An Energy Performance Evaluation of Commercially Available Window Glazing in Darwin’s Tropical Climate

A total of 40% of the world’s energy produced is utilized to maintain thermal comfort for the occupants of the building. Governments are taking measures collectively to regulate energy efficient buildings to reduce carbon emissions globally. Windows account for more than half of total energy losses in the buildings. The employment of energy efficient glazing in the construction industry is not common in Australia. This paper investigates several types of commercially available windows and their effectiveness in the hot and humid climate of Darwin. Although extensive literature is available for cold regions, these windows have not been studied in hot and humid climates such as the climate in Darwin. Building cooling loads of an academic building were calculated using Autodesk Revit Architecture and Carrier HAP. Double glazed variants offered approximately a 5% reduction in cooling loads and had a payback period of nearly 7 to 9 years, depending on the type of gas used to fill the pane cavity. The results indicate that triple glazed, or aerogel-based windows will provide about 11–12 % of energy saving in cooling loads. These can be a viable alternative and have a payback period of 11 years, while their average service life expectancy is 30 years. It was found that the feasibility of efficient glazing depends on market price, building usage, and energy efficiency of an overall building envelope

Efficacy and Safety of Alemtuzumab Through 9 Years of Follow-up in Patients with Highly Active Disease: Post Hoc Analysis of CARE-MS I and II Patients in the TOPAZ Extension Study

Background: Alemtuzumab efficacy versus subcutaneous interferon-β-1a (SC IFNB-1a) was demonstrated over 2 years in patients with relapsing-remitting multiple sclerosis, with continued efficacy over 7 additional years. Alemtuzumab is included as a recommended treatment for patients with highly active disease (HAD) by the American Academy of Neurology Practice Guidelines, and the label indication in Europe was recently restricted to the treatment of HAD patients. There is currently no consensus definition for HAD, and alemtuzumab efficacy across various HAD definitions has not been explored previously. Objectives: In this post hoc analysis, we assess the efficacy and safety of alemtuzumab in Comparison of Alemtuzumab and Rebif® Efficacy in Multiple Sclerosis (CARE-MS) trial patients who met criteria for at least one of four separate definitions of HAD (one primary and three alternatives). Over 2 years, alemtuzumab-treated HAD patients were compared with SC IFNB-1a-treated HAD patients, with additional 7-year follow-up in patients from the alemtuzumab arm. Methods: Patients in the CARE-MS studies received either alemtuzumab (baseline: 5 days; 12 months later: 3 days) or SC IFNB-1a (3 times weekly). Alemtuzumab-treated patients who enrolled in the extensions could receive additional courses ≥ 12 months apart. Four definitions of HAD were applied to assess alemtuzumab efficacy: the pre-specified primary definition (two or more relapses in the year prior to baseline and at least one gadolinium [Gd]-enhancing lesion at baseline) and three alternative definitions that focused on relapse, magnetic resonance imaging (MRI), or prior treatment response criteria. Efficacy outcomes were annualized relapse rate, change in Expanded Disability Status Scale score, 6-month confirmed disability worsening, 6-month confirmed disability improvement, MRI disease activity, and brain volume change. Adverse events were summarized for HAD patients meeting the primary definition. Results: In the pooled CARE-MS population, 208 alemtuzumab-treated patients met the primary HAD definition. Annualized relapse rate was 0.27 in years 0–2 and 0.16 in years 3–9. Over 9 years, 62% of patients were free of 6-month confirmed disability worsening, 50% had 6-month confirmed disability improvement, and median cumulative change in brain volume was − 2.15%. During year 9, 62% had no evidence of disease activity, and 69% were free of MRI disease activity. Similar efficacy outcomes were observed using an alternative relapse-driven HAD definition. For patients meeting alternative HAD definitions focused on either higher MRI lesion counts or disease activity while on prior therapy, reduced efficacy for some endpoints was seen. Safety was consistent with the overall CARE-MS population through year 9. Conclusions: Over 9 years, alemtuzumab efficacy was maintained in CARE-MS HAD patients based on four HAD definitions. These results support intervention with alemtuzumab in patients with early indicators of HAD, including frequent relapse without high MRI activity. No safety signals were observed over 9 years that were unique to the HAD populations. ClinicalTrials.gov Identifiers: NCT00530348; NCT00548405; NCT00930553; NCT02255656

Use of multiple strategies to understand the complex genetic architecture of ADHD

