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Background: Since the introduction of digital health technologies in National Health Service (NHS), health professionals are starting to use email, text, and other digital methods to consult with their patients in a timely manner. There is lack of evidence regarding the economic impact of digital consulting in the United Kingdom (UK) NHS. Objective: This study aimed to estimate the direct costs associated with digital consulting as an adjunct to routine care at 18 clinics serving young people aged 16-24 years with long-term conditions. Methods: This study uses both quantitative and qualitative approaches. Semistructured interviews were conducted with 173 clinical team members on the impacts of digital consulting. A structured questionnaire was developed and used for 115 health professionals across 12 health conditions at 18 sites in the United Kingdom to collect data on time and other resources used for digital consulting. A follow-up semistructured interview was conducted with a single senior clinician at each site to clarify the mechanisms through which digital consulting use might lead to outcomes relevant to economic evaluation. We used the two-part model to see the association between the time spent on digital consulting and the job role of staff, type of clinic, and the average length of the working hours using digital consulting. Results: When estimated using the two-part model, consultants spent less time on digital consulting compared with nurses (95.48 minutes; P<.001), physiotherapists (55.3 minutes; P<.001), and psychologists (31.67 minutes; P<.001). Part-time staff spent less time using digital consulting than full-time staff despite insignificant result (P=.15). Time spent on digital consulting differed across sites, and no clear pattern in using digital consulting was found. Health professionals qualitatively identified the following 4 potential economic impacts for the NHS: decreasing adverse events, improving patient well-being, decreasing wait lists, and staff workload. We did not find evidence to suggest that the clinical condition was associated with digital consulting use. Conclusions: Nurses and physiotherapists were the greatest users of digital consulting. Teams appear to use an efficient triage system with the most expensive members digitally consulting less than lower-paid team members. Staff report showed concerns regarding time spent digitally consulting, which implies that direct costs increase. There remain considerable gaps in evidence related to cost-effectiveness of digital consulting, but this study has highlighted important cost-related outcomes for assessment in future cost-effectiveness trials of digital consulting. [ABSTRACT FROM AUTHOR]

Most living creatures have a circadian rhythm that is generated by a precisely regulated transcriptional-translational feedback loop of clock genes. Brain and muscle ARNT-like 1 (BMAL1) is one of the core clock genes and transcription factors that represents a positive arm of this autoregulatory circadian clock system. Despite the indispensable role of BMAL1 in the circadian rhythm, the molecular mechanisms underlying translational control of BMAL1 are largely unknown. Here, using murine NIH-3T3 cells, gene constructs, and a variety of biochemical approaches, including RNAi- and luciferase reporter gene-based assays, along with immunoblotting, in vitro transcription, quantitative real-time PCR, and real-time bioluminescence experiments, we show that translation of Bmal1 is negatively regulated by an RNA-binding protein, heterogeneous nuclear ribonucleoprotein Q (hnRNP Q). Interestingly, we found that hnRNP Q rhythmically binds to a specific region of the Bmal1 mRNA 5' UTR and controls its time-dependent expression. Moreover, we demonstrate that knockdown of hnRNP Q modulates BMAL1 protein oscillation amplitude without affecting mRNA rhythmic patterns. Furthermore, hnRNPQdepletion increases the mRNA oscillation amplitudes of BMAL1-regulated target genes. Together, our results suggest that hnRNPQplays a pivotal role in both Bmal1 translation and BMAL1-regulated gene expression. [ABSTRACT FROM AUTHOR]

Objectives: Gout is an inflammatory arthritis of the joints and soft tissues occurring due to deposition of monosodium urate (MSU) crystals, which are caused by persistent hyperuricemia. Soyeom pharmacopuncture is one treatment method that has been traditionally used for pain management in Oriental medicine. However, studies on its effect in reducing gout pain have been insufficient. Therefore, we selected Soyeom pharmacopuncture among natural products used in Korea as the new target of our study.Methods: The effects of Soyeom pharmacopuncture were examined in mouse models of acute gout induced by injection of MSU crystals into footpads. IL-1β, IL-6, and TNF-α production were examined by immunoblotting and enzyme-linked immunosorbent assay as hallmarks of NLRP3 inflammasome and cytokine activation.Results: Soyeom pharmacopuncture reduced foot edema in gout-induced mice, as well as IL-1β, nitrite, IL-6, and TNF-α production. Moreover, Soyeom pharmacopuncture also reduced MSU-induced gout inflammatory gene expressions, specifically those in the NF-kB pathway.Conclusion: Pharmacopuncture may serve as a new solution for other inflammatory diseases as well. Through active follow-up studies, we could thoroughly understand the clinical value of Soyeom pharmacopuncture.

