Cost Changes in UK Design and Build Projects

The UK construction industry has seen many improvements over recent years, however one of the main ongoing issues is cost. Many projects face the problem of exceeding their initial budget resulting in unanticipated additional costs. It is important to avoid the client going over budget as this can ultimately affect the feasibility of a project. This research aim to investigate the factors driving cost changes in design and build projects within the residential sector in the UK construction industry. The gap in knowledge this study intends to contribute, is to investigate and proffer solutions to the causes of variance between contract sum and final account in design and build procurement option in the UK residential building projects. The research began with a brief literature review on different procurement routes and the factors which drive cost changes in construction projects. The findings of the literature review were used as the basis of the positivist research approach. The research used a mixed methodological approach, consisting of a questionnaire survey and semi-structured interviews to investigate the research problem. This research identified the design and build procurement route has succeeded in improving overall cost performance of construction projects by allocating the responsibilities of certain additional costs to contractors. However, despite these improvements, cost overruns are still problematic. Regardless of the chosen procurement route, complete design information at tender stage is essential to reducing cost overruns. This research established that subcontractors‟ performance ultimately depends upon the quality of site management. It is recommended to minimise any additional costs to a project, firstly design information should be complete at the time of tender and secondly the construction phase of the project should be managed by suitably qualified and experienced site management team. However, this study was limited to the residential building industry in the UK, hence further studies is highly recommended in developing countries as factors that causes this differences in contract sum and final account may be prioritised differently from the analysis within this study

Prophylaxis pharmacotherapy to prevent the onset of post traumatic brain injury depression: a systematic review

YesBackground: Depression is a common psychiatric problem following traumatic brain injury (TBI) with reported prevalence rates of 30-77% in the first year post-TBI. Given the negative influence of post-TBI depression on cognition, interpersonal, social, physical and occupational functioning; early initiation of pharmacotherapy to prevent post-TBI depression has been considered. This systematic review will synthesize the available evidence from published studies on the effectiveness and harms of pharmacotherapy for the secondary prevention of post-TBI depression. Method: Studies published before November 2017 were reviewed. Six databases were searched, with additional searching of key additional documents. Studies meeting inclusion criteria were evaluated for methodological quality. Results: Six articles addressing five studies met inclusion criteria. Study designs included three randomised controlled trials (RCT), two retrospective cohorts and one case-control. Prophylactic pharmacotherapy included antidepressants, beta-blockers and statins. In one RCT, the number-needed-to-treat with sertraline to prevent one case of depression post-TBI at 24 weeks was 5.9 (95%CI: 3.1-71.1). Prescribing beta-blockers prior to TBI reduced the depression risk regardless of the specific brain trauma. TBI patients with pre-existing hyperlipidemia not treated with statins had an increased depression risk compared to those without hyperlipidemia. Conclusion: Early initiation of sertraline prophylaxis in nondepressed TBI patients shows promise to reduce the odds of post-TBI depression developing. However, in the absence of rigorous study of tolerability, existing data are insufficient to recommend sertraline prophylaxis. Optimal timing and treatment duration with identification of patients most likely to benefit from prophylaxis require further consideration. Dedicated prospective studies assessing the effects of beta-blockers and statins on post-TBI depression are required.The Transport Accident Commission (TAC), through the Institute for Safety, Compensation and Recovery Research (ISCRR) at Monash University, provided funding for this review

COVID-19 and X-linked agammaglobulinemia (XLA) - insights from a monogenic antibody deficiency

Purpose of review The clinical outcomes from COVID-19 in monogenic causes of predominant antibody deficiency have pivotal implications for our understanding of the antiviral contribution of humoral immunity. This review summarizes the lessons learned from COVID-19 infection in X-linked agammaglobulinemia (XLA) due to genetic defects in Bruton's tyrosine kinase (BTK). Recent findings Key molecular pathways underlying the development of severe COVID-19 are emerging, highlighting the possible contribution of BTK to hyperinflammation. SARS-CoV-2 specific T-cell responses and complement activation appear insufficient to achieve viral clearance in some B-cell deficient individuals. Whilst appearing efficacious in this group, use of convalescent plasma has been recently associated with the evolution of viral escape variants. Early data suggests individuals with XLA can mount a viral-specific T-cell vaccine response, however, the clinical significance of this is still emerging. Summary In contrast to reports made early in the pandemic, we show XLA patients remain susceptible to severe disease. Persistent infection was common and is likely to carry a significant symptom burden and risk of novel variant evolution. COVID-19 infection in this vulnerable, antibody deficient group due to genetic, therapeutic or disease causes may require prompt and specific intervention for both patient and societal benefit

Capturing complexity in the evaluation of a major area-based initiative in community empowerment:what can a multi-site, multi team, ethnographic approach offer?