Attention-Deficit/Hyperactivity Disorder (ADHD) is a highly prevalent, clinically heterogeneous neurodevelopmental disorder with a complex etiology implicating both genetic and environmental factors. Although it is well accepted that multiple genes are involved in the pathophysiology of ADHD, no genetic risk variants have been identified beyond doubt. In addition, environmental factors, including, maternal smoking and maternal exposure to stress during pregnancy have been consistently associated with this disorder.This thesis will describe multiple genetic strategies that may help reduce the "clinical heterogeneity" and "etiological complexity" of ADHD phenotype facilitating the identification of genetic variants, which may help, in dissecting pathways to the disorder.1. By using the "endophenotypes" approach and selecting COMT gene, which is firmly implicated in the modulation of brain catecholamines, we found a tentative association between Catechol-O-Methyltransferase alleles/haplotypes and the modulation of Executive Functions in ADHD children.2. We used "gene/environment interplay" i.e. stratifying ADHD children based on exposure to maternal smoking during pregnancy and maternal stress during pregnancy and investigated the implication of latrophilin3 gene LPHN3, a candidate gene consistently shown to be involved in ADHD (based on linkage studies, and candidate association studies) in increasing the risk for ADHD. This approach allowed the uncovering of differential associations between single nucleotide polymorphisms (SNPs) within the LPHN3 and a number of endophenotypes in patients according to their exposure to maternal stress during pregnancy.3. "Comorbidity" with obesity was employed as a tool to index a more homogenous subgroup of ADHD children and facilitate the identification of genetic variants implicate in ADHD. Using this scheme, we comprehensively (behaviorally and clinically) characterized children with ADHD in relation to their BMI/weight categories. We showed that, self-regulation deficits, usually hypothesized to mediate obesity in children with ADHD, are not more present in children with ADHD and obesity compared to the non-obese ADHD children. Furthermore, in a group of children not exposed to maternal smoking during pregnancy, we observed a novel association between ADHD pertinent phenotypes and a Fat Mass and Obesity (FTO) gene polymorphism that has been strongly associated to obesity by genome-wide association studies (GWAS). In summary, this research work demonstrates the usefulness of multiple strategies to reduce the clinical heterogeneity and etiological complexity of ADHD which may facilitate identification of genetic risk variants and the interaction of these with environmental factors. This in turn may help in elucidating the pathophysiology of ADHD.Le trouble déficit de l'attention avec hyperactivité (TDAH) est un trouble neurodéveloppemental très répandu, ayant une présentation clinique hétérogène et une étiologie complexe impliquant des facteurs génétiques et environnementaux. Bien qu'il soit généralement admis que plusieurs gènes sont impliqués dans la physiopathologie du TDAH, aucune variante génétique augmentant le risque n'a été identifiée avec certitude. En outre, les facteurs environnementaux, y compris, le tabagisme maternel et l'exposition maternelle au stress pendant la grossesse ont été systématiquement associés à ce trouble. Cette thèse décrira comment l'utilisation de stratégies multiples mettant à profit les données épidémiologiques peut aider à réduire "l'hétérogénéité clinique" et la "complexité étiologique" du TDAH. Ces stratégies facilitent l'identification des variantes génétiques, qui à leur tour peuvent aider à disséquer les différentes trajectoires physiopathologiques conduisant au TDAH.1. En utilisant l'approche des "endophénotypes" cognitifs, et en sélectionnant le gèneCOMT (Catéchol-O-Méthyltransferase) qui est impliqué dans le métabolisme des neuroamines, nous avons identifié une association entre les allèles/haplotypes de ce gène et la modulation des certaines fonctions exécutive (EF) chez les enfants ayant le TDAH.2. Nous avons utilisé "la stratification" des enfants ayant le TDAH en fonction de l'exposition au tabagisme et au stress maternel pendant la grossesse pour investiguer l'implication du gène LPHN3, un gène candidat impliqués dans le TDAH (sur la base d'études de liaison et d'association). Cette stratégie a permis la découverte d'associations différentielles entre des polymorphismes (SNP) du gène LPHN3 et un certain nombre d'endophénotypes chez les patients en fonction de leur exposition au stress maternel pendant la grossesse.3. Enfin, nous avons utilisé la "comorbidité" fréquemment rapporté entre obésité etTDAH comme un outil pour indexer un sous-groupe plus homogène d'enfants TDAH et faciliter l'identification des variantes génétiques communes au TDAH et à l'obésité. Nous avons comparé des enfants atteints de TDAH catégorisés selon leur Indice de masse corporelle (IMC)/catégories de poids par rapport à leurs caractéristiques comportementales et cliniques. Nous avons montré que les déficits d'autorégulation, une hypothèse souvent avancée pour expliquer la grand prévalence de l'obésité chez les enfants TDAH, ne sont pas associés avec l'obésité observées chez les enfants TDAH. Dans un deuxième temps, nous avons exploré l'association entre des phénotypes pertinents au TDAH et un gène hautement impliqué dans la régulation de la masse adipeuse appelé FTO. Nous avons identifié une association hautement significative entre ce gène et un grands nombre de traits pertinent pour le TDAH, particulièrement chez les enfants qui n'out pas été exposés au tabagisme au cours de la grossesse.En conclusion, ce travail suggère que l'utilisation de plusieurs stratégies visant à réduire "l'hétérogénéité clinique" et "La complexité étiologique" du TDAH peuvent faciliter l'identification des variantes de risques génétiques et l'interaction de celles-ci avec les facteurs environnementaux, ce qui à son tour peut aider à élucider les mécanismes neurobiologiques qui mènent au TDAH

