Optimization of in silico designed fatty acid synthase modulators derived from the lead molecule orlistat

Orlistat; or tetrahydrolipstatin has been found to have inhibitory effects on human Fatty Acid Synthase (hFASN), an enzyme overexpressed in many tumors responsible for energy upkeep and fatty acid synthesis. The crystalline structure of hFASN was used to extract Orlistat; analysis it’spharmacophoric moieties and generate a library using Orlistat as a scaffold to be utilized within a database for high throughput screening. Two distinct methods were used; and over 1,200 unique molecules have been generated, all compliant with Lipinski’s rule of 5.peer-reviewe

Soft-bottom fishes and spatial protection: findings from a temperate marine protected area

Numerous studies over the last decades have focused on marine protected areas (MPAs) and their effects on fish communities. However, there is a knowledge gap regarding how species that live associated with soft-substrates (e.g., sand, mud) respond to spatial protection. We analyzed abundance, biomass and total lengths of the soft-bottom fishes in a multiple-use MPA in the north-eastern Atlantic, the Luiz Saldanha Marine Park (Portugal), during and after the implementation of its management plan. Data were collected by experimental fishing in areas with three different levels of protection, during the implementation period and for three years after full implementation of the MPA. Univariate analysis detected significant biomass increases between the two periods. Fish assemblages were mainly structured by depth and substrate, followed by protection level. Community composition analyses revealed significant differences between protection levels and between the two periods. Species exhibited a broad variation in their response to protection, and we hypothesize that factors such as species habitat preferences, body size and late maturity might be underlying determinants. Overall, this study provides some evidence of protection effectiveness in soft-bottom fish communities, supported by the significant increase in biomass in the protected areas and the positive trends of some species.project LIFE-BIOMARES [LIFE06 NAT/P/000192]; project BUFFER (ERA-Net BiodivERsA); company SECIL-Companhia Geral de Cal e Cimento S.A.; FCT-Foundation for Science and Technology [CCMAR/Multi/04326/2013, SFRH/BD/80771/2011]; Foundation for Science and Technology [SFRH/BD/80771/2011]; 2012 Sesimbra Scientific Priz

Structural and compositional variations of basic Cu(II) chlorides in the herbertsmithite and gillardite structure field.

© 2017 The Mineralogical Society. This document is the author’s final accepted version of the journal article. You are advised to consult the published version if you wish to cite from it

The reliability of evidence review methodology in environmental science and conservation

Given the proliferation of primary research articles, the importance of reliable environmental evidence reviews for informing policy and management decisions is increasing. Although conducting reviews is an efficient method of synthesising the fragmented primary evidence base, reviews that are of poor methodological reliability have the potential to misinform by not accurately reflecting the available evidence base. To assess the current value of evidence reviews for decision-making we appraised a systematic sample of articles published in early 2015 (N = 92) using the Collaboration for Environmental Evidence Synthesis Assessment Tool (CEESAT). CEESAT assesses the methodology of policy-relevant evidence reviews according to elements important for objectivity, transparency and comprehensiveness. Overall, reviews performed poorly with a median score of 2.5/39 and a modal score of zero (range 0–30, mean 5.8), and low scores were ubiquitous across subject areas. In general, reviews that applied meta-analytical techniques achieved higher scores than narrative syntheses (median 18.3 and 2.0 respectively), as a result of the latter consistently failing to adequately report methodology or how conclusions were drawn. However, some narrative syntheses achieved high scores, illustrating that the reliability of reviews should be assessed on a case-by-case basis. Given the potential importance of reviews for informing management and policy, as well as research, it is vital that overall methodological reliability is improved. Although the increasing number of systematic reviews and meta-analyses highlight that some progress is being made, our findings suggest little or no improvement in the last decade. To motivate progress, we recommend that an annual assessment of the methodological reliability of evidence reviews be conducted. To better serve the environmental policy and management communities we identify a requirement for independent critical appraisal of review methodology thus enabling decision-makers to select reviews that are most likely to accurately reflect the evidence base

Health-related quality of life of children with attention-deficit/hyperactivity disorder versus children with diabetes and healthy controls

