Internet-based treatment for panic disorder : does frequency of therapist contact make a difference?

Internet-based interventions with therapist support have proven effective for treating a range of mental health conditions. This study examined whether frequency of therapist contact affected treatment outcomes. Fifty-seven people with panic disorder (including 32 with agoraphobia) were randomly allocated to an 8-week Internet-based cognitive behavioural treatment intervention (Panic Online) with either frequent (three e-mails per week) or infrequent (one e-mail per week) support from a psychologist. Posttreatment, intention-to-treat analyses revealed that both treatments were effective at improving panic disorder and agoraphobia severity ratings, panicrelated cognitions, negative affect, and psychological and physical quality of life domains, with no differences between conditions. High end-state functioning was achieved by 28.6% of the frequent and infrequent participants, respectively. Therapist alliance, treatment credibility, and satisfaction also did not differ between groups, despite significantly greater therapist time invested in the frequent contact condition. The results provide evidence that the effectiveness of Internet-based mental health interventions may be independent of the frequency of therapist support and may, therefore, be more cost-effective than previously reported.<br /

A qualitative evaluation of priority-setting by the health benefits package advisory panel in Kenya.

Kenya's Ministry of Health established the Health Benefits Package Advisory Panel (HBPAP) in 2018 to develop a benefits package for universal health coverage. This study evaluated HBPAP's process for developing the benefits package against the normative procedural (acceptable way of doing things) and outcome (acceptable consequences) conditions of an ideal healthcare priority-setting process as outlined in the study's conceptual framework. We conducted a qualitative case study using in-depth interviews with national level respondents (n = 20) and document reviews. Data were analysed using a thematic approach. HBPAP's process partially fulfilled the procedural and outcome conditions of the study's evaluative framework. Concerning the procedural conditions, transparency and publicity were partially met, and were limited by the lack of publication of HBPAP's report. While HBPAP used explicit and evidence-based priority-setting criteria, challenges included the lack of primary data and local cost-effectiveness threshold, weak health information systems, short timelines, and political interference. While a wide range of stakeholders were engaged, this was limited by short timelines and inadequate financial resources. Empowerment of non-HBPAP members was limited by their inadequate technical knowledge and experience in priority-setting. Lastly, appeals and revisions were limited by short timelines and lack of implementation of the proposed benefits package. Concerning the outcome conditions, stakeholder understanding was limited by the technical nature of the process and short timelines while stakeholder acceptance and satisfaction were limited by lack of transparency. HBPAP's benefits package was not implemented due to stakeholder interests and opposition. Priority-setting processes for benefits package development in Kenya could be improved by publicizing the outcome of the process, allocating adequate time and financial resources, strengthening health information systems, generating local evidence, and enhancing stakeholder awareness and engagement to increase their empowerment, understanding and acceptance of the process. Managing politics and stakeholder interests is key in enhancing the success of priority-setting processes

An exported protein-interacting complex involved in the trafficking of virulence determinants in Plasmodium-infected erythrocytes

The malaria parasite, Plasmodium falciparum, displays the P. falciparum erythrocyte membrane protein 1 (PfEMP1) on the surface of infected red blood cells (RBCs). We here examine the physical organization of PfEMP1 trafficking intermediates in infected RBCs and determine interacting partners using an epitope-tagged minimal construct (PfEMP1B). We show that parasitophorous vacuole (PV)-located PfEMP1B interacts with components of the PTEX (Plasmodium Translocon of EXported proteins) as well as a novel protein complex, EPIC (Exported Protein-Interacting Complex). Within the RBC cytoplasm PfEMP1B interacts with components of the Maurer\u27s clefts and the RBC chaperonin complex. We define the EPIC interactome and, using an inducible knockdown approach, show that depletion of one of its components, the parasitophorous vacuolar protein-1 (PV1), results in altered knob morphology, reduced cell rigidity and decreased binding to CD36. Accordingly, we show that deletion of the Plasmodium berghei homologue of PV1 is associated with attenuation of parasite virulence in vivo

Search for new particles in events with energetic jets and large missing transverse momentum in proton-proton collisions at root s=13 TeV

A search is presented for new particles produced at the LHC in proton-proton collisions at root s = 13 TeV, using events with energetic jets and large missing transverse momentum. The analysis is based on a data sample corresponding to an integrated luminosity of 101 fb(-1), collected in 2017-2018 with the CMS detector. Machine learning techniques are used to define separate categories for events with narrow jets from initial-state radiation and events with large-radius jets consistent with a hadronic decay of a W or Z boson. A statistical combination is made with an earlier search based on a data sample of 36 fb(-1), collected in 2016. No significant excess of events is observed with respect to the standard model background expectation determined from control samples in data. The results are interpreted in terms of limits on the branching fraction of an invisible decay of the Higgs boson, as well as constraints on simplified models of dark matter, on first-generation scalar leptoquarks decaying to quarks and neutrinos, and on models with large extra dimensions. Several of the new limits, specifically for spin-1 dark matter mediators, pseudoscalar mediators, colored mediators, and leptoquarks, are the most restrictive to date.Peer reviewe

Combined searches for the production of supersymmetric top quark partners in proton-proton collisions at root s=13 TeV

A combination of searches for top squark pair production using proton-proton collision data at a center-of-mass energy of 13 TeV at the CERN LHC, corresponding to an integrated luminosity of 137 fb(-1) collected by the CMS experiment, is presented. Signatures with at least 2 jets and large missing transverse momentum are categorized into events with 0, 1, or 2 leptons. New results for regions of parameter space where the kinematical properties of top squark pair production and top quark pair production are very similar are presented. Depending on themodel, the combined result excludes a top squarkmass up to 1325 GeV for amassless neutralino, and a neutralinomass up to 700 GeV for a top squarkmass of 1150 GeV. Top squarks with masses from 145 to 295 GeV, for neutralino masses from 0 to 100 GeV, with a mass difference between the top squark and the neutralino in a window of 30 GeV around the mass of the top quark, are excluded for the first time with CMS data. The results of theses searches are also interpreted in an alternative signal model of dark matter production via a spin-0 mediator in association with a top quark pair. Upper limits are set on the cross section for mediator particle masses of up to 420 GeV

Measurements of Higgs boson production cross sections and couplings in the diphoton decay channel at root s=13 TeV

Measurements of Higgs boson production cross sections and couplings in events where the Higgs boson decays into a pair of photons are reported. Events are selected from a sample of proton-proton collisions at root s = 13TeV collected by the CMS detector at the LHC from 2016 to 2018, corresponding to an integrated luminosity of 137 fb(-1). Analysis categories enriched in Higgs boson events produced via gluon fusion, vector boson fusion, vector boson associated production, and production associated with top quarks are constructed. The total Higgs boson signal strength, relative to the standard model (SM) prediction, is measured to be 1.12 +/- 0.09. Other properties of the Higgs boson are measured, including SM signal strength modifiers, production cross sections, and its couplings to other particles. These include the most precise measurements of gluon fusion and vector boson fusion Higgs boson production in several different kinematic regions, the first measurement of Higgs boson production in association with a top quark pair in five regions of the Higgs boson transverse momentum, and an upper limit on the rate of Higgs boson production in association with a single top quark. All results are found to be in agreement with the SM expectations.Peer reviewe

Observation of tW production in the single-lepton channel in pp collisions at root s=13 TeV

A measurement of the cross section of the associated production of a single top quark and a W boson in final states with a muon or electron and jets in proton-proton collisions at root s = 13 TeV is presented. The data correspond to an integrated luminosity of 36 fb(-1) collected with the CMS detector at the CERN LHC in 2016. A boosted decision tree is used to separate the tW signal from the dominant t (t) over bar background, whilst the subleading W+jets and multijet backgrounds are constrained using data-based estimates. This result is the first observation of the tW process in final states containing a muon or electron and jets, with a significance exceeding 5 standard deviations. The cross section is determined to be 89 +/- 4 (stat) +/- 12 (syst) pb, consistent with the standard model.Peer reviewe

Measurement of the top quark mass using events with a single reconstructed top quark in pp collisions at root s=13 TeV

Abstract:A measurement of the top quark mass is performed using a data sample en-riched with single top quark events produced in thetchannel. The study is based on proton-proton collision data, corresponding to an integrated luminosity of 35.9 fb−1, recorded at√s= 13TeV by the CMS experiment at the LHC in 2016. Candidate events are selectedby requiring an isolated high-momentum lepton (muon or electron) and exactly two jets,of which one is identified as originating from a bottom quark. Multivariate discriminantsare designed to separate the signal from the background. Optimized thresholds are placedon the discriminant outputs to obtain an event sample with high signal purity. The topquark mass is found to be172.13+0.76−0.77GeV, where the uncertainty includes both the sta-tistical and systematic components, reaching sub-GeV precision for the first time in thisevent topology. The masses of the top quark and antiquark are also determined separatelyusing the lepton charge in the final state, from which the mass ratio and difference aredetermined to be0.9952+0.0079−0.0104and0.83+1.79−1.35GeV, respectively. The results are consistentwithCPTinvariance

Search for a heavy Higgs boson decaying into two lighter Higgs bosons in the tau tau bb final state at 13 TeV