Catechol-O-Methyltransferase (COMT) Val 108158 Met polymorphism and ADHD : pharmaco-behavioural genetic and neurocognitive study

The catechol-O-methyltransferase (COMT) gene is the predominant means of dopamine deactivation within the prefrontal cortex (PFC), a brain locus implicated in Attention deficit/hyperactivity disorder (ADHD). Dopamine dysregulation is a significant contributor to the pathophysiology of ADHD and Methylphenidate (MPH), an effective treatment for ADHD, and acts at least in part, through modulation of dopamine levels in the PFC. Thus, we tested the hypothesis that the Catechol-O-Methyltransferase (COMT) Val108/158 Met polymorphism modulates behavioral dimensions relevant for ADHD and/or response of these behavioral dimensions to MPH and/or neuropsychological functions considered relevant for ADHD. No genotype or genotype by treatment interaction effects were observed for behavioral response to MPH. No genotype effects were observed using the family-based approach. Marginal genotype effects were observed between the Met/Met genotype and some but not all aspects of executive functioning. Overall, these results do not support the implication of the COMT Val108/158 Met polymorphism in ADHD, ADHD relevant behaviours or response to methylphenidate, but weakly implicate COMT gene in some aspects of executive functions in children with ADHD. Given that gene effects on behaviours are likely to be very small, a much large sample would be needed in order to establish these results, both negative and positive, with better confidence

Comprehensive phenotype/genotype analyses of the norepinephrine transporter gene (SLC6A2) in ADHD: relation to maternal smoking during pregnancy.

Despite strong pharmacological evidence implicating the norepinephrine transporter in ADHD, genetic studies have yielded largely insignificant results. We tested the association between 30 tag SNPs within the SLC6A2 gene and ADHD, with stratification based on maternal smoking during pregnancy, an environmental factor strongly associated with ADHD.Children (6-12 years old) diagnosed with ADHD according to DSM-IV criteria were comprehensively evaluated with regard to several behavioral and cognitive dimensions of ADHD as well as response to a fixed dose of methylphenidate (MPH) using a double-blind placebo controlled crossover trial. Family-based association tests (FBAT), including categorical and quantitative trait analyses, were conducted in 377 nuclear families.A highly significant association was observed with rs36021 (and linked SNPs) in the group where mothers smoked during pregnancy. Association was noted with categorical DSM-IV ADHD diagnosis (Z=3.74, P=0.0002), behavioral assessments by parents (CBCL, P=0.00008), as well as restless-impulsive subscale scores on Conners'-teachers (P=0.006) and parents (P=0.006). In this subgroup, significant association was also observed with cognitive deficits, more specifically sustained attention, spatial working memory, planning, and response inhibition. The risk allele was associated with significant improvement of behavior as measured by research staff (Z=3.28, P=0.001), parents (Z=2.62, P=0.009), as well as evaluation in the simulated academic environment (Z=3.58, P=0.0003).By using maternal smoking during pregnancy to index a putatively more homogeneous group of ADHD, highly significant associations were observed between tag SNPs within SLC6A2 and ADHD diagnosis, behavioral and cognitive measures relevant to ADHD and response to MPH. This comprehensive phenotype/genotype analysis may help to further understand this complex disorder and improve its treatment. Clinical trial registration information - Clinical and Pharmacogenetic Study of Attention Deficit with Hyperactivity Disorder (ADHD); www.clinicaltrials.gov; NCT00483106

NNALS A A critique of the literature on etiology of eating disorders

AbstRACt The development of eating disorders including anorexia nervosa, bulimia nervosa, binge eating disorder, and atypical eating disorders that affect many young women and even men in the productive period of their lives is complex and varied. While numbers of presumed risk factors contributing to the development of eating disorders are increasing, previous evidence for biological, psychological, developmental, and sociocultural effects on the development of eating disorders have not been conclusive. Despite the fact that a huge body of research has carefully examined the possible risk factors associated with the eating disorders, they have failed not only to uncover the exact etiology of eating disorders, but also to understand the interaction between different causes of eating disorders. This failure may be due complexities of eating disorders, limitations of the studies or combination of two factors. In this review, some risk factors including biological, psychological, developmental, and sociocultural are discussed

Body weight and ADHD: examining the role of self-regulation.