The impact of attention-deficit/hyperactivity disorder (ADHD) on health-related quality of life (HRQoL) is reported to be similar to that of other mental health and physical disorders. In this cross-sectional study, we hypothesized that children with ADHD and children with type 1 diabetes mellitus (T1DM) would have significantly worse HRQoL compared with healthy children, and that better clinical status in ADHD and T1DM would be associated with better HRQoL. Children were recruited from three outpatient services in Scotland. Responses to two frequently used validated HRQoL instruments, the Paediatric Quality of Life Inventory (PedsQL) and Child Health and Illness Profile-child edition (CHIP-CE), were obtained from parents/carers and children (6–16 years) with/without ADHD or T1DM. Child and parent/carer-completed HRQoL measurements were evaluated for 213 children with ADHD, 58 children with T1DM and 117 healthy children (control group). Significantly lower self and parent/carer ratings were observed across most PedsQL (P < 0.001) and CHIP-CE (P < 0.05) domains (indicating reduced HRQoL) for the ADHD group compared with the T1DM and control groups. Parent/carer and child ratings were significantly correlated for both measures of HRQoL (PedsQL total score: P < 0.001; CHIP-CE all domains: P < 0.001), but only with low-to-moderate strength. Correlation between ADHD severity and HRQoL was significant with both PedsQL and CHIP-CE for all parent/carer (P < 0.01) and most child (P < 0.05) ratings; more ADHD symptoms were associated with poorer HRQoL. These data demonstrate that ADHD has a significant impact on HRQoL (as observed in both parent/carer and child ratings), which seems to be greater than that for children with T1DM

Does a child’s language ability affect the correspondence between parent and teacher ratings of ADHD symptoms?

Background: Rating scales are often used to identify children with potential Attention-Deficit/Hyperactivity Disorder (ADHD), yet there are frequently discrepancies between informants which may be moderated by child characteristics. The current study asked whether correspondence between parent and teacher ratings on the Strengths and Weakness of ADHD symptoms and Normal behaviour scale (SWAN) varied systematically with child language ability. Method: Parent and teacher SWAN questionnaires were returned for 200 children (aged 61–81 months); 106 had low language ability (LL) and 94 had typically developing language (TL). After exploring informant correspondence (using Pearson correlation) and the discrepancy between raters, we report inter-class correlation coefficients, to assess inter-rater reliability, and Cohen’s kappa, to assess agreement regarding possible ADHD caseness. Results: Correlations between informant ratings on the SWAN were moderate. Children with LL were rated as having increased inattention and hyperactivity relative to children with TL; teachers, however, rated children with LL as having more inattention than parents. Inter-rater reliability of the SWAN was good and there were no systematic differences between the LL and TL groups. Case agreement between parent and teachers was fair; this varied by language group with poorer case agreement for children with LL. Conclusion: Children’s language abilities affect the discrepancy between informant ratings of ADHD symptomatology and the agreement between parents and teachers regarding potential ADHD caseness. The assessment of children’s core language ability would be a beneficial addition to the ADHD diagnostic process.</p

Response of benthic fauna to experimental bottom fishing: A global meta‐analysis

This is the final version. Available on open access from Wiley via the DOI in this recordBottom-contact fishing gears are globally the most widespread anthropogenic sources of direct disturbance to the seabed and associated biota. Managing these fishing disturbances requires quantification of gear impacts on biota and the rate of recovery following disturbance. We undertook a systematic review and meta-analysis of 122 experiments on the effects-of-bottom fishing to quantify the removal of benthos in the path of the fishing gear and to estimate rates of recovery following disturbance. A gear pass reduced benthic invertebrate abundance by 26% and species richness by 19%. The effect was strongly gear-specific, with gears that penetrate deeper into the sediment having a significantly larger impact than those that penetrate less. Sediment composition (% mud and presence of biogenic habitat) and the history of fishing disturbance prior to an experimental fishing event were also important predictors of depletion, with communities in areas that were not previously fished, predominantly muddy or biogenic habitats being more strongly affected by fishing. Sessile and low mobility biota with longer life-spans such as sponges, soft corals and bivalves took much longer to recover after fishing (>3 year) than mobile biota with shorter life-spans such as polychaetes and malacostracans (<1 year). This meta-analysis provides insights into the dynamics of recovery. Our estimates of depletion along with estimates of recovery rates and large-scale, high-resolution maps of fishing frequency and habitat will support more rigorous assessment of the environmental impacts of bottom-contact gears, thus supporting better informed choices in trade-offs between environmental impacts and fish production

