Evaluation of Rapid Syphilis Testing Using the Syphilis Health Check in Florida, 2015–2016

The Syphilis Health Check (SHC) had low estimated specificity (91.5%) in one Florida county. We investigated use of SHC by a range of Florida publicly-funded programs between 2015 and 2016 to estimate specificity, positive predictive value (PPV), field staff acceptance, and impacts on programmatic outcomes. All reported SHC results were extracted from routinely collected program data. Field staff were surveyed about SHC’s utility. Analyses investigated differences between SHC and traditional syphilis testing outcomes. Of 3,630 SHC results reported, 442 were reactive; 92 (20.8%) had prior diagnoses of syphilis; 7 (1.6%) had no further testing. Of the remaining 343; 158 (46.0%) were confirmed cases, 168 (49.0%) were considered false-positive, and 17 (5.0%) were not cases but not clearly false-positive. Estimated specificity of SHC was 95.0%. Overall, 48.5% of positives became confirmed cases (PPV). PPV varied according to prevalence of syphilis in populations tested. Staff (90%) thought SHC helped identify new cases but expressed concern regarding discordance between reactive SHC and lab-based testing. Programmatic outcomes assessment showed shorter time to treatment and increased numbers of partners tested for the SHC group; these enhanced outcomes may better mitigate the spread of syphilis compared to traditional syphilis testing alone, but more research is needed

An update on oral cavity cancer:epidemiological trends, prevention strategies and novel approaches in diagnosis and prognosis

In the UK, the incidence of oral cavity cancer continues to rise, with an increase of around 60% over the past 10 years. Many patients still present with advanced disease, often resulting in locoregional recurrence and poor outcomes, which has not changed significantly for over four decades. Changes in aetiology may also be emerging, given the decline of smoking in developed countries. Therefore, new methods to better target prevention, improve screening and detect recurrence are needed. High-throughput ‘omics’ technologies appear promising for future individual-level diagnosis and prognosis. However, given this is a relatively rare cancer with significant intra-tumour heterogeneity and variation in patient response, reliable biomarkers have been difficult to elucidate. From a public health perspective, implementing these novel technologies into current services would require substantial practical, financial and ethical considerations. This may be difficult to justify and implement at present, therefore focus remains on early detection using new patient-led follow-up strategies. This paper reviews the latest evidence on epidemiological trends in oral cavity cancer to help identify at risk groups, population-based approaches for prevention, in addition to potential cutting-edge approaches in the diagnosis and prognosis of this disease. Keywords: Epidemiology, Oral Cancer, Survival, Risk Factors, Squamous Cell Carcinoma, Mouth Neoplasm

Calculating 14C mean residence times of inorganic carbon derived from oxidation of organic carbon in groundwater using the principles of 87Sr/86Sr and cation ratio mixing

The model radiocarbon age of inorganic carbon (IC) in groundwater is a key parameter for understanding groundwater chemical history and physical parameters such as groundwater residence times and flow rates. Current interpretations are based on the principle that bulk IC derives from multiple sources such as oxidation of organic carbon (OC), carbonate dissolution, and soil zone processes as well as from rainwater. Using this principle, multiple adjustment methods have been developed to calculate rainwater-related recharge ages. Of further interest, however, is the radiocarbon age of oxidised OC. This is a key measurement given that OC oxidation controls the mobility of many important geochemical components such as Fe, As, Mn and U. In this instance, conventional approaches tacitly assume that the majority of IC comes from the oxidation of OC and that other sources have a negligible effect on the bulk age. In reality, however, there are multiple sources of IC which can all effect bulk radiocarbon ages. We present a new approach to calculate the age of IC derived from a specific source. This approach uses strontium isotopes (87Sr/86Sr) coupled with elemental ratios to trace and quantify the mixing of different sources of IC. We demonstrate the approach by calculating the model radiocarbon age of IC sourced from the oxidation of OC for a case study of an aquifer in the Cambodian lowlands located adjacent to the Mekong river south of Phnom Penh. The results show that, although bulk IC is younger and more isotopically (δ13C) depleted than bulk organic carbon (OC), IC derived from oxidation of OC has a similar age and isotopic signature to bulk OC. Furthermore, at our site, the age of the IC formed from the oxidation of organic carbon predates modelled groundwater flow by at least a millennium indicating that in-aquifer oxidation is an important process, something previously questioned at the site. This highlights the utility of the new approach to disentangling the origin of the sources of bulk IC, so critical to the interpretation of its model radiocarbon age and isotopic signature

Interferon-γ inhibits interleukin-1β-induced matrix metalloproteinase production by synovial fibroblasts and protects articular cartilage in early arthritis