Attention-Deficit/Hyperactivity Disorder (ADHD) is a complex and heterogeneous childhood disorder that often coexists with other psychiatric and somatic disorders. Recently, a link between ADHD and body weight dysregulation has been reported and often interpreted as impaired self-regulation that is shared between the two conditions. The objective of this study is to investigate the relation between body weight/BMI and cognitive, emotional and motor characteristics in children with ADHD.284 ADHD children were stratified by weight status/BMI according to WHO classification and compared with regard to their neurocognitive characteristics, motivational style, and motor profile as assessed by a comprehensive battery of tests. All comparisons were adjusted for demographic characteristics of relevance including, socioeconomic status (SES).Both Obese and overweight ADHD children exhibited significantly lower SES compared to normal weight ADHD children. No significant differences were observed between the three groups with regards to their neurocognitive, emotional and motor profile.Our findings provide evidence that differences in weight/BMI are not accounted for by cognitive, motivational and motor profiles. Socio-economic characteristics are strongly associated with overweight and obesity in ADHD children and may inform strategies aimed at promoting healthier weight

Linkage disequilibrium between <i>SLC6A2</i> markers.

<p>Five SNPs towards the 5′end of <i>SLC6A2</i> (rs41154, rs187714, rs4783899, rs2397771, rs192303) are in strong linkage disequilibrium (LD) with rs36021. LD = linkage disequilibrium</p

Association between <i>SLC6A2</i> SNPs and ADHD cognitive dimensions in the sample where mothers did not smoke during pregnancy.

<p>WISC = Wechsler Intelligence Scale, SOPT = Self-Ordered Pointing Task, FW = Finger Windows, CPT = Continuous Performance Test, SE = standard error, RT = reaction time, ISI = inter-stimulus interval, WCST = Wisconsin Card Sorting Test, TOL = Tower of London.</p><p>Standard scores were used for all WCST and TOL measures, and T-scores were used for CPT measures (excl. overall index).</p><p>Three major haplotype blocks in <i>SLC6A2</i> are depicted above: Block 1 (rs1362621, rs2397771, rs168924, rs2242446, rs3785143, rs192303, rs41154); Block 2 (rs36017, rs10521329, rs3785155, rs5564, rs11568324, rs2279805, rs8047672, rs5569, rs998424, rs36009); and Block 3 (rs1800887, rs2242447, rs15534).</p><p>Significance (p) value ranges are depicted as follows: For OVER-TRANSMISSION of alleles = <b>+4</b> (≤0.00001), <b>+3</b> (0.0001–0.0009), <b>+2</b> (0.001–0.009), and <b>+1</b> (0.01–0.049).</p><p>For UNDER-TRANSMISSION of alleles = −<b>4</b> (≤0.00001), −<b>3</b> (0.0001–0.0009), −<b>2</b> (0.001–0.009) and −<b>1</b> (0.01–0.049).</p

Association between <i>SLC6A2</i> SNPs and ADHD behavioural dimensions in the group where mothers smoked during pregnancy (MSDP).

<p>ADHD = Attention-Deficit/Hyperactivity Disorder, DISC = Diagnostic Interview Schedule for Children, ODD = Oppositional Defiant Disorder, CD = Conduct Disorder, CBCL = Child Behaviour Checklist, Conners’ P = Conners’ Parents, Conners’ T = Conners’ Teachers, RI = Restless-Impulsive, EL = Emotional Lability.</p><p>Three major haplotype blocks in <i>SLC6A2</i> are depicted above: Block 1 (rs1362621, rs2397771, rs168924, rs2242446, rs3785143, rs192303, rs41154); Block 2 (rs36017, rs10521329, rs3785155, rs5564, rs11568324, rs2279805, rs8047672, rs5569, rs998424, rs36009); and Block 3 (rs1800887, rs2242447, rs15534).</p><p>Significance (p) value ranges are depicted as follows: For OVER-TRANSMISSION of alleles = <b>+4</b> (≤0.00001), <b>+3</b> (0.0001–0.0009), <b>+2</b> (0.001–0.009), and <b>+1</b> (0.01–0.049).</p><p>For UNDER-TRANSMISSION of alleles = −<b>4</b> (≤0.00001), −<b>3</b> (0.0001–0.0009), −<b>2</b> (0.001–0.009) and −<b>1</b> (0.01–0.049).</p