Strategic sustainable development in the UK construction industry, through the Framework of Strategic Sustainable Development, using Building Information Modelling

The UK Government has set out ambitious plans for all new domestic and commercial buildings to be zero carbon rated by 2016 and 2020 respectively. These are some of the most progressive environmental targets for the built environment in the western world. There are also sustainability principles (SP) that need to be addressed by the UK construction industry, particularly negative impacts such as waste and pollution. Currently, 100 million tonnes of construction waste, including 13 million tonnes of unused materials, is generated each year, with only 20% currently capable of being recycled. The majority of this waste ends up in landfill, contributing to further pollution of the biosphere. The literature suggests that these negative impacts result from a variety of causes, including ineffective leadership, ingrained cultures, outdated technologies and poor logistics. There are a number of innovative projects within the UK, particularly at a local level, that pose the question as to whether bottom up approaches may be more successful than top down policies, as set by national and local government. This paper presents a case study demonstrating the former approach within the construction industry. Research and consultancy has been undertaken collaboratively between industry, academia and professional practice in the production of 15 individually designed sustainable dwellings in the North East of England. This project has employed Building Information Modelling (BIM) as a new collaborative working platform, aligned to the Modern Method of Construction (MMC). By situating this inquiry within an authentic case study it has highlighted currently ineffective strategies, policies and leadership which have prevented full exploitation of the potential of BIM and MMC towards sustainable production. This inquiry supports the integration of the Framework of Sustainable Strategic Development (FSSD) into construction procurement, as a method for implementing bottom up leadership in a value driven project

Risk factors and comorbidity of ICD?11 PTSD and complex PTSD: Findings from a trauma?exposed population based sample of adults in the United Kingdom

Background: Following the recently published 11th version of the WHO International Classification of Diseases (ICD-11), we sought to examine the risk factors and comorbidities associated with posttraumatic stress disorder (PTSD) and Complex PTSD (CPTSD). Method: Cross-sectional and retrospective design. The sample consisted of 1051 trauma-exposed participants from a nationally representative panel of the UK adult population. Results: 5.3% (95% CI = 4.0%-6.7%) met the diagnostic criteria for PTSD and 12.9% (95% CI = 10.9%-15.0%) for CPTSD. Diagnosis of PTSD was independently associated with being female, being in a relationship, and the recency of traumatic exposure. CPTSD was independently associated with younger age, interpersonal trauma in childhood, and interpersonal trauma in adulthood. Growing up in an urban environment was associated with diagnosis of PTSD and CPTSD. High rates of physical and mental health comorbidity were observed for PTSD and CPTSD. Those with CPTSD were more likely to endorse symptoms reflecting Major Depressive Disorder (OR = 21.85, 95 CI = 12.51 – 38.04) and Generalized Anxiety Disorder (OR = 24.63, 95 CI = 14.77 – 41.07). Presence of PTSD (OR = 3.13, 95 CI = 1.81 – 5.41) and CPTSD (OR = 3.43, 95 CI = 2.37 – 4.70) increased the likelihood of suicidality by more than three times. Nearly half the participants with PTSD and CPTSD reported the presence of a chronic illness. Conclusions: CPTSD is a more common, co-morbid, debilitating condition compared PTSD. Further research is now required to identify effective interventions for its treatment

Do cladistic and morphometric data capture common patterns of morphological disparity?

The distinctly non-random diversity of organismal form manifests itself in discrete clusters of taxa that share a common body plan. As a result, analyses of disparity require a scalable comparative framework. The difficulties of applying geometric morphometrics to disparity analyses of groups with vastly divergent body plans are overcome partly by the use of cladistic characters. Character-based disparity analyses have become increasingly popular, but it is not clear how they are affected by character coding strategies or revisions of primary homology statements. Indeed, whether cladistic and morphometric data capture similar patterns of morphological variation remains a moot point. To address this issue, we employ both cladistic and geometric morphometric data in an exploratory study of disparity focussing on caecilian amphibians. Our results show no impact on relative intertaxon distances when different coding strategies for cladistic characters were used or when revised concepts of homology were considered. In all instances, we found no statistically significant difference between pairwise Euclidean and Procrustes distances, although the strength of the correlation among distance matrices varied. This suggests that cladistic and geometric morphometric data appear to summarize morphological variation in comparable ways. Our results support the use of cladistic data for characterizing organismal disparity

