/BPA Global Group consists of the leading global manufacturers of bisphenol A and polycarbonate plastic, which for many years have supported and conducted scientific research to understand whether bisphenol A has the potential to cause health or environmental effects and to support scientifically sound public policy. As indicated by the signatures at the end of the attachment, the comments were prepare

Atomic-scale structure and properties of highly stable antiphase boundary defects in Fe3O4

The complex and intriguing properties of the ferrimagnetic half metal magnetite (Fe3O4) are of continuing fundamental interest as well as being important for practical applications in spintronics, magnetism, catalysis and medicine. There is considerable speculation concerning the role of the ubiquitous antiphase boundary (APB) defects in magnetite, however, direct information on their structure and properties has remained challenging to obtain. Here we combine predictive first principles modelling with high-resolution transmission electron microscopy to unambiguously determine the three-dimensional structure of APBs in magnetite. We demonstrate that APB defects on the {110} planes are unusually stable and induce antiferromagnetic coupling between adjacent domains providing an explanation for the magnetoresistance and reduced spin polarization often observed. We also demonstrate how the high stability of the {110} APB defects is connected to the existence of a metastable bulk phase of Fe3O4, which could be stabilized by strain in films or nanostructures

Moral enhancement: do means matter morally?

One of the reasons why moral enhancement may be controversial, is because the advantages of moral enhancement may fall upon society rather than on those who are enhanced. If directed at individuals with certain counter-moral traits it may have direct societal benefits by lowering immoral behavior and increasing public safety, but it is not directly clear if this also benefits the individual in question. In this paper, we will discuss what we consider to be moral enhancement, how different means may be used to achieve it and whether the means we employ to reach moral enhancement matter morally. Are certain means to achieve moral enhancement wrong in themselves? Are certain means to achieve moral enhancement better than others, and if so, why? More specifically, we will investigate whether the difference between direct and indirect moral enhancement matters morally. Is it the case that indirect means are morally preferable to direct means of moral enhancement and can we indeed pinpoint relevant intrinsic, moral differences between both? We argue that the distinction between direct and indirect means is indeed morally relevant, but only insofar as it tracks an underlying distinction between active and passive interventions. Although passive interventions can be ethical provided specific safeguards are put in place, these interventions exhibit a greater potential to compromise autonomy and disrupt identity

Abnormal septal convexity into the left ventricle occurs in subclinical hypertrophic cardiomyopathy.

BACKGROUND: Sarcomeric gene mutations cause hypertrophic cardiomyopathy (HCM). In gene mutation carriers without left ventricular (LV) hypertrophy (G + LVH-), subclinical imaging biomarkers are recognized as predictors of overt HCM, consisting of anterior mitral valve leaflet elongation, myocardial crypts, hyperdynamic LV ejection fraction, and abnormal apical trabeculation. Reverse curvature of the interventricular septum (into the LV) is characteristic of overt HCM. We aimed to assess LV septal convexity in subclinical HCM. METHODS: Cardiovascular magnetic resonance was performed on 36 G + LVH- individuals (31 ± 14 years, 33 % males) with a pathogenic sarcomere mutation, and 36 sex and age-matched healthy controls (33 ± 12 years, 33 % males). Septal convexity (SCx) was measured in the apical four chamber view perpendicular to a reference line connecting the mid-septal wall at tricuspid valve insertion level and the apical right ventricular insertion point. RESULTS: Septal convexity was increased in G + LVH- compared to controls (maximal distance of endocardium to reference line: 5.0 ± 2.5 mm vs. 1.6 ± 2.4 mm, p ≤ 0.0001). Expected findings occurred in G + LVH- individuals: longer anterior mitral valve leaflet (23.5 ± 3.0 mm vs. 19.9 ± 3.1 mm, p ≤ 0.0001), higher relative wall thickness (0.31 ± 0.05 vs. 0.29 ± 0.04, p ≤ 0.05), higher LV ejection fraction (70.8 ± 4.3 % vs. 68.3 ± 4.4 %, p ≤ 0.05), and smaller LV end-systolic volume index (21.4 ± 4.4 ml/m(2) vs. 23.7 ± 5.8 ml/m(2), p ≤ 0.05). Other morphologic measurements (LV angles, sphericity index, and eccentricity index) were not different between G + LVH- and controls. CONCLUSIONS: Septal convexity is an additional previously undescribed feature of subclinical HCM

