50 research outputs found
Design management: changing roles of the professions
This paper sets out to explore how recent changes in
procurement in construction have affected the roles that
professions play in the design process. It discusses how
professions that traditionally took the role of design
manager now find themselves participating within
previously unforeseen contexts, working in multidisciplinary
teams led by contractors and with changed
responsibilities at the design stage. Supply chain members
who were not previously involved during the early project
phases are being engaged at the earliest phases of the
project life cycle and even taking leadership roles while
designers sometimes work as supply chain partners.
A study of design in construction and other sectors shows
that in dealing with design management issues it is critical
to deepen appreciation for the unique characteristics of
design and the design process. The paper argues that
contractors and designers taking on design management
roles in a dynamic industry seeking to explore best
practice and innovative approaches to procurement and in
the delivery of projects need to acquire new skills,
management education and develop the necessary
qualities
Foetal echocardiographic assessment of borderline small left ventricles can predict the need for postnatal intervention
Abstract Background We sought to prospectively determine foetal echocardiographic factors associated with neonatal interventions in borderline hypoplastic left ventricles. Methods Foetuses were included who had a left ventricle that was 2-4 standard deviations below normal for length or diameter and had forward flow across the mitral and aortic valves. Factors associated with an intervention in the first month of life or no need for intervention were sought using univariate and multivariate logistic regression models. Results From 2005 to 2008, 47 foetuses meeting the criteria had an additional diagnosis (+foetal coarctation/+transverse arch hypoplasia): atrioventricular septal defect 7 (+2/+0), double outlet right ventricle 2 (+0/+0), Shone's complex 19 (+9/+4), and ventricular disproportion 19 (+13/+11; 4 both). There were seven pregnancies terminated, three foetal demises, and five had compassionate care. There were 32 livebirths that either had a biventricular repair (n = 20, n = 2 dead), univentricular palliation (n = 2, both alive), or no intervention (n = 9). Overall survival of livebirths to 6 months of age was 79%. Factors associated with early intervention on first foetal echocardiogram were: obstructed or retrograde arch flow (p = 0.08, odds ratio 3.3), coarctation (p = 0.05, odds ratio 11.4), and left ventricle outflow obstruction (p = 0.05, odds ratio 12.5). Neonatal factors included: Shone's diagnosis (p = 0.02, odds ratio 4.9), bicuspid aortic valve (p = 0.005, odds ratio 11.7), and larger tricuspid valve z-score (p = 0.05, odds ratio 3.6). A neonatal factor associated with no intervention was a larger mitral valve z-score (mean −3.8 versus −4.2 intervention group, p = 0.04, odds ratio 2.8). Discussion The need for early intervention in foetuses with borderline hypoplastic left ventricle can be predicted by foetal echocardiograph
Postcoital Bioavailability and Antiviral Activity of 0.5% PRO 2000 Gel: Implications for Future Microbicide Clinical Trials
The pharmacokinetics and pharmacodynamics of vaginal microbicides are typically assessed among sexually abstinent women. However, the physical act of sex may modulate gel distribution, and preclinical studies demonstrate seminal plasma interferes with the antiviral activity of several microbicides. This study compared the biological activity and concentration of PRO 2000 in cervicovaginal lavage (CVL) collected in the absence or following coitus.CVL samples were collected from ten heterosexual couples at baseline, after sex, after a single dose of 0.5% PRO 2000 gel and sex, and after gel application without sex. The impact of CVL on HIV-1 infection of TZM-bl cells and HSV-2 infection of CaSki cells was monitored by luciferase and plaque assay, respectively. PRO 2000 concentrations were measured by fluorescence.CVL collected after PRO 2000 application significantly inhibited HIV-1 and HSV-2 (p = 0.01). However, the antiviral activity was reduced following sex and no significant protective effect was observed in postcoital CVL obtained in the presence compared to the absence of PRO 2000 for HIV (p = 0.45) or HSV-2 (p = 0.56). Less PRO 2000 was recovered in postcoital CVL, which, in conjunction with interference by seminal plasma, may have contributed to lower antiviral activity.Postcoital responses to PRO 2000 differ from precoital measures and the results obtained may provide insights into the clinical trial findings in which there was no significant protection against HIV-1 or HSV-2. Postcoital studies should be incorporated into clinical studies before embarking on large-scale efficacy trials
A Randomized Trial to Assess Anti-HIV Activity in Female Genital Tract Secretions and Soluble Mucosal Immunity Following Application of 1% Tenofovir Gel
Preclinical and early phase clinical microbicide studies have not consistently predicted the outcome of efficacy trials. To address this gap, candidate biomarkers of microbicide pharmacodynamics and safety were evaluated in a double-blind, placebo-controlled trial of tenofovir gel, the first microbicide to demonstrate significant protection against HIV acquisition.30 women were randomized to apply a single daily dose of tenofovir or placebo gel for 14 consecutive days. Anti-HIV activity was measured in cervicovaginal lavage (CVL) on Days 0, 3, 7, 14 and 21 by luciferase assay as a surrogate marker of pharmacodynamics. Endogenous activity against E. coli and HSV-2 and concentrations of immune mediators were quantified in CVL as candidate biomarkers of safety. Tenofovir levels were measured in CVL and blood.A significant increase in anti-HIV activity was detected in CVL from women who applied tenofovir gel compared to their endogenous anti-HIV activity in genital tract secretions on Day 0 and compared to activity in CVL from women in the placebo group. The activity correlated significantly with CVL concentration of tenofovir (r = 0.6, p<0.001) and fit a sigmoid E(max) pharmacodynamic model. Anti-HIV activity in CVL from women who applied tenofovir persisted when virus was introduced in semen, whereas endogenous anti-HIV activity decreased. Tenofovir did not trigger an inflammatory response or induce sustained loss in endogenous antimicrobial activity or immune mediators.Tenofovir gel had no deleterious impact on soluble mucosal immunity. The increased anti-HIV activity in CVL, which persisted in the presence of semen and correlated with tenofovir concentration, is consistent with the efficacy observed in a recent clinical trial. These results promote quantified CVL anti-HIV activity as a surrogate of tissue pharmacodynamics and as a potential biomarker of adherence to product. This simple, feasible and inexpensive bioassay may promote the development of models more predictive of microbicide efficacy.ClinicalTrials.gov NCT00594373
Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis
BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London
Performance of swabs, lavage, and diluents to quantify biomarkers of female genital tract soluble mucosal mediators
Background: Measurement of immune mediators and antimicrobial activity in female genital tract secretions may provide biomarkers predictive of risk for HIV-1 acquisition and surrogate markers of microbicide safety. However, optimal methods for sample collection do not exist. This study compared collection methods. Methods: Secretions were collected from 48 women (24 with bacterial vaginosis [BV]) using vaginal and endocervical Dacron and flocked swabs. Cervicovaginal lavage (CVL) was collected with 10 mL of Normosol-R (n = 20), saline (n = 14), or water (n = 14). The concentration of gluconate in Normosol-R CVL was determined to estimate the dilution factor. Cytokine and antimicrobial mediators were measured by Luminex or ELISA and corrected for protein content. Endogenous anti-HIV-1 and anti-E. coli activity were measured by TZM-bl assay or E. coli growth. Results: Higher concentrations of protein were recovered by CVL, despite a 10-fold dilution of secretions, as compared to swab eluents. After protein correction, endocervical swabs recovered the highest mediator levels regardless of BV status. Endocervical and vaginal flocked swabs recovered significantly higher levels of anti-HIV-1 and anti-E. coli activity than Dacron swabs (P<0.001). BV had a significant effect on CVL mediator recovery. Normosol-R tended to recover higher levels of most mediators among women with BV, whereas saline or water tended to recover higher levels among women without BV. Saline recovered the highest levels of anti-HIV-1 activity regardless of BV status. Conclusions: Endocervical swabs and CVL collected with saline provide the best recovery of most mediators and would be the optimal sampling method(s) for clinical trials. © 2011 Dezzutti et al
Socioeconomic deprivation and illness trajectory in the Scottish population after COVID-19 hospitalization
Background
The associations between deprivation and illness trajectory after hospitalisation for coronavirus disease-19 (COVID-19) are uncertain.
Methods
A prospective, multicentre cohort study was conducted on post-COVID-19 patients, enrolled either in-hospital or shortly post-discharge. Two evaluations were carried out: an initial assessment and a follow-up at 28–60 days post-discharge. The study encompassed research blood tests, patient-reported outcome measures, and multisystem imaging (including chest computed tomography (CT) with pulmonary and coronary angiography, cardiovascular and renal magnetic resonance imaging). Primary and secondary outcomes were analysed in relation to socioeconomic status, using the Scottish Index of Multiple Deprivation (SIMD). The EQ-5D-5L, Brief Illness Perception Questionnaire (BIPQ), Patient Health Questionnaire-4 (PHQ-4) for Anxiety and Depression, and the Duke Activity Status Index (DASI) were used to assess health status.
Results
Of the 252 enrolled patients (mean age 55.0 ± 12.0 years; 40% female; 23% with diabetes), deprivation status was linked with increased BMI and diabetes prevalence. 186 (74%) returned for the follow-up. Within this group, findings indicated associations between deprivation and lung abnormalities (p = 0.0085), coronary artery disease (p = 0.0128), and renal inflammation (p = 0.0421). Furthermore, patients with higher deprivation exhibited worse scores in health-related quality of life (EQ-5D-5L, p = 0.0084), illness perception (BIPQ, p = 0.0004), anxiety and depression levels (PHQ-4, p = 0.0038), and diminished physical activity (DASI, p = 0.002). At the 3-month mark, those with greater deprivation showed a higher frequency of referrals to secondary care due to ongoing COVID-19 symptoms (p = 0.0438). However, clinical outcomes were not influenced by deprivation.
Conclusions
In a post-hospital COVID-19 population, socioeconomic deprivation was associated with impaired health status and secondary care episodes. Deprivation influences illness trajectory after COVID-19
An ordinal game theory approach to the analysis and selection of partners in public:Private partnership projects
Nowadays, public–private partnership projects have become a standard for delivering public services in both developed and developing countries. In this paper, we are concerned with the analysis of private sector proposals and the selection of the private sector partner to whom to award the contract. To the best of our knowledge, this problem has not been addressed within a game theory framework. To fill this gap, we model this decision problem as a static non-cooperative game of complete information and propose a new ordinal game theory algorithm for finding an optimal generalized Nash equilibrium. The proposed algorithm determines a single ranking of proposals or bidders that takes account of multiple performance criteria and reflects both the public sector and the private sector perspectives, and can handle any number of private sector players and any number of contractual terms. An illustrative scenario is provided to guide the reader through the workings of the proposed ordinal game theory algorithm. The proposed ordinal game theory-based analysis framework can be used by the private sector to analyse any set of potential proposals most likely to be submitted by bidders and to assist with the choice of bidding strategies, and by the public sector player to analyse any set of potential proposals most likely to be submitted under any set of contractual terms and to assist with the choice of a realistic set of contractual terms and their performance measures