Transcriptional upregulation of c-MET is associated with invasion and tumor budding in colorectal cancer

c-MET and its ligand HGF are frequently overexpressed in colorectal cancer (CRC) and increased c-MET levels are found in CRC liver metastases. This study investigated the role of the HGF/c-MET axis in regulating migration/invasion in CRC, using pre-clinical models and clinical samples. Pre-clinically, we found marked upregulation of c-MET at both protein and mRNA levels in several invasive CRC cells. Down-regulation of c-MET using RNAi suppressed migration/invasion of parental and invasive CRC cells. Stimulation of CRC cells with rh-HGF or co-culture with HGF-expressing colonic myofibroblasts, resulted in significant increases in their migratory/invasive capacity. Importantly, HGF-induced c-MET activation promoted rapid downregulation of c-MET protein levels, while the MET transcript remained unaltered. Using RNA in situ hybridization (RNA ISH), we further showed that MET mRNA, but not protein levels, were significantly upregulated in tumor budding foci at the invasive front of a cohort of stage III CRC tumors (p < 0.001). Taken together, we show for the first time that transcriptional upregulation of MET is a key molecular event associated with CRC invasion and tumor budding. This data also indicates that RNA ISH, but not immunohistochemistry, provides a robust methodology to assess MET levels as a potential driving force of CRC tumor invasion and metastasis

SWOG S1400B (NCT02785913), a Phase II Study of GDC-0032 (Taselisib) for Previously Treated PI3K-Positive Patients with Stage IV Squamous Cell Lung Cancer (Lung-MAP Sub-Study).

BackgroundS1400B is a biomarker-driven Lung-MAP substudy evaluating the phosphatidylinositol 3-kinase (PI3K) inhibitor taselisib (GDC-0032) in patients with PI3K pathway-activated squamous NSCLC (sqNSCLC).MethodsEligible patients had tumoral phosphatidylinositol-4,5-biphosphate 3 kinase catalytic subunit alpha (PIK3CA) alterations by next-generation sequencing and disease progression after at least one line of platinum-based therapy. Patients received 4-mg taselisib orally daily. The primary analysis population (PAP) was a subset of patients having substitution mutations believed to be associated with clinical benefit of PI3K inhibitors. Primary endpoint was response by Response Evaluation Criteria in Solid Tumors version 1.1; secondary endpoints included progression-free survival, overall survival and duration of response.ResultsTwenty-six patients treated with taselisib comprised the full evaluable population (FEP); 21 patients comprised the PAP. Median age for patients in the FEP was 68 years (range: 53-83 years), 19 were male (73%). The study was closed for futility at interim analysis with one responder in the PAP (5% response rate, 95% confidence interval [CI]: 0%-24%). Two possibly treatment-related deaths (one respiratory failure, one cardiac arrest) were observed; one patient had grades 4 and 11 had grade 3 adverse events. Median progression-free survival and overall survival in the PAP group were 2.9 months (95% CI: 1.8-4.0 mo) and 5.9 months (95% CI: 4.2-7.8 mo), respectively. These numbers were nearly the same in the FEP.ConclusionsStudy S1400B evaluating taselisib in PIK3CA-altered sqNSCLC failed to meet its primary endpoint and was closed after an interim futility analysis. The trial is unique in cataloguing the diversity of PIK3CA mutations in sqNSCLC

Psychological interventions for ICD-11 complex PTSD symptoms: systematic review and meta-analysis

