Minimum Baseline Research Articles

Sacral nerve modulation for irritable bowel syndrome: A randomized, double-blinded, placebo-controlled crossover study.

Irritable bowel syndrome (IBS) is among the most common gastrointestinal disorders, and a substantial proportion of patients have an insufficient response to treatment. In a single-blinded study, sacral nerve modulation (SNM) significantly reduced symptoms of IBS. The aim of the present double-blinded, randomized, placebo-controlled study was to evaluate the effect of SNM for IBS. We included patients with diarrhea-predominant or mixed IBS and a minimum baseline IBS-specific symptom score of 40 points (Gastrointestinal Symptom Rating Scale-IBS version). Patients underwent a 6-week period of SNM. In the first 4weeks, the patients were randomized 1:1 to have the neurostimulator set subsensory or OFF for 2weeks and then the opposite for another 2weeks. Patients and investigators were blinded to settings. In the remaining 2weeks, the stimulation was set suprasensory. IBS-specific symptoms and quality of life were assessed with validated questionnaires and bowel diaries. Twenty-one patients were randomized and eligible for analysis. The IBS-specific symptom score was reduced with borderline significance during stimulation (subsensory-OFF median change -1 (-26, 9), OFF-subsensory median change 8 (-11, 36); P=0.0572). Pain was significantly reduced during stimulation (subsensory-OFF median change -1.5 (-4, 1), OFF-subsensory median change 1 (-4, 3); P=0.0188), along with the number of daily bowel movements (subsensory-OFF median change 0 (-1.8, 0.2), OFF-subsensory median change 0.2 (-0.5, 1.1); P=0.0373). The median placebo effect was 14% (0, 55). Sacral nerve modulation for IBS seems promising but should be considered experimental until larger multicenter studies have been performed.

Abstract P2-12-01: Dose- and exposure-response relationship and biomarker correlation analysis in breast tumors from patients treated with capivasertib, an AKT inhibitor, in the STAKT randomized, placebo controlled pre-surgical study

Abstract Background: Capivasertib (AZD5363), an AKT1,2,3 inhibitor, significantly improved progression-free and overall survival when added to paclitaxel in triple negative breast cancer (BC) patients (Schmid et al. ASCO 2018). We have previously reported in STAKT, robust target inhibition at 480mg BD versus placebo, including significant decreases in the primary biomarkers (PBs) - Ki67, pPRAS40 & pGSK3β - in primary BCs (Robertson et al. SABCS 2017). We now report the dose- and exposure-response relationship of capivasertib and the correlation between primary and secondary (pAKT, pS6, nuclear FOXO3a) tumor biomarkers. Design: STAKT was a two-stage, double blind, randomized, placebo controlled 'window-of-opportunity' trial in newly diagnosed ER+ BC patients. Stage 1 assessed capivasertib at a dose of 480mg BD p.o. versus placebo. Stage 2 assessed capivasertib at two lower doses 360mg and 240mg BD. Tumor biopsies were taken prior to 1st dose and after 4.5 days of dosing. Evaluable patients (who required pre-defined minimum baseline PD values for PBs) included placebo (n=11), capivasertib at 480mg (n=17), 360mg (n=5) and 240mg (n=6). Blood samples for pharmacokinetic (PK) studies were scheduled at pre-dose; 2, 4, optional 6 & 8 hrs post first dose on Day 1; ˜2-4 h post last dose on Day 5 (before biopsy). The % change from baseline for PBs were evaluated against the following exposure variables (placebo=0): i) Dose, ii) Observed Cmax Day 1 (˜2h post-dose), iii) Observed plasma concentration on Day 5, iv) Model-predicted plasma concentration Day 5 at time of biopsy, and v) Model-predicted AUC on Day 5. Spearman correlation coefficient measured the strength and direction of association between biomarkers. Results: · Significant mean reductions in % change from baseline were observed for the PBs pGSK3β (-39%; p<0.006), pPRAS40 (-50%; p<0.0001) and Ki67 (-23%; p=0.052) at 480mg versus placebo. At 360mg and 240mg, mean % changes from baseline in pGSK3β were -27% and -9%, respectively; in pPRAS40 -45% and -28%, respectively; and in Ki67 0% and +22%, respectively. · Dose-response relationships for individual % change from baseline could be described by an Emax model for all PBs. Overall, the correlation to PK exposure (observed or predicted) was similar to the correlation to dose. · Correlation coefficient analyses between biomarkers at capivasertib 480mg BD identified- i) Positive correlations for pGSK3β with Ki67 (ρ = 0.52, p-value < 0.05) & with pS6 (ρ = 0.54, p-value<0.05); ii) Negative correlations between FOXO3a and Ki67 (ρ = -0.75, p-value<0.001) pGSK3β (ρ = -0.71, p-value<0.001) & also pS6 (ρ = -0.61, p-value<0.001).Correlation coefficients for lower doses are not robust due to small sample size in these groups. Conclusions · Capivasertib caused dose- and concentration- dependent effects on biomarkers after only 4.5 days. · Significant changes in the PBs were demonstrated at 480 mg BD. Biomarker changes was observed at 360mg and 240mg BD, but statistical analysis was limited by the small sample size at lower doses. · Correlation between a number of tumor biomarkers (relative changes) were identified for capivasertib 480mg BD. Citation Format: Gee J, Coleman RE, Cheung KL, Evans A, Holcombe C, Skene A, Rea D, Ahmed S, Jahan A, Horgan K, Rauchhaus P, Littleford R, Finlay P, Cheung A, Cullberg M, de Bruin E, Foxley A, Koulai L, Pass M, Schiavon G, Rugman P, Deb R, Robertson JFR. Dose- and exposure-response relationship and biomarker correlation analysis in breast tumors from patients treated with capivasertib, an AKT inhibitor, in the STAKT randomized, placebo controlled pre-surgical study [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-12-01.