From Russia with Love: The Impact of Relocated Firms on Incumbent Survival

We identify the impact of local firm concentration on incumbent performance with a quasi natural experiment. When Germany was divided after World War II, many firms in the machine tool industry fled the Soviet occupied zone to prevent expropriation. We show that the regional location decisions of these firms upon moving to western Germany were driven by non-economic factors and heuristics rather than existing industrial conditions. Relocating firms increased the likelihood of incumbent failure in destination regions, a pattern that differs sharply from new entrants. We further provide evidence that these effects are due to increased competition for local resources

Study protocol: the sleeping sound with attention-deficit/hyperactivity disorder project

<p>Abstract</p> <p>Background</p> <p>Up to 70% of children with Attention-Deficit/Hyperactivity Disorder (ADHD) experience sleep problems including difficulties initiating and maintaining sleep. Sleep problems in children with ADHD can result in poorer child functioning, impacting on school attendance, daily functioning and behaviour, as well as parental mental health and work attendance. The Sleeping Sound with ADHD trial aims to investigate the efficacy of a behavioural sleep program in treating sleep problems experienced by children with ADHD. We have demonstrated the feasibility and the acceptability of this treatment program in a pilot study.</p> <p>Methods/Design</p> <p>This randomised controlled trial (RCT) is being conducted with 198 children (aged between 5 to 12 years) with ADHD and moderate to severe sleep problems. Children are recruited from public and private paediatric practices across the state of Victoria, Australia. Upon receiving informed written consent, families are randomised to receive either the behavioural sleep intervention or usual care. The intervention consists of two individual, face-to-face consultations and a follow-up phone call with a trained clinician (trainee consultant paediatrician or psychologist), focusing on the assessment and management of child sleep problems. The primary outcome is parent- and teacher-reported ADHD symptoms (ADHD Rating Scale IV). Secondary outcomes are child sleep (actigraphy and parent report), behaviour, daily functioning, school attendance and working memory, as well as parent mental health and work attendance. We are also assessing the impact of children's psychiatric comorbidity (measured using a structured diagnostic interview) on treatment outcome.</p> <p>Discussion</p> <p>To our knowledge, this is the first RCT of a behavioural intervention aiming to treat sleep problems in children with ADHD. If effective, this program will provide a feasible non-pharmacological and acceptable intervention improving child sleep and ADHD symptoms in this patient group.</p> <p>Trial Registration</p> <p>Current Controlled Trials ISRCTN68819261.</p> <p> ISRCTN: <a href="http://www.controlled-trials.com/ISRCTN68819261">ISRCTN68819261</a></p

Is there a difference between child self-ratings and parent proxy-ratings of the quality of life of children with a diagnosis of Attention Deficit Hyperactivity Disorder (ADHD)? A systematic review of the literature

There are contemporary indicators that parent proxy-ratings and child self-ratings of a child’s quality of life (QoL) are not interchangeable. This review examines dual informant studies to assess parent–child agreement on the QoL of children with attention-deficit/hyperactivity disorder. A systematic search of four major databases (PsycINFO, MEDLINE, EMBASE and Cochrane databases) was completed, and related peer-reviewed journals were hand-searched. Studies which reported quantitative QoL ratings for matched parent and child dyads were screened in accordance with relevant inclusion and exclusion criteria. Key findings were extracted from thirteen relevant studies, which were rated for conformity to the recommendations of an adapted version of the STROBE statement guidelines for observational studies. In the majority of studies reviewed, children rated their QoL more highly than their parents. There was some evidence for greater agreement on the physical health domain than psychosocial domains