Exploring mechanisms and contexts in a Peer Education Project to improve mental health literacy in schools in England: a qualitative realist evaluation.

Poor adolescent mental health calls for universal prevention. The Mental Health Foundation's 'Peer Education Project' equips older students ('peer educators') to teach younger students ('peer learners') about mental health. The peer-led lessons cover defining good and bad mental health, risk and protective factors, self-care, help-seeking and looking after one another. While previous pre-post evaluations have suggested effectiveness, the mechanisms through which the intervention improves mental health literacy remain unclear. We purposively recruited seven secondary schools across England from 2020 to 2022 and collected data through five observations, 12 staff interviews and 15 student focus groups (totalling 134 students; 46 peer educators aged 14-18 years and 88 peer learners aged 11-13 years). Our realist analysis adopted retroductive logic, intertwining deductive and inductive approaches to test the initial programme theory against insights arising from the data. We developed Context-Mechanisms-Outcome configurations related to four themes: (i) modelling behaviours and forming supportive relationships, (ii) relevant and appropriate content, (iii) peer educators feeling empowered and (iV) a school culture that prioritises mental health support. Our refined programme theory highlights key mechanisms, contexts conducive to achieving the outcomes and ways to improve training, recruitment and delivery to maximise effectiveness for similar peer-led initiatives.

Intermittent systemic exposure to lipopolysaccharide-induced inflammation disrupts hippocampal long-term potentiation and impairs cognition in aging male mice.

Age-related cognitive decline, a common component of the brain aging process, is associated with significant impairment in daily functioning and quality of life among geriatric adults. While the complexity of mechanisms underlying cognitive aging are still being elucidated, microbial exposure and the multifactorial inflammatory cascades associated with systemic infections are emerging as potential drivers of neurological senescence. The negative cognitive and neurobiological consequences of a single pathogen-associated inflammatory experience, such as that modeled through treatment with lipopolysaccharide (LPS), are well documented. Yet, the brain aging impacts of repeated, intermittent inflammatory challenges are less well studied. To extend the emerging literature assessing the impact of infection burden on cognitive function among normally aging mice, here, we repeatedly exposed adult mice to intermittent LPS challenges during the aging period. Male 10-month-old C57BL6 mice were systemically administered escalating doses of LPS once every two weeks for 2.5 months. We evaluated cognitive consequences using the non-spatial step-through inhibitory avoidance task, and both spatial working and reference memory versions of the Morris water maze. We also probed several potential mechanisms, including cortical and hippocampal cytokine/chemokine gene expression, as well as hippocampal neuronal function via extracellular field potential recordings. Though there was limited evidence for an ongoing inflammatory state in cortex and hippocampus, we observed impaired learning and memory and a disruption of hippocampal long-term potentiation. These data suggest that a history of intermittent exposure to LPS-induced inflammation is associated with subtle but significantly impaired cognition among normally aging mice. The broader impact of these findings may have important implications for standard of care involving infections in aging individuals or populations at-risk for dementia.

Barriers and predictors of medication use for childhood ADHD: findings from a UK population-representative cohort.

PURPOSE: Little is known about sociodemographic and clinical factors that predict and act as barriers to ADHD medication independently of symptom severity. We examined the proportion of children using medication for ADHD, age of initiation of medication, and predictors of medication use in a population-representative cohort. METHODS: Data from the Millennium Cohort Study on child ADHD, medication use for ADHD at age 14 (in 2014-2015) and child, parent and sociodemographic variables were collated. Logistic regression models were used to identify factors that predict medication use for ADHD (the main outcome measure), adjusting for symptom severity at age seven. RESULTS: The weighted prevalence of ADHD was 3.97% (N = 11,708). 45.57% of children with ADHD (N = 305) were taking medication. The median age at initiation was 9 years (range 3-14). Male gender (AOR 3.66, 95% CI 1.75, 7.66) and conduct problems at age seven (AOR 1.24 95% CI 1.04, 1.47) and 14 predicted medication use at age 14 after adjusting for symptom severity. CONCLUSIONS: Our study is the first to assess predictors of medication whist adjusting for ADHD symptom severity. Girls with ADHD were less likely to be prescribed medication, even when they displayed similar ADHD symptom levels to boys. Conduct problems also predicted medication independently of ADHD symptoms. ADHD may be more often medicated in boys because clinicians may think a prototypical ADHD child is male, and perhaps conduct problems make boys more disruptive in the classroom, leading to boys being more often treated.

DFT calculation of oxygen adsorption on platinum nanoparticles: coverage and size effects.

Catalysts made of Pt nanoparticles and Pt alloys are considered state-of-the-art catalysts for the anodic and cathodic reactions involved in hydrogen fuel cells. The optimal size of such nanoparticles for each chemical reaction is an unsolved problem that depends on environmental variables, such as reactant concentration, solvent, temperature, etc. From a theoretical point of view, this problem has been tackled mainly by observing how single key adsorbates react with different nanoparticles under controlled conditions. In this work, we use large-scale DFT calculations to examine the interplay between the Pt nanoparticle size and O coverage effects. We examine single O adsorptions for three adsorption sites on cuboctahedral platinum nanoparticles with different sizes. As we grow the nanoparticle size, the binding strength decreases and we observed a quick convergence of the adsorption energies with increasing nanoparticle size, which correlates with the calculated d-band centre for (111) Pt facets on such nanoparticles. We also carried out a detailed study of the effect of oxygen coverage with varying fractions of O monolayer coverage, computing adsorption energies per O atom for Pt55, Pt147 and Pt309 nanoparticles with several O coverages. In general, an increase of O coverage led to weaker adsorption energies per O atom, and when analysing the results in terms of oxygen monolayers, this effect is more pronounced for larger nanoparticles. The O coverage dependency of the adsorption energy per O atom is analysed in terms of the O distribution for each nanoparticle size and electronic changes that the adsorbed oxygen causes to the Pt nanoparticle. In studying nanoparticle size and oxygen coverage effects simultaneously, we offer insights with DFT accuracy to help on heterogeneous catalyst design.

Ethanol, O, and CO adsorption on Pt nanoparticles: effects of nanoparticle size and graphene support.

Pt nanoparticles dispersed over carbonaceous supports are widely used as catalysts for different applications, making studies on the interplay between size and support effects indispensable for rational catalyst design. Here, we use DFT calculations to simulate the interaction between O, CO, and ethanol with free platinum cuboctahedral nanoparticles with up to 147 atoms and with the same Pt nanoparticles supported on a single layer of graphene with up to 720 carbon atoms. We compute adsorption energies for each adsorbate on different adsorption sites for supported and unsupported Pt nanoparticles. We show that as the Pt nanoparticle grows the adsorption energy decreases, and that the size effect is more important for O and CO adsorption than for ethanol. We observe that the generalized coordination number of each adsorption site controls the interaction strength for O and CO to a much larger extent than for ethanol. Electronic charge redistributions and density of states projected on the d band of the interacting Pt facets are used to obtain a better understanding of the differences between the electronic interactions for each adsorbate. For Pt nanoparticles supported on graphene, the support effects weaken the adsorption energies for all the adsorbates, but this effect rapidly decreases with larger nanoparticles, and it is only significant for our smallest nanoparticle Pt13. By demonstrating that the effects of nanoparticle size and support are different for ethanol as compared with O and CO, we conclude that it should be possible to modify different parameters in the catalyst design in order to tune the Pt nanoparticle to interact with specific adsorbates.

The predictors of persistent DSM-IV disorders in 3-year follow-ups of the British Child and Adolescent Mental Health Surveys 1999 and 2004.

BACKGROUND: The identification of the factors that influence the persistence of psychiatric disorder may assist practitioners to focus on young people who are particularly prone to poor outcomes, but population-based samples of sufficient size are rare. METHOD: This secondary analysis combined data from two large, population-based cross-sectional surveys in Great Britain (1999 and 2004) and their respective follow-ups (2002 and 2007), to study homotypic persistence among the 998 school-age children with psychiatric disorder at baseline. Psychiatric disorder was measured using the Development and Well-Being Assessment applying DSM-IV criteria. Factors relating to the child, family, and the severity and type of psychopathology at baseline were analysed using logistic regression. RESULTS: Approximately 50% of children with at least one psychiatric disorder were assigned the same diagnostic grouping at 3-year follow-up. Persistent attention-deficit/hyperactivity disorder and anxiety were predicted by poor peer relationship scores. Persistent conduct disorder was predicted by intellectual disability, rented housing, large family size, poor family function and by severer baseline psychopathology scores. CONCLUSIONS: Homotypic persistence was predicted by different factors for different groups of psychiatric disorders. Experimental research in clinical samples should explore whether these factors also influence response to interventions.

Educators' experiences of managing students with ADHD: a qualitative study.

BACKGROUND: The symptoms of attention-deficit/hyperactivity disorder are associated with difficulty coping with the social, behavioural and academic components of school. Compared with medication and other non-pharmacological treatment, there is less evidence relating to school-based interventions to support children with ADHD. There is additionally an absence of any research focused on the experiences and practices of educators in the UK around how they work with children who are inattentive, impulsive and hyperactive. METHODS: Forty-two educational practitioners from primary, secondary and alternate provision schools in the UK participated in focus groups or individual interviews that explored (1) their experiences of managing students with ADHD in the classroom and (2) factors that helped and hindered them in this endeavour. Transcripts were analysed using thematic analysis. RESULTS: Analysis identified six themes: broad strategies, student-centred, inclusive strategies, labelling, medication and relationships. Participants' experiences of managing students with ADHD drew upon a wide range of strategies that typically involved responding to individual needs in an inclusive manner, so individuals with ADHD could access the classroom with their peers. Participants spoke about three factors that helped and hindered managing students with ADHD. Labelling of students with ADHD was reported, with the negative aspects of labelling, such as stigmatization, affecting the classroom. Educators reported mixed experiences regarding the helpfulness of medication; where helpful, it allowed the use of strategies in the classroom. Although students with ADHD were described as having rollercoaster relationships, positive relationships were considered key to the support of children with these difficulties. CONCLUSIONS: This study suggests that factors such as attitudes towards ADHD, relationships experienced by students with ADHD and other treatments being delivered need to be carefully considered before strategies are put in place in the classroom. This study supports the need for further work on the implementation of evidence-based school interventions for ADHD.

Effect of graphene support on large Pt nanoparticles.

State-of-the-art catalysts are often created via deposition of monolayers, sub-monolayers or nanoparticles of the catalytic material over supports, aiming to increase the surface area and decrease the loading of the catalytic material and therefore the overall cost. Here, we employ large-scale DFT calculations to simulate platinum clusters with up to 309 atoms interacting with single layer graphene supports with up to 880 carbon atoms. We compute the adsorption, cohesion and formation energies of two and three-dimensional Pt clusters interacting with the support, including dispersion interactions via a semi-empirical dispersion correction and a vdW functional. We find that three-dimensional Pt clusters are more stable than the two-dimensional when interacting with the support, and that the difference between their stabilities increases with the system size. Also, the dispersion interactions are more pronounced as we increase the nanoparticle size, being essential to a reliable description of larger systems. We observe inter-atomic expansion (contraction) on the closest (farthest) Pt facets from the graphene sheet and charge redistribution with overall charge being transferred from the platinum clusters to the support. The Pt-Pt expansion, which is related to the charge transfer in the system, correlates with the adsorption energy per Pt atom in contact with the graphene. These, and other electronic and structural observations show that the effect of the support cannot be neglected. Our study provides for the first time, to the best of our knowledge, quantitative results on the non-trivial combination of size and support effects for nanoparticles sizes which are relevant to catalyst design.

Feasibility of salivary cortisol collection in patients and companions attending dementia diagnostic meetings in memory clinics.

OBJECTIVES: Receiving a diagnosis of dementia is life-changing for the individual and their companion. The aim of the study was to explore the feasibility of collecting salivary cortisol from patients who are informed if they have dementia and their companions. Patients and companions collected nine saliva samples in three batches: 1-2 weeks before, immediately before, and immediately after the diagnostic meeting. Each batch consisted of three samples taken in the evening, after awaking and 30 mins post-waking. RESULTS: 22.7% (N = 10) of 44 invited patients and nine companions agreed, with 18.2% patients (N = 8) and 15.9% companions (N = 7) providing samples. Participants found that saliva collection was demanding and disrupted routines. On a purely descriptive level, some indications of an increased cortisol stress response in patients diagnosed with dementia were found in this very small sample. Researchers should expect low recruitment rates in this elderly population. Simpler collection procedures, e.g. pre-labelled packages with date/time, possible omission of morning samples and objective rather than self-report assessment of waking and saliva collection times-using actigraphy wrist-watches bleeps to prompt people at the timepoints and electronic track caps-might improve adherence and improve the accuracy of timepoints when swabs were actually collected.