Introduction: The first few months after symptom onset represents a pathologically distinct phase in rheumatoid arthritis (RA). We used relevant experimental models to define the pathological role of interferon-γ (IFN-γ) during early inflammatory arthritis. Methods: We studied IFN-γ's capacity to modulate interleukin-1β (IL-1β) induced degenerative responses using RA fibroblast-like synoviocytes (FLS), a bovine articular cartilage explant (BACE)/RA-FLS co-culture model and an experimental inflammatory arthritis model (murine antigen-induced arthritis (AIA)). Results: IFN-γ modulated IL-1β driven matrix metalloproteinases (MMP) synthesis resulting in the down-regulation of MMP-1 and MMP-3 production in vitro. IFN-γ did not affect IL-1β induced tissue inhibitor of metalloproteinase-1 (TIMP-1) production by RA FLS but skewed the MMP/TIMP-1 balance sufficiently to attenuate glycosaminoglycan-depletion in our BACE model. IFN-γ reduced IL-1β expression in the arthritic joint and prevented cartilage degeneration on Day 3 of AIA. Conclusions: Early therapeutic intervention with IFN-γ may be critical to orchestrate tissue-protective responses during inflammatory arthritis

Dual in-aquifer and near surface processes drive arsenic mobilization in Cambodian groundwaters

Millions of people globally, and particularly in South and Southeast Asia, face chronic exposure to arsenic from reducing groundwater in which arsenic release is widely attributed to the reductive dissolution of arsenic-bearing iron minerals, driven by metal reducing bacteria using bioavailable organic matter as an electron donor. However, the nature of the organic matter implicated in arsenic mobilization, and the location within the subsurface where these processes occur, remains debated. In a high resolution study of a largely pristine, shallow aquifer in Kandal Province, Cambodia, we have used a complementary suite of geochemical tracers (including 14C, 3H, 3He, 4He, Ne, δ18O, δD, CFCs and SF6) to study the evolution in arsenic-prone shallow reducing groundwaters along dominant flow paths. The observation of widespread apparent 3H-3He ages of 30 m, and the relationships between age-related tracers and arsenic suggest that this surface-derived organic matter is likely to contribute to in-aquifer arsenic mobilization. A strong relationship between 3H-3He age and depth suggests the dominance of a vertical hydrological control with an overall vertical flow velocity of ~0.4 ± 0.1 m·yr−1 across the field area. A calculated overall groundwater arsenic accumulation rate of ~0.08 ± 0.03 μM·yr−1 is broadly comparable to previous estimates from other researchers for similar reducing aquifers in Bangladesh. Although apparent arsenic groundwater accumulation rates varied significantly with site (e.g. between sand versus clay dominated sequences), rates are generally highest near the surface, perhaps reflecting the proximity to the redox cline and/or depth-dependent characteristics of the OM pool, and confounded by localized processes such as continued in-aquifer mobilization, sorption/desorption, and methanogenesis

Appetite, gut hormone and energy intake responses to low volume sprint interval and traditional endurance exercise.

Sprint interval exercise improves several health markers but the appetite and energy balance response is unknown. This study compared the effects of sprint interval and endurance exercise on appetite, energy intake and gut hormone responses. Twelve healthy males [mean (SD): age 23 (3) years, body mass index 24.2 (2.9) kg m(-2), maximum oxygen uptake 46.3 (10.2) mL kg(-1) min(-1)] completed three 8 h trials [control (CON), endurance exercise (END), sprint interval exercise (SIE)] separated by 1 week. Trials commenced upon completion of a standardised breakfast. Sixty minutes of cycling at 68.1 (4.3) % of maximum oxygen uptake was performed from 1.75-2.75 h in END. Six 30-s Wingate tests were performed from 2.25-2.75 h in SIE. Appetite ratings, acylated ghrelin and peptide YY (PYY) concentrations were measured throughout each trial. Food intake was monitored from buffet meals at 3.5 and 7 h and an overnight food bag. Appetite (P 0.05). Therefore, relative energy intake (energy intake minus the net energy expenditure of exercise) was lower in END than that in CON (15.7 %; P = 0.006) and SIE (11.5 %; P = 0.082). An acute bout of endurance exercise resulted in lower appetite perceptions in the hours after exercise than sprint interval exercise and induced a greater 24 h energy deficit due to higher energy expenditure during exercise

Early satellite cell communication creates a permissive environment for long-term muscle growth

Using in vivo muscle stem cell (satellite cell)-specific extracellular vesicle (EV) tracking, satellite cell depletion, in vitro cell culture, and single-cell RNA sequencing, we show satellite cells communicate with other cells in skeletal muscle during mechanical overload. Early satellite cell EV communication primes the muscle milieu for proper long-term extracellular matrix (ECM) deposition and is sufficient to support sustained hypertrophy in adult mice, even in the absence of fusion to muscle fibers. Satellite cells modulate chemokine gene expression across cell types within the first few days of loading, and EV delivery of miR 206 to fibrogenic cells represses Wisp1 expression required for appropriate ECM remodeling. Late-stage communication from myogenic cells during loading is widespread but may be targeted toward endothelial cells. Satellite cells coordinate adaptation by influencing the phenotype of recipient cells, which extends our understanding of their role in muscle adaptation beyond regeneration and myonuclear donation

