Search

Kinetic inductance traveling-wave parametric amplifiers (KI-TWPAs) have a wide instantaneous bandwidth with a near quantum-limited noise performance and a relatively high dynamic range. Because of this, they are suitable readout devices for cryogenic detectors and superconducting qubits and have a variety of applications in quantum sensing. This work discusses the design, fabrication, and performance of a KI-TWPA based on four-wave mixing in a NbTiN microstrip transmission line. This device amplifies a signal band from 4 to 8 GHz without contamination from image tones, which are produced in a separate higher frequency band. The 4–8 GHz band is commonly used to read out cryogenic detectors, such as microwave kinetic inductance detectors and Josephson junction-based qubits. We report a measured maximum gain of over 20 dB using four-wave mixing with a 1 dB gain compression point of −58 dBm at 15 dB of gain over that band. The bandwidth and peak gain are tunable by adjusting the pump-tone frequency and power. Using a Y-factor method, we measure an amplifier-added noise of 0.5 ≤ Nadded ≤ 1.5 photons from 4.5 to 8 GHz.

Abstract The heterogeneity inherent in today’s biotherapeutics, especially as a result of heavy glycosylation, can affect a molecule’s safety and efficacy. Characterizing this heterogeneity is crucial for drug development and quality assessment, but existing methods are limited in their ability to analyze intact glycoproteins or other heterogeneous biotherapeutics. Here, we present an approach to the molecular assessment of biotherapeutics that uses proton-transfer charge-reduction with gas-phase fractionation to analyze intact heterogeneous and/or glycosylated proteins by mass spectrometry. The method provides a detailed landscape of the intact molecular weights present in biotherapeutic protein preparations in a single experiment. For glycoproteins in particular, the method may offer insights into glycan composition when coupled with a suitable bioinformatic strategy. We tested the approach on various biotherapeutic molecules, including Fc-fusion, VHH-fusion, and peptide-bound MHC class II complexes to demonstrate efficacy in measuring the proteoform-level diversity of biotherapeutics. Notably, we inferred the glycoform distribution for hundreds of molecular weights for the eight-times glycosylated fusion drug IL22-Fc, enabling correlations between glycoform sub-populations and the drug’s pharmacological properties. Our method is broadly applicable and provides a powerful tool to assess the molecular heterogeneity of emerging biotherapeutics.

The BioPhorum Development Group is an industry collaboration enabling the sharing of common practices for the development of biopharmaceuticals. Bioassays are an important part of an analytical control system. Utilization of ready-to-use cells can increase operational flexibility and improve efficiency by providing frozen cell banks uniform stock while removing challenges associated with maintaining cultured cells. The BioPhorum Development Group-Bioassay workstream conducted an intercompany benchmarking survey and group discussions around the use of ready-to-use cells for bioassays. The results of the collaboration provide alignment on nomenclature, production, qualification and implementation of ready-to-use cells to support the assay life cycle.

Abstract Background Globally, around 13% of children experience dental anxiety (DA). This group of patients frequently miss dental appointments, have greater reliance on treatment under general anaesthesia (GA) and have poorer oral health-related quality of life (OHRQoL) than their non-dentally anxious peers. Recently, a low-intensity cognitive behavioural therapy (CBT)-based, self-help approach has been recommended for management of childhood anxiety disorders. A feasibility study conducted in secondary care found this guided self-help CBT resource reduced DA and a randomised controlled trial was recommended. The present study aims to establish the clinical and cost-effectiveness of a guided self-help CBT intervention to reduce DA in children attending primary dental care sites compared to usual care. Methods This 4-year randomised controlled trial will involve 600 children (aged 9–16 years) and their parent/carers in 30 UK primary dental care sites. At least two dental professionals will participate in each site. They will be assigned, using random allocation, to receive the CBT training and deliver the intervention or to deliver usual care. Children with DA attending these sites, in need of treatment, will be randomly allocated to be treated either by the intervention (CBT) or control (usual care) dental professional. Children will complete questionnaires relating to DA, OHRQoL and HRQoL before treatment, immediately after treatment completion and 12 months post-randomisation. Attendance, need for sedation/GA and costs of the two different approaches will be compared. The primary outcome, DA, will be measured using the Modified Child Dental Anxiety Scale. Scores will be compared between groups using a linear mixed model. Discussion Treating dentally anxious patients can be challenging and costly. Consequently, these children are frequently referred to specialist services for pharmacological interventions. Longer waiting times and greater travel distances may then compound existing healthcare inequalities. This research will investigate whether the intervention has the potential to reduce DA and improve oral health outcomes in children over their life-course, as well as upskilling primary dental healthcare professionals to better manage this patient group. Trial registration This clinical trial has been registered with an international registry and has been allocated an International Standard Randomised Controlled Trial Number (ISRCTN27579420).

