Factors associated with failed ‘test of cure’ in the NHS cervical screening programme: a retrospective cohort study

Objective: To determine predictive factors associated with failed ‘test of cure’ (TOC) in the NHS Cervical Screening Programme (NHSCSP). Methods: Retrospective cohort study of all patients treated by large loop excision of transformation zone (LLETZ) between 1st April 2014 and 1st April 2019. Those with no documented HPV genotype on referral, no TOC outcome, those having a hysterectomy, chemotherapy and/or radiotherapy were excluded from final analysis. Results: Patients referred with a singular HPV genotype of HPV 16, HPV 18, or HPV Other types (HPV O) were significantly more likely to pass TOC than those referred with multiple HPV genotypes (p 51 yrs. and infection with multiple hr-HPV types were predictors of post treatment hr-HPV persistence. Knowledge of HPV genotype both at referral, and following treatment, could allow a more individualised, and patient-centred, approach to both the management and follow up of CIN. HPV genotype should be reported as standard on all cervical screening sample results. The term HPV O should not be utilised and instead actual HPV genotype should be reported. This would enable us to optimise not only future research but would also allow future monitoring of the efficacy of vaccination programmes

Temperature and Photoperiod Effects on Sterility in a Cytoplasmic Male-Sterile Soybean

Manual cross-pollination to produce large quantities of hybrid soybean seed is difficult and time consuming. An environmentally stable sterility system is one of the necessary components to produce large quantities of hybrid seed. The objective of this study was to subject cytoplasmic male-sterile (CMS) BC5F1 plants, from a cross of a Chinese Glycine max wild-type soybean with a Chinese wild annual soybean G. soja (male parent) and controls, to a variety of different temperature and photoperiod treatments to test whether CMS is stable under various environmental conditions. Plants were grown in growth chambers under controlled temperature, photoperiod, and irradiance regimes until pod set, and then they were transferred to a glasshouse until they matured. Plants were evaluated for time of anthesis after photoperiod induction (13 h light/11 h dark) and fertility or sterility. Anther squash and pod set data showed that sterility of the CMS line was stable under all environmental conditions tested, whereas fertility-restored control plants remained fertile. Extreme environmental conditions led to delayed floral induction and/or stunted growth

β1-Adrenergic Receptor and Sphingosine- 1-Phosphate Receptor 1 Reciprocal Down-Regulation Influences Cardiac Hypertrophic Response and Progression Toward Heart Failure: Protective Role of S1PR1 Cardiac Gene Therapy

YesThe Sphingosine-1-phosphate receptor 1 (S1PR1) and β1-adrenergic receptor (β1AR) are G protein-coupled receptors (GPCRs) expressed in the heart. These two GPCRs have opposing actions on adenylyl cyclase due to differential G protein-coupling. Importantly, both of these receptors can be regulated by the actions of GPCR kinase-2 (GRK2), which triggers desensitization and down-regulation processes. Although, classical signaling paradigms suggest that simultaneous activation of β1ARs and S1PR1s in a myocyte would simply be opposing action on cAMP production, in this report we have uncovered a direct interaction between these two receptors with a regulatory involvement of GRK2. In HEK293 cells overexpressing both β1AR and S1PR1, we demonstrate that β1AR down-regulation can occur after sphingosine 1-phosphate (S1PR1 agonist) stimulation while S1PR1 down-regulation can be triggered by isoproterenol (βAR agonist) treatment. This cross-talk between these two distinct GPCRs appears to have physiological significance since they interact and show reciprocal regulation in mouse hearts undergoing chronic βAR stimulation and also in a rat model of post-ischemic heart failure (HF). We demonstrate that restoring cardiac plasma membrane levels of S1PR1 produce beneficial effects counterbalancing deleterious β1AR overstimulation in HF

Computed tomography chest imaging offers no advantage over chest X-ray in the initial assessment of gestational trophoblastic neoplasia

Background The International Federation of Gynaecology and Obstetrics (FIGO) score identifies gestational trophoblastic neoplasia (GTN) patients as low- or high-risk of single-agent chemotherapy resistance (SACR). Computed tomography (CT) has greater sensitivity than chest X-ray (CXR) in detecting pulmonary metastases, but effects upon outcomes remain unclear. Methods Five hundred and eighty-nine patients underwent both CXR and CT during GTN assessment. Treatment decisions were CXR based. The number of metastases, risk scores, and risk category using CXR versus CT were compared. CT-derived chest assessment was evaluated as impact upon treatment decision compared to patient outcome, incidence of SACR, time-to-normal human chorionic gonadotrophin hormone (TNhCG), and primary chemotherapy resistance (PCR). Results Metastasis detection (p < 0.0001) and FIGO score (p = 0.001) were higher using CT versus CXR. CT would have increased FIGO score in 188 (31.9%), with 43 re-classified from low- to high-risk, of whom 23 (53.5%) received curative single-agent chemotherapy. SACR was higher when score (p = 0.044) or risk group (p < 0.0001) changed. Metastases on CXR (p = 0.019) but not CT (p = 0.088) lengthened TNhCG. Logistic regression analysis found no difference between CXR (area under the curve (AUC) = 0.63) versus CT (AUC = 0.64) in predicting PCR. Conclusions CT chest would improve the prediction of SACR, but does not influence overall treatment outcome, TNhCG, or prediction of PCR. Lower radiation doses and cost mean ongoing CXR-based assessment is recommended

Self-managed, computerised word finding therapy as an add-on to usual care for chronic aphasia post-stroke : an economic evaluation

