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Background Congenital cytomegalovirus (CMV) is the most common congenital infection globally, however information about CMV is not routinely included in antenatal education in the United Kingdom. This feasibility study aimed to gather the essential data needed to design and power a large randomised controlled trial (RCT) to investigate the efficacy of a digital intervention in reducing the risk of CMV acquisition in pregnancy. In order to do this, we carried out a single-centre RCT, which explored the knowledge, attitudes and risk reduction behaviours in women in the intervention and treatment as usual groups, pre- and post-intervention. Methods CMV seronegative women living with a child less than four years old, receiving antenatal care at a single UK tertiary centre, were randomised to the digital intervention or ‘treatment as usual’ groups. Participants completed questionnaires before the digital intervention and after and at 34 gestational weeks, and responses within groups and between groups were compared using tailored randomisation tests. CMV serology was tested in the first trimester and at the end of pregnancy. Results Of the 878 women screened, 865 samples were analysed with 43% ( n  = 372) being CMV seronegative and therefore eligible to take part in the RCT; of these, 103 (27.7%) women were enrolled and 87 (84%) of these completed the study. Most participants ( n  = 66; 64%) were unfamiliar with CMV at enrolment, however at 34 gestational weeks, women in the intervention group ( n  = 51) were more knowledgeable about CMV compared to the treatment as usual group ( n  = 52) and reported engaging in activities that may increase the risk of CMV transmission less frequently. The digital intervention was highly acceptable to pregnant women. Overall, four participants seroconverted over the course of the study: two from each study group. Conclusions A large multi-centre RCT investigating the efficacy of a CMV digital intervention is feasible in the United Kingdom; this study has generated essential data upon which to power such a study. This single-centre feasibility RCT demonstrates that a digital educational intervention is associated with increase in knowledge about CMV and can result in behaviour change which may reduce the risk of CMV acquisition in pregnancy. Trial registration Clinicaltrials.gov, NCT03511274 , Registered 27.04.18, http://www.Clinicaltrials.gov

Background The widespread global access to antiretroviral drugs has led to considerable reductions in morbidity and mortality but, unfortunately, the risk of virologic failure increases with the emergence, and potential transmission, of drug resistant viruses. Detecting and quantifying HIV-1 drug resistance has therefore become the standard of care when designing new antiretroviral regimens. The sensitivity of Sanger sequencing-based HIV-1 genotypic assays is limited by its inability to identify minority members of the quasispecies, i.e., it only detects variants present above ~ 20% of the viral population, thus, failing to detect minority variants below this threshold. It is clear that deep sequencing-based HIV-1 genotyping assays are an important step change towards accurately monitoring HIV-infected individuals. Methods We implemented and verified a clinically validated HIV-1 genotyping assay based on deep sequencing (DEEPGEN™) in two clinical laboratories in the United Kingdom: St. George’s University Hospitals Healthcare NHS Foundation Trust (London) and at NHS Lothian (Edinburgh), to characterize minority HIV-1 variants in 109 plasma samples from ART-naïve or -experienced individuals. Results Although subtype B HIV-1 strains were highly prevalent (44%, 48/109), most individuals were infected with non-B subtype viruses (i.e., A1, A2, C, D, F1, G, CRF02_AG, and CRF01_AE). DEEPGEN™ was able to accurately detect drug resistance-associated mutations not identified using standard Sanger sequencing-based tests, which correlated significantly with patient’s antiretroviral treatment histories. A higher proportion of minority PI-, NRTI-, and NNRTI-resistance mutations was detected in NHS Lothian patients compared to individuals from St. George’s, mainly M46I/L and I50 V (associated with PIs), D67 N, K65R, L74I, M184 V/I, and K219Q (NRTIs), and L100I (NNRTIs). Interestingly, we observed an inverse correlation between intra-patient HIV-1 diversity and CD4 + T cell counts in the NHS Lothian patients. Conclusions This is the first study evaluating the transition, training, and implementation of DEEPGEN™ between three clinical laboratories in two different countries. More importantly, we were able to characterize the HIV-1 drug resistance profile (including minority variants), coreceptor tropism, subtyping, and intra-patient viral diversity in patients from the United Kingdom, providing a rigorous foundation for basing clinical decisions on highly sensitive and cost-effective deep sequencing-based HIV-1 genotyping assays in the country.

PurposeThe digital platform-based sharing economy has become ubiquitous all over the world. In this paper, we explore how market actors’ conflicting interpretations of digital platforms’ business models give form and shape value co-creation and capture practices in contexts marked by weak institutions and underdeveloped markets.Design/methodology/approachIntegrating insights from the broader literature on digital platforms and the contemporary turn to “meaning-making” in social theory, we adopt a problematization method to unpack the collective contest over the interpretation of value co-creation and capture from ridesharing platforms in contexts marked by weak institutions and underdeveloped markets.FindingsCollective contest over the interpretation of digital business models may give rise to competing meanings that may enable (or impede) digital platform providers’ ability to co-create and capture value. We present an integrative framework that delineates how firms caught up in such collective contests in contexts marked by weak institutions and underdeveloped markets may utilise such conditions as marketing resources to reset their organising logic in ways that reconcile the conflicting perspectives.Practical implicationsThe paper presents propositions constituting a contribution to a meaning-making perspective on ridesharing digital platforms by offering insights into how digital business models could potentially be localised and adapted to address and align with the peculiarities of contexts. It goes further to present a theoretical model to extend our understanding of the different sources of contestation of meaning of digital platforms.Originality/valueThe meaning-making perspective on digital platforms extends our understanding of how the collective contest over interpretations of value co-creation and capture may offer a set of contradictory frames that yield possibilities for ridesharing platform providers, and their users, to assimilate the organising logic of digital business models into new categories of understanding.