Abstract Background Dental caries is common in young people and has wide-ranging ramifications for health and quality of life. Text messaging interventions show promise as a means to promote oral health behaviour change among young people. This paper reports the internal pilot of the Brushing RemInder 4 Good oral HealTh (BRIGHT) trial, which is evaluating an intervention comprising an oral health classroom lesson and text messages about toothbrushing, on caries in young people. Pilot trial objectives were to evaluate the feasibility and appropriateness of recruitment and data collection methods, the randomisation strategy, and intervention delivery against progression criteria for the main trial. Methods This is an internal pilot trial embedded within an assessor-blinded, two-arm, cluster randomised controlled trial. Participants were pupils aged 11–13 years (in year 7/S1 or year 8/S2) in secondary schools in England, Scotland, and Wales with above average pupil eligibility for free school meals. Following completion of pupil baseline questionnaires and dental assessments, year groups within schools were randomised to the intervention or control arm. Approximately 12 weeks later, participants completed a follow-up questionnaire, which included questions about sources of oral health advice to assess intervention contamination between year groups. At the end of the pilot phase, trial conduct was reviewed against pre-specified progression criteria. Results Ten schools were recruited for the pilot, with 20 year groups and 1073 pupils randomised (average of 54 pupils per year group). Data collection methods and intervention delivery were considered feasible, the response rate to the follow-up questionnaire was over 80%, there was an indication of a positive effect on self-reported toothbrushing, and interest was obtained from 80% of the schools required for the main trial. Despite partial intervention contamination between year groups, within-school randomisation at the level of the year-group was considered appropriate for the main trial, and the sample size was revised to account for partial contamination. Facilitators and barriers to recruitment and data collection were identified and strategies refined for the main trial. Conclusions Progression to the main trial of BRIGHT, with some design refinements, was concluded. The internal pilot was an efficient way to determine trial feasibility and optimise trial processes. Trial registration ISRCTN registry, ISRCTN12139369 , registered 10/05/2017

Abstract Background The Brushing RemInder 4 Good oral HealTh (BRIGHT) trial is investigating the clinical and cost-effectiveness of a multi-component behaviour change intervention to reduce the prevalence of dental caries in young people from deprived areas aged 11–13 years. Mobile health has gained popularity in delivering behaviour change interventions for improving oral health. The intervention, based on behaviour change theory, consists of two components; a single classroom-based session embedded in the school curriculum and a series of follow-up text messages (SMS) delivered twice daily to participants. This element of the process evaluation aimed to explore the acceptability of the BRIGHT intervention for pupils and school staff. Methods Qualitative study, based on the concept of acceptability. Focus groups were conducted with 50 pupils, from six secondary schools across the UK, who had received the intervention. Semi-structured interviews were conducted with 12 members of staff. Purposive maximum variation sampling was used. Interviews were transcribed verbatim and analysed using a framework approach. Results In line with the theoretical framework of acceptability, affective attitude, perceived effectiveness, ethicality, burden and self-efficacy were identified as factors that affect the acceptability of the BRIGHT intervention. Pupil participants appreciated learning about the consequences of inadequate brushing particularly the photographs of carious teeth during the classroom-based session. More detailed information on brushing techniques and follow-up lessons on oral health were recommended by pupils. In terms of the SMS, the data suggest that pupil participants found them to be helpful reminders for brushing their teeth. To further improve acceptability, more choice over the timing of the messages and greater interactivity to reduce tedium were suggested. Staff participants recognised the value of the lesson and reported that in general the content was suitable for their pupils. Having the lesson material prepared for them, having the necessary support and whether it was included in the curriculum, were factors that improved acceptability. Conclusion Overall, pupils and staff found the BRIGHT intervention acceptable and made some suggestions which could be adopted in any subsequent implementation of the intervention.