Breaking the ecosystem services glass ceiling: realising impact

Through changes in policy and practice, the inherent intent of the ecosystem services (ES) concept is to safeguard ecosystems for human wellbeing. While impact is intrinsic to the concept, little is known about how and whether ES science leads to impact. Evidence of impact is needed. Given the lack of consensus on what constitutes impact, we differentiate between attributional impacts (transitional impacts on policy, practice, awareness or other drivers) and consequential impacts (real, on-the-ground impacts on biodiversity, ES, ecosystem functions and human wellbeing) impacts. We conduct rigorous statistical analyses on three extensive databases for evidence of attributional impact (the form most prevalently reported): the IPBES catalogue (n = 102), the Lautenbach systematic review (n = 504) and a 5-year in-depth survey of the OPERAs Exemplars (n = 13). To understand the drivers of impacts, we statistically analyse associations between study characteristics and impacts. Our findings show that there exists much confusion with regard to defining ES science impacts, and that evidence of attributional impact is scarce: only 25% of the IPBES assessments self-reported impact (7% with evidence); in our meta-analysis of Lautenbach’s systematic review, 33% of studies provided recommendations indicating intent of impacts. Systematic impact reporting was imposed by design on the OPERAs Exemplars: 100% reported impacts, suggesting the importance of formal impact reporting. The generalised linear models and correlations between study characteristics and attributional impact dimensions highlight four characteristics as minimum baseline for impact: study robustness, integration of policy instruments into study design, stakeholder involvement and type of stakeholders involved. Further in depth examination of the OPERAs Exemplars showed that study characteristics associated with impact on awareness and practice differ from those associated with impact on policy: to achieve impact along specific dimensions, bespoke study designs are recommended. These results inform targeted recommendations for ES science to break its impact glass ceiling.

Healthcare resource utilization and costs associated with incremental systemic corticosteroid exposure in asthma.