A novel fuel cell design foroperandoenergy-dispersive x-ray absorption measurements.

A polymer electrolyte fuel cell has been designed to allowoperandox-ray absorption spectroscopy (XAS) measurements of catalysts. The cell has been developed to operate under standard fuel cell conditions, with elevated temperatures and humidification of the gas-phase reactants, both of which greatly impact the catalyst utilisation. X-ray windows in the endplates of the cell facilitate collection of XAS spectra during fuel cell operation while maintaining good compression in the area of measurement. Results of polarisation curves and cyclic voltammograms showed that theoperandocell performs well as a fuel cell, while also providing XAS data of suitable quality for robust XANES analysis. The cell has produced comparable XAS results when performing a cyclic voltammogram to an establishedin situcell when measuring the Pt LIII edge. Similar trends of Pt oxidation, and reduction of the formed Pt oxide, have been presented with a time resolution of 5 s for each spectrum, paving the way for time-resolved spectral measurements of fuel cell catalysts in a fully-operating fuel cell.

Over-expression of miR-34a induces rapid cognitive impairment and Alzheimer's disease-like pathology.

Autosomal dominant Alzheimer disease (AD) is caused by rare mutations in one of three specific genes. This is in contrast to idiopathic, late-onset AD (LOAD), which has a more polygenetic risk profile and represents more than 95% of cases. Previously, we have demonstrated that increased expression of microRNA (miRNA)-34a (miR-34a) in AD brain targets genes linked to synaptic plasticity, energy metabolism, and resting state network activity. Here we report the generation of a heterozygous, conditional miR-34a overexpression mouse (miR-34a+/-(TetR-TetO-miR-34a) Transgenic Mice). Doxycycline-treated mice of either sex exhibited profound behavioral impairment compared to untreated groups with only 1-2 months of over-expression of miR-34a. Cognitive impairment of individual mice in T- and Y-maze tasks correlated with elevated miR-34a expression in many parts of the brain including the hippocampus and prefrontal cortex, regions which are known to be involved in this task and implicated in LOAD dysfunction. Immunocytochemistry of brain sections from mice show high amyloid ß and phosphorylated tau-specific staining in the hippocampus and cortex. Analysis of protein samples from these mice revealed that miR-34a targets specific genes involved in memory formation, amyloid precursor protein (APP) metabolism and phosphorylation-dephosphorylation of tau. Thus, our results suggest that the polygenetic dysfunction caused by miR-34a may occur in LOAD and disclose miR-34a as a potential therapeutic target. SIGNIFICANCE STATEMENT: Late-onset Alzheimer disease (LOAD) is associated with multiple gene alleles, a polygenetic profile of risk factors that is difficult to model in animals. Our approach to modeling LOAD was to produce a conditional over-expressing, miR-34a mouse using doxycycline-induction to activate expression. We observed that miR-34a over-expression results in a rapid cognitive impairment, associated with accumulation of intracellular Aß and tau hyperphosphorylation in multiple brain regions. Targets for miR-34a, including ADAM10, NMDAR 2B, and SIRT1 RNAs, were profoundly reduced by miR-34a over-expression. Collectively, these results indicate that a rapid, profound cognitive decline and Alzheimer's disease neuropathology can be induced with miR-34a over-expression, suggesting that this animal model may represent a polygenetic risk factor model for LOAD.

AMnO3 (A = Sr, La, Ca, Y) Perovskite Oxides as Oxygen Reduction Electrocatalysts.

