A situation analysis of mental health services and legislation in Ghana: challenges for transformation

Objective: To conduct a situation analysis of the status of mental health care in Ghana and to propose options for scaling up the provision of mental health care. Method: A survey of the existing mental health system in Ghana was conducted using the WHO Assessment Instrument for Mental Health Systems. Documentary analysis was undertaken of mental health legislation, utilizing the WHO Legislation checklists. Semi-structured interviews and focus group discussions were conducted with a broad range of mental health stakeholders (n=122) at the national, regional and district levels. Results: There are shortfalls in the provision of mental health care including insufficient numbers of mental health professionals, aging infrastructure, widespread stigma, inadequate funding and an inequitable geographical distribution of services. Conclusion: Community-based services need to be delivered in the primary care setting to provide accessible and humane mental health care. There is an urgent need for legislation reform, to improve mental health care delivery and protect human rights.Key words: Mental health; Legislation; Ghan

Defining the mode of action of cisplatin combined with NUC-1031, a phosphoramidate modification of gemcitabine

Funding: DP and GMZ were funded by Nucana plc (XIUN20-18695) (https://www.nucana.com).The combination of gemcitabine with platinum agents is a widely used chemotherapy regimen for a number of tumour types. Gemcitabine plus cisplatin remains the current therapeutic choice for biliary tract cancer. Gemcitabine is associated with multiple cellular drug resistance mechanisms and other limitations and has thereforelined in use. NUC-1031 (Acelarin) is a phosphorylated form of gemcitabine, protected by the addition of a phosphoramidate moiety, developed to circumvent the key limitations and generate high levels of the cytotoxic metabolite, dFdCTP. The rationale for combination of gemcitabine and cisplatin is determined by in vitro cytotoxicity. This, however, does not offer an explanation of how these drugs lead to cell death. In this study we investigate the mechanism of action for NUC-1031 combined with cisplatin as a rationale for treatment. NUC-1031 is metabolised to dFdCTP, detectable up to 72 h post-treatment and incorporated into DNA, to stall the cell cycle and cause DNA damage in biliary tract and ovarian cancer cell lines. In combination with cisplatin, DNA damage was increased and occurred earlier compared to monotherapy. The damage associated with NUC-1031 may be potentiated by a second mechanism, via binding the RRM1 subunit of ribonucleotide reductase and perturbing the nucleotide pools; however, this may be mitigated by increased RRM1 expression. The implication of this was investigated in case studies from a Phase I clinical trial to observe whether baseline RRM1 expression in tumour tissue at time of diagnosis correlates with patient survival.Peer reviewe

From mental health policy development in Ghana to implementation: What are the barriers?

Objective: This paper identifies the key barriers to mental health policy implementation in Ghana and suggests ways of overcoming them. Method: The study used both quantitative and qualitative methods. Quantitatively, the WHO Mental Health Policy and Plan Checklist and the WHO Mental Health Legislation Checklist were employed to analyse the content of mental health policy, plans and legislation in Ghana. Qualitative data was gathered using in-depth interviews and focus group discussions with key stakeholders in mental health at the macro, meso and micro levels. These were used to identify barriers to the implementation of mental health policy, and steps to overcoming these. Results: Barriers to mental health policy implementation identified by participants include: low priority and lack of political commitment to mental health; limited human and financial resources; lack of intersectoral collaboration and consultation; inadequate policy dissemination; and an absence of research-based evidence to inform mental health policy. Suggested steps to overcoming the barriers include: revision of mental health policy and legislation; training and capacity development and wider consultation. Conclusion: These results call for well-articulated plans to address the barriers to the implementation of mental health policy in Ghana to reduce the burden associated with mental disorders.Key Words: Mental health; Policy; Implementation; Barriers; Legislatio

A redox switch in angiotensinogen modulates angiotensin release.

Blood pressure is critically controlled by angiotensins, which are vasopressor peptides specifically released by the enzyme renin from the tail of angiotensinogen-a non-inhibitory member of the serpin family of protease inhibitors. Although angiotensinogen has long been regarded as a passive substrate, the crystal structures solved here to 2.1 Å resolution show that the angiotensin cleavage site is inaccessibly buried in its amino-terminal tail. The conformational rearrangement that makes this site accessible for proteolysis is revealed in our 4.4 Å structure of the complex of human angiotensinogen with renin. The co-ordinated changes involved are seen to be critically linked by a conserved but labile disulphide bridge. Here we show that the reduced unbridged form of angiotensinogen is present in the circulation in a near 40:60 ratio with the oxidized sulphydryl-bridged form, which preferentially interacts with receptor-bound renin. We propose that this redox-responsive transition of angiotensinogen to a form that will more effectively release angiotensin at a cellular level contributes to the modulation of blood pressure. Specifically, we demonstrate the oxidative switch of angiotensinogen to its more active sulphydryl-bridged form in the maternal circulation in pre-eclampsia-the hypertensive crisis of pregnancy that threatens the health and survival of both mother and child