A search for a heavy Higgs boson H decaying into the observed Higgs boson h with a mass of 125 GeV and another Higgs boson h(S) is presented. The h and h(S) bosons are required to decay into a pair of tau leptons and a pair of b quarks, respectively. The search uses a sample of proton-proton collisions collected with the CMS detector at a center-of-mass energy of 13TeV, corresponding to an integrated luminosity of 137 fb(-1). Mass ranges of 240-3000 GeV for m(H) and 60-2800 GeV for m(hS) are explored in the search. No signal has been observed. Model independent 95% confidence level upper limits on the product of the production cross section and the branching fractions of the signal process are set with a sensitivity ranging from 125 fb (for m(H) = 240 GeV) to 2.7 fb (for m(H) = 1000 GeV). These limits are compared to maximally allowed products of the production cross section and the branching fractions of the signal process in the next-to-minimal supersymmetric extension of the standard model.Peer reviewe

Abiraterone acetate plus prednisolone with or without enzalutamide for patients with metastatic prostate cancer starting androgen deprivation therapy: final results from two randomised phase 3 trials of the STAMPEDE platform protocol

Background: Abiraterone acetate plus prednisolone (herein referred to as abiraterone) or enzalutamide added at the start of androgen deprivation therapy improves outcomes for patients with metastatic prostate cancer. Here, we aimed to evaluate long-term outcomes and test whether combining enzalutamide with abiraterone and androgen deprivation therapy improves survival. Methods: We analysed two open-label, randomised, controlled, phase 3 trials of the STAMPEDE platform protocol, with no overlapping controls, conducted at 117 sites in the UK and Switzerland. Eligible patients (no age restriction) had metastatic, histologically-confirmed prostate adenocarcinoma; a WHO performance status of 0–2; and adequate haematological, renal, and liver function. Patients were randomly assigned (1:1) using a computerised algorithm and a minimisation technique to either standard of care (androgen deprivation therapy; docetaxel 75 mg/m2 intravenously for six cycles with prednisolone 10 mg orally once per day allowed from Dec 17, 2015) or standard of care plus abiraterone acetate 1000 mg and prednisolone 5 mg (in the abiraterone trial) orally or abiraterone acetate and prednisolone plus enzalutamide 160 mg orally once a day (in the abiraterone and enzalutamide trial). Patients were stratified by centre, age, WHO performance status, type of androgen deprivation therapy, use of aspirin or non-steroidal anti-inflammatory drugs, pelvic nodal status, planned radiotherapy, and planned docetaxel use. The primary outcome was overall survival assessed in the intention-to-treat population. Safety was assessed in all patients who started treatment. A fixed-effects meta-analysis of individual patient data was used to compare differences in survival between the two trials. STAMPEDE is registered with ClinicalTrials.gov (NCT00268476) and ISRCTN (ISRCTN78818544). Findings: Between Nov 15, 2011, and Jan 17, 2014, 1003 patients were randomly assigned to standard of care (n=502) or standard of care plus abiraterone (n=501) in the abiraterone trial. Between July 29, 2014, and March 31, 2016, 916 patients were randomly assigned to standard of care (n=454) or standard of care plus abiraterone and enzalutamide (n=462) in the abiraterone and enzalutamide trial. Median follow-up was 96 months (IQR 86–107) in the abiraterone trial and 72 months (61–74) in the abiraterone and enzalutamide trial. In the abiraterone trial, median overall survival was 76·6 months (95% CI 67·8–86·9) in the abiraterone group versus 45·7 months (41·6–52·0) in the standard of care group (hazard ratio [HR] 0·62 [95% CI 0·53–0·73]; p&lt;0·0001). In the abiraterone and enzalutamide trial, median overall survival was 73·1 months (61·9–81·3) in the abiraterone and enzalutamide group versus 51·8 months (45·3–59·0) in the standard of care group (HR 0·65 [0·55–0·77]; p&lt;0·0001). We found no difference in the treatment effect between these two trials (interaction HR 1·05 [0·83–1·32]; pinteraction=0·71) or between-trial heterogeneity (I2 p=0·70). In the first 5 years of treatment, grade 3–5 toxic effects were higher when abiraterone was added to standard of care (271 [54%] of 498 vs 192 [38%] of 502 with standard of care) and the highest toxic effects were seen when abiraterone and enzalutamide were added to standard of care (302 [68%] of 445 vs 204 [45%] of 454 with standard of care). Cardiac causes were the most common cause of death due to adverse events (five [1%] with standard of care plus abiraterone and enzalutamide [two attributed to treatment] and one (&lt;1%) with standard of care in the abiraterone trial). Interpretation: Enzalutamide and abiraterone should not be combined for patients with prostate cancer starting long-term androgen deprivation therapy. Clinically important improvements in survival from addition of abiraterone to androgen deprivation therapy are maintained for longer than 7 years. Funding: Cancer Research UK, UK Medical Research Council, Swiss Group for Clinical Cancer Research, Janssen, and Astellas