Abstract Advanced high strength steel (AHSS) is a steel of multi-phase microstructure that is processed under several conditions to meet the current high-performance requirements from the industry. Deep neural network (DNN) has emerged as a promising tool in materials science for the task of estimating the phase volume fraction of these steels. Despite its advantages, one of its major drawbacks is its requirement of a sufficient amount of training data with correct labels to the network. This often comes as a challenge in many areas where obtaining data and labeling it is extremely labor-intensive. To overcome this challenge, an unsupervised way of learning DNN, which does not require any manual labeling, is proposed. Information maximizing generative adversarial network (InfoGAN) is used to learn the underlying probability distribution of each phase and generate realistic sample points with class labels. Then, the generated data is used for training an MLP classifier, which in turn predicts the labels for the original dataset. The result shows a mean relative error of 4.53% at most, while it can be as low as 0.73%, which implies the estimated phase fraction closely matches the true phase fraction. This presents the high feasibility of using the proposed methodology for fast and precise estimation of phase volume fraction in both industry and academia.

Alzheimer’s disease and Parkinson’s disease are the two most common neurodegenerative diseases in the world, and their incidence rates are increasing as our society ages. This creates a significant social and economic burden. Although the exact cause and treatment methods for these diseases are not yet known, research suggests that Alzheimer’s disease is caused by amyloid precursor protein, while α-synuclein acts as a causative agent in Parkinson’s disease. The accumulation of abnormal proteins such as these can lead to symptoms such as loss of protein homeostasis, mitochondrial dysfunction, and neuroinflammation, which ultimately result in the death of nerve cells and the progression of neurodegenerative diseases. The medications currently available for these diseases only delay their progression and have many adverse effects, which has led to increased interest in developing natural products with fewer adverse effects. In this study, we selected specific keywords and thesis content to investigate natural products that are effective in treating Alzheimer’s and Parkinson’s diseases. We reviewed 16 papers on natural products and found that they showed promising mechanisms of action such as antioxidant, anti-inflammatory, and mitochondrial function improvement. Other natural products with similar properties could also be considered potential treatments for neurodegenerative diseases, and they can be consumed as part of a healthy diet rather than as medicine.

Abstract Background Paricalcitol is known to attenuate ischemic-reperfusion injury of various organs. However, it is not known whether paricalcitol prevents neuronal injury after global cerebral ischemia. The purpose of this study is to investigate the neuroprotective effect of paricalcitol in a rat model of transient global cerebral ischemia. Methods This is a prospective, randomized experimental study. Male Sprague-Dawley rats that survived 10 min of four-vessel occlusion were randomly assigned to two treatment groups: one group was treated with paricalcitol 1 μg/kg IP, and the other was given an equivalent volume of normal saline IP. Drugs were administered at 5 min, 1 day, 2 days, and 3 days after ischemia. Neurologic function was assessed at 2 h, 1 day, 2 days, 3 days, and 4 days after ischemia. We tested motor function 3 days after ischemia using the rotarod test. Also, we tested memory function 4 days after ischemia using the passive avoidance test. We assessed neuronal degeneration in the hippocampus of surviving rats 4 days after ischemia. Results Eight rats were allocated to each group. No significant differences were found between the groups in terms of survival rate, motor coordination, or memory function. The neurological function score 2-h post-ischemia was significantly higher in the paricalcitol group (p = 0.04). Neuronal degeneration was significantly less in the paricalcitol group compared with the control group (p = 0.01). Conclusions Paricalcitol significantly attenuated neuronal injury in the hippocampus. Although motor coordination, memory function, and survival rate were not significantly improved by paricalcitol treatment in this study, paricalcitol remains a potential neuroprotective drug after global cerebral ischemia.

