a quasi-experimental study

Funding Information: This study was elaborated based on the work of Miguelhete Lisboa doctoral program, a Fundação Calouste Gulbenkian scholarship holder, and used grants obtained from The Special Programme for Research and Training in Tropical Diseases (TDR) and co-sponsored by the United Nations Children’s Fund (UNICEF), United Nations Development Programme (UNDP), World Bank, and World Health Organization (WHO)—award ID number: B40151/ 2014. The FCG and WHO/TDR were not involved in the design of the study and collection; analysis and interpretation of data; and writing the manuscript; therefore, the authors are responsible for all information. Publisher Copyright: © 2020 The Author(s).Background In-hospital logistic management barriers (LMB) are considered to be important risk factors for delays in TB diagnosis and treatment initiation (TB-dt), which perpetuates TB transmission and the development of TB morbidity and mortality. We assessed the contribution of hospital auxiliary workers (HAWs) and 24-h TB laboratory services using Xpert (24h-Xpert) on the delays in TB-dt and TB mortality at Beira Central Hospital, Mozambique. Methods A quasi-experimental design was used. Implementation strategy—HAWs and laboratory technicians were selected and trained, accordingly. Interventions—having trained HAW and TB laboratory technicians as expediters of TB LMB issues and assurer of 24h-Xpert, respectively. Implementation outcomes—time from hospital admission to sputum examination results, time from hospital admission to treatment initiation, proportion of same-day TB cases diagnosed, initiated TB treatment, and TB patient with unfavorable outcome after hospitalization (hospital TB mortality). A nonparametric test was used to test the differences between groups and adjusted OR (95% CI) were computed using multivariate logistic regression. Results We recruited 522 TB patients. Median (IQR) age was 34 (16) years, and 52% were from intervention site, 58% males, 60% new case of TB, 12% MDR-TB, 72% TB/HIV co-infected, and 43% on HIV treatment at admission. In the intervention hospital, 93% of patients had same-day TB-dt in comparison with a median (IQR) time of 15 (2) days in the control hospital. TB mortality in the intervention hospital was lower than that in the control hospital (13% vs 49%). TB patients admitted to the intervention hospital were nine times more likely to obtain an early laboratory diagnosis of TB, six times more likely to reduce delays in TB treatment initiation, and eight times less likely to die, when compared to those who were admitted to the control hospital, adjusting for other factors. Conclusion In-hospital delays in TB-dt and high TB mortality in Mozambique are common and probably due, in part, to LMB amenable to poor-quality TB care. Task shifting of TB logistic management services to HAWs and lower laboratory technicians, to ensure 24h-Xpert through “on-the-spot strategy,” may contribute to timely TB detection, proper treatment, and reduction of TB mortality.publishersversionpublishe

healthcare workers’ perspective from Beira, Mozambique

Funding Information: This study was elaborated based on the work of first Miguelhete Lisboa?s doctoral program, a Funda??o Calouste Gulbenkian (FCG) scholarship holder (ID: P-135647/SBG/2014) and, used grants obtained from World Health Organization, The Special Programme for Research and Training in Tropical Diseases (WHO/TDR) and co-sponsored by the United Nations Children?s Fund, United Nations Development Programme, World Bank and WHO ? award ID number: B40151/2014. The FCG and WHO/TDR were neither involved in the design of the study and collection, analysis, interpretation of data, nor in the writing of manuscript or decision to publish. Therefore, the authors are responsible for all information. The authors acknowledge the Tutorial Commission of the doctoral program of Miguelhete Lisboa (Professors Sonia Dias and Miguel Viveiros at Instituto de Higiene e Medicina Tropical Universidade Nova de Lisboa, Portugal); people who helped in the collection and data management: Marques Nhamonga, Joaquim Lequechane and Estefano Colove; the Centro de Investiga??o Operacional da Beira directorate and all colleagues, the Beira Central Hospital directorate and all healthcare workers. Publisher Copyright: © 2020 Lisboa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background: Mozambique is one of the countries with the deadly implementation gaps in the tuberculosis (TB) care and services delivery. In-hospital delays in TB diagnosis and treatment, transmission and mortality still persist, in part, due to poor-quality of TB care cascade. Objective: We aimed to assess, from the healthcare workers’ (HCW) perspective, factors associated with poor-quality TB care cascade and explore local sustainable suggestions to improve in-hospital TB management. Methods: In-depth interviews and focus group discussions were conducted with different categories of HCW. Audio-recording and written notes were taken, and content analysis was performed through atlas.ti7. Results: Bottlenecks within hospital TB care cascade, lack of TB staff and task shifting, centralized and limited time of TB laboratory services, and fear of healthcare workers getting infected by TB were mentioned to be the main factors associated with implementation gaps. Interviewees believe that task shifting from nurses to hospital auxiliary workers, and from higher and well-trained to lower HCW are accepted and feasible. The expansion and use of molecular TB diagnostic tools are seen by the interviewees as a proper way to fight effectively against both sensitive and MDR TB. Ensuring provision of N95 respiratory masks is believed to be an essential requirement for effective engagement of the HCW on high-quality in-hospital TB care. For monitoring and evaluation, TB quality improvement teams in each health facility are considered to be an added value. Conclusion: Shortage of resources within the national TB control programme is one of the potential factors for poor-quality of the TB care cascade. Task shifting of TB care and services delivery, decentralization of the molecular TB diagnostic tools, and regular provision of N95 respiratory masks should contribute not just to reduce the impact of resource scarceness, but also to ensure proper TB diagnosis and treatment to both sensitive and MDR TB.publishersversionpublishe