A series of perovskite-type manganites AMnO3 (A = Sr, La, Ca and Y) particles were investigated as electrocatalysts for the oxygen reduction reaction. AMnO3 materials were synthesized by means of an ionic-liquid method, yielding phase pure particles at different temperatures. Depending on the calcination temperature, particles with mean diameter between 20 and 150 nm were obtained. Bulk versus surface composition and structure are probed by X-ray photoelectron spectroscopy and extended X-ray absorption fine structure. Electrochemical studies were performed on composite carbon-oxide electrodes in alkaline environment. The electrocatalytic activity is discussed in terms of the effective Mn oxidation state, A:Mn particle surface ratio and the Mn-O distances.

Development of a PtSn bimetallic catalyst for direct fuel cells using bio-butanol fuel.

Pt and PtSn catalysts were studied for n-butanol electro-oxidation at various temperatures. PtSn showed a higher activity towards butanol electro-oxidation compared to Pt in acidic media. The onset potential for n-butanol oxidation on PtSn is ∼520 mV lower than that found on Pt, and significantly lower activation energy was found for PtSn compared with that for Pt.

Diltiazem and atenolol in essential hypertension: additivity of effects on blood pressure and cardiac conduction with combination therapy.

In 15 patients with mild to moderate essential hypertension, the effects of diltiazem (120 mg twice daily) were compared with those of atenolol (50 mg once daily), the two drugs in combination, and placebo in a randomized double-blind cross-over study with treatment phases of 4 weeks duration. Blood pressure was reduced in the active treatment phases (supine blood pressure: diltiazem, 172/92 mmHg; atenolol, 172/92 mmHg; diltiazem plus atenolol, 164/88 mmHg; pooled estimate of s.e.m. by analysis of variance = 3/1) compared with placebo (180/101 mmHg). Factorial analysis confirmed fully additive antihypertensive effects of the drugs in combination. The time interval from the beginning of the P wave to the beginning of the QRS complex (P-R interval) was longer during combination therapy (0.184s) compared with either diltiazem (0.175s) or atenolol (0.174s) alone, or placebo (0.164s); s.e.m. by analysis of variance = 0.003. No clinically significant conduction disturbances occurred. Plasma atrial natriuretic peptide was elevated by atenolol but not diltiazem. Thus, in subjects with uncomplicated essential hypertension, diltiazem and atenolol had equal antihypertensive efficacy when used alone, and fully additive effects in combination, on both blood pressure and cardiac conduction.

Lack of effect of fish oil supplementation on blood pressure in treated hypertensives.

Fish and fish oils have been reported to reduce blood pressure in normotensives and untreated hypertensives. The present study examined the effect of dietary supplementation with fish oil on blood pressure in 20 treated hypertensives with controlled blood pressures who continued their usual antihypertensive drug treatment throughout. A double-blind, randomized crossover design was used, with two phases, each of 8 weeks' duration. In one phase, subjects took fifteen 1 g fish oil capsules (Lipitac; Reckitt and Colman Pharmaceuticals, Sydney, Australia) daily, and in the other, 15 capsules of identical appearance containing 1 g olive oil daily. There was no difference between the treatment phases for any blood pressure parameter, heart rate or body weight, but blood pressure was lower in both phases compared with pretreatment values. The fasting plasma triglyceride concentration was 30% lower in the fish oil phase (P less than 0.001), but there was no difference between the phases for plasma concentrations of total or high-density lipoprotein (HDL) cholesterol. We conclude that, in treated hypertensives with controlled blood pressures, any additional fall in blood pressure produced by dietary supplementation with fish oil is so small that the requirement for antihypertensive drug therapy is unlikely to be reduced.

Optimal size of cuff bladder for indirect measurement of arterial pressure in adults.