BackgroundAlthough systemic corticosteroid (SCS) treatment, irrespective of duration or dosage, is associated with adverse outcomes for patients with asthma, the longitudinal effects of this treatment on adverse outcomes, healthcare resource utilization (HCRU), and healthcare costs are unknown.MethodsWe identified patients initiating intermittent or long‐term SCS who were diagnosed with active asthma from UK general practice with linked secondary care data. Control (non‐SCS) patients were matched by sex and index date with those initiating SCS. Minimum baseline period was 1 year prior to index date; minimum follow‐up duration was 2 years post–index date. Cumulative incidence of SCS‐associated adverse outcomes and associated HCRU and costs were compared between SCS and non‐SCS patient groups and among average SCS daily exposure categories. Associations between exposure and annualized HCRU and costs were assessed, adjusted for confounders.ResultsAnalyses included 9413 matched pairs. Median (interquartile range) follow up was as follows: SCS group: 7.1 (4.1‐11.8) years; control group: 6.4 (3.8‐10.0) years. Greater SCS dosages were correlated with greater cumulative incidence. For example, patients with type 2 diabetes receiving an average daily dosage of ≥7.5 mg had a 15‐year cumulative incidence (37.5%) that was 1.5‐5 times greater than those receiving lower dosages. HCRU and costs increased annually for SCS patients but not for non‐SCS patients. Increases in all‐cause adverse outcome (excluding asthma)–associated HCRU and costs were dose‐dependent.ConclusionsOver the long term, adverse outcomes associated with SCS initiation were relatively frequent and costly, with a positive dosage–response relationship with SCS exposure.

DUPILUMAB EFFICACY IN UNCONTROLLED, MODERATE-TO-SEVERE ALLERGIC ASTHMA IN THE PHASE 3 LIBERTY ASTHMA QUEST STUDY

Introduction Dupilumab, a fully human interleukin (IL)-4 receptor-α monoclonal antibody inhibiting IL-4/IL-13 signaling pathways, key drivers of Type 2 inflammation, is approved for treating adults with inadequately controlled moderate-to-severe atopic dermatitis. In the phase 3 LIBERTY ASTHMA QUEST study (NCT02414854), dupilumab 200mg and 300mg administered every 2 weeks versus matched placebo reduced annualized severe exacerbation rates and improved pre-bronchodilator forced expiratory volume in 1 second (FEV1) and quality-of-life measures, and was generally well tolerated in patients with uncontrolled, moderate-to-severe asthma (≥12 years, without minimum baseline Type 2 inflammatory biomarkers). This post-hoc analysis assessed the efficacy of dupilumab in patients with and without allergic asthma. Methods Allergic asthma was defined as total serum IgE ≥30 kU/L and ≥1 positive perennial aeroallergen-specific IgE (≥0.35 kU/L) at baseline. Endpoints were annualized severe exacerbation rates over the 52-week treatment period and change from baseline to Week 12 in pre-bronchodilator FEV1 (L). Results 56% (n=1,066) of the intent-to-treat population met the criteria for allergic asthma. In patients with and without allergic asthma, dupilumab vs placebo significantly reduced annualized severe exacerbation rates during the treatment period (all P1 (L) at Week 12 (all PFigure). In both subgroups, improvements were greater with higher baseline blood eosinophil and FeNO levels. The most frequent adverse event in the dupilumab-treated groups versus placebo was injection-site reactions (15%/18% versus 5%/10%, respectively). Conclusions Add-on dupilumab reduced severe exacerbations and improved lung function in patients with allergic and non-allergic uncontrolled, moderate-to-severe asthma and was generally well tolerated. Figure. Change from baseline to Week 12 in pre-bronchodilator FEV1 (L) and annualized severe exacerbation rate during the 52-week treatment period in patients with and without allergic asthma and in subgroups defined by baseline blood-eosinophil counts and FeNO levels.