Injuries to racehorses and their jockeys are not limited to the racetrack and high-speed work. To optimise racehorse-jockey dyads’ health, well-being, and safety, it is important to understand their kinematics under the various exercise conditions they are exposed to. This includes trot work on roads, turf and artificial surfaces when accessing gallop tracks and warming up. This study quantified the forelimb hoof kinematics of racehorses trotting over tarmac, turf and artificial surfaces as their jockey adopted rising and two-point seat positions. A convenience sample of six horses was recruited from the British Racing School, Newmarket, and the horses were all ridden by the same jockey. Inertial measurement units (HoofBeat) were secured to the forelimb hooves of the horses and enabled landing, mid-stance, breakover, swing and stride durations, plus stride length, to be quantified via an in-built algorithm. Data were collected at a frequency of 1140 Hz. Linear Mixed Models were used to test for significant differences in the timing of these stride phases and stride length amongst the different surface and jockey positions. Speed was included as a covariate. Significance was set at p < 0.05. Hoof landing and mid-stance durations were negatively correlated, with approximately a 0.5 ms decrease in mid-stance duration for every 1 ms increase in landing duration (r2 = 0.5, p < 0.001). Hoof landing duration was significantly affected by surface (p < 0.001) and an interaction between jockey position and surface (p = 0.035). Landing duration was approximately 4.4 times shorter on tarmac compared to grass and artificial surfaces. Mid-stance duration was significantly affected by jockey position (p < 0.001) and surface (p = 0.001), speed (p < 0.001) and jockey position*speed (p < 0.001). Mean values for mid-stance increased by 13 ms with the jockey in the two-point seat position, and mid-stance was 19 ms longer on the tarmac than on the artificial surface. There was no significant difference in the breakover duration amongst surfaces or jockey positions (p ≥ 0.076) for the ridden dataset. However, the mean breakover duration on tarmac in the presence of a rider decreased by 21 ms compared to the in-hand dataset. Swing was significantly affected by surface (p = 0.039) and speed (p = 0.001), with a mean swing phase 20 ms longer on turf than on the artificial surface. Total stride duration was affected by surface only (p = 0.011). Tarmac was associated with a mean stride time that was significantly reduced, by 49 ms, compared to the turf, and this effect may be related to the shorter landing times on turf. Mean stride length was 14 cm shorter on tarmac than on grass, and stride length showed a strong positive correlation with speed, with a 71 cm increase in stride length for every 1 m s−1 increase in speed (r2 = 0.8, p < 0.001). In summary, this study demonstrated that the durations of the different stride cycle phases and stride length can be sensitive to surface type and jockey riding position. Further work is required to establish links between altered stride time variables and the risk of musculoskeletal injury.

Abstract Background Dental caries in adolescents remains a significant public health problem with few oral health promotion interventions aimed at reducing dental caries in secondary school-aged students. Previous oral health and mobile health (mHealth) research has suggested the need for the development of a school-based behaviour change intervention incorporating a digital component. This study aimed to describe the development process of a behaviour change intervention to improve the oral health of students aged 11–16 years attending secondary schools in the UK. Methods A six-step process was used to develop the complex intervention informed by behaviour change theory and involving students, young people, parents and teachers in the process. The steps were: (1) identifying the target behaviours, namely tooth brushing with a fluoride toothpaste (2) identifying the theoretical basis and developing the causal model (3) reviewing the relevant literature and developing the logic model (4) designing the intervention with young people, parents and school staff (5) specifying the intervention content and (6) translating this content into features of the intervention and piloting. Results The resultant intervention included a quality-assured classroom-based session (CBS) (guided by a lesson plan and teaching resources), delivered by school teachers which was embedded within the school curriculum. This CBS was followed by a series of (Short Message Service) SMS texts delivered twice daily to student’s mobile telephones with the content, duration and timing of the messages informed by involvement of students and young people. Conclusions An intervention to improve the oral health of secondary school students through improved tooth brushing was rigorously developed based on behaviour change theory and work with young people, parents and school staff. Further research is needed to evaluate the outcomes and processes involved following the delivery of this intervention. BRIGHT Trial Trial Registration ISRCTN12139369.