Spectrum of PEX1 and PEX6 variants in Heimler syndrome

Heimler syndrome (HS) consists of recessively inherited sensorineural hearing loss, amelogenesis imperfecta (AI) and nail abnormalities, with or without visual defects. Recently HS was shown to result from hypomorphic mutations in PEX1 or PEX6, both previously implicated in Zellweger Syndrome Spectrum Disorders (ZSSD). ZSSD are a group of conditions consisting of craniofacial and neurological abnormalities, sensory defects and multi-organ dysfunction. The finding of HS-causing mutations in PEX1 and PEX6 shows that HS represents the mild end of the ZSSD spectrum, though these conditions were previously thought to be distinct nosological entities. Here, we present six further HS families, five with PEX6 variants and one with PEX1 variants, and show the patterns of Pex1, Pex14 and Pex6 immunoreactivity in the mouse retina. While Ratbi et al. found more HS-causing mutations in PEX1 than in PEX6, as is the case for ZSSD, in this cohort PEX6 variants predominate, suggesting both genes play a significant role in HS. The PEX6 variant c.1802G>A, p.(R601Q), reported previously in compound heterozygous state in one HS and three ZSSD cases, was found in compound heterozygous state in three HS families. Haplotype analysis suggests a common founder variant. All families segregated at least one missense variant, consistent with the hypothesis that HS results from genotypes including milder hypomorphic alleles. The clinical overlap of HS with the more common Usher syndrome and lack of peroxisomal abnormalities on plasma screening suggest that HS may be under-diagnosed. Recognition of AI is key to the accurate diagnosis of HS

Recurrent respiratory papillomatosis: an overview of current thinking and treatment

Human papillomaviruses (HPV) infection in benign laryngeal papillomas is well established. The vast majority of recurrent respiratory papillomatosis lesions are due to HPV types 6 and 11. Human papillomaviruses are small non-enveloped viruses (>8 kb), that replicate within the nuclei of infected host cells. Infected host basal cell keratinocytes and papillomas arise from the disordered proliferation of these differentiating keratinocytes. Surgical debulking of papillomas is currently the treatment of choice; newer surgical approaches utilizing microdebriders are replacing laser ablation. Surgery aims to secure an adequate airway and improve and maintain an acceptable quality of voice. Adjuvant treatments currently used include cidofovir, indole-3-carbinol, ribavirin, mumps vaccine, and photodynamic therapy. The recent licensing of prophylactic HPV vaccines is a most interesting development. The low incidence of RRP does pose significant problems in recruitment of sufficient numbers to show statistical significance. Large multi-centre collaborative clinical trials are therefore required. Even so, sufficient clinical follow-up data would take several years

The experience of admission to psychiatric hospital among Chinese adult patients in Hong Kong