In recent years, there has been growing emphasis on the need to develop ways of capturing ‘complexity’ in the evaluation of health initiatives in order to produce better evidence about ‘how’ and under what conditions such interventions work. Used alone, conventional methods of evaluation that attempt to reduce intervention processes and outcomes to a small number of discrete and finite variables, are typically not well suited to this task. Among the research community there have been increasing calls to take more seriously qualitative methods as an alternative or complementary approach to intervention evaluation. Ethnography has been identified as being particularly well suited to the purpose of capturing the full messiness that ensues when health interventions are introduced into complex settings (or systems). In this paper we reflect on our experience of taking a long term multi-site, multi team, ethnographic approach to capture complex, dynamic system processes in the first phase of an evaluation of a major area-based community empowerment initiative being rolled out in 150 neighbourhoods in England. We consider the utility of our approach for capturing the complexity inherent to understanding the changes that ensue when the initiative is delivered into multiple diverse contexts/systems as well as the opportunities and challenges that emerge in the research process

Patient Outcomes at Twelve Months after Early Decompressive Craniectomy for Diffuse Traumatic Brain Injury in the Randomized DECRA Clinical Trial

Functional outcomes at 12 months were a secondary outcome of the randomized DECRA trial of early decompressive craniectomy for severe diffuse traumatic brain injury (TBI) and refractory intracranial hypertension. In the DECRA trial, patients were randomly allocated 1:1 to either early decompressive craniectomy or intensive medical therapies (standard care). We conducted planned secondary analyses of the DECRA trial outcomes at 6 and 12 months, including all 155 patients. We measured functional outcome using the Glasgow Outcome Scale-Extended (GOS-E). We used ordered logistic regression, and dichotomized the GOS-E using logistic regression, to assess outcomes in patients overall and in survivors. We adjusted analyses for injury severity using the International Mission for Prognosis and Analysis of Clinical Trials in TBI (IMPACT) model. At 12 months, the odds ratio (OR) for worse functional outcomes in the craniectomy group (OR 1.68; 95% confidence interval [CI]: 0.96-2.93; p = 0.07) was no longer significant. Unfavorable functional outcomes after craniectomy were 11% higher (59% compared with 48%), but were not significantly different from standard care (OR 1.58; 95% CI: 0.84-2.99; p = 0.16). Among survivors after craniectomy, there were fewer good (OR 0.33; 95% CI: 0.12-0.91; p = 0.03) and more vegetative (OR 5.12; 95% CI: 1.04-25.2; p = 0.04) outcomes. Similar outcomes in survivors were found at 6 months after injury. Vegetative (OR 5.85; 95% CI: 1.21-28.30; p = 0.03) and severely disabled outcomes (OR 2.49; 95% CI: 1.21-5.11; p = 0.01) were increased. Twelve months after severe diffuse TBI and early refractory intracranial hypertension, decompressive craniectomy did not improve outcomes and increased vegetative survivors

Hematopoietic stem cell transplantation and vasculopathy associated with STAT3-dominant-negative hyper-IgE syndrome

Dominant negative mutations in the transcription-factor STAT3 underlie the rare primary immunodeficiency Job's syndrome. Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) has shown promise in correction of the underlying immunological defect, with one report suggesting HSCT can prevent development of wider connective tissue complications. Here, we report the case of a 26 year old male who developed an acute ST-elevation myocardial infarction due to coronary artery ectasia and thrombosis, occurring despite pediatric allogeneic HSCT for STAT3-HIES and a predicted 10-year conventional cardiovascular risk of 0.1%. Vasculopathy associated with STAT3-HIES may persist or arise following HSCT and can precipitate life-threatening complications. This has implications for counseling and vascular surveillance, and highlights the need for further studies to determine the risk, pathogenesis, and optimal management of the vasculopathy associated with STAT3-HIES

Quantification of human C1 esterase inhibitor protein using an automated turbidimetric immunoassay

BACKGROUND: Impaired levels or function of C1 inhibitor (C1-INH) results in angioedema due to increased bradykinin. It is important to distinguish between angioedema related to C1-INH deficiency and that caused by other mechanisms, as treatment options are different. In hereditary (HAE) and acquired (AAE) angioedema, C1-INH concentration is measured to aid patient diagnosis. Here, we describe an automated turbidimetric assay to measure C1-INH concentration on the Optilite® analyzer. METHODS: Linearity, precision, and interference were established over a range of C1-INH concentrations. The 95th percentile reference interval was generated from 120 healthy adult donors. To compare the Optilite C1-INH assay with a predicate assay used in a clinical laboratory, samples sent for C1-INH investigation were used. The predicate results were provided to allow comparison. RESULTS: The Optilite C1-INH assay was linear across the measuring range at the standard sample dilution. Intra and interassay variability was <6%. The 95th percentile adult reference interval for the assay was 0.21-0.38 g/L. There was a strong correlation between the Optilite concentrations and those generated with the predicate assay (R2 = 0.94, P < 0.0001, slope y = 0.83x). All patients with Type I HAE (n = 24) and AAE (n = 3) tested had concentrations below the measuring range in both assays, while all patients with unspecified angioedema (UAE), not diagnosed with HAE or AAE had values within the reference range. CONCLUSION: The Optilite assay allows the automated and precise quantification of C1-INH concentrations in patient samples. It could therefore be used as a tool to aid the investigation of patients with angioedema