DUPILUMAB REDUCES SEVERE EXACERBATION RATE AND IMPROVES LUNG FUNCTION IN ADOLESCENT PATIENTS WITH UNCONTROLLED, MODERATE-TO-SEVERE ASTHMA: FROM THE LIBERTY ASTHMA QUEST STUDY

DUPILUMAB REDUCES SEVERE EXACERBATION RATE AND IMPROVES LUNG FUNCTION IN ADOLESCENT PATIENTS WITH UNCONTROLLED, MODERATE-TO-SEVERE ASTHMA: FROM THE LIBERTY ASTHMA QUEST STUDY

Deformation of static datum: Turkish CORS network (TUSAGA-Aktif) is considered

The geocentric datum of Turkish CORS Network (TUSAGA-Aktif) is a semi-kinematic datum realized with respect to the International Terrestrial Reference Frame (ITRF 96) at the reference epoch of 1 January 2005 (2005.00). This realization was maintained by ITRF no net rotation (NNR) velocities of CORS stations. Up-to-date ITRF NNR velocities were determined by General Command of Mapping in Turkey using 7 years of CORS stations data from 2008 to 2015. In accordance with Turkish surveying regulation, there are two types of coordinate computation of the control points performed with Global Navigation Satellite System relative positioning technique based on the datum. Coordinates of the first-order and the second-order control points are computed in semi-kinematic datum, whereas the third-order control points are computed in static datum. Generally, CORS stations of TUSAGA-Aktif are used as fiducial stations for coordinate computation of these control points. In this study, baseline deformation effect of static datum on the three-dimensional position of the points are investigated. 20 CORS stations within TUSAGA-Aktif were chosen to simulate the rover and the fiducial stations. The results show that relative displacement from the reference epoch (2005.00) between the rover-fiducial stations at the measurement time and the positioning error of the rover station are in a good agreement. The differences are in the order of mm to cm level. The results also show that when more than one fiducial station used in static datum processing, mean relative displacement between the rover-fiducial stations at the measurement time and the positioning error of the rover are also in a good agreement. The results emphasized that, velocities of the fiducial stations should be known by the users for conducting static datum processing with minimum baseline deformation as much as possible.

Using binaural beat sensitivity to explore mechanisms of bimodal temporal envelope beat sensitivity

Current cochlear implant (CI) fitting strategies aim to maximize speech perception through the CI by allocating all spectral information across the electrode array without regard to tonotopic placement of each electrode along the basilar membrane. For patients with considerable residual hearing in the non-implanted ear, this approach may not be optimal for binaural hearing. This study aims to explore fitting procedures in which CI maps better complement information from the acoustic ear by reducing the frequency mismatch between them. We investigate the mechanisms of binaural temporal-envelope beat sensitivity in normal-hearing listeners using bandpass filtered pulse trains with parameters including stimulus level, filter bandwidth, filter slope, and spectral overlap using bandpass filtered pulse trains. We find the minimum baseline interaural timing difference and spectral mismatch that normal-hearing listeners can tolerate while maintaining their ability to detect interaural timing differences. Initial results consistently demonstrate maximum sensitivity to binaural beats when place of stimulation is matched across ears. The outcomes of this study will provide new information on binaural interactions in normal-hearing listeners and guide methodology for incoming single-sided-deafness patients as we adjust their CI maps in an effort to reduce the frequency-mismatch. [Work supported by NIH grant F32DC016815-01.]

Long-term high-frequency measurements of dibromomethane in the atmosphere at algae-rich and algae-poor coastal sites

Dibromomethane (CH2Br2), a natural stratospheric ozone depleting substance, is mostly emitted from the ocean, but the relative importance of coastal (or macroalgae) and open ocean emissions is unknown. We made long-term high-frequency measurements of CH2Br2 concentrations at two remote coastal sites in Japan, on the subtropical Hateruma Island (poor in macroalgae) and at Cape Ochiishi (rich in macroalgae). CH2Br2 concentrations at Hateruma showed prominent seasonal variation, being lower in summer (around 0.94 ppt) than in winter (around 1.23 ppt). In contrast, CH2Br2 concentrations at Ochiishi were highly variable, often exceeding 2 ppt in the summer but with minimum baseline concentrations close to those from Hateruma; in the winter the concentrations were almost constant at about 1.3 ppt. Analysis of the data suggested that (1) emissions from macroalgae were not likely to extend offshore, but instead were localized near the shore, (2) strong macroalgal emissions of CH2Br2 were almost limited to the summer, but it was not reflected in the seasonality of the baseline concentrations of CH2Br2 in the atmosphere, and therefore (3) macroalgal or coastal emissions of CH2Br2 in the temperate zone might have a rather limited contribution to the global CH2Br2 sources. These findings are especially important for the understanding of the tropospheric and stratospheric bromine budget.

Perspectives on trading cost and availability for corrective maintenance at the equipment type level

Characterising maintenance costs has always been challenging due to a lack of accurate prior cost data and the uncertainties around equipment usage and reliability. Since preventive maintenance does not completely prevent corrective repairs in demanding environments, any unscheduled maintenance can have a large impact on the overall maintenance costs. This introduces the requirement to set up support contracts with minimum baseline solutions that warrant the target demand within certain costs and risks. This article investigates a process that has been developed to estimate performance based support contract costs attributed to corrective maintenance. These can play a dominant role in the through-life support of high values assets. The case context for the paper is the UK Ministry of Defence. The developed approach allows benchmarking support contract solutions, and enabling efficient planning decisions. Emphasis is placed on learning from feedback, testing and validating current methodologies for estimating corrective maintenance costs and availability at the Equipment Type level. These are interacting sub-equipment's that have unique availability requirements and hence have a much larger impact on the capital maintenance expenditure. The presented case studies demonstrate the applicability of the approach towards adequate savings and improved availability estimates.

Baseline screening and psychosocial results from the UK SIGNIFY study: A whole-body MRI screening study in TP53 mutation carriers and matched controls.

1520 Background: In the United Kingdom, current screening guidelines for TP53 germline mutation carriers solely recommends annual breast MRI, despite the wide spectrum of malignancies typically seen in this group. Some centres employ family specific screening with most centres having an “open-door” policy. Recent evidence suggests there may be a survival benefit with more intensive screening, including whole-body MRI. There are no published data on the psychological impact of such screening programmes. Methods: This study sought to investigate the role of one-off non-contrast whole-body MRI (WB MRI) in the screening of asymptomatic TP53 mutation carriers aged over 18 years. Clinical and psychological endpoints were assessed. Scans were read by radiologists blinded to participant carrier status. The incidence of malignancies diagnosed in TP53 mutation carriers against general population controls was calculated. The incidences of non-malignant relevant disease and irrelevant disease were measured, as well as the number of investigations required to determine relevance of findings. A series of questionnaires is used to assess the psychological impact of screening. Results: 44 TP53 mutation carriers and 44 population controls were recruited. In TP53 mutation carriers, six of 44 (13.6%, 95% CI: 5.2%-27.4%) participants were diagnosed with cancer during the study, all of which would be considered life threatening if untreated. Two were found to have two primary cancers. Two participants with cancer had abnormalities on the MRI which were initially thought to be benign (a pericardial cyst and a uterine fibroid) but transpired to be sarcomas. No controls were diagnosed with cancer. Fifteen carriers (34.1%, 95% CI: 20.5%-49.9%) and 7 controls (15.9%, 95% CI: 6.6%-30.1%) underwent further investigations following the WB MRI for abnormalities that transpired to be benign (p = 0.049). To date, there is no evidence of clinically significant adverse psychosocial effects. Conclusions: The cancer detection rate in this group justifies a minimum baseline non-contrast WB MRI in germline TP53 mutation carriers. Clinical trial information: NCT01737255.