<p>Abstract</p> <p>Background</p> <p>The paper reports on a study to evaluate the psychometric properties and cultural appropriateness of the Chinese translation of the Admission Experience Survey (AES).</p> <p>Methods</p> <p>The AES was translated into Chinese and back-translated. Content validity was established by focus groups and expert panel review. The Chinese version of the Admission Experience Survey (C-AES) was administered to 135 consecutively recruited adult psychiatric patients in the Castle Peak Hospital (Hong Kong SAR, China) within 48 hours of admission. Construct validity was assessed by comparing the scores from patients admitted voluntarily versus patients committed involuntarily, and those received physical or chemical restraint versus those who did not. The relationship between admission experience and psychopathology was examined by correlating C-AES scores with the Brief Psychiatric Rating Scale (BPRS) scores.</p> <p>Results</p> <p>Spearman's item-to-total correlations of the C-AES ranged from 0.50 to 0.74. Three factors from the C-AES were extracted using factor analysis. Item 12 was omitted because of poor internal consistency and factor loading. The factor structure of the Process Exclusion Scale (C-PES) corresponded to the English version, while some discrepancies were noted in the Perceived Coercion Scale (C-PCS) and the Negative Pressure Scale (C-NPS). All subscales had good internal consistencies. Scores were significantly higher for patients either committed involuntarily or subjected to chemical or physical restrain, independent on severity of psychotic symptoms.</p> <p>Conclusion</p> <p>The Chinese AES is a psychometrically sound instrument assessing the three different aspects of the experience of admission, namely "negative pressure, "process exclusion" and "perceived coercion". The potential of C-AES in exploring subjective experience of psychiatric admission and effects on treatment adherence should be further explored.</p

Critical Limb Ischemia

Critical limb ischemia (CLI), defined as chronic ischemic rest pain, ulcers, or gangrene attributable to objectively proven arterial occlusive disease, is the most advanced form of peripheral arterial disease. Traditionally, open surgical bypass was the only effective treatment strategy for limb revascularization in this patient population. However, during the past decade, the introduction and evolution of endovascular procedures have significantly increased treatment options. In a certain subset of patients for whom either surgical or endovascular revascularization may not be appropriate, primary amputation remains a third treatment option. Definitive high-level evidence on which to base treatment decisions, with an emphasis on clinical and cost effectiveness, is still lacking. Treatment decisions in CLI are individualized, based on life expectancy, functional status, anatomy of the arterial occlusive disease, and surgical risk. For patients with aortoiliac disease, endovascular therapy has become first-line therapy for all but the most severe patterns of occlusion, and aortofemoral bypass surgery is a highly effective and durable treatment for the latter group. For infrainguinal disease, the available data suggest that surgical bypass with vein is the preferred therapy for CLI patients likely to survive 2 years or more, and for those with long segment occlusions or severe infrapopliteal disease who have an acceptable surgical risk. Endovascular therapy may be preferred in patients with reduced life expectancy, those who lack usable vein for bypass or who are at elevated risk for operation, and those with less severe arterial occlusions. Patients with unreconstructable disease, extensive necrosis involving weight-bearing areas, nonambulatory status, or other severe comorbidities may be considered for primary amputation or palliative measures

“Having diabetes shouldn’t stop them”: healthcare professionals’ perceptions of physical activity in children with Type 1 diabetes

Background Healthcare professionals (HCP) working with children who have Type 1 Diabetes Mellitus (T1DM) have an important role in advising about and supporting the control of blood glucose level in relation to physical activity. Regular physical activity has known benefits for children with T1DM, but children with chronic conditions may face barriers to participation. The perceptions of HCPs were explored in an effort to understand what influences physical activity in children with T1DM and to inform the practice of those working with children who have T1DM. Methods Semi-structured interviews with 11 HCPs involved in the care of children with T1DM in the UK were conducted. Interviews were recorded, transcribed verbatim and data were analysed using thematic analysis. Results The factors perceived to influence participation in physical activity are presented as five major themes and eleven sub-themes. Themes included the positive influence of social support, the child’s motivation to be active, the potential for formal organisations such as school and diabetes clinic to support physical activity, the challenges faced by those who have T1DM and the perceived barriers to HCPs fulfilling their role of promoting physical activity. Conclusions Healthcare professionals recognised their role in helping children with T1DM and their parents to incorporate physical activity into diabetes management and everyday life, but perceived barriers to the successful fulfilment of this role. The findings highlight the potential for clinical and non-clinical supportive systems to be sensitive to these challenges and facilitate children’s regular participation in physical activity