This study tested the hypothesis that a sphygmomanometer cuff bladder long enough to encircle the arm in most adults ('obese cuff') would provide a more accurate and precise estimate of intra-arterial pressure than the usual 'standard' cuff bladder. In 53 patients undergoing diagnostic coronary angiography (35 males, 18 females, aged 36-79 years), indirect blood pressure, measured in the left arm with a random-zero sphygmomanometer, was compared with simultaneously measured femoral intra-arterial pressure. Duplicate indirect measurements were made with each of two cuffs containing bladders measuring 39 x 15 cm ('obese') and 23 x 12 cm ('standard'). The obese cuff bladder encircled 80% or more of the arm circumference in all subjects, whereas the standard cuff bladder met this requirement in only 19% of the subjects. For both systolic and diastolic pressure there was marked interindividual variability in the differences between indirect and direct measurements with both cuffs. With the obese cuff there was no systematic error in the diastolic blood pressure measurement. The standard cuff consistently overestimated diastolic pressure by 7.7 +/- 8.3 mmHg (mean +/- s.d.). For both cuffs, the difference between indirect and direct diastolic pressure increased with arm size (P less than 0.05). Both cuffs underestimated systolic blood pressure, the obese cuff by 15.5 +/- 11.7 mmHg and the standard cuff by 7.6 +/- 12.1 mmHg. These systolic blood pressure underestimates were greater at higher blood pressures (P less than 0.01) and with smaller arms (P less than 0.05). Age was not related to measurement error with either cuff.(ABSTRACT TRUNCATED AT 250 WORDS)

Binding isotherms by continuous-flow dynamic dialysis.

The classical dynamic dialysis technique for the determination of a protein-ligand binding isotherm has been modified by the introduction of a flow cell in which the dialysate on the sink side of the membrane is continuously eluted with a constant flow of eluting buffer and its ligand concentration measured. This new experimental method is termed continuous-flow dynamic dialysis (CFDD). A transfer function procedure for extracting the binding isotherm from the dialysis data is described. This is a more general technique (requiring only a verifiable assumption of linearity) than that previously used, in which the system was modelled using Fick's first law and which relied on the establishment of quasi-steady state conditions across the membrane. The present analysis uses the Laplace transform to effect deconvolution of the impulse response function of the cell from the dialysis data and, using a Fourier series approach, directly yields numerical data representing the free ligand concentration in equilibrium with the protein-ligand complex. The protein-ligand binding isotherm is obtained in parametric form, with time as the parameter.

Treatment of hypertension with enalapril and hydrochlorothiazide or enalapril and atenolol: contrasts in hypotensive interactions.

To determine the nature of the resultant effect on blood pressure when angiotensin converting enzyme (ACE) inhibitors are combined with other hypotensive agents in the treatment of uncomplicated essential hypertension, two randomized, double-blind, crossover trials were conducted. In each trial there were four treatment phases, each 4 weeks in duration, comprising a 2 X 2 factorial experiment. Twenty-one patients completed the first study in which the effects of enalapril (10 mg twice daily) were compared with hydrochlorothiazide (25 mg twice daily), with the two drugs in combination and with placebo. All blood pressure parameters were reduced in the three active treatment phases compared with placebo (P less than 0.001). Enalapril and hydrochlorothiazide were equally effective and in combination their hypotensive effects were fully additive. Sixteen patients completed the second study which compared the effects of enalapril (20 mg daily), atenolol (50 mg daily), the two drugs in combination and placebo. All blood pressure parameters were again reduced in all phases compared with placebo (P less than 0.001). Enalapril and atenolol were also equally effective, but in combination their hypotensive effects were less than fully additive, with attenuation of the potential additive response by 30-50%. These results indicate that a diuretic-ACE inhibitor combination can be expected to have a greater hypotensive effect than a beta-blocker-ACE inhibitor combination. Both hydrochlorothiazide and atenolol increased plasma atrial natriuretic peptide (ANP) concentrations (P less than 0.01), suggesting that ANP could contribute to the hypotensive effects of these two drug classes.

Preparation, structure, and stability of Pt and Pd monolayer modified Pd and Pt electrocatalysts.

A controlled surface reaction technique has been successfully employed to prepare a series of Pt modified Pd/C (Pt/Pd/C) and Pd modified Pt/C (Pd/Pt/C) catalysts. The resulting catalyst materials were characterised by TEM, XRD, electrochemistry, and EXAFS techniques. In the case of the Pd/Pt/C carbon catalysts, core-shell structural arrangements were found, with a 0.04 A contraction of the Pd-Pd bond distance for the 1 Pd/Pt/C being observed. A greater degree of alloying was found for the Pt/Pd/C catalysts where the surface had a mixed composition with a large proportion of the Pt in the interior of the nanoparticle. However, strong Pt characteristics were exhibited in the voltammetry of Pt/Pd/C catalysts, most notably a large increase in the stability with respect to the electrochemical environment compared to Pd alone.