<i>Mytilus edulis</i> and <i>Psammechinus miliaris</i> as bioindicators of ecotoxicological risk by maritime exhaust gas scrubber water

Approximately 15 % of the global anthropogenic emissions of sulfur oxides (SOx) come from shipping. To meet sulfur emission regulations for marine vessels, many shipping companies have chosen to use exhaust gas cleaning systems (EGCS), commonly known as scrubbers. The resulting washwater from scrubbers contains various pollutants such as polycyclic aromatic hydrocarbons (PAHs), trace metals, and nitrates, is then directly discharged into the surrounding surface water, transferring potential atmospheric pollutants to the marine environment. The aim of this study was to investigate the impact of EGCS discharge water on blue mussels (Mytilus edulis) and sea-urchin (Psammechinus miliaris) embryos and larvae. Chronic toxicity tests were performed using a fertilization test and a larval development bioassay exposed to scrubber water dilutions (0.001, 0.01, 0.1, 1, 2, 5, 10, 20, 40 and 100 % of the original sample). Negative effects on fertilization success and larvae development in both species at very low concentrations were observed (EC10 &lt; 1 %) indicating the severe impact of EGCS discharges on these species. EGCS effluents showed different effects depending on the species and life stages. Sea urchin embryos were more sensitive than the blue mussel embryos. However, blue mussel larvae were much more sensitive than sea urchin larvae. These results emphasize the potential toxic effects of direct exposure -not dietary- to scrubber water discharges on marine invertebrate. EGCS discharge limits are urgent to prevent further potentially irreversible damage to the marine environment

Neoadjuvant PARP inhibitor scheduling in BRCA1 and BRCA2 related breast cancer: PARTNER, a randomized phase II/III trial

Poly (ADP-ribose) polymerase inhibitors (PARPi) exploit DNA repair deficiency in germline BRCA1 and BRCA2 pathogenic variant (gBRCAm) cancers. Haematological toxicity limits chemotherapy-PARPi treatment combinations. In preclinical models we identified a schedule combining olaparib and carboplatin that avoids enhanced toxicity but maintains anti-tumour activity. We investigated this schedule in a neoadjuvant, phase II-III, randomised controlled trial for gBRCAm breast cancers (ClinicalTrials.gov ID:NCT03150576; PARTNER). The research arm included carboplatin (Area Under the Curve 5, 3-weekly); paclitaxel (80 mg/m 2, weekly) day 1, plus olaparib (150 mg twice daily) day 3-14 (4 cycles), followed by anthracycline-containing chemotherapy (3 cycles); control arm gave chemotherapy alone. The primary endpoint, pathological complete response rate, showed no statistical difference between research 64.1% (25/39); control 69.8% (30/43) (p = 0.59). However, estimated survival outcomes at 36-months demonstrated improved event-free survival: research 96.4%, control 80.1% (p = 0.04); overall survival: research 100%, control 88.2% (p = 0.04) and breast cancer specific survival: research 100%, control 88.2% (p = 0.04). There were no statistical differences in relapse-free survival and distant disease-free survival, both were: research 96.4%, control 87.9% (p = 0.20). Similarly, local recurrence-free survival and time to second cancer were both: research 96.4%, control 87.8% (p = 0.20). The PARTNER trial identified a safe, tolerable schedule combining neoadjuvant chemotherapy with olaparib. This combination demonstrated schedule-dependent overall survival benefit in early-stage gBRCAm breast cancer. This result needs confirmation in larger trials. </p

Modelling diabetes and depression in Pakistan: using economic modelling to inform intervention design and a clinical trial of a behavioural activation intervention

Objectives: the ‘Developing and evaluating an adapted behavioural activation intervention for depression and diabetes in South Asia (DiaDeM)’ trial investigates a psychological intervention, behavioural activation (BA), on people with both diabetes and depression in Bangladesh and Pakistan. This study aimed to aid the intervention and trial design. Design: this was a modelling study using microsimulation to assess the intervention's cost-effectiveness. Diabetes was modelled using the UK Prospective Diabetes Study (UKPDS) model based on Pakistani patients and depression was modelled using Patient Health Questionnaire-9 trajectories allowing for multiple depressive episodes. It was assumed that diabetes-related adverse events increased depression recurrence, while depression impacted HbA1c, increasing diabetes-related events.The model estimated (i) maximum cost of BA which would be cost-effectiveness (headroom analysis) to inform intervention design, and (ii) value of reducing uncertainty around different measures (value of information analysis) to prioritise data collection in the DiaDeM studySetting: analysis was conducted from a Pakistani healthcare perspective over a lifetime with costs and outcomes discounted at 3%.Interventions: BA plus usual care was compared against usual care. BA involved six sessions by a trained (non-mental health) facilitator. The usual care comparator was the prevailing mix of pharmacological and non-pharmacological treatments used in Pakistan.Primary and secondary outcome measures: the primary outcome was disability-adjusted life-years (DALYs). Secondary outcomes included life years, healthcare costs and the rate of depression and diabetes-related events.Results: over their lifetime, individuals receiving BA plus usual care avoid 3.2 (95% credible interval: 2.7, 3.8) years of mild depression and experience fewer diabetes-related events. BA plus usual care resulted in an additional 0.27 (0.03, 0.52) life years, 0.98 (0.45, 1.86) DALYs averted, and had incremental healthcare costs of -$97 (-$517, $142), excluding BA costs. The maximum cost per BA course at which was cost effective is$83 ($9,$214). Value of information analysis found the most important measures to include in the trial are impact of depression on diabetes and PHQ-9 over time. Conclusions: this is the first model to jointly model depression and diabetes for South Asia and uses novel methods to reflect the diseases and inform intervention and trial design. This evidence has helped to inform the design of the DiaDeM intervention and the trial to evaluate it

Antipsychotic polypharmacy and high-dose antipsychotic therapy compared to antipsychotic monotherapy at standard doses in schizophrenia – a systematic review

Background: schizophrenia is considered to have a lifetime prevalence of around 1%. Up to 30% of patients diagnosed with schizophrenia are subsequently categorised as treatment resistant. Current guidelines advise against the use of antipsychotic polypharmacy (APP) or high-dose antipsychotic therapy (HDAT) in the treatment of schizophrenia; however, these treatment approaches continue to be used in up to 25% of cases.Aims: tis review was to evaluate the evidence for the efficacy and tolerability of APP and HDAT as an alternative to antipsychotic monotherapy at standard doses in the treatment of schizophrenia.Methods: this is a systematic review. We searched PubMed, EMBASE and PsycINFO, for eligible trials published prior to 24 March 2023. The protocol was registered on PROSPERO (CRD42023408785). Quality assessment was conducted using the Revised Cochrane risk-of-bias tool for randomised trials.Results:A total of 14 studies were included in this review. Two studies demonstrated clinically significant improvement with APP compared to standard treatment. There was no clear evidence that APP or HDAT is definitively less tolerable than antipsychotic monotherapy at a standard dose.Conclusions: this review found limited evidence for the efficacy of APP and HDAT in the treatment of schizophrenia over the use of antipsychotic monotherapy at a standard dose. The relative tolerability was unclear. Management of treatment-resistant schizophrenia remains a prominent clinical issue and further research, including high-quality large-scale Randomised Controlled Trials (RCTs) of APP and HDAT in patients who have been unresponsive to clozapine, would be of significant benefit to the field of psychiatry

Explicit formulas for forced convection in a shrouded longitudinal-fin heat sink with clearance

We consider laminar forced convection in a shrouded longitudinal-fin heat sink (LFHS) with tip clearance, as described by the pioneering study of (Sparrow, Baliga &amp; Patankar 1978 J. Heat Trans. 100). The base of the LFHS is isothermal but the fins, while thin, are not isothermal, i.e. the conjugate heat transfer problem is of interest. Whereas Sparrow et al. numerically solved the fully developed flow and thermal problems for a range of geometries and fin conductivities, we consider the physically realistic asymptotic limit where the fins are closely spaced, i.e. the spacing is small relative to their height and the clearance above them. The flow problem in this limit was considered by (Miyoshi et al. 2024, J. Fluid Mech. 991, A2), and we consider the corresponding thermal problem. Usingmatched asymptotic expansions, we find explicit solutions for the temperature field (in both the fluid and fins) and conjugate Nusselt numbers (local and average). The structure of the asymptotic solutions provides further insight into the results of Sparrow et al.: the flow is highest in the gap above the fins, hence heat transfer predominantly occurs close to the fin tips. The new formulas are compared with numerical solutions and are found to be accurate for practical LFHSs. Significantly, existing analytical results for ducts are for boundaries that are either wholly isothermal, wholly isoflux or with one of these conditions on each wall. Consequently, this study provides the first analytical results for conjugate Nusselt numbers for flow through ducts

Near to eye projection systems

AR displays experience limited FOV, low efficiency and high weight partly due to the use of SRGs. Investigated here are improvements to HUDs, replacing gratings with novel structures and high throughput fabrication. Design and fabrication improved upon current systems for diffractive elements and materials. Fabrication produced these in a high transparency, high refractive index glass. Structures were evaluated and improvements over conventional gratings found, enabling improved optics for novel augmented reality devices.A new type of diffractive structure was produced, demonstrating to our knowledge the structure of this kind in transparent materials. Silicon oxynitride deposition for low-absorption hydrogen-free layers with a tuneable refractive index range greater than other methods, was demonstrated at ambient temperatures.<br/

Indifference, resistance, possibility: probation staff perspectives on the introduction of professional registration

Rehabilitating Probation is a three-year research project (2022–2025), exploring the most recent iteration of probation reform in England and Wales. This article takes as its focus the responses from interviews with a mixed sample of probation staff in one case study region (n = 56) to questions they were asked about their knowledge of the Professional Register and what implications they felt it would have for their careers. Our sweep of interviews, running from March 2024 through to September 2024, captures the views of staff in the months leading up to the formal establishment of the Professional Registration policy framework that set out the requirements and guidance for probation staff around professional registration, probation professional registration standards, and loss of authority to practice. Our findings suggest that although some staff in our sample expressed a cautious support for professional registration, there was also a high level of indifference – and in some cases resistance - among those interviewed suggesting a need to articulate more clearly what the purpose of Professional Registration is and what its implementation means for those working within the Probation Service.</p

Nanojoule-energy-level, polarization-maintaining, dissipative-soliton mode-locked thulium fiber laser at 1876 nm

We report an environmentally robust, dissipative-soliton, mode-locked Tm-doped fiber laser operating in the short-wavelength infrared region at 1876 nm, using all-polarization-maintaining (all-PM) fibers. Self-starting, mode-locked operation is enabled by a single-wall carbon nanotube (SWNT) based saturable absorber (SA). Cavity dispersion is managed by using a commercially available PM dispersion compensating fiber (DCF). A PM fiber Lyot filter enables dissipative-soliton mode locking at a central wavelength of 1876 nm. The laser generates stable pulses at a repetition rate ∼ 19.2 MHz with an average power ∼ 21.5 mW, corresponding to a pulse energy ∼ 1.1 nJ. The output pulse has a duration of 4.2 ps and can be compressed down to 391 fs using a grating-based compressor. A higher pulse energy ∼ 3.2 nJ can be obtained with a compressed pulse width of 566 fs by varying the net cavity dispersion. To the best of our knowledge, this is the first nJ-energy-level, all-fiberized PM dissipative-soliton mode-locked Tm-doped fiber laser based on SWNT, with potential for applications in high-penetration nonlinear biomedical imaging microscopy

Advancing pediatric and longitudinal DNA methylation studies with CellsPickMe, an integrated blood cell deconvolution method

Prospective birth cohorts offer the potential to interrogate the relation between early life environment and embedded biological processes such as DNA methylation (DNAme). These association studies are frequently conducted in the context of blood, a heterogeneous tissue composed of diverse cell types. Accounting for this cellular heterogeneity across samples is essential, as it is a main contributor to inter-individual DNAme variation. Integrated blood cell deconvolution of pediatric and longitudinal birth cohorts poses a major challenge, as existing methods fail to account for the distinct cell population shift between birth and adolescence. In this paper, we critically evaluated the reference-based deconvolution procedure and optimized its prediction accuracy for longitudinal birth cohorts using DNAme data from the Canadian Healthy Infant Longitudinal Development (CHILD) cohort. The optimized algorithm, CellsPickMe, integrates cord and adult references and picks DNAme features for each population of cells with machine learning algorithms. It demonstrated improved deconvolution accuracy in cord, pediatric, and adult blood samples compared to existing benchmark methods. CellsPickMe supports blood cell deconvolution across early developmental periods under a single framework, enabling cross-time-point integration of longitudinal DNAme studies. Given the increased resolution of cell populations predicted by CellsPickMe, this R package empowers researchers to explore immune system dynamics using DNAme data in population studies across the life course

Unconventional bulk-Fermi-arc links paired third-order exceptional points splitting from a defective triple point

Exceptional degeneracies, unique to open systems, are important in non-Hermitian topology. While bulk-Fermi-arcs connecting second-order exceptional points (EP2s) have been observed, the existence of bulk-Fermi-arcs linking higher-order exceptional points remains unexplored. Here, we introduce an unconventional bulk-Fermi-arc in systems with parity-time and pseudo-Hermitian symmetries, which links paired third-order exceptional points (EP3s), where three eigenvalues share identical real parts but distinct imaginary parts. We realize these systems using topological circuits and experimentally demonstrate this unconventional bulk-Fermi-arc. A winding number defined from resultant vector shows that the bulk-Fermi-arc is stabilized by the exchange of Riemannian sheets. Furthermore, analysis via eigenframe deformation and rotation reveals that the EP3 pair is topologically nontrivial and equivalent to a single defective triple point. The EP3s can split from the triple point by varying system parameters, with this splitting protected by topological equivalence. This finding offers insights into non-Hermitian topology with potential applications in wave engineering