Performance and calibration of quark/gluon-jet taggers using 140 fb⁻¹ of pp collisions at √s=13 TeV with the ATLAS detector

The identification of jets originating from quarks and gluons, often referred to as quark/gluon tagging, plays an important role in various analyses performed at the Large Hadron Collider, as Standard Model measurements and searches for new particles decaying to quarks often rely on suppressing a large gluon-induced background. This paper describes the measurement of the efficiencies of quark/gluon taggers developed within the ATLAS Collaboration, using √s=13 TeV proton–proton collision data with an integrated luminosity of 140 fb-1 collected by the ATLAS experiment. Two taggers with high performances in rejecting jets from gluon over jets from quarks are studied: one tagger is based on requirements on the number of inner-detector tracks associated with the jet, and the other combines several jet substructure observables using a boosted decision tree. A method is established to determine the quark/gluon fraction in data, by using quark/gluon-enriched subsamples defined by the jet pseudorapidity. Differences in tagging efficiency between data and simulation are provided for jets with transverse momentum between 500 GeV and 2 TeV and for multiple tagger working points

Combination of searches for heavy spin-1 resonances using 139 fb−1 of proton-proton collision data at √s = 13 TeV with the ATLAS detector

A combination of searches for new heavy spin-1 resonances decaying into diferent pairings of W, Z, or Higgs bosons, as well as directly into leptons or quarks, is presented. The data sample used corresponds to 139 fb−1 of proton-proton collisions at √ s = 13 TeV collected during 2015–2018 with the ATLAS detector at the CERN Large Hadron Collider. Analyses selecting quark pairs (qq, bb, tt¯, and tb) or third-generation leptons (τν and τ τ ) are included in this kind of combination for the frst time. A simplifed model predicting a spin-1 heavy vector-boson triplet is used. Cross-section limits are set at the 95% confdence level and are compared with predictions for the benchmark model. These limits are also expressed in terms of constraints on couplings of the heavy vector-boson triplet to quarks, leptons, and the Higgs boson. The complementarity of the various analyses increases the sensitivity to new physics, and the resulting constraints are stronger than those from any individual analysis considered. The data exclude a heavy vector-boson triplet with mass below 5.8 TeV in a weakly coupled scenario, below 4.4 TeV in a strongly coupled scenario, and up to 1.5 TeV in the case of production via vector-boson fusion

Measurement and interpretation of same-sign W boson pair production in association with two jets in pp collisions at √s = 13 TeV with the ATLAS detector

This paper presents the measurement of fducial and diferential cross sections for both the inclusive and electroweak production of a same-sign W-boson pair in association with two jets (W±W±jj) using 139 fb−1 of proton-proton collision data recorded at a centre-of-mass energy of √ s = 13 TeV by the ATLAS detector at the Large Hadron Collider. The analysis is performed by selecting two same-charge leptons, electron or muon, and at least two jets with large invariant mass and a large rapidity diference. The measured fducial cross sections for electroweak and inclusive W±W±jj production are 2.92 ± 0.22 (stat.) ± 0.19 (syst.)fb and 3.38±0.22 (stat.)±0.19 (syst.)fb, respectively, in agreement with Standard Model predictions. The measurements are used to constrain anomalous quartic gauge couplings by extracting 95% confdence level intervals on dimension-8 operators. A search for doubly charged Higgs bosons H±± that are produced in vector-boson fusion processes and decay into a same-sign W boson pair is performed. The largest deviation from the Standard Model occurs for an H±± mass near 450 GeV, with a global signifcance of 2.5 standard deviations

Improving topological cluster reconstruction using calorimeter cell timing in ATLAS

Clusters of topologically connected calorimeter cells around cells with large absolute signal-to-noise ratio (topo-clusters) are the basis for calorimeter signal reconstruction in the ATLAS experiment. Topological cell clustering has proven performant in LHC Runs 1 and 2. It is, however, susceptible to out-of-time pile-up of signals from soft collisions outside the 25 ns proton-bunch-crossing window associated with the event’s hard collision. To reduce this effect, a calorimeter-cell timing criterion was added to the signal-to-noise ratio requirement in the clustering algorithm. Multiple versions of this criterion were tested by reconstructing hadronic signals in simulated events and Run 2 ATLAS data. The preferred version is found to reduce the out-of-time pile-up jet multiplicity by ∼50% for jet pT ∼ 20 GeV and by ∼80% for jet pT 50 GeV, while not disrupting the reconstruction of hadronic signals of interest, and improving the jet energy resolution by up to 5% for 20 < pT < 30 GeV. Pile-up is also suppressed for other physics objects based on topo-clusters (electrons, photons, τ -leptons), reducing the overall event size on disk by about 6% in early Run 3 pileup conditions. Offline reconstruction for Run 3 includes the timing requirement