Abstract Background Almost one-half of 12–15 year olds living in deprived areas of the UK have dental caries (tooth decay) with few oral health promotion programmes aimed at children of this age. Mobile phone-based interventions such as short messaging service (SMS) interventions have been found effective at changing certain behaviours and improving health outcomes. This protocol describes the BRIGHT Trial, investigating the clinical and cost-effectiveness of a behaviour change intervention—classroom-based session (CBS) embedded in the curriculum and a series of SMS delivered to participants twice daily to remind them to brush their teeth, compared to usual curriculum and no SMS—to reduce the prevalence of dental caries in young people from deprived areas. Objectives To investigate the clinical and cost-effectiveness of a complex intervention to improve the oral health of young people living in deprived areas. Methods/design This is a school-based, assessor-blinded, two-arm cluster-randomised controlled trial with an internal pilot trial. Overall, the trial will involve approximately 5040 11–13 year olds in 42 schools with a 3-year follow-up. The trial will take place in secondary schools in England, Scotland and Wales. The primary outcome is the presence of carious lesions in permanent teeth at 3 years. Secondary outcomes are: number of carious teeth, frequency of twice-daily toothbrushing, plaque levels, gingivitis, child health-related quality of life and oral health-related quality of life. A cost-utility analysis will be conducted. Discussion The findings of the trial have implications for embedding oral health interventions into school curricula guidance produced by national bodies, including departments for education and dental public health and guideline-development organisations. Trial registration ISRCTN registry, ISRCTN12139369. Registered on 10 May 2017.

The athletic performance and safety of racehorses is influenced by hoof–surface interactions. This intervention study assessed the effect of eight horseshoe–surface combinations on hoof acceleration patterns at impact and foot-off in 13 galloping Thoroughbred racehorses retired from racing. Aluminium, barefoot, GluShu (aluminium–rubber composite) and steel shoeing conditions were trialled on turf and artificial (Martin Collins Activ-Track) surfaces. Shod conditions were applied across all four hooves. Tri-axial accelerometers (SlamStickX, range ±500 g, sampling rate 5000 Hz) were attached to the dorsal hoof wall (x: medio-lateral, medial = positive; y: along dorsal hoof wall, proximal = positive; and z: perpendicular to hoof wall, dorsal = positive). Linear mixed models assessed whether surface, shoeing condition or stride time influenced maximum (most positive) or minimum (most negative) accelerations in x, y and z directions, using ≥40,691 strides (significance at p < 0.05). Day and horse–rider pair were included as random factors, and stride time was included as a covariate. Collective mean accelerations across x, y and z axes were 22–98 g at impact and 17–89 g at foot-off. The mean stride time was 0.48 ± 0.07 s (mean ±2 SD). Impact accelerations were larger on turf in all directions for forelimbs and hindlimbs (p ≤ 0.015), with the exception of the forelimb z-minimum, and in absolute terms, maximum values were typically double the minimum values. The surface type affected all foot-off accelerations (p ≤ 0.022), with the exception of the hindlimb x-maximum; for example, there was an average increase of 17% in z-maximum across limbs on the artificial track. The shoeing condition influenced all impact and foot-off accelerations in the forelimb and hindlimb datasets (p ≤ 0.024), with the exception of the hindlimb impact y-maximum. Barefoot hooves generally experienced the lowest accelerations. The stride time affected all impact and foot-off accelerations (p < 0.001). Identifying factors influencing hoof vibrations upon landing and hoof motion during propulsion bears implication for injury risk and racing outcomes.