Diverse specificities, phenotypes, and antiviral activities of cytomegalovirus-specific CD8+ T cells.

UNLABELLED: CD8(+) T cells specific for pp65, IE1, and IE2 are present at high frequencies in human cytomegalovirus (HCMV)-seropositive individuals, and these have been shown to have phenotypes associated with terminal differentiation, as well as both cytokine and proliferative dysfunctions, especially in the elderly. However, more recently, T cell responses to many other HCMV proteins have been described, but little is known about their phenotypes and functions. Consequently, in this study, we chose to determine the diversity of HCMV-specific CD8(+) T cell responses to the products of 11 HCMV open reading frames (ORFs) in a cohort of donors aged 20 to 80 years old as well as the ability of the T cells to secrete gamma interferon (IFN-γ). Finally, we also tested their functional antiviral capacity using a novel viral dissemination assay. We identified substantial CD8(+) T cell responses by IFN-γ enzyme-linked immunospot (ELISPOT) assays to all 11 of these HCMV proteins, and across the cohort, individuals displayed a range of responses, from tightly focused to highly diverse, which were stable over time. CD8(+) T cell responses to the HCMV ORFs were highly differentiated and predominantly CD45RA(+), CD57(+), and CD28(-), across the cohort. These highly differentiated cells had the ability to inhibit viral spread even following direct ex vivo isolation. Taken together, our data argue that HCMV-specific CD8(+) T cells have effective antiviral activity irrespective of the viral protein recognized across the whole cohort and despite viral immune evasion. IMPORTANCE: Human cytomegalovirus (HCMV) is normally carried without clinical symptoms and is widely prevalent in the population; however, it often causes severe clinical disease in individuals with compromised immune responses. HCMV is never cleared after primary infection but persists in the host for life. In HCMV carriers, the immune response to HCMV includes large numbers of virus-specific immune cells, and the virus has evolved many mechanisms to evade the immune response. While this immune response seems to protect healthy people from subsequent disease, the virus is never eliminated. It has been suggested that this continuous surveillance by the immune system may have deleterious effects in later life. The study presented in this paper examined immune responses from a cohort of donors and shows that these immune cells are effective at controlling the virus and can overcome the virus' lytic cycle immune evasion mechanisms.This work was funded by British Medical Research Council Grant G0701279 and supported by the NIHR Cambridge BRC Cell Phenotyping hub.This is the accepted manuscript version. The final published version is available from ASM at http://jvi.asm.org/content/early/2014/07/03/JVI.01477-14.abstract

Balanced and Restored Cross-Sections Representing Post-Miocene Crustal Extension of Fluvial Deposits, North-Central Montana to Southeast Idaho

This research is part of a larger project based on the theory of the existence of a pre-ice age, Amazon-scale river that had headwaters in the southern Colorado Plateau and flowed north through the western United States and Canada before discharging into the Labrador Sea. Stream-rounded fluvial deposits in Montana and Idaho provide evidence of sediment provenance in Nevada and Utah, as there are no confirmed bedrock sources for these sediments in Montana or Idaho. The Miocene river bed has been offset and tilted by dozens of extensional faults in the region. Some faults bound large mountain ranges including the Lost River, Lemhi, Beaverhead, Tendoy, Blacktail Deer, Ruby, Madison, and Big Belt Mountains. The reconstructed trend of the Miocene river bed provides a reference line against which to measure active faulting. We constructed five balanced cross-sections of the deformed subsurface along the Miocene river bed from north-central Montana to southeast Idaho across the faulted mountain ranges and restored the cross-sections to represent an un-deformed subsurface. This provided valuable insight into crustal deformation in these regions. Knowing the timing and extent of crustal deformation has many scientific and societal benefits. Western Montana and adjacent Idaho occupy the Inter-mountain Seismic Zone and have the potential for large earthquakes. Detailed cross-sections through this zone can provide information for development projects in faulted areas, and target potential aquifer locations where the thick river gravel has been down-faulted into the sub-surface. This research will be an important contribution to understanding the evolution of the tectonic landscape of Montana and Idaho

Independent predictors of failure up to 7.5 years after 35 386 single-brand cementless total hip replacements: a retrospective cohort study using National Joint Registry data

The popularity of cementless total hip replacement (THR) has surpassed cemented THR in England and Wales. This retrospective cohort study records survival time to revision following primary cementless THR with the most common combination (accounting for almost a third of all cementless THRs), and explores risk factors independently associated with failure, using data from the National Joint Registry for England and Wales. Patients with osteoarthritis who had a DePuy Corail/Pinnacle THR implanted between the establishment of the registry in 2003 and 31 December 2010 were included within analyses. There were 35 386 procedures. Cox proportional hazard models were used to analyse the extent to which the risk of revision was related to patient, surgeon and implant covariates. The overall rate of revision at five years was 2.4% (99% confidence interval 2.02 to 2.79). In the final adjusted model, we found that the risk of revision was significantly higher in patients receiving metal-on-metal (MoM: hazard ratio (HR) 1.93, p < 0.001) and ceramic-on-ceramic bearings (CoC: HR 1.55, p = 0.003) compared with the best performing bearing (metal-on-polyethylene). The risk of revision was also greater for smaller femoral stems (sizes 8 to 10: HR 1.82, p < 0.001) compared with mid-range sizes. In a secondary analysis of only patients where body mass index (BMI) data were available (n = 17 166), BMI ≥ 30 kg/m2 significantly increased the risk of revision (HR 1.55, p = 0.002). The influence of the bearing on the risk of revision remained significant (MoM: HR 2.19, p < 0.001; CoC: HR 2.09, p = 0.001). The risk of revision was independent of age, gender, head size and offset, shell, liner and stem type, and surgeon characteristics. We found significant differences in failure between bearing surfaces and femoral stem size after adjustment for a range of covariates in a large cohort of single-brand cementless THRs. In this study of procedures performed since 2003, hard bearings had significantly higher rates of revision, but we found no evidence that head size had an effect. Patient characteristics, such as BMI and American Society of Anesthesiologists grade, also influence the survival of cementless components

Modular differential equations for characters of RCFT

We discuss methods, based on the theory of vector-valued modular forms, to determine all modular differential equations satisfied by the conformal characters of RCFT; these modular equations are related to the null vector relations of the operator algebra. Besides describing effective algorithmic procedures, we illustrate our methods on an explicit example.Comment: 13 page

Hierarchical Level of Detail Optimisation for Constant Framerate Rendering of Radiosity Scenes

The predictive hierarchical level of detail optimization algorithm of Mason and Blake is experimentally evaluated in the form of a practical application to hierarchical radiosity. In a novel approach the recursively subdivided patch hierarchy generated by a perceptually refined hierarchical radiosity algorithm is treated as a hierarchical level of detail scene description. In this way we use the Mason-Blake algorithm to successfully maintain constant frame rates during the interactive rendering of the radiosity-generated scene. We establish that the algorithm is capable of maintaining uniform frame rendering times, but that the execution time of the optimization algorithm itself is significant and is strongly dependent on frame-to-frame coherence and the granularity of the level of detail description. To compensate we develop techniques which effectively reduce and limit the algorithm execution time: We restrict the execution times of the algorithm to guard against pathological situations and propose simplification transforms that increase the granularity of the scene description, at minimal cost to visual quality. We demonstrate that using these techniques the algorithm is capable of maintaining interactive frame rates for scenes of arbitrary complexity. Furthermore we provide guidelines for the appropriate use of predictive level of detail optimization algorithms derived from our practical experience

Adding abiraterone to androgen deprivation therapy in men with metastatic hormone-sensitive prostate cancer: a systematic review and meta-analysis

BACKGROUND: There is a need to synthesise the results of numerous randomised controlled trials evaluating the addition of therapies to androgen deprivation therapy (ADT) for men with metastatic hormone-sensitive prostate cancer (mHSPC). This systematic review aims to assess the effects of adding abiraterone acetate plus prednisone/prednisolone (AAP) to ADT. METHODS: Using our framework for adaptive meta-analysis (FAME), we started the review process before trials had been reported and worked collaboratively with trial investigators to anticipate when eligible trial results would emerge. Thus, we could determine the earliest opportunity for reliable meta-analysis and take account of unavailable trials in interpreting results. We searched multiple sources for trials comparing AAP plus ADT versus ADT in men with mHSPC. We obtained results for the primary outcome of overall survival (OS), secondary outcomes of clinical/radiological progression-free survival (PFS) and grade III-IV and grade V toxicity direct from trial teams. Hazard ratios (HRs) for the effects of AAP plus ADT on OS and PFS, Peto Odds Ratios (Peto ORs) for the effects on acute toxicity and interaction HRs for the effects on OS by patient subgroups were combined across trials using fixed-effect meta-analysis. FINDINGS: We identified three eligible trials, one of which was still recruiting (PEACE-1 (NCT01957436)). Results from the two remaining trials (LATITUDE (NCT01715285) and STAMPEDE (NCT00268476)), representing 82% of all men randomised to AAP plus ADT versus ADT (without docetaxel in either arm), showed a highly significant 38% reduction in the risk of death with AAP plus ADT (HR = 0.62, 95% confidence interval [CI] = 0.53-0.71, p = 0.55 × 10(-10)), that translates into a 14% absolute improvement in 3-year OS. Despite differences in PFS definitions across trials, we also observed a consistent and highly significant 55% reduction in the risk of clinical/radiological PFS (HR = 0.45, 95% CI = 0.40-0.51, p = 0.66 × 10(-36)) with the addition of AAP, that translates to a 28% absolute improvement at 3 years. There was no evidence of a difference in the OS benefit by Gleason sum score, performance status or nodal status, but the size of the benefit may vary by age. There were more grade III-IV acute cardiac, vascular and hepatic toxicities with AAP plus ADT but no excess of other toxicities or death. INTERPRETATION: Adding AAP to ADT is a clinically effective treatment option for men with mHSPC, offering an alternative to docetaxel for men who are starting treatment for the first time. Future research will need to address which of these two agents or whether their combination is most effective, and for whom

A Human Development Framework for CO2 Reductions

Although developing countries are called to participate in CO2 emission reduction efforts to avoid dangerous climate change, the implications of proposed reduction schemes in human development standards of developing countries remain a matter of debate. We show the existence of a positive and time-dependent correlation between the Human Development Index (HDI) and per capita CO2 emissions from fossil fuel combustion. Employing this empirical relation, extrapolating the HDI, and using three population scenarios, the cumulative CO2 emissions necessary for developing countries to achieve particular HDI thresholds are assessed following a Development As Usual approach (DAU). If current demographic and development trends are maintained, we estimate that by 2050 around 85% of the world's population will live in countries with high HDI (above 0.8). In particular, 300Gt of cumulative CO2 emissions between 2000 and 2050 are estimated to be necessary for the development of 104 developing countries in the year 2000. This value represents between 20% to 30% of previously calculated CO2 budgets limiting global warming to 2{\deg}C. These constraints and results are incorporated into a CO2 reduction framework involving four domains of climate action for individual countries. The framework reserves a fair emission path for developing countries to proceed with their development by indexing country-dependent reduction rates proportional to the HDI in order to preserve the 2{\deg}C target after a particular development threshold is reached. Under this approach, global cumulative emissions by 2050 are estimated to range from 850 up to 1100Gt of CO2. These values are within the uncertainty range of emissions to limit global temperatures to 2{\deg}C.Comment: 14 pages, 7 figures, 1 tabl

A low balance between microparticles expressing tissue factor pathway inhibitor and tissue factor is associated with thrombosis in Behçet’s Syndrome

Thrombosis is common in Behçet’s Syndrome (BS), and there is a need for better biomarkers for risk assessment. As microparticles expressing Tissue Factor (TF) can contribute to thrombosis in preclinical models, we investigated whether plasma microparticles expressing Tissue Factor (TF) are increased in BS. We compared blood plasma from 72 healthy controls with that from 88 BS patients (21 with a history of thrombosis (Th+) and 67 without (Th−). Using flow cytometry, we found that the total plasma MP numbers were increased in BS compared to HC, as were MPs expressing TF and Tissue Factor Pathway Inhibitor (TFPI) (all p 0.7 had a history of clinical thrombosis. We conclude that TF-expressing MP are increased in BS and that an imbalance between microparticulate TF and TFPI may predispose to thrombosis