Baseline results from the UK SIGNIFY study: a whole-body MRI screening study in TP53 mutation carriers and matched controls

In the United Kingdom, current screening guidelines for TP53 germline mutation carriers solely recommends annual breast MRI, despite the wide spectrum of malignancies typically seen in this group. This study sought to investigate the role of one-off non-contrast whole-body MRI (WB MRI) in the screening of asymptomatic TP53 mutation carriers. 44 TP53 mutation carriers and 44 population controls were recruited. Scans were read by radiologists blinded to participant carrier status. The incidence of malignancies diagnosed in TP53 mutation carriers against general population controls was calculated. The incidences of non-malignant relevant disease and irrelevant disease were measured, as well as the number of investigations required to determine relevance of findings. In TP53 mutation carriers, 6 of 44 (13.6, 95% CI 5.2–27.4%) participants were diagnosed with cancer during the study, all of which would be considered life threatening if untreated. Two were found to have two primary cancers. Two participants with cancer had abnormalities on the MRI which were initially thought to be benign (a pericardial cyst and a uterine fibroid) but transpired to be sarcomas. No controls were diagnosed with cancer. Fifteen carriers (34.1, 95% CI 20.5–49.9%) and seven controls (15.9, 95% CI 6.7–30.1%) underwent further investigations following the WB MRI for abnormalities that transpired to be benign (p = 0.049). The cancer detection rate in this group justifies a minimum baseline non-contrast WB MRI in germline TP53 mutation carriers. This should be adopted into national guidelines for management of adult TP53 mutation carriers in addition to the current practice of contrast enhanced breast MRI imaging.

A Practical Framework for Energy-Efficient Node Activation in Heterogeneous LTE Networks

This paper presents a framework to activate and deactivate micronodes in a heterogeneous multicell LTE network, based on load and energy efficiency consideration. The framework exploits historical data (i.e., per-macro-cell load curves) to select a set of candidate switch-on/switch-off instants of microcells, assuming a limited number of state changes is allowed in a day. The switching instants are instead determined online, by taking into account the actual traffic as well as the load curves. Moreover, intercell interference is fully accounted for. Our simulations show that this framework allows a multicell network to sustain peak-hour load when necessary and to reconfigure to a minimum coverage baseline whenever feasible, thus saving power (up to 25% in our scenarios). Moreover, the framework is robust, meaning that deviations of the actual traffic with respect to the prediction offered by the load curves can easily be handled.

Climate Projection Outlook in Lake Haramaya Watershed, Eastern Ethiopia

Smallholder farmers in Ethiopia generally face widespread problems driven by climate change. For this reason, the study of climate change at watershed level might be critical to solve the problem from its root. The study was conducted in Lake Haramaya Watershed, Eastern Ethiopia to project ad characterize the climatic condition of the coming thirty years (2020-2050). Thirty-four years of rainfall, maximum and minimum temperature baseline data were collected from National Meteorological Agency of Ethiopia. Whereas, thirty years (2020-2050) projected rainfall, maximum and minimum temperatures were downscaled from MarkSim web version for IPCC AR5 data (CMIP5) using five climate models namely: BCC-CSM1-1, CSIRO-Mk3-6-0, HadGEM2-ES, MIROC-ESM, MIROCESM- CHEM, and MIROC5 under two Representative Concentration Pathways (RCPs): RCP4.5 and RCP8.5. The results of the study revealed that the annual mean rainfall will be increased by 20.70 and 24.14% under RCP4.5 and RCP8.5, respectively compared to baseline average value of 777.51 mm/yr. The annual rainfall under RCP4.5 ranges from 769.6 to 1090 mm/yr having the CV value of about 11%; whereas, under RCP8.5, it will range from 771.9 to 1129 mm/yr with the CV value of 13.17%. Kiremt (JJAS) season rainfall will increase from the baseline of 107.55 mm/yr to 135.79 and 136.27 mm/yr under RCP4.5 and RCP8.5, respectively. Moreover, a study indicated that the annual and seasonal temperature under RCP4.5 and RCP8.5 will be expected to increase during 2020-2050 period. Under high emission scenario of RCP8.5, the annual maximum temperature could rise from 24.73°C baseline to 25.41°C.

LOW-FREQUENCY OBSERVATIONS OF LINEARLY POLARIZED STRUCTURES IN THE INTERSTELLAR MEDIUM NEAR THE SOUTH GALACTIC POLE

ABSTRACT We present deep polarimetric observations at 154 MHz with the Murchison Widefield Array (MWA), covering 625 deg2 centered on α = 0hand δ = −27°. The sensitivity available in our deep observations allows an in-band, frequency-dependent analysis of polarized structure for the first time at long wavelengths. Our analysis suggests that the polarized structures are dominated by intrinsic emission but may also have a foreground Faraday screen component. At these wavelengths, the compactness of the MWA baseline distribution provides excellent snapshot sensitivity to large-scale structure. The observations are sensitive to diffuse polarized emission at ∼54′ resolution with a sensitivity of 5.9 mJy beam−1 and compact polarized sources at ∼2.′4 resolution with a sensitivity of 2.3 mJy beam−1 for a subset (400 deg2) of this field. The sensitivity allows the effect of ionospheric Faraday rotation to be spatially and temporally measured directly from the diffuse polarized background. Our observations reveal large-scale structures (∼1°–8° in extent) in linear polarization clearly detectable in ∼2 minute snapshots, which would remain undetectable by interferometers with minimum baseline lengths of >110 m at 154 MHz. The brightness temperature of these structures is on average 4 K in polarized intensity, peaking at 11 K. Rotation measure synthesis reveals that the structures have Faraday depths ranging from −2 to 10 rad m−2 with a large fraction peaking at approximately +1 rad m−2. We estimate a distance of 51 ± 20 pc to the polarized emission based on measurements of the in-field pulsar J2330–2005. We detect four extragalactic linearly polarized point sources within the field in our compact source survey. Based on the known polarized source population at 1.4 GHz and non-detections at 154 MHz, we estimate an upper limit on the depolarization ratio of 0.08 from 1.4 GHz to 154 MHz.

PrEP as a feature in the optimal landscape of combination HIV prevention in sub-Saharan Africa.

IntroductionThe new WHO guidelines recommend offering pre-exposure prophylaxis (PrEP) to people who are at substantial risk of HIV infection. However, where PrEP should be prioritised, and for which population groups, remains an open question. The HIV landscape in sub-Saharan Africa features limited prevention resources, multiple options for achieving cost saving, and epidemic heterogeneity. This paper examines what role PrEP should play in optimal prevention in this complex and dynamic landscape.MethodsWe use a model that was previously developed to capture subnational HIV transmission in sub-Saharan Africa. With this model, we can consider how prevention funds could be distributed across and within countries throughout sub-Saharan Africa to enable optimal HIV prevention (that is, avert the greatest number of infections for the lowest cost). Here, we focus on PrEP to elucidate where, and to whom, it would optimally be offered in portfolios of interventions (alongside voluntary medical male circumcision, treatment as prevention, and behaviour change communication). Over a range of continental expenditure levels, we use our model to explore prevention patterns that incorporate PrEP, exclude PrEP, or implement PrEP according to a fixed incidence threshold.ResultsAt low-to-moderate levels of total prevention expenditure, we find that the optimal intervention portfolios would include PrEP in only a few regions and primarily for female sex workers (FSW). Prioritisation of PrEP would expand with increasing total expenditure, such that the optimal prevention portfolios would offer PrEP in more subnational regions and increasingly for men who have sex with men (MSM) and the lower incidence general population. The marginal benefit of including PrEP among the available interventions increases with overall expenditure by up to 14% (relative to excluding PrEP). The minimum baseline incidence for the optimal offer of PrEP declines for all population groups as expenditure increases. We find that using a fixed incidence benchmark to guide PrEP decisions would incur considerable losses in impact (up to 7%) compared with an approach that uses PrEP more flexibly in light of prevailing budget conditions.ConclusionsOur findings suggest that, for an optimal distribution of prevention resources, choices of whether to implement PrEP in subnational regions should depend on the scope for impact of other possible interventions, local incidence in population groups, and total resources available. If prevention funding were to become restricted in the future, it may be suboptimal to use PrEP according to a fixed incidence benchmark, and other prevention modalities may be more cost-effective. In contrast, expansions in funding could permit PrEP to be used to its full potential in epidemiologically driven prevention portfolios and thereby enable a more cost-effective HIV response across Africa.

CQC inspections: meeting the fundamental standards of care

In the fifth paper in a mini-series discussing inspections of renal units, Peter Ellis and Jane Abbott explore the fundamental standards that set the minimum baseline that is expected of people working in kidney care. These standards address the basics requirements in care, from the importance of consent to the duty of candour, that all staff caring for patients must respect.

Evaluation of the Effect of Protective Sleeve on Output Intensity of Light Emitting Diode Light Cure Units

Aim: The purpose of this study was to compare the difference in the output intensity of Light Emitting Diode (LED) light cure (LC) devices with and without a protective sleeve and its clinical significance. Materials and Methods: The output intensity of 152 LC units in dental offices across the state of Odisha were examined. The collection of related information included an average number of exposures per day and the charging status. LED Radiometer (SDI Ltd, VIC, AUS) was used for measuring output intensity. Results: Out of all the 152 LC devices examined, 137 were found to emit light intensity above minimum baseline values when used with a protective sleeve. The decrease in output intensity, when used with a protective sleeve was statistically significant (p<0.05). 78 LC devices with direct current supply, maintained better intensity than battery operated ones. 74 battery operated LC devices showed statistically significant differences (p<0.05) in intensity output based on the number of exposures/day. Devices that were being charged daily maintained significantly (p<0.05) better intensity output than those being charged once or twice a week. Conclusion: LED Light cure devices can be safely used along with a protective sleeve to improve cross infection control without affecting its output intensity. Battery operated LED devices must be charged at least 3 times/ week to prevent a significant decrease in output intensity

The Use of a Dynamic Elastomeric Fabric Orthosis in Supporting the Management of Athletic Pelvic and Groin Injury.

Athletic pelvic and groin injuries are a common yet challenging problem. Pelvic belts have been successfully used to reduce pain and improve function but are not a practical solution for athletes. Therefore, there is scope to explore the use of a more dynamic intervention developed to aid in the management of this type of injury. To undertake a preliminary investigation into the effectiveness of a dynamic elastomeric fabric orthosis (DEFO) in supporting the management of athletic pelvic and groin injury. A case series with an AB design. Daily assessments were undertaken over 15 days; the onset of intervention was randomized with a minimum baseline period of 6 d. Follow-up assessment was undertaken after 1 mo. Community and university. 8 athletes presenting with pelvic or groin injury confirmed through clinical screening. A bespoke DEFO. Force produced on bilateral resisted hip adduction and self-scored pain (using a numerical rating scale of 0-10) at rest and during an active straight-leg raise and a broad jump. In 7 cases a significant improvement was observed on at least 1 measure (2-SD method, celeration line, and/or the point of nonoverlapping data). The remaining case showed minimal symptoms during testing.

Electroconvulsive Therapy May Be Effective Treatment for Major Depression

A long recovery from disorientation following electroconvulsive therapy seems to be a sign that the therapy has eff ectively treated an elderly patient who has major depression, suggests a longitudinal cohort study conducted in Norway. The study comprised 57 Norwegianspeaking inpatients, age 60–85, who had major depressive disorders. To enter the study, a patient needed to have a minimum baseline score of 18 on the 17-item Hamilton Rating Scale for Depression (HRSD17). Among the study’s exclusion criteria were a diagnosis of dementia, Parkinson’s disease, schizophrenia, or schizoaffective disorder, and any use of ECT during the previous 6 months. All study participants received the seizureinducing ECT twice a week. The intensity of therapy varied per patient and session, and age and sex of a patient were among the criteria used to determine the