Abstract Background Although spatial effects contribute to inequalities in health care service utilisation and other health outcomes in low and middle income countries, there have been no attempts to incorporate the impact of neighbourhood effects into equity analyses based on concentration indices. This study aimed to decompose and estimate the contribution of spatial effects on inequalities in uptake of HIV tests in Malawi. Methods We developed a new method of reflecting spatial effects within the concentration index using a spatial weight matrix. Spatial autocorrelation is presented using a spatial lag model. We use data from the Malawi Demographic Health Survey (n = 24,562) to illustrate the new methodology. Need variables such as ‘Any STI last 12 month’, ‘Genital sore/ulcer’, ‘Genital discharge’ and non need variables such as Education, Literacy, Wealth, Marriage, and education were used in the concentration index. Using our modified concentration index that incorporates spatial effects, we estimate inequalities in uptake of HIV testing amongst both women and men living in Malawi in 2015–2016, controlling for need and non-need variables. Results For women, inequalities due to need variables were estimated at − 0.001 and − 0.0009 (pro-poor) using the probit and new spatial probit estimators, respectively, whereas inequalities due to non-need variables were estimated at 0.01 and 0.0068 (pro-rich) using the probit and new spatial probit estimators. The results suggest that spatial effects increase estimated inequalities in HIV uptake amongst women. Horizontal inequity was almost identical (0.0103 vs 0.0102) after applying the spatial lag model. For men, inequalities due to need variables were estimated at − 0.0002 using both the probit and new spatial probit estimators; however, inequalities due to non-need variables were estimated at − 0.006 and − 0.0074 for the probit and new spatial probit models. Horizontal inequity was the same for both models (− 0.0057). Conclusion Our findings suggest that men from lower socioeconomic groups are more likely to receive an HIV test after adjustment for spatial effects. This study develops a novel methodological approach that incorporates estimation of spatial effects into a common approach to equity analysis. We find that a significant component of inequalities in HIV uptake in Malawi driven by non-need factors can be explained by spatial effects. When the spatial model was applied, the inequality due to non need in Lilongwe for men and horizontal inequity in Salima for women changed the sign. This approach can be used to explore inequalities in other contexts and settings to better understand the impact of spatial effects on health service use or other health outcomes, impacting on recommendations for service delivery.

Abstract Spatial weight matrices play a key role in econometrics to capture spatial effects. However, these constructs are prone to clustering and can be challenging to analyse in common statistical packages such as STATA. Multiple observations of survey participants in the same location (or cluster) have traditionally not been dealt with appropriately by statistical packages. It is common that participants are assigned Geographic Information System (GIS) data at a regional or district level rather than at a small area level. For example, the Demographic Health Survey (DHS) generates GIS data at a cluster level, such as a regional or district level, rather than providing coordinates for each participant. Moreover, current statistical packages are not suitable for estimating large matrices such as 20,000 × 20,000 (reflective of data within large health surveys) since the statistical package limits the N to a smaller number. In addition, in many cases, GIS information is offered at an aggregated level of geographical areas. To alleviate this problem, this paper proposes a bootstrap approach that generates an inverse distance spatial weight matrix for application in econometric analyses of health survey data. The new approach is illustrated using DHS data on uptake of HIV testing in low and middle income countries.

Although different regions of the brain are dedicated to specific functions, the intra- and inter-regional heterogeneity of astrocytes and microglia in these regions has not yet been fully understood. Recently, an advancement in various technologies, such as single-cell RNA sequencing, has allowed for the discovery of astrocytes and microglia with distinct molecular fingerprints and varying functions in the brain. In addition, the regional heterogeneity of astrocytes and microglia exhibits different functions in several situations, such as aging and neurodegenerative diseases. Therefore, investigating the region-specific astrocytes and microglia is important in understanding the overall function of the brain. In this review, we summarize up-to-date research on various intra- and inter-regional heterogeneities of astrocytes and microglia, and provide information on how they can be applied to aging and neurodegenerative diseases.

Protein aggregates of cofilin and actin have been found in neurons under oxygen–glucose deprivation. However, the regulatory mechanism behind the expression of Cfl1 during oxygen–glucose deprivation remains unclear. Here, we found that heterogeneous nuclear ribonucleoproteins (hnRNP) Q and hnRNP A1 regulate the translation of Cfl1 mRNA, and formation of cofilin–actin aggregates. The interaction between hnRNP A1 and Cfl1 mRNA was interrupted by hnRNP Q under normal conditions, while the changes in the expression and localization of hnRNP Q and hnRNP A1 increased such interaction, as did the translation of Cfl1 mRNA under oxygen–glucose deprived conditions. These findings reveal a new translational regulatory mechanism of Cfl1 mRNA in hippocampal neurons under oxygen–glucose deprivation.

Although proliferation of keratinocytes, a major type of skin cells, is a key factor in maintaining the function of skin, their ability to proliferate tends to diminish with age. To solve such a problem, researchers in medical and skin cosmetic fields have tried to utilize epidermal growth factor (EGF), but achieved limited success. Therefore, a small natural compound that can mimic the activity of EGF is highly desired in both medical and cosmetic fields. Here, using the modified biosensor system, we observed that natural small-compound isoprocurcumenol, which is a terpenoid molecule derived from turmeric, can activate EGFR signaling. It increased the phosphorylation of ERK and AKT, and upregulated the expression of genes related to cell growth and proliferation, such as c-myc, c-jun, c-fos, and egr-1. In addition, isoprocurcumenol induced the proliferation of keratinocytes in both physical and UVB-induced cellular damage, indicative of its function in skin regeneration. These findings reveal that EGF-like isoprocurcumenol promotes the proliferation of keratinocytes and further suggest its potential as an ingredient for medical and cosmetics use.

Abstract Background Child maltreatment is a significant public health problem. Group Family Nurse Partnership (gFNP) is a new intervention for young, expectant mothers implemented successfully in pilot studies. This study was designed to determine the effectiveness and cost-effectiveness of gFNP in reducing risk factors for maltreatment with a potentially vulnerable population. Methods A multi-site, randomized controlled, parallel-arm trial and prospective economic evaluation was conducted, with allocation via remote randomization (minimization by site, maternal age group) to gFNP or usual care. Participants were expectant mothers aged below 20 years with at least one live birth, or aged 20–24 years with no live births and with low educational qualifications. Data from maternal interviews at baseline and when infants were 2, 6 and 12 months, and video-recording at 12 months, were collected by researchers blind to allocation. Cost information came from weekly logs completed by gFNP family nurses and other service delivery data reported by participants. Primary outcomes measured at 12 months were parenting attitudes (Adult-Adolescent Parenting Index, AAPI-2) and maternal sensitivity (CARE Index). The economic evaluation was conducted from a UK NHS and personal social services perspective with cost-effectiveness expressed in terms of incremental cost per quality-adjusted life year (QALY) gained. The main analyses were intention-to-treat with additional complier average causal effects (CACE) analyses. Results Between August 2013 and September 2014, 492 names of potential participants were received of whom 319 were eligible and 166 agreed to take part, 99 randomly assigned to receive gFNP and 67 to usual care. There were no between-arm differences in AAPI-2 total (7 · 5/10 in both, SE 0.1), difference adjusted for baseline, site and maternal age group 0 · 06 (95% CI − 0 · 15 to 0 · 28, p = 0 · 59) or CARE Index (intervention 4 · 0 (SE 0 · 3); control 4 · 7 (SE 0 · 4); difference adjusted for site and maternal age group − 0 · 68 (95% CI − 1 · 62 to 0 · 16, p = 0 · 25) scores. The probability that gFNP is cost-effective based on the QALY measure did not exceed 3%. Conclusions The trial did not support gFNP as a means of reducing the risk of child maltreatment in this population but slow recruitment adversely affected group size and consequently delivery of the intervention. Trial registration ISRCTN78814904 . Registered on 17 May 2013.

Semiconductors are promising for high performance spintronics but the low functioning temperature hampers their applications. Here the authors achieve a strong room temperature modulation of spin-dependent resistance in GaN nanowires, which marks an important step towards practical spintronic devices.

THeterogeneous nuclear ribonucleoprotein (HNRNP) A1 is the most abundant and ubiquitously expressed member of the HNRNP protein family. In recent years, it has become more evident that HNRNP A1 contributes to the development of neurodegenerative diseases. However, little is known about the underlying role of HNRNP A1 in cancer development. Here, we report that HNRNP A1 expression is significantly increased in lung cancer tissues and is negatively correlated with the overall survival of patients with lung cancer. Additionally, HNRNP A1 positively regulates vaccinia-related kinase 1 (VRK1) translation via binding directly to the 3′ untranslated region (UTR) of VRK1 mRNA, thus increasing cyclin D1 (CCND1) expression by VRK1-mediated phosphorylation of the cAMP response element–binding protein (CREB). Furthermore, HNRNP A1 binding to the cis-acting region of the 3′UTR of VRK1 mRNA contributes to increased lung cancer cell proliferation. Thus, our study unveils a novel role of HNRNP A1 in lung carcinogenesis via post-transcriptional regulation of VRK1 expression and suggests its potential as a therapeutic target for patients with lung cancer.

Background: Human immunodeficiency virus (HIV) is a significant contributor to Malawi's burden of disease. Despite a number of studies describing socio-economic differences in HIV prevalence, there is a paucity of evidence on socio-economic inequity in HIV testing in Malawi. Objective: To assess horizontal inequity (HI) in HIV testing in Malawi. Design: Data from the Demographic and Health Surveys (DHSs) 2004 and 2010 in Malawi are used for the analysis. The sample size for DHS 2004 was 14,571 (women =11,362 and men=3,209), and for DHS 2010 it was 29,830 (women=22,716 and men=7,114). The concentration index is used to quantify the amount of socio-economic-related inequality in HIV testing. The inequality is a primary method in this study. Corrected need, a further adjustment of the standard decomposition index, was calculated. Standard HI was compared with corrected need-adjusted inequity. Variables used to measure health need include symptoms of sexually transmitted infections. Non-need variables include wealth, education, literacy and marital status. Results: Between 2004 and 2010, the proportion of the population ever tested for HIV increased from 15 to 75% among women and from 16 to 54% among men. The need for HIV testing among men was concentrated among the relatively wealthy in 2004, but the need was more equitably distributed in 2010. Standard HI was 0.152 in 2004 and 0.008 in 2010 among women, and 0.186 in 2004 and 0.04 in 2010 among men. Rural–urban inequity also fell in this period, but HIV testing remained pro-rich among rural men (HI 0.041). The main social contributors to inequity in HIV testing were wealth in 2004 and education in 2010. Conclusions: Inequity in HIV testing in Malawi decreased between 2004 and 2010. This may be due to the increased support to HIV testing by global donors over this period.

Artificial intelligence has become the primary issue in the era of Industry 4.0, accelerating the realization of a self-driven smart factory. It is transforming various manufacturing sectors including the assembly line for a camera lens module. The recent development of bezel-less smartphones necessitates a large-scale production of the camera lens module. However, assembling the necessary parts of a module needs much room to be improved since the procedure followed by its inspection is costly and time-consuming. Consequently, the collection of labeled data is often limited. In this study, a reliable means to predict the state of an unseen camera lens module using simple semi-supervised regression is proposed. Here, an experimental study to investigate the effect of different numbers of training samples is demonstrated. The increased amount of data using simple pseudo-labeling means is shown to improve the general performance of deep neural network for the prediction of Modulation Transfer Function (MTF) by as much as 18%, 15% and 25% in terms of RMSE, MAE and R squared. The cross-validation technique is used to ensure a generalized predictive performance. Furthermore, binary classification is conducted based on a threshold value for MTF to finally demonstrate the better prediction outcome in a real-world scenario. As a result, the overall accuracy, recall, specificity and f1-score are increased by 11.3%, 9%, 1.6% and 7.6% showing that the classification of camera lens module has been improved through the suggested semi-supervised regression method.

Neuronal axons are guided to their target during the development of the brain. Axon guidance allows the formation of intricate neural circuits that control the function of the brain, and thus the behavior. As the axons travel in the brain to find their target, they encounter various axon guidance cues, which interact with the receptors on the tip of the growth cone to permit growth along different signaling pathways. Although many scientists have performed numerous studies on axon guidance signaling pathways, we still have an incomplete understanding of the axon guidance system. Lately, studies on axon guidance have shifted from studying the signal transduction pathways to studying other molecular features of axon guidance, such as the gene expression. These new studies present evidence for different molecular features that broaden our understanding of axon guidance. Hence, in this review we will introduce recent studies that illustrate different molecular features of axon guidance. In particular, we will review literature that demonstrates how axon guidance cues and receptors regulate local translation of axonal genes and how the expression of guidance cues and receptors are regulated both transcriptionally and post-transcriptionally. Moreover, we will highlight the pathological relevance of axon guidance molecules to specific diseases.

Non-alcoholic steatohepatitis (NASH), a type of non-alcoholic fatty liver disease, is characterized as steatosis and inflammation in the liver. NLRP3 inflammasome activation is associated with NASH pathology. We hypothesized that suppressing the NLRP3 inflammasome could be effective in preventing NASH. We searched substances that could inhibit the activation of the NLRP3 inflammasome and identified sweroside as an NLRP3 inhibitor. We investigated whether sweroside can be applied to prevent the pathological symptoms associated with NASH in a methionine–choline-deficient (MCD) diet-induced NASH mouse model. The activation of the NLRP3 inflammasome was determined by detecting the production of caspase-1 and IL-1β from pro-caspase-1 and pro-IL-1β in primary mouse macrophages and mouse liver. In a NASH model, mice were fed an MCD diet for two weeks with daily intraperitoneal injections of sweroside. Sweroside effectively inhibited NLRP3 inflammasome activation in primary macrophages as shown by a decrease in IL-1β and caspase-1 production. In a MCD diet-induced NASH mouse model, intraperitoneal injection of sweroside significantly reduced serum aspartate transaminase and alanine transaminase levels, hepatic immune cell infiltration, hepatic triglyceride accumulation, and liver fibrosis. The improvement of NASH symptoms by sweroside was accompanied with its inhibitory effects on the hepatic NLRP3 inflammasome as hepatic IL-1β and caspase-1 were decreased. Furthermore, sweroside blocked de novo synthesis of mitochondrial DNA in the liver, contributing to suppression of the NLRP3 inflammasome. These results suggest that targeting the NLRP3 inflammasome with sweroside could be beneficially employed to improve NASH symptoms.

Background: Young people (aged 16–24 years) with long-term health conditions tend to disengage from health services, resulting in poor health outcomes. They are prolific users of digital communications. Innovative UK NHS clinicians use digital communication with these young people. The NHS plans to use digital communication with patients more widely. Objectives: To explore how health-care engagement can be improved using digital clinical communication (DCC); understand effects, impacts, costs and necessary safeguards; and provide critical analysis of its use, monitoring and evaluation. Design: Observational mixed-methods case studies; systematic scoping literature reviews; assessment of patient-reported outcome measures (PROMs); public and patient involvement; and consensus development through focus groups. Setting: Twenty NHS specialist clinical teams from across England and Wales, providing care for 13 different long-term physical or mental health conditions. Participants: One hundred and sixty-five young people aged 16–24 years living with a long-term health condition; 13 parents; 173 clinical team members; and 16 information governance specialists. Interventions: Clinical teams and young people variously used mobile phone calls, text messages, e-mail and voice over internet protocol. Main outcome measures: Empirical work – thematic and ethical analysis of qualitative data; annual direct costs; did not attend, accident and emergency attendance and hospital admission rates plus clinic-specific clinical outcomes. Scoping reviews–patient, health professional and service delivery outcomes and technical problems. PROMs: scale validity, relevance and credibility. Data sources: Observation, interview, structured survey, routinely collected data, focus groups and peer-reviewed publications. Results: Digital communication enables access for young people to the right clinician when it makes a difference for managing their health condition. This is valued as additional to traditional clinic appointments. This access challenges the nature and boundaries of therapeutic relationships, but can improve them, increase patient empowerment and enhance activation. Risks include increased dependence on clinicians, inadvertent disclosure of confidential information and communication failures, but clinicians and young people mitigate these risks. Workload increases and the main cost is staff time. Clinical teams had not evaluated the impact of their intervention and analysis of routinely collected data did not identify any impact. There are no currently used generic outcome measures, but the Patient Activation Measure and the Physicians’ Humanistic Behaviours Questionnaire are promising. Scoping reviews suggest DCC is acceptable to young people, but with no clear evidence of benefit except for mental health. Limitations: Qualitative data were mostly from clinician enthusiasts. No interviews were achieved with young people who do not attend clinics. Clinicians struggled to estimate workload. Only eight full sets of routine data were available. Conclusions: Timely DCC is perceived as making a difference to health care and health outcomes for young people with long-term conditions, but this is not supported by evidence that measures health outcomes. Such communication is challenging and costly to provide, but valued by young people. Future work: Future development should distinguish digital communication replacing traditional clinic appointments and additional timely communication. Evaluation is needed that uses relevant generic outcomes. Study registration: Two of the reviews in this study are registered as PROSPERO CRD42016035467 and CRD42016038792. Funding: The National Institute for Health Research Health Services and Delivery Research programme.

Background: Effective programmes to help children manage their weight are required. ‘Families for Health’ focuses on a parenting approach, designed to help parents develop their parenting skills to support lifestyle change within the family. Families for Health version 1 showed sustained reductions in mean body mass index (BMI) z-score after 2 years in a pilot project. Objective: The aim was to evaluate its effectiveness and cost-effectiveness in a randomised controlled trial (RCT). Design: The trial was a multicentre, investigator-blind RCT, with a parallel economic and process evaluation, with follow-up at 3 and 12 months. Randomisation was by family unit, using a 1 : 1 allocation by telephone registration, stratified by three sites, with a target of 120 families. Setting: Three sites in the West Midlands, England, UK. Participants: Children aged 6–11 years who were overweight (≥ 91st centile BMI) or obese (≥ 98th centile BMI), and their parents/carers. Recruitment was via referral or self-referral. Interventions: Families for Health version 2 is a 10-week, family-based community programme with parallel groups for parents and children, addressing parenting, lifestyle, social and emotional development. Usual care was the treatment for childhood obesity provided within each locality. Main outcome measures: Joint primary outcome measures were change in children’s BMI z-score and incremental cost per quality-adjusted life-year (QALY) gained at 12 months’ follow-up (QALYs were calculated using the European Quality of Life-5 Dimensions Youth version). Secondary outcome measures included changes in children’s waist circumference, percentage body fat, physical activity, fruit/vegetable consumption and quality of life. Parents’ BMI and mental well-being, family eating/activity, parent–child relationships and parenting style were also assessed. The process evaluation documented recruitment, reach, dose delivered, dose received and fidelity, using mixed methods. Results: The study recruited 115 families (128 children; 63 boys and 65 girls), with 56 families randomised to the Families for Health arm and 59 to the ‘usual-care’ control arm. There was 80% retention of families at 3 months (Families for Health, 46 families; usual care, 46 families) and 72% retention at 12 months (Families for Health, 44 families; usual care, 39 families). The change in BMI z-score at 12 months was not significantly different in the Families for Health arm and the usual-care arm [0.114, 95% confidence interval (CI) –0.001 to 0.229; p = 0.053]. However, within-group analysis showed that the BMI z-score was significantly reduced in the usual-care arm (–0.118, 95% CI –0.203 to –0.034; p = 0.007), but not in the Families for Health arm (–0.005, 95% CI –0.085 to 0.078; p = 0.907). There was only one significant difference between groups for secondary outcomes. The economic evaluation, taking a NHS and Personal Social Services perspective, showed that mean costs 12 months post randomisation were significantly higher for Families for Health than for usual care (£998 vs. £548; p

Ion exchange is a ubiquitous phenomenon central to wide industrial applications, ranging from traditional (bio)chemical separation to the emerging chimie douce synthesis of materials with metastable structure for batteries and other energy applications. The exchange process is complex, involving substitution and transport of different ions under non-equilibrium conditions, and thus difficult to probe, leaving a gap in mechanistic understanding of kinetic exchange pathways toward final products. Herein, we report in situ tracking kinetic pathways of Li+/Na+ substitution during solvothermal ion-exchange synthesis of LixNa1.5-xVOPO4F0.5 (0 ≤ x ≤ 1.5), a promising multi-Li polyanionic cathode for batteries. The real-time observation, corroborated by first-principles calculations, reveals a selective replacement of Na+ by Li+, leading to peculiar Na+/Li+/vacancy orderings in the intermediates. Contradicting the traditional belief of facile topotactic substitution via solid solution reaction, an abrupt two-phase transformation occurs and predominantly governs the kinetics of ion exchange and transport in the 1D polyanionic framework, consequently leading to significant difference of Li stoichiometry and electrochemical properties in the exchanged products. The findings may help to pave the way for rational design of ion exchange synthesis for making new materials. [ABSTRACT FROM AUTHOR]