Improving the mental health and mental health support available to adolescents in out-of-home care via Adolescent-Focused Low-Intensity Life Story Work: a realist review

Objectives: Life Story Work (LSW) is used to promote the mental health and well-being of children and adolescents living in out-of-home care. LSW should be offered to all but is conventionally delivered in high-intensity ways. Low-intensity approaches are more accessible but there is significant variation and little guidance for supporting adolescents. We aimed to create guidance for Adolescent-Focused Low-Intensity LSW. // Design: Realist review. // Data sources: MEDLINE, Embase, PsycINFO, Sociology Collection (ProQuest), CINAHL, CDAS, Web of Science (SCIE, SSCI), Social Care Online and grey literature sources. Searches were performed between December 2021 and March 2022. // Eligibility criteria: Documents on children and adolescents in care, LSW and/or low-intensity interventions to improve mental health were included. Documents focusing on parenting style and contact with birth family were excluded. // Analysis: Documents were analysed using a realist logic of analysis. In consultation with Content Expert Groups (comprising professionals and care leavers), we developed an initial programme theory. Data relating to and challenging the initial programme theory were extracted and context-mechanism-outcome-configurations developed, critiqued and refined in an iterative fashion. Interpretations were drawn from context-mechanism-outcome-configurations to enhance the programme theory. // Results: 75 documents contributed to the analysis. Generally, studies were small-scale and lacked in-depth methods and evaluation descriptions. Findings indicated important factors contribute to the development of high-quality Adolescent-Focused Low-Intensity LSW. Adolescent-Focused Low-Intensity LSW should be person-centred, begin in the now, involve co-construction, record everyday positive life events and be supported by trained carer(s). Context-mechanism-outcome-configurations relating to these themes are reported. // Conclusions: Using this knowledge we developed initial practice guidance to support social care to deliver better quality Adolescent-Focused Low-Intensity LSW more consistently. To address gaps in our knowledge about the impact of Adolescent-Focused Low-Intensity LSW, further primary research is needed to strengthen understandings of how this intervention works (or not) in different contexts. // PROSPERO registration number: CRD42021279816

Balancing continuous, integrated, and batch processing

We are building a new disposable manufacturing system to support the development and manufacturing of mAb and mAb-related products. We have made choices that are different than many others in the field of continuous and integrated processing. These choices avoid many misperceptions about continuous processing, are consistent with a staged approach to implementation, and facilitate manufacturing in either large-scale disposable or stainless manufacturing facilities. We have avoided the use of long-term steady-state perfusion. This mode of perfusion suffers from long development times, long manufacturing duration, extended Process Performance Qualification, large media consumption and perceived concerns about product quality variability and contamination. The system uses a short duration (\u3c15 days) non-steady state perfusion with perfusion rates as low as 0.3 bioreactor volumes per day. On-line UPLC is used to monitor product titer and quality. As a consequence of non-steady state perfusion operation, the integrated downstream is capable of handling day to day variability of 0.5g/L/day to 4g/L/day. The downstream avoids the use of SMB or PCC; rather, it integrates two batch chromatographic steps, a continuous virus inactivation step, and avoids in-process pooling. The product is stored after the second chromatography step for the duration of the batch. When the batch is complete, the pooled product is batched through a virus reduction filter and UFDF to make the bulk drug substance. Running these last two processes on the entire product pool at once allows an easy definition of a batch, without worry about pooling drug substance with different product quality profiles. The result is an integrated, semi-continuous manufacturing process that mitigates many of the concerns felt by the batch-processing community

Noninvasive detection of graft injury after heart transplant using donor-derived cell-free DNA: A prospective multicenter study

Standardized donor-derived cell-free DNA (dd-cfDNA) testing has been introduced into clinical use to monitor kidney transplant recipients for rejection. This report describes the performance of this dd-cfDNA assay to detect allograft rejection in samples from heart transplant (HT) recipients undergoing surveillance monitoring across the United States. Venous blood was longitudinally sampled from 740 HT recipients from 26 centers and in a single-center cohort of 33 patients at high risk for antibody-mediated rejection (AMR). Plasma dd-cfDNA was quantified by using targeted amplification and sequencing of a single nucleotide polymorphism panel. The dd-cfDNA levels were correlated to paired events of biopsy-based diagnosis of rejection. The median dd-cfDNA was 0.07% in reference HT recipients (2164 samples) and 0.17% in samples classified as acute rejection (35 samples; P = .005). At a 0.2% threshold, dd-cfDNA had a 44% sensitivity to detect rejection and a 97% negative predictive value. In the cohort at risk for AMR (11 samples), dd-cfDNA levels were elevated 3-fold in AMR compared with patients without AMR (99 samples, P = .004). The standardized dd-cfDNA test identified acute rejection in samples from a broad population of HT recipients. The reported test performance characteristics will guide the next stage of clinical utility studies of the dd-cfDNA assay

