A pantothenate suxotroph of BCG rxpressing Gag confers enhanced HIV-specific immunogenicity compared to wildtype and perfingolysin expressing strains

In tuberculosis vaccine studies, perfingolysin expressing strains (pfo) of recombinant Mycobacterium bovis (rBCG) have been shown to enhance immunogenicity as compared to wildtype strains whilst pantothenate auxotrophic strains (ΔpanCD) have been shown to be safer and more immunogenic. Our group has recently shown that rBCGΔpanCD expressing HIV-1 Gag is more immunogenic than the wildtype Pasteur strain of BCG in the murine model. In this study, a wild type strain, a ΔpanCDstrain, a pfo strain and a ΔpanCD strain expressing perfringolysin (ΔpanCDpfo) of Danish BCG were used as vectors to express HIV-1 subtype C Gag. Gag specific immune responses induced by a prime with each rBCG-Gag vaccine and boost with modified vaccinia Ankara (MVA) were compared

Point-of-Care Testing for Pharyngitis in the Pharmacy.

Pharyngitis (also known as sore throat) is a common, predominately viral, self-limiting condition which can be symptomatically managed without antibiotic treatment. Inappropriate antibiotic use for pharyngitis contributes to the development and spread of antibiotic resistance. However, a small proportion of sore throats caused by group A streptococcal (GAS) infection may benefit from the provision of antibiotics. Establishing the cause of infection is therefore an important step in effective antibiotic stewardship. Point-of-care (POC) tests, where results are available within minutes, can distinguish between viral and GAS pharyngitis and can therefore guide treatment in primary healthcare settings such as community pharmacies, which are often the first point of contact with the healthcare system. In this opinion article, the evidence for the use of POC testing in the community pharmacy has been discussed. Evidence suggests that pharmacy POC testing can promote appropriate antibiotic use and reduce the need for general practitioner consultations. Challenges to implementation include cost, training and 'who prescribes', with country and regional differences presenting a particular issue. Despite these challenges, POC testing for pharyngitis has become widely available in pharmacies in some countries and may represent a strategy to contain antibiotic resistance and contribute to antimicrobial stewardship

Long-term stability of TES satellite radiance measurements

The utilization of Tropospheric Emission Spectrometer (TES) Level 2 (L2) retrieval products for the purpose of assessing long term changes in atmospheric trace gas composition requires knowledge of the overall radiometric stability of the Level 1B (L1B) radiances. The purpose of this study is to evaluate the stability of the radiometric calibration of the TES instrument by analyzing the difference between measured and calculated brightness temperatures in selected window regions of the spectrum. The Global Modeling and Assimilation Office (GMAO) profiles for temperature and water vapor and the Real-Time Global Sea Surface Temperature (RTGSST) are used as input to the Optimal Spectral Sampling (OSS) radiative transfer model to calculate the simulated spectra. The TES reference measurements selected cover a 4-year period of time from mid 2005 through mid 2009 with the selection criteria being; observation latitudes greater than −30° and less than 30°, over ocean, Global Survey mode (nadir view) and retrieved cloud optical depth of less than or equal to 0.01. The TES cloud optical depth retrievals are used only for screening purposes and no effects of clouds on the radiances are included in the forward model. This initial screening results in over 55 000 potential reference spectra spanning the four year period. Presented is a trend analysis of the time series of the residuals (observation minus calculations) in the TES 2B1, 1B2, 2A1, and 1A1 bands, with the standard deviation of the residuals being approximately equal to 0.6 K for bands 2B1, 1B2, 2A1, and 0.9 K for band 1A1. The analysis demonstrates that the trend in the residuals is not significantly different from zero over the 4-year period. This is one method used to demonstrate that the relative radiometric calibration is stable over time, which is very important for any longer term analysis of TES retrieved products (L2), particularly well-mixed species such as carbon dioxide and methane

Across-track extension of retrieved cloud and aerosol properties for the EarthCARE mission: the ACMB-3D product

The narrow cross section of cloud and aerosol properties retrieved by L2 algorithms that operate on data from EarthCARE's nadir-pointing sensors is broadened across-track by an algorithm that is described and demonstrated here. This scene construction algorithm (SCA) consists of four components. At its core is a radiance-matching procedure that works with measurements made by EarthCARE's Multi-Spectral Imager (MSI). In essence, an off-nadir pixel gets filled with retrieved profiles that are associated with a (nearby) nadir pixel whose MSI radiances best match those of the off-nadir pixel. The SCA constructs a 3D array of cloud and aerosol (and surface) properties for entire frames that measure ∼6000 km along-track by 150 km across-track (i.e., the MSI's full swath). Constructed domains out to ∼15 km across-track on both sides of nadir are used explicitly downstream as input for 3D radiative transfer models that predict top-of-atmosphere (TOA) broadband solar and thermal fluxes and radiances. These quantities are compared to commensurate measurements made by EarthCARE's Broadband Radiometer (BBR), thus facilitating a continuous closure assessment of the retrievals. Three 6000 km ×200 km frames of synthetic EarthCARE observations were used to demonstrate the SCA. The main conclusion is that errors in modelled TOA fluxes that stem from use of 3D domains produced by the SCA are expected to be less than ±5 W m−2 and rarely larger than ±10 W m−2. As such, the SCA, as purveyor of information needed to run 3D radiative transfer models, should help more than hinder the radiative closure assessment of EarthCARE's L2 retrievals.</p

Symptom lead times in lung and colorectal cancers: What are the benefits of symptom-based approaches to early diagnosis?