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A two-equation turbulence closure model (k-ω) using an h-adaptive grid technique and finite element method (FEM) has been developed to simulate low Mach flow and heat transfer. These flows are applicable to many flows in engineering and environmental sciences. Of particular interest in the engineering modeling areas are: combustion, solidification, and heat exchanger design. Flows for indoor air quality modeling and atmospheric pollution transport are typical types of environmental flows modeled with this method. The numerical method is based on a hybrid finite element model using an equal-order projection process. The model includes thermal and species transport, localized mesh refinement (h-adaptive) and Petrov-Galerkin weighting for stabilizing advection. This work develops the continuum model of a two-equation turbulence closure method. The fractional step solution method is stated along with the h-adaptive grid method (Carrington and Pepper, 2002). Solutions are presented for 2d flow over a backward-facing step.

Emission of pollutants and their accumulation due to poor ventilation and air exchange are serious problems currently under investigation by many researchers. Of particular concern are issues involving air quality within buildings. Toxic fumes and airborne diseases are known to produce undesirable odors, eye and nose irritations, sickness, and occasionally death. Other products such as tobacco smoke and carbon monoxide can also have serious health effects on people exposed to a poorly ventilated environment; studies indicate that indirect or passive smoking can also lead to lung cancer.

Research at the intersection of strategy, organizational theory, and entrepreneurship explores what facilitates the creation of high-performing entrepreneurial ventures. While prior research has recognized that the venture creation process is often characterized by change, the relationship between various forms of change and entrepreneurial performance remains an important area for further research. This dissertation begins to address this gap, investigating how the distinct changes faced by entrepreneurs relate to venture outcomes. This dissertation answers this question over two research projects, starting with a comprehensive literature review of how venture teams manage internal and external changes. The subsequent empirical study unpacks the role of external change. The empirical analysis uses a survey dataset comprising over one thousand entrepreneurial ventures to unpack the performance implications of a changing macroeconomic environment. This dissertation provides insight into how entrepreneurs address external changes and manage internal ones to create successful ventures. Overall, this dissertation contributes to entrepreneurship, strategy, and organizations research and practice.

The proliferation of crises facing organisations is challenging how individuals make sense and respond to their new environments. This research investigates cognitive shifts in both leaders and followers in response to a cumulative crisis to ascertain the fluctuations in achieving cognitive consensus within a single case study firm. Cognitive vision formation theory and followership theory are integrated to account for the role of both leaders and followers throughout the crisis. 91 cognitive maps of leaders and followers were elicited during three phases of data collection over a four year period and analysed following a standardised procedure to explain how and where consensus was formed. Distance ratios are calculated to measure within and between group consensus and cognitive shifts. This research makes several key and original contributions to knowledge. First, during the initial stages of responding to a crisis it is the followers that are the locus of consensus rather than leaders and subsequently the cognitively diverse leadership teams converges towards follower teams which builds consensus as the crisis first unfolds. Second, following the initial stages, a bottom-up diffusion of consensus process is observed with middle-managers emerging as the locus of consensus between the middle and latter stages. Third, the inclusion of a midpoint in data collection provides fresh empirical evidence that the scope of cognitive consensus fluctuates rather than builds over a sustained period of time. Fourth, this fluctuation requires cognitive shifts in individuals which are detected as being initially higher in leaders than followers during responses to the crisis. Fifth, preliminary empirical evidence demonstrates that degree of cognitive shifts are also greater over a longer period of time than in the initial response to the crisis. Finally, a theoretical framework is developed to map the four different types of cognitive shifts individuals experience during a cumulative crisis. The thesis concludes with a call for future longitudinal multi-level research to further investigate the antecedents of cognitive shifts and empirically test the theoretical framework. Additionally, more attention is now required into the strategic role of followers and middle managers during a crisis.

BackgroundNucleic acid amplification tests are being increasingly used for the routine diagnosis of Neisseria gonorrhoeae (GC), although culture remains essential for monitoring antimicrobial resistance. The authors investigated how symptoms and infection site influenced test sensitivity.MethodsThis was a retrospective study at two centres of patients diagnosed as having GC by Aptima Combo 2 (AC2) confirmed with Aptima GC and/or culture.ResultsThe study included 251 men (71%) and 105 women (29%). The sensitivity for AC2 and culture in the lower genital tract of men with symptoms was 99% (95% CI 95% to 100%) and 79% (95% CI 71% to 85%) and for asymptomatic men was 94% (95% CI 69% to 100%) and 29% (95% CI 11% to 56%), respectively. At the rectum, the sensitivity in symptomatic men was 91% (95% CI 57% to 100%) and 55% (95% CI 25% to 82%) and in asymptomatic men 75% (95% CI 47% to 92%) and 44% (95% CI 21% to 69%) for AC2 and culture, respectively. In symptomatic women, the sensitivity from the genital site was 100% (95% CI 95% to 100%) and 53% (95% CI 38% to 68%) and for asymptomatic women 100% (95% CI 87% to 100%) and 47% (95% CI 30% to 65%) for AC2 and culture, respectively.ConclusionsThe AC2 with AGC confirmation performs well at genital and extra-genital sites for detecting GC. Culture for GC using transport swabs performs poorly in asymptomatic men, symptomatic and asymptomatic women and at extra-genital sites. With the improved performance of nucleic acid amplification tests and the increase in GC antimicrobial resistance, research is needed into how best to optimise GC culture in settings where direct plating is not feasible.