Which clinical research questions are the most important?:Development and preliminary validation of the Australia & New Zealand Musculoskeletal (ANZMUSC) Clinical Trials Network Research Question Importance Tool (ANZMUSC-RQIT)

Background and aimsHigh quality clinical research that addresses important questions requires significant resources. In resource-constrained environments, projects will therefore need to be prioritized. The Australia and New Zealand Musculoskeletal (ANZMUSC) Clinical Trials Network aimed to develop a stakeholder-based, transparent, easily implementable tool that provides a score for the 'importance' of a research question which could be used to rank research projects in order of importance.MethodsUsing a mixed-methods, multi-stage approach that included a Delphi survey, consensus workshop, inter-rater reliability testing, validity testing and calibration using a discrete-choice methodology, the Research Question Importance Tool (ANZMUSC-RQIT) was developed. The tool incorporated broad stakeholder opinion, including consumers, at each stage and is designed for scoring by committee consensus.ResultsThe ANZMUSC-RQIT tool consists of 5 dimensions (compared to 6 dimensions for an earlier version of RQIT): (1) extent of stakeholder consensus, (2) social burden of health condition, (3) patient burden of health condition, (4) anticipated effectiveness of proposed intervention, and (5) extent to which health equity is addressed by the research. Each dimension is assessed by defining ordered levels of a relevant attribute and by assigning a score to each level. The scores for the dimensions are then summed to obtain an overall ANZMUSC-RQIT score, which represents the importance of the research question. The result is a score on an interval scale with an arbitrary unit, ranging from 0 (minimal importance) to 1000. The ANZMUSC-RQIT dimensions can be reliably ordered by committee consensus (ICC 0.73-0.93) and the overall score is positively associated with citation count (standardised regression coefficient 0.33, pConclusionWe propose that the ANZMUSC-RQIT is a useful tool for prioritising the importance of a research question

Modular Synthesis of Semiconducting Graft Co-polymers to Achieve "clickable" Fluorescent Nanoparticles with Long Circulation and Specific Cancer Targeting

Semiconducting polymer nanoparticles (SPNs) have been explored for applications in cancer theranostics because of their high absorption coefficients, photostability and biocompatibility. However, SPNs are susceptible to aggregation and protein fouling in physiological conditions, which can be detrimental for in vivo applications. Here, we describe a method for achieving colloidally stable and low-fouling SPNs by grafting PEG onto the backbone of the fluorescent semiconducting polymer, poly(9,9'-dioctylfluorene-5-fluoro-2,1,3-benzothiadiazole) (F8BT-F), in a simple one-step substitution reaction, post-polymerisation. Further, by utilising azide-functionalised PEG we site-specifically "click" anti-HER2 antibodies, Fab fragments, or affibodies onto the SPN surface, which allows the functionalised SPNs to specifically target HER2-positive cancer cells. In vivo, our PEGylated SPNs were found to have excellent circulation efficiencies in zebrafish embryos for up to seven days post-injection. SPNs functionalised with affibodies were then shown to be able to target HER2 expressing cancer cells in a zebrafish xenograft model. The covalent PEGylated SPN system described herein shows great potential for cancer theranostics. This article is protected by copyright. All rights reserved

The SAMI Galaxy Survey: Quenching of Star Formation in Clusters I. Transition Galaxies

We use integral-field spectroscopy from the SAMI Galaxy Survey to identify galaxies that show evidence of recent quenching of star formation. The galaxies exhibit strong Balmer absorption in the absence of ongoing star formation in more than 10% of their spectra within the SAMI field of view. These Hd-strong (HDS) galaxies (HDSGs) are rare, making up only similar to 2% (25/1220) of galaxies with stellar mass log(M-*/M-circle dot) > 10. The HDSGs make up a significant fraction of nonpassive cluster galaxies (15%; 17/115) and a smaller fraction (2.0%; 8/387) of the nonpassive population in low-density environments. The majority (9/17) of cluster HDSGs show evidence of star formation at their centers, with the HDS regions found in the outer parts of the galaxy. Conversely, the HDS signal is more evenly spread across the galaxy for the majority (6/8) of HDSGs in low-density environments and is often associated with emission lines that are not due to star formation. We investigate the location of the HDSGs in the clusters, finding that they are exclusively within 0.6R(200) of the cluster center and have a significantly higher velocity dispersion relative to the cluster population. Comparing their distribution in projected phase space to those derived from cosmological simulations indicates that the cluster HDSGs are consistent with an infalling population that has entered the central 0.5r(200,3D) cluster region within the last similar to 1 Gyr. In the eight of nine cluster HDSGs with central star formation, the extent of star formation is consistent with that expected of outside-in quenching by ram pressure stripping. Our results indicate that the cluster HDSGs are currently being quenched by ram pressure stripping on their first passage through the cluster