This is the final version of the article. Available from Cancer Research UK via the DOI in this record.Background: Individuals with undiagnosed lung and colorectal cancers present with non-specific symptoms in primary care more often than matched controls. Increased access to diagnostic services for patients with symptoms generates more early-stage diagnoses, but the mechanisms for this are only partially understood. Methods: We re-analysed a UK-based case-control study to estimate the Symptom Lead Time (SLT) distribution for a range of potential symptom criteria for investigation. Symptom Lead Time is the time between symptoms caused by cancer and eventual diagnosis, and is analogous to Lead Time in a screening programme. We also estimated the proportion of symptoms in lung and colorectal cancer cases that are actually caused by the cancer. Results: Mean Symptom Lead Times were between 4.1 and 6.0 months, with medians between 2.0 and 3.2 months. Symptom Lead Time did not depend on stage at diagnosis, nor which criteria for investigation are adopted. Depending on the criteria, an estimated 27-48% of symptoms in individuals with as yet undiagnosed lung cancer, and 12-32% with undiagnosed colorectal cancer are not caused by the cancer. Conclusions: In most cancer cases detected by a symptom-based programme, the symptoms are caused by cancer. These cases have a short lead time and benefit relatively little. However, in a significant minority of cases cancer detection is serendipitous. This group experiences the benefits of a standard screening programme, a substantial mean lead time and a higher probability of early-stage diagnosis.This work was supported by the National Institute for Health Research (NIHR) Programme Grants for Applied Research Programme, RP-PG-0608-10045

Effect of pre-existing conditions on bladder cancer stage at diagnosis: a cohort study using electronic primary care records in the UK

This is the final version. Available on open access from the Royal College of General Practitioners via the DOI in this recordBackground Pre-existing concurrent medical conditions (multimorbidity) complicate cancer diagnosis when they provide plausible diagnostic alternatives for cancer symptoms. Aim To investigate associations in bladder cancer between: first, pre-existing condition count and advanced-stage diagnosis; and, second, comorbidities that share symptoms with bladder cancer and advanced-stage diagnosis. Design and setting This observational UK cohort study was set in the Clinical Practice Research Datalink with Public Health England National Cancer Registration and Analysis Service linkage. Method Included participants were aged ≥40 years with an incident diagnosis of bladder cancer between 1 January 2000 and 31 December 2015, and primary care records of attendance for haematuria, dysuria, or abdominal mass in the year before diagnosis. Stage at diagnosis (stage 1 or 2 versus stage 3 or 4) was the outcome variable. Putative explanatory variables using logistic regression were examined, including patient-level count of pre-existing conditions and ‘alternative-explanations’, indicating whether pre-existing condition(s) were plausible diagnostic alternatives for the index cancer symptom. Results In total, 1468 patients (76.4% male) were studied, of which 399 (35.6%) males and 217 (62.5%) females had alternative explanations for their index cancer symptom, the most common being urinary tract infection with haematuria. Females were more likely than males to be diagnosed with advanced-stage cancer (adjusted odds ratio [aOR] 1.62; 95% confidence interval [CI] = 1.20 to 2.18; P = 0.001). Alternative explanations were strongly associated with advanced-stage diagnosis in both sexes (aOR 1.69; 95% CI = 1.20 to 2.39; P = 0.003). Conclusion Alternative explanations were associated with advanced-stage diagnosis of bladder cancer. Females were more likely than males to be diagnosed with advanced-stage disease, but the effect was not driven entirely by alternative explanations.USF Health Morsani College of Medicine, Research, Innovation and Scholarly EndeavorsCancer Research UKNational Institute for Health Research (NIHR

Broadband radiative quantities for the EarthCARE mission: the ACM-COM and ACM-RT products

The EarthCARE satellite mission's objective is to retrieve profiles of aerosol and water cloud physical properties from measurements made by its cloud-profiling radar, backscattering lidar, and passive multi-spectral imager. These retrievals, together with other geophysical properties, are input into broadband (BB) radiative transfer (RT) models that predict radiances and fluxes commensurate with measurements made and inferred from EarthCARE's BB radiometer (BBR). The scientific goal is that modelled and “observed” BB top-of-atmosphere (TOA) fluxes differ, on average, by less than ±10 W m−2. When sound synergistic retrievals from the ACM-CAP process (ACM: ATLID – backscattering lidar, CPR – cloud-profiling radar, and MSI – multi-spectral imager; CAP: clouds, aerosols, and precipitation) are available, they are acted on by the RT models. When they are not available, the RT models act on “composite” profiles of properties retrieved from measurements made by individual sensors. Compositing is performed in the ACM-COM (COM: composite) process. The majority of this report describes the RT models – and their products – that make up EarthCARE's ACM-RT process. Profiles of BB shortwave (SW) and longwave (LW) fluxes and heating rates (HRs) are computed by 1D RT models for each ∼ 1 km nadir column of inferred properties. Three-dimensional RT models compute radiances for the BBR's three viewing directions, with the SW model also computing flux and HR profiles; the 3D LW model produces upwelling flux at just one level. All 3D RT products are averages over 5×21 km “assessment domains” that are constructed using MSI data. Some of ACM-RT's products are passed forward to the “radiative closure assessment” process that quantifies, for each assessment domain, the likelihood that EarthCARE's goal has been achieved. As EarthCARE represents the first mission to make “operational” use of 3D RT models, emphasis is placed on differences between 1D and 3D RT results. For upwelling SW flux at 20 km altitude, 1D and 3D values can be expected to differ by more than EarthCARE's scientific goal of ±10 W m−2 at least 50 % of the time.</p

Input aggregation bias in technical efficiency with multiple criteria analysis

We extend the Tauer (2001) and Färe et al. (2004) analyses of aggregation bias in technical efficiency measurement to multiple criteria decision analysis. We show input aggregation conditions consistent with multiple criteria evaluation of overall efficiency in conjunction with variation in aggregation bias