Background The 11th revision to the WHO International Classification of Diseases (ICD-11) identified complex post-traumatic stress disorder (CPTSD) as a new condition. There is a pressing need to identify effective CPTSD interventions. Methods We conducted a systematic review and meta-analysis of randomised controlled trials (RCTs) of psychological interventions for post-traumatic stress disorder (PTSD), where participants were likely to have clinically significant baseline levels of one or more CPTSD symptom clusters (affect dysregulation, negative self-concept and/or disturbed relationships). We searched MEDLINE, PsycINFO, EMBASE and PILOTS databases (January 2018), and examined study and outcome quality. Results Fifty-one RCTs met inclusion criteria. Cognitive behavioural therapy (CBT), exposure alone (EA) and eye movement desensitisation and reprocessing (EMDR) were superior to usual care for PTSD symptoms, with effects ranging from g = −0.90 (CBT; k = 27, 95% CI −1.11 to −0.68; moderate quality) to g = −1.26 (EMDR; k = 4, 95% CI −2.01 to −0.51; low quality). CBT and EA each had moderate–large or large effects on negative self-concept, but only one trial of EMDR provided useable data. CBT, EA and EMDR each had moderate or moderate–large effects on disturbed relationships. Few RCTs reported affect dysregulation data. The benefits of all interventions were smaller when compared with non-specific interventions (e.g. befriending). Multivariate meta-regression suggested childhood-onset trauma was associated with a poorer outcome. Conclusions The development of effective interventions for CPTSD can build upon the success of PTSD interventions. Further research should assess the benefits of flexibility in intervention selection, sequencing and delivery, based on clinical need and patient preferences

Inferring PDZ Domain Multi-Mutant Binding Preferences from Single-Mutant Data

Many important cellular protein interactions are mediated by peptide recognition domains. The ability to predict a domain's binding specificity directly from its primary sequence is essential to understanding the complexity of protein-protein interaction networks. One such recognition domain is the PDZ domain, functioning in scaffold proteins that facilitate formation of signaling networks. Predicting the PDZ domain's binding specificity was a part of the DREAM4 Peptide Recognition Domain challenge, the goal of which was to describe, as position weight matrices, the specificity profiles of five multi-mutant ERBB2IP-1 domains. We developed a method that derives multi-mutant binding preferences by generalizing the effects of single point mutations on the wild type domain's binding specificities. Our approach, trained on publicly available ERBB2IP-1 single-mutant phage display data, combined linear regression-based prediction for ligand positions whose specificity is determined by few PDZ positions, and single-mutant position weight matrix averaging for all other ligand columns. The success of our method as the winning entry of the DREAM4 competition, as well as its superior performance over a general PDZ-ligand binding model, demonstrates the advantages of training a model on a well-selected domain-specific data set

Explorations, Vol. 6, No. 1

Cover: Panthera pardus, Chui in Kiswatuli, was photographed by Dr. Linda Karbonit ar Dr. James A. Sherburne in Serengeti National Park, Tanzania. Karbonit was accompanying Sherburne who was working on the design and development of the University of Maine, U.S. Fish and Wildlife Service, assistance program in wildlife training and conservation education to Tanzania’s National Parks. Sherburne, who has worked in Tanzania for several years, was there most recently in 1988 and 1989 working on the parks project. He serves as the Director of International Natural Resources and Agricultural Programs at the University of Maine. Articles include: Research and Economic Development: from the U.S. Senate Statement, December 22, 1989, by Sen. George J. Mitchell Politics and Research: Providing a Key for Economic Development, by Sen. William S. Cohen. Publisher’s Perspective, by Gregory N. Brown, Vice President, Research and Public Service What’s EPSCoR? Editorial Reflections, by Carole J. Bombard Past and Present: Marine Geologists Explore the Old and Teach the Young, by Daniel Belknap and Joseph Kelley High Biological Productivity: Salt Marshes, by Mark E. Wood Barrier Beaches, by William Duffy Sediment Budgets & Bluff Slump, by Rebecca Smith Coastal Environments and Change, by Andrew Walsh Mapping What You Can\u27t See, by Donald Robbins Casco Bay: Sea Level and the Shoreline, by Bradley W.B. Hay Christmas at Sea, by Molly Horvath A Short Course and the Local Economy, by Richard Hale and James Philp Dr. Bernard Lown: Alumnus Receives Golden Door Award The Sky is Falling . . . well, maybe, by Carole J. Bombard A Growing Interest in Timberland, by Robert A. Strong and Bret P. Vicar