Objective: To examine the cost-effectiveness of self-managed computerised word finding therapy as an add-on to usual care for people with aphasia post-stroke. Design: Cost-effectiveness modelling over a life-time period, taking a UK National Health Service (NHS) and personal social service perspective. Setting: Based on the Big CACTUS randomised controlled trial, conducted in 21 UK NHS speech and language therapy departments. Participants: Big CACTUS included 278 people with long-standing aphasia post-stroke. Interventions: Computerised word finding therapy plus usual care; usual care alone; usual care plus attention control. Main measures: Incremental cost-effectiveness ratios (ICER) were calculated, comparing the cost per quality adjusted life year (QALY) gained for each intervention. Credible intervals (CrI) for costs and QALYs, and probabilities of cost-effectiveness, were obtained using probabilistic sensitivity analysis. Subgroup and scenario analyses investigated cost-effectiveness in different subsets of the population, and the sensitivity of results to key model inputs. Results: Adding computerised word finding therapy to usual care had an ICER of £42,686 per QALY gained compared with usual care alone (incremental QALY gain: 0.02 per patient (95% CrI: −0.05 to 0.10); incremental costs: £732.73 per patient (95% CrI: £674.23 to £798.05)). ICERs for subgroups with mild or moderate word finding difficulties were £22,371 and £21,262 per QALY gained respectively. Conclusion: Computerised word finding therapy represents a low cost add-on to usual care, but QALY gains and estimates of cost-effectiveness are uncertain. Computerised therapy is more likely to be cost-effective for people with mild or moderate, as opposed to severe, word finding difficulties

PREDICT-GTN 1: Can we improve the FIGO scoring system in gestational trophoblastic neoplasia?

Gestational trophoblastic neoplasia (GTN) patients are treated according to the eight-variable International Federation of Gynaecology and Obstetrics (FIGO) scoring system, that aims to predict first-line single-agent chemotherapy resistance. FIGO is imperfect with one-third of low-risk patients developing disease resistance to first-line single-agent chemotherapy. We aimed to generate simplified models that improve upon FIGO. Logistic regression (LR) and multilayer perceptron (MLP) modelling (n = 4191) generated six models (M1-6). M1, all eight FIGO variables (scored data); M2, all eight FIGO variables (scored and raw data); M3, nonimaging variables (scored data); M4, nonimaging variables (scored and raw data); M5, imaging variables (scored data); and M6, pretreatment hCG (raw data) + imaging variables (scored data). Performance was compared to FIGO using true and false positive rates, positive and negative predictive values, diagnostic odds ratio, receiver operating characteristic (ROC) curves, Bland-Altman calibration plots, decision curve analysis and contingency tables. M1-6 were calibrated and outperformed FIGO on true positive rate and positive predictive value. Using LR and MLP, M1, M2 and M4 generated small improvements to the ROC curve and decision curve analysis. M3, M5 and M6 matched FIGO or performed less well. Compared to FIGO, most (excluding LR M4 and MLP M5) had significant discordance in patient classification (McNemar's test P < .05); 55-112 undertreated, 46-206 overtreated. Statistical modelling yielded only small gains over FIGO performance, arising through recategorisation of treatment-resistant patients, with a significant proportion of under/overtreatment as the available data have been used a priori to allocate primary chemotherapy. Streamlining FIGO should now be the focus

The PHENIX Experiment at RHIC

The physics emphases of the PHENIX collaboration and the design and current status of the PHENIX detector are discussed. The plan of the collaboration for making the most effective use of the available luminosity in the first years of RHIC operation is also presented.Comment: 5 pages, 1 figure. Further details of the PHENIX physics program available at http://www.rhic.bnl.gov/phenix

Developing, monitoring, and reporting of fidelity in aphasia trials : core recommendations from the collaboration of aphasia trialists (CATs) trials for aphasia panel

BACKGROUND Developing, monitoring, and reporting of fidelity are essential and integral components to the design of randomised controlled trials (RCTs) in stroke and aphasia. Treatment fidelity refers to the degree to which an intervention is delivered as intended and is directly related to the quality of the evidence generated by RCTs. Clear documentation of treatment fidelity in trials assists in the evaluation of the clinical implications of potential benefits attributed to the intervention. Consideration of the implementation requirements of a research-based intervention as intended in a clinical context is necessary to achieve similar outcomes for a clinical population. Despite this, treatment fidelity is rarely reported in RCTs of aphasia intervention. AIM To describe fidelity strategies and develop core recommendations for developing, monitoring, and reporting of fidelity in aphasia intervention RCTs. SCOPE Relevant conceptual frameworks were considered. The Behaviour Change Consortium comprehensive framework of fidelity was adopted. It includes five areas: study design, training providers, delivery of treatment, treatment receipt, and treatment enactment. We explored fidelity in RCTs with a range of complex aphasia interventions (e.g., ASK, Big CACTUS, COMPARE, FCET2EC, POLAR, SUPERB, and VERSE) and described how different trial design factors (e.g., phase of trial, explanatory vs. pragmatic, number and location of sites, and number and type of treatment providers) influenced the fidelity strategies chosen. Strategies were mapped onto the five areas of the fidelity framework with a detailed exploration of how fidelity criteria were developed, measured, and monitored throughout each trial. This information was synthesised into a set of core recommendations to guide aphasia researchers towards the adequate measurement, capture, and reporting of fidelity within future aphasia intervention studies. CONCLUSIONS/RECOMMENDATIONS Treatment fidelity should be a core consideration in planning an intervention trial, a concept that goes beyond treatment adherence alone. A range of strategies should be selected depending on the phase and design of the trial being undertaken and appropriate investment of time and costs should be considered

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results