Synthesis and characterization of smooth ultrananocrystalline diamond films via low pressure bias-enhanced nucleation and growth

This letter describes the fundamental process underlying the synthesis of ultrananocrystalline diamond (UNCD) films, using a new low-pressure, heat-assisted bias-enhanced nucleation (BEN)/bias enhanced growth (BEG) technique, involving H2/CH4 gas chemistry. This growth process yields UNCD films similar to those produced by the Ar-rich/CH4 chemistries, with pure diamond nanograins (3–5 nm), but smoother surfaces (~6 nm rms) and higher growth rate (~1 µm/h). Synchrotron-based x-Ray absorption spectroscopy, atomic force microscopy, and transmission electron microscopy studies on the BEN-BEG UNCD films provided information critical to understanding the nucleation and growth mechanisms, and growth condition-nanostructure-property relationships

Are diamonds a MEMS\u27 best friend?

Next-generation military and civilian communication systems will require technologies capable of handling data/ audio, and video simultaneously while supporting multiple RF systems operating in several different frequency bands from the MHz to the GHz range [1]. RF microelectromechanical/nanoelectromechanical (MEMS/NEMS) devices, such as resonators and switches, are attractive to industry as they offer a means by which performance can be greatly improved for wireless applications while at the same time potentially reducing overall size and weight as well as manufacturing costs

Improving the mental health and mental health support available to adolescents with social care-experience via low-intensity life story work: A realist review protocol

Introduction: Adolescents are the fastest growing group entering social care and are most at risk of mental ill-health. Life Story Work (LSW) is an existing transdiagnostic intervention thought to improve the well-being and mental health of children and adolescents under the care of a local authority by assisting the processing of trauma. Yet LSW is poorly evidenced, lacks standardisation and focuses on younger children. LSW is also high-intensity, relying on specialist input over several months. Adolescent-focused low-intensity-LSW is a promising alternative. However, there is poor evidence on how LSW, let alone low-intensity-LSW should be delivered to adolescents. We aim to identify why, how, in what contexts, for whom and to what extent low-intensity-LSW interventions can be delivered to adolescents with care-experience. Methods and analysis: Undertaking a realist review, we will: (1) develop an initial programme theory (PrT) of adolescent-focused low-intensity-LSW by consulting with two key expert panels (care-experienced and professional stakeholders), and by searching the literature to identify existing relevant theories; (2) undertake a comprehensive literature search to identify secondary data to develop and refine our emerging PrT. Searches will be run between 12/2021-06/2022 in databases including MEDLINE, PsycINFO, ASSIA and relevant sources of grey literature; (3) select, extract and organise data; (4) synthesise evidence using a realist logic of analysis and undertake further iterative data searching and consultation with our expert panels; (5) write up and share the refined PrT with our expert panels for their final comments. From this process guidance will be developed to help improve the delivery of LSW to support the mental health needs of adolescents with care-experience. Ethics and dissemination: Ethical approval is not required. Dissemination will include input from expert panels. We will develop academic, practice and youth focused outputs targeting adolescents, their carers, social, healthcare, and educational professionals, academics, and policymakers. PROSPERO registration number: CRD42021279816

Erythrocyte G Protein as a Novel Target for Malarial Chemotherapy

BACKGROUND: Malaria remains a serious health problem because resistance develops to all currently used drugs when their parasite targets mutate. Novel antimalarial drug targets are urgently needed to reduce global morbidity and mortality. Our prior results suggested that inhibiting erythrocyte G(s) signaling blocked invasion by the human malaria parasite Plasmodium falciparum. METHODS AND FINDINGS: We investigated the erythrocyte guanine nucleotide regulatory protein G(s) as a novel antimalarial target. Erythrocyte “ghosts” loaded with a G(s) peptide designed to block G(s) interaction with its receptors, were blocked in β-adrenergic agonist-induced signaling. This finding directly demonstrates that erythrocyte G(s) is functional and that propranolol, an antagonist of G protein–coupled β-adrenergic receptors, dampens G(s) activity in erythrocytes. We subsequently used the ghost system to directly link inhibition of host G(s) to parasite entry. In addition, we discovered that ghosts loaded with the peptide were inhibited in intracellular parasite maturation. Propranolol also inhibited blood-stage parasite growth, as did other β(2)-antagonists. β-blocker growth inhibition appeared to be due to delay in the terminal schizont stage. When used in combination with existing antimalarials in cell culture, propranolol reduced the 50% and 90% inhibitory concentrations for existing drugs against P. falciparum by 5- to 10-fold and was also effective in reducing drug dose in animal models of infection. CONCLUSIONS: Together these data establish that, in addition to invasion, erythrocyte G protein signaling is needed for intracellular parasite proliferation and thus may present a novel antimalarial target. The results provide proof of the concept that erythrocyte G(s) antagonism offers a novel strategy to fight infection and that it has potential to be used to develop combination therapies with existing antimalarials

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal