Focused deterrence: A protocol for a realist multisite randomised controlled trial for evaluating a violence prevention intervention in the UK.

INTRODUCTION: Focused deterrence (FD) is a frequently cited intervention for preventing violence, particularly against violent urban gangs. The Youth Endowment Fund (YEF) believes it could be effective in the UK, based primarily on research conducted in the US. However, we contend that these studies have inadequate methodological designs, lack of rigorous testing, and small sample sizes. Therefore, the evidence supporting focused deterrence as an effective method, particularly outside the US, is inconclusive. The aim of the protocol is to better understand the potential effects of FD in the context of the UK, using a multisite evaluation experimental design to more closely investigate the evidence of its likely impact. METHODS: We planned a realist randomised controlled trial. The design is focused on a multisite trial consisting of two-arm randomised experiments in five locations. Each trial location will test their implementation of a core programme specified by the funder. The multisite nature will allow us to understand differential impacts between locations, improving the external validity of the results. Participants will be randomly selected from a wider pool of eligible individuals for the intervention. We estimate a sample size of approximately N = 1,700 individuals is required. Based on this pooled sample size, a relative reduction of 26% would be detectable in 80% of trials. The trial is coupled with a formative process evaluation of delivery and fidelity. The formative evaluation will use a mixed methods design. The qualitative aspect will include semi-structured cross-sectional and longitudinal interviews with programme leads, programme delivery team, and programme participants, as well as observations of the meetings between the programme delivery team (i.e., community navigators/mentors) and programme participants. The quantitative data for the formative evaluation will be gathered by the sites themselves and consist of routine outcome performance monitoring using administrative data. Sampling for interviews and observations will vary, with the researchers aiming for a higher number of individuals included in the first round of cross-sectional interviews and retaining as many as possible for repeat interviews and observations. DISCUSSION: This protocol outlines the process and impact evaluation methodology for the most extensive multisite evaluation of focused deterrence to date in the UK. Spanning five distinct sites with seven trials, the evaluation includes a cohort of 2,000 individuals, marking it as the only multisite trial of focused deterrence. Employing an integrated realist evaluation framework, the study uses qualitative and quantitative research methods. The anticipated findings will offer pivotal insights for formulating future violence prevention policies in the UK. They are also expected to contribute significantly to the corpus of literature on violence prevention and intervention evaluation. TRIAL REGISTRATION: Protocol registration: ISRCTN: 11650008 4th June 2023.

Multi-omic Profiling Reveals Early Immunological Indicators for Identifying COVID-19 Progressors.

The pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to a rapid response by the scientific community to further understand and combat its associated pathologic etiology. A focal point has been on the immune responses mounted during the acute and post-acute phases of infection, but the immediate post-diagnosis phase remains relatively understudied. We sought to better understand the immediate post-diagnosis phase by collecting blood from study participants soon after a positive test and identifying molecular associations with longitudinal disease outcomes. Multi-omic analyses identified differences in immune cell composition, cytokine levels, and cell subset-specific transcriptomic and epigenomic signatures between individuals on a more serious disease trajectory (Progressors) as compared to those on a milder course (Non-progressors). Higher levels of multiple cytokines were observed in Progressors, with IL-6 showing the largest difference. Blood monocyte cell subsets were also skewed, showing a comparative decrease in non-classical CD14-CD16+ and intermediate CD14+CD16+ monocytes. Additionally, in the lymphocyte compartment, CD8+ T effector memory cells displayed a gene expression signature consistent with stronger T cell activation in Progressors. Importantly, the identification of these cellular and molecular immune changes occurred at the early stages of COVID-19 disease. These observations could serve as the basis for the development of prognostic biomarkers of disease risk and interventional strategies to improve the management of severe COVID-19.

Selection of Durable, Environmentally Friendly, and Cost-Effective Asphalt Mixtures.

In recent years, due to the advent of several additives and innovations, asphalt mix design has become more complex. The mixes meeting the volumetric mix design requirements may still fail prematurely in the field. Thus, a transition from a simplistic volumetric-based mix design to a performance-based mix design is required, which was also envisioned in the Strategic Highway Research Program (SHRP) and Superpave mix design. In addition to performance verification, asphalt mix designs should also be evaluated for the life-cycle costs and environmental impact to encourage durable as well as sustainable and cost-effective alternatives. In this study, three asphalt mixtures with different reclaimed asphalt pavement (RAP) contents and additives were evaluated for cracking and rutting performance by using different performance thresholds for asphalt mixtures that are generally used in the construction of high-volume roads in Oregon. A balanced mix design process was followed to determine the required binder content for the three mixtures. Based on the life cycle cost and environmental impact analyses, the mixture with warm mix additive (WMA) was selected as the most economically and environmentally viable asphalt mixture to be used for construction in Oregon.

Strategies to reduce the energy content of foods pre-ordered for lunch in the workplace: a randomised controlled trial in an experimental online canteen.

BACKGROUND: Prompting employees to swap their usual lunches for lower-energy alternatives may help align energy intake with public health recommendations. We tested the effect of offering lower-energy swaps with and without physical activity calorie equivalent (PACE) information on the energy of lunches pre-ordered in an online hypothetical workplace canteen. METHODS: UK employed adults (n = 2,150) were invited to hypothetically pre-order their lunch from the canteen through a custom-made online platform. They were randomised 1:1:1 to: (i) control: no swaps offered; (ii) lower-energy swaps offered; or (iii) lower-energy swaps offered with PACE information. The primary outcome was the total energy ordered using analysis of covariance and controlling for the energy content of the initial items ordered. Secondary outcomes were swap acceptance rate and intervention acceptability. RESULTS: Participants were 54% female, had a mean age of 36.8 (SD = 11.6) and a BMI of 26.3 (SD = 5.6). Compared with an average 819 kcal energy ordered in the control, both the swaps and swaps + PACE interventions significantly reduced average energy ordered by 47 kcal (95% CI: -82 to -13, p = 0.003) and 66 kcal (95% CI: -100 to -31, p < 0.001), respectively. Compared with offering swaps only, the swaps + PACE intervention led to significantly higher swap acceptance (OR: 1.63, 95% CI: 1.27 to 2.09, p < 0.001) but did not significantly reduce energy ordered (-19 kcal, 95% CI: -53 to 16, p = 0.591). About 65% and 16% of intervention participants found the swap interventions acceptable and unacceptable, respectively, with the swaps + PACE intervention being considered more acceptable than swaps only (OR: 1.32, 95%CI: 1.09 to 1.60, p < 0.004). CONCLUSION: Offering lower-energy swaps with or without PACE information reduced the energy of pre-ordered lunches experimentally. Both interventions hold promise for reducing the energy of purchased foods and drinks. Trial Registration As Predicted reference number: 56358, 22/01/21, https://aspredicted.org/pw2qr.pdf.

Experience of Using an Online Pre-Ordering System for A Workplace Canteen That Offers Lower-Energy Swaps: A Think-Aloud Study.

Online systems that allow employees to pre-order their lunch may help reduce energy intake. We investigated the acceptability of a pre-ordering website for a workplace canteen that prompts customers to swap to lower-energy swaps and the factors influencing swap acceptance. Employees (n = 30) placed a hypothetical lunch order through a pre-ordering website designed for their canteen while thinking aloud. Semi-structured interview questions supported data collection. Data were analysed using thematic analysis. Acceptability was generally high, but potentially context dependent. Practical considerations, such as reminders to pre-order, user-friendliness, provision of images of menu items and energy information while browsing, an ability to reserve pre-ordered meals, and a swift collection service facilitated acceptability. The restrictive timeframe within which orders could be placed, a lack of opportunity to see foods before ordering, and prompts to swap being perceived as threatening autonomy were barriers to acceptability. Swap acceptance was facilitated by the provision of physical activity calorie equivalents (PACE) information, and swap similarity in terms of taste, texture, and expected satiety as well as the perception that alternatives provided meaningful energy savings. Online canteen pre-ordering systems that prompt lower-energy swaps may be an acceptable approach to help reduce energy intake in the workplace.

Sex differences in adolescent physical aggression: Evidence from sixty-three low-and middle-income countries.

A great deal of research shows that adolescent and adult males are more likely to engage in physical aggression and violence than females are. However, few studies have examined cross-cultural variation in sex differences, particularly among low- and middle-income countries [LMICs]. Based on social role and sexual selection theories, we derived two hypotheses regarding possible variations in sex differences across societal contexts: 1) sex differences increase with societal gender polarization (social role theory) and 2) sex differences are exacerbated in societies where socio-economic opportunities are scarce, unequal, or insecure (prediction derived from sexual selection theory). The current study examined the prevalence of and variation in sex differences in physical aggression, as measured by frequent fighting, among 247,909 adolescents in 63 low- and middle-income countries. The results show that, overall, males were over twice as likely (OR = 2.68; 95% CI = 2.60-2.76) to report frequent fighting in the past 12 months than females. However, sex differences vary significantly across LMICs, wherein countries with higher female prevalence rates have smaller sex differences in frequent fighting. Contrary to expectations derived from social role theory, sex differences in physical aggression decrease as societal gender inequality increased. In regards to sexual selection theory, we find no evidence that sex differences in frequent fighting varies according to societal rule of law or income inequality.

School-based interventions for reducing disciplinary school exclusion: a systematic review.

This Campbell systematic review examines the impact of interventions to reduce exclusion from school. School exclusion, also known as suspension in some countries, is a disciplinary sanction imposed by a responsible school authority, in reaction to students' misbehaviour. Exclusion entails the removal of pupils from regular teaching for a period during which they are not allowed to be present in the classroom (in-school) or on school premises (out-of-school). In some extreme cases the student is not allowed to come back to the same school (expulsion). The review summarises findings from 37 reports covering nine different types of intervention. Most studies were from the USA, and the remainder from the UK. Included studies evaluated school-based interventions or school-supported interventions to reduce the rates of exclusion. Interventions were implemented in mainstream schools and targeted school-aged children from four to 18, irrespective of nationality or social background. Only randomised controlled trials are included. The evidence base covers 37 studies. Thirty-three studies were from the USA, three from the UK, and for one study the country was not clear. School-based interventions cause a small and significant drop in exclusion rates during the first six months after intervention (on average), but this effect is not sustained. Interventions seemed to be more effective at reducing some types of exclusion such as expulsion and in-school exclusion. Four intervention types - enhancement of academic skills, counselling, mentoring/monitoring, and skills training for teachers - had significant desirable effects on exclusion. However, the number of studies in each case is low, so this result needs to be treated with caution. There is no impact of the interventions on antisocial behaviour. Variations in effect sizes are not explained by participants' characteristics, the theoretical basis of the interventions, or the quality of the intervention. Independent evaluator teams reported lower effect sizes than research teams who were also involved in the design and/or delivery of the intervention. Plain language summary: Interventions can reduce school exclusion but the effect is temporary: Some interventions - enhancement of academic skills, counselling, mentoring/monitoring, and skills training for teachers - appear to have significant effects on exclusion.The review in brief: Interventions to reduce school exclusion are intended to mitigate the adverse effects of this school sanction. Some approaches, namely those involving enhancement of academic skills, counselling, mentoring/monitoring and those targeting skills training for teachers, have a temporary effect in reducing exclusion. More evaluations are needed to identify the most effective types of intervention; and whether similar effects are also found in different countries.What is this review about?: School exclusion is associated with undesirable effects on developmental outcomes. It increases the likelihood of poor academic performance, antisocial behavior, and poor employment prospects. This school sanction disproportionally affects males, ethnic minorities, those who come from disadvantaged economic backgrounds, and those with special educational needs.This review assesses the effectiveness of programmes to reduce the prevalence of exclusion.What are the main findings of this review?: What studies are included? Included studies evaluated school-based interventions or school-supported interventions to reduce the rates of exclusion. Interventions were implemented in mainstream schools and targeted school-aged children from four to 18, irrespective of nationality or social background. Only randomised controlled trials are included.The evidence base covers 37 studies. Thirty-three studies were from the USA, three from the UK, and for one study the country was not clear.School-based interventions cause a small and significant drop in exclusion rates during the first six months after intervention (on average), but this effect is not sustained. Interventions seemed to be more effective at reducing some types of exclusion such as expulsion and in-school exclusion.Four intervention types - enhancement of academic skills, counselling, mentoring/ monitoring, and skills training for teachers - had significant desirable effects on exclusion. However, the number of studies in each case is low, so this result needs to be treated with caution.There is no impact of the interventions on antisocial behaviour.Variations in effect sizes are not explained by participants' characteristics, the theoretical basis of the interventions, or the quality of the intervention. Independent evaluator teams reported lower effect sizes than research teams who were also involved in the design and/or delivery of the intervention.What do the findings of this review mean?: School-based interventions are effective at reducing school exclusion immediately after, and for a few months after, the intervention (6 months on average). Four interventions presented promising and significant results in reducing exclusion, that is, enhancement of academic skills, counselling, mentoring/monitoring, skills training for teachers. However, since the number of studies for each sub-type of intervention was low, we suggest these results should be treated with caution.Most of the studies come from the USA. Evaluations are needed from other countries in which exclusion is common. Further research should take advantage of the possibility of conducting cluster-randomised controlled trials, whilst ensuring that the sample size is sufficiently large.How up-to-date is this review?: The review authors searched for studies published up to December 2015. This Campbell systematic review was published in January 2018. Executive Summary/Abstract: BACKGROUND: Schools are important institutions of formal social control (Maimon, Antonaccio, & French, 2012). They are, apart from families, the primary social system in which individuals are socialised to follow specific codes of conduct. Violating these codes of conduct may result in some form of punishment. School punishment is normally accepted by families and students as a consequence of transgression, and in that sense school isoften the place where children are first introduced to discipline, justice, or injustice (Whitford & Levine-Donnerstein, 2014).A wide range of punishments may be used in schools, from verbal reprimands to more serious actions such as detention, fixed term exclusion or even permanent exclusion from the mainstream education system. It must be said that in some way, these school sanctions resemble the penal system and its array of alternatives to punish those that break the law.School exclusion, also known as suspension in some countries, is defined as a disciplinary sanction imposed by a responsible school authority, in reaction to students' misbehaviour. Exclusion entails the removal of pupils from regular teaching for a period during which they are not allowed to be present in the classroom or, in more serious cases, on school premises.Based on the previous definition, this review uses school exclusion and school suspension as synonyms, unless the contrary is explicitly stated. Most of the available research has found that exclusion correlates with subsequent negative sequels on developmental outcomes. Exclusion or suspension of students is associated with failure within the academic curriculum, aggravated antisocial behaviour, and an increased likelihood of involvement with punitive social control institutions (i.e., the Juvenile Justice System). In the long-term, opportunities for training and employment seem to be considerably reduced for those who have repeatedly been excluded. In addition to these negative correlated outcomes, previous evidence suggest that the exclusion of students involves a high economic cost for taxpayers and society.Research from the last 20 years has concluded quite consistently that this disciplinary measure disproportionally targets males, ethnic minorities, those who come from disadvantaged economic backgrounds, and those presenting special educational needs. In other words, suspension affects the most vulnerable children in schools.Different programmes have attempted to reduce the prevalence of exclusion. Although some of them have shown promising results, so far, no comprehensive systematic review has examined these programmes' overall effectiveness.OBJECTIVES: The main goal of the present research is to systematically examine the available evidence for the effectiveness of different types of school-based interventions aimed at reducing disciplinary school exclusion. Secondary goals include comparing different approaches and identifying those that could potentially demonstrate larger and more significant effects.The research questions underlying this project are as follows: Do school-based programmes reduce the use of exclusionary sanctions in schools?Are some school-based approaches more effective than others in reducing exclusionary sanctions?Do participants' characteristics (e.g., age, gender, ethnicity) affect the impact of school-based programmes on exclusionary sanctions in schools?Do characteristics of the interventions, implementation, and methodology affect the impact of school-based programmes on exclusionary sanctions in schools? SEARCH METHODS: The authors conducted a comprehensive search to locate relevant studies reporting on the impact of school-based interventions on exclusion from 1980 onwards. Twenty-seven different databases were consulted, including databases that contained both published and unpublished literature. In addition, we contacted researchers in the field of school-exclusion for further recommendations of relevant studies; we also assessed citation lists from previous systematic and narrative reviews and research reports. Searches were conducted fromSeptember 1 to December 1, 2015.SELECTION CRITERIA: The inclusion and exclusion criteria for manuscripts were defined before we started our searches. To be eligible, studies needed to have: evaluated school-based interventions or school-supported interventions intended to reduce the rates of suspension; seen the interventions as an alternative to exclusion; targeted school-aged children from four to 18 in mainstream schools irrespective of nationality or social background; and reported results of interventions delivered from 1980 onwards. In terms of methodological design, we included randomised controlled trialsonly, with at least one experimental group and onecontrol or placebo group.DATA COLLECTION AND ANALYSIS: Initial searches produced a total of 42,749 references from 27 different electronic databases. After screening the title, abstract and key words, we kept 1,474 relevant hits. 22 additional manuscripts were identified through other sources (e.g., assessment of citation lists, contribution of authors). After removing duplicates, we ended up with a total of 517 manuscripts. Two independent coders evaluated each report, to determine inclusion or exclusion.The second round of evaluation excluded 472 papers, with eight papers awaiting classification, and 37 studies kept for inclusion in meta-analysis. Two independent evaluators assessed all the included manuscripts for risk of quality bias by using EPOC tool.Due to the broad scope of our targeted programmes, meta-analysis was conducted under a random-effect model. We report the impact of the intervention using standardised differences of means, 95% confidence intervals along with the respective forest plots. Sub-group analysis and meta-regression were used for examining the impact of the programme. Funnel plots and Duval and Tweedie's trim-and-fill analysis were used to explore the effect of publication bias.RESULTS: Based on our findings, interventions settled in school can produce a small and significant drop in exclusion rates (SMD=.30; 95% CI .20 to .41; p<.001). This means that those participating in interventions are less likely to be suspended than those allocated to control/placebo groups. These results are based on measures of impact collected immediately during the first six months after treatment (on average). When the impact was tested in the long-term (i.e., 12 or more months after treatment), the effects of the interventions were not sustained. In fact, there was a substantive reduction in the impact of school-based programmes (SMD=.15; 95%CI -.06 to .35), and it was no longer statistically significant.We ran analysis testing the impact of school-based interventions on different types of exclusion. Evidence suggests that interventions are more effective at reducing expulsion and in-school exclusion than out-of-school exclusion. In fact, the impact of intervention in out-of-school exclusion was close to zero and not statistically significant.Nine different types of school-based interventions were identified across the 37 studies included in the review. Four of them presented favourable and significant results in reducing exclusion (i.e., enhancement of academic skills, counselling, mentoring/monitoring, skills training for teachers). Since the number of studies for each sub-type of intervention was low, we suggest that results should be treated with caution.A priori defined moderators (i.e., participants' characteristics, the theoretical basis of the interventions, and quality of the intervention)showed not to be effective at explaining the heterogeneity present in our results. Among three post-hoc moderators, the role of the evaluator was found to be significant: independent evaluator teams reported lower effect sizes than research teams who were also involved in the design and/or delivery of the intervention.Two researchers independently evaluated the quality of the evidence involved in this review by using the EPOC tool. Most of the studies did not present enough information for the judgement of quality bias.AUTHORS' CONCLUSIONS: The evidence suggests that school-based interventions are effective at reducing school exclusion immediately after, and for a few months after, the intervention. Some specific types of interventions show more promising and stable results than others, namely those involving mentoring/monitoring and those targeting skills training for teachers. However, based on the number of studies involved in our calculations, we suggest that results must be cautiously interpreted. Implications for policy and practice arising from our results are discussed.

'Lowering the threshold of effective deterrence'-Testing the effect of private security agents in public spaces on crime: A randomized controlled trial in a mass transit system.

Supplementing local police forces is a burgeoning multibillion-dollar private security industry. Millions of formal surveillance agents in public settings are tasked to act as preventative guardians, as their high visibility presence is hypothesized to create a deterrent threat to potential offenders. Yet, rigorous evidence is lacking. We randomly assigned all train stations in the South West of England that experienced crime into treatment and controls conditions over a six-month period. Treatment consisted of directed patrol by uniformed, unarmed security agents. Hand-held trackers on every agent yielded precise measurements of all patrol time in the stations. Count-based regression models, estimated marginal means and odds-ratios are used to assess the effect of these patrols on crimes reported to the police by victims, as well as new crimes detected by police officers. Outcomes are measured at both specified target locations to which security guards were instructed to attend, as well as at the entire station complexes. Analyses show that 41% more patrol visits and 29% more minutes spent by security agents at treatment compared to control stations led to a significant 16% reduction in victim-generated crimes at the entirety of the stations' complexes, with a 49% increase in police-generated detections at the target locations. The findings illustrate the efficacy of private policing for crime prevention theory.

Pragmatic randomised controlled trial to evaluate the effectiveness and cost effectiveness of a multi-component intervention to reduce substance use and risk-taking behaviour in adolescents involved in the criminal justice system: A trial protocol (RISKIT-CJS).

BACKGROUND: Adolescence is a critical developmental stage when young people make lifestyle choices that have the potential to impact on their current and future health and social wellbeing. The relationship between substance use and criminal activity is complex but there is clear evidence that the prevalence of problematic substance use is far higher among adolescent offenders than the general adolescent population. Adolescent offenders are a marginalized and vulnerable population who are significantly more likely to experience health and social inequalities in later life than their non-offending peers. There is a paucity of evidence on effective interventions to address substance use and risk-taking behaviours in adolescent offender populations but it is clear that preventative or abstinence orientated interventions are not effective. RISKIT-CJS is an intervention developed in collaboration with young people taking account of the current best evidence. Feasibility and pilot studies have found the intervention addresses the needs of adolescents, is acceptable and has demonstrated potential in reducing substance use and risk-taking behavior. METHODS: The study is a mixed method, two-armed, prospective, pragmatic randomized controlled trial with individual randomisation to either treatment as usual alone or the RISKIT-CJS intervention in addition to treatment as usual. Adolescents, aged 13 to 17 years inclusive, engaged with the criminal justice system who are identified as having problematic substance use are eligible to participate. The study will be conducted across three geographical areas; South and South East England, London and North East England between March 2017 and February 2019. DISCUSSION: The study represents an ambitious programme of work to address an area of need for a marginalized and vulnerable population. TRIAL REGISTRATION: ISRCTN77037777 registered 15/09/2016.

London Education and Inclusion Project (LEIP): Results from a Cluster-Randomized Controlled Trial of an Intervention to Reduce School Exclusion and Antisocial Behavior.

School exclusion as a disciplinary measure remains a controversial issue. In spite of numerous attempts to reduce this practice, no solutions with documented effectiveness exist. This article reports results of a cluster-randomized controlled field trial carried out in 36 schools across London. The trial is an independent evaluation of a 12-week-long intervention, Engage in Education-London (EiE-L), delivered by Catch22. The intervention was aimed at students in secondary school who are most at risk of school exclusion. It targeted their social communication and broader social skills with the aim of reducing school exclusions and problem behaviors. The study employed a multi-informant design that included students and teacher reports as well as official records for exclusions and arrests. Data were analyzed through intent-to-treat analyses based on self-reports from 644 students and 685 teacher reports for students who were nominated for the study and for whom data was available at baseline or post-intervention. At baseline data collection the students ranged in age from 12.85 to 15.03, with M = 14.03; 71 % were male and included a number of ethnic minorities, the largest of which was black African/black Caribbean comprising 40 % of the sample. The results suggested a small but statistically significant negative effect on the primary outcome of exclusion and null effects for the secondary outcomes that measured behavioral and socio-emotional outcomes. The study's findings are discussed in terms of the possible reasons for the null effects and negative (iatrogenic) effect.

An ecological analysis of prison overcrowding and suicide rates in England and Wales, 2000-2014.

Prisoners are at a greatly increased risk of suicides compared to the general population. Differences in suicide risk can be partly explained by individual risk factors, but the contribution of prison characteristics remains unclear. Overcrowded prisons have higher suicide rates, but this may be related to prison function, security level, population size and turnover. The aim of the current study was to investigate the contribution of each of these prison characteristics to suicide rates, using data from the Ministry of Justice for adult prisons in England and Wales from 2000 to 2014. Negative binomial regression analysis showed that larger population size, higher turnover, higher security and public management were associated with higher suicide rates. When controlling for these factors, overcrowding was not found to be related to suicide rates. Questions remain about the causal mechanisms underlying variation in prison suicides and the impact of the lived experience of overcrowding. Further research is needed to examine the relative contribution of prison and prisoner characteristics to suicides.

Intercellular signaling through secreted proteins induces free-energy gradient-directed cell movement.

Controlling cell migration is important in tissue engineering and medicine. Cell motility depends on factors such as nutrient concentration gradients and soluble factor signaling. In particular, cell-cell signaling can depend on cell-cell separation distance and can influence cellular arrangements in bulk cultures. Here, we seek a physical-based approach, which identifies a potential governed by cell-cell signaling that induces a directed cell-cell motion. A single-cell barcode chip (SCBC) was used to experimentally interrogate secreted proteins in hundreds of isolated glioblastoma brain cancer cell pairs and to monitor their relative motions over time. We used these trajectories to identify a range of cell-cell separation distances where the signaling was most stable. We then used a thermodynamics-motivated analysis of secreted protein levels to characterize free-energy changes for different cell-cell distances. We show that glioblastoma cell-cell movement can be described as Brownian motion biased by cell-cell potential. To demonstrate that the free-energy potential as determined by the signaling is the driver of motion, we inhibited two proteins most involved in maintaining the free-energy gradient. Following inhibition, cell pairs showed an essentially random Brownian motion, similar to the case for untreated, isolated single cells.

London Education and Inclusion Project (LEIP): Exploring Negative and Null Effects of a Cluster-Randomised School-Intervention to Reduce School Exclusion--Findings from Protocol-Based Subgroup Analyses.

UNLABELLED: This paper presents subgroup analyses from the London Education and Inclusion Project (LEIP). LEIP was a cluster-randomised controlled trial of an intervention called Engage in Education-London (EiE-L) which aimed to reduce school exclusions in those at greatest risk of exclusion. Pupils in the control schools attended an hour-long employability seminar. Minimisation was used to randomly assign schools to treatment and control following baseline data collection. The study involved 36 schools (17 in treatment--373 pupils; 19 in control--369 pupils) with >28% free school meal eligibility across London and utilised on pupil self-reports, teacher reports as well as official records to assess the effectiveness of EiE-L. Due to multiple data sources, sample sizes varied according to analysis. Analyses of pre-specified subgroups revealed null and negative effects on school exclusion following the intervention. Our findings suggest that the design and implementation of EiE-L may have contributed to the negative outcomes for pupils in the treatment schools when compared to those in the control schools. These findings call into question the effectiveness of bolt-on short-term interventions with pupils, particularly those at the highest risk of school exclusion and when they are faced with multiple problems. This is especially pertinent given the possibility of negative outcomes. TRIAL REGISTRATION: Controlled Trials: ISRCTN23244695.

Using ambulance data to reduce community violence: critical literature review.

BACKGROUND: Previous work has demonstrated that much violence requiring medical help is not recorded by the police. Sharing emergency department data on victims of violence is associated with reductions in community violence and is well established throughout the UK. We undertook a critical literature review to determine whether sharing ambulance data was useful to identify violence hotspots and offered unique information for violence prevention. METHOD: A search of the major medical and criminological databases was undertaken using search terms related to the ambulance service, violence and assault, as well as data collection. The search was conducted within the NICE Evidence, Cochrane Library, Google Scholar, Criminal Justice Abstracts, Scopus and National Criminal Justice Reference Service databases, along with the websites of various relevant institutions. RESULTS: Overall, 36 papers were identified by abstract scanning and bibliography search, of which 10 were considered relevant. A further nine papers were detected in the grey literature, and two were considered to be useful in providing evidence for use of ambulance data in violence surveillance. Two of the identified papers were interventional studies, and the other 10 were observational studies. DISCUSSION: Although the standard of evidence was generally low, most studies demonstrated that ambulance services detected a substantial proportion of assaults that were not recorded by the police or the emergency departments. We identified only two interventional studies, but they were of low quality. Although the interventional evidence base is currently weak, ambulance data provide a unique source of information about the epidemiology of community violence and have the potential to improve current violent crime surveillance methods.

Microfluidics-based single-cell functional proteomics for fundamental and applied biomedical applications.

We review an emerging microfluidics-based toolkit for single-cell functional proteomics. Functional proteins include, but are not limited to, the secreted signaling proteins that can reflect the biological behaviors of immune cells or the intracellular phosphoproteins associated with growth factor-stimulated signaling networks. Advantages of the microfluidics platforms are multiple. First, 20 or more functional proteins may be assayed simultaneously from statistical numbers of single cells. Second, cell behaviors (e.g., motility) may be correlated with protein assays. Third, extensions to quantized cell populations can permit measurements of cell-cell interactions. Fourth, rare cells can be functionally identified and then separated for further analysis or culturing. Finally, certain assay types can provide a conduit between biology and the physicochemical laws. We discuss the history and challenges of the field then review design concepts and uses of the microchip platforms that have been reported, with an eye toward biomedical applications. We then look to the future of the field.

Is parental socio-economic status related to the initiation of substance abuse by young people in an English city? An event history analysis.

This paper aims to examine the relationship between parental socio-economic status (SES) and adolescent substance use. The central question posed in the title is approached in two stages. First, theoretical and empirical research in this area is reviewed. Second, data from an ongoing longitudinal study of young people in England (the Peterborough Adolescent and Young Adult Development Study--PADS+) are used to highlight the nature of this relationship in one city. Results from discrete-time event history analyses show that when examining what predicts initiation of substance use, familial and demographic factors emerge as important predictors, but SES does not appear to be relevant. The concluding discussion focuses on whether support is found for hypotheses derived from the existing literature and implications for future research.

A robotics platform for automated batch fabrication of high density, microfluidics-based DNA microarrays, with applications to single cell, multiplex assays of secreted proteins.

Microfluidics flow-patterning has been utilized for the construction of chip-scale miniaturized DNA and protein barcode arrays. Such arrays have been used for specific clinical and fundamental investigations in which many proteins are assayed from single cells or other small sample sizes. However, flow-patterned arrays are hand-prepared, and so are impractical for broad applications. We describe an integrated robotics/microfluidics platform for the automated preparation of such arrays, and we apply it to the batch fabrication of up to eighteen chips of flow-patterned DNA barcodes. The resulting substrates are comparable in quality with hand-made arrays and exhibit excellent substrate-to-substrate consistency. We demonstrate the utility and reproducibility of robotics-patterned barcodes by utilizing two flow-patterned chips for highly parallel assays of a panel of secreted proteins from single macrophage cells.