Horseshoes influence how horses' hooves interact with different ground surfaces, during the impact, loading and push-off phases of a stride cycle. Consequently, they impact on the biomechanics of horses' proximal limb segments and upper body. By implication, different shoe and surface combinations could drive changes in the magnitude and stability of movement patterns in horse-jockey dyads. This study aimed to quantify centre of mass (COM) displacements in horse-jockey dyads galloping on turf and artificial tracks in four shoeing conditions: 1) aluminium; 2) barefoot; 3) GluShu; and 4) steel. Thirteen retired racehorses and two jockeys at the British Racing School were recruited for this intervention study. Tri-axial acceleration data were collected close to the COM for the horse (girth) and jockey (kidney-belt), using iPhones (Apple Inc.) equipped with an iOS app (SensorLog, sample rate = 50 Hz). Shoe-surface combinations were tested in a randomized order and horse-jockey pairings remained constant. Tri-axial acceleration data from gallop runs were filtered using bandpass Butterworth filters with cut-off frequencies of 15 Hz and 1 Hz, then integrated for displacement using Matlab. Peak displacement was assessed in both directions (positive 'maxima', negative 'minima') along the cranio-caudal (CC, positive = forwards), medio-lateral (ML, positive = right) and dorso-ventral (DV, positive = up) axes for all strides with frequency ≥2 Hz (mean = 2.06 Hz). Linear mixed-models determined whether surfaces, shoes or shoe-surface interactions (fixed factors) significantly affected the displacement patterns observed, with day, run and horse-jockey pairs included as random factors; significance was set at p

Abstract Background Parental supervised brushing (PSB) when initiated in infancy can lead to long-term protective home-based oral health habits thereby reducing the risk of dental caries. However, PSB is a complex behaviour with many barriers reported by parents hindering its effective implementation. Within the UK, oral health advice is delivered universally to parents by health visitors and their wider teams when children are aged between 9 and 12 months. Nevertheless, there is no standardised intervention or training upon which health visitors can base this advice, and they often lack the specialised knowledge needed to help parents overcome barriers to performing PSB and limiting sugary foods and drinks. Working with health visitors and parents of children aged 9–24 months, we have co-designed oral health training and resources (Health Visitors delivering Advice in Britain on Infant Toothbrushing (HABIT) intervention) to be used by health visitors and their wider teams when providing parents of children aged 9–12 months with oral health advice. The aim of the study is to explore the acceptability of the HABIT intervention to parents and health visitors, to examine the mechanism of action and develop suitable objective measures of PSB. Methods/design Six health visitors working in a deprived city in the UK will be provided with training on how to use the HABIT intervention. Health visitors will then each deliver the intervention to five parents of children aged 9–12 months. The research team will collect measures of PSB and dietary behaviours before and at 2 weeks and 3 months after the HABIT intervention. Acceptability of the HABIT intervention to health visitors will be explored through semi-structured diaries completed after each visit and a focus group discussion after delivery to all parents. Acceptability of the HABIT intervention and mechanism of action will be explored briefly during each home visit with parents and in greater details in 20–25 qualitative interviews after the completion of data collection. The utility of three objective measures of PSB will be compared with each other and with parental-self reports. Discussion This study will provide essential information to inform the design of a definitive cluster randomised controlled trial. Trial registration There is no database for early phase studies such as ours.

Understanding the effect of horseshoe–surface combinations on hoof kinematics at gallop is relevant for optimising performance and minimising injury in racehorse–jockey dyads. This intervention study assessed hoof breakover duration in Thoroughbred ex-racehorses from the British Racing School galloping on turf and artificial tracks in four shoeing conditions: aluminium, barefoot, aluminium–rubber composite (GluShu) and steel. Shoe–surface combinations were tested in a randomized order and horse–jockey pairings (n = 14) remained constant. High-speed video cameras (Sony DSC-RX100M5) filmed the hoof-ground interactions at 1000 frames per second. The time taken for a hoof marker wand fixed to the lateral hoof wall to rotate through an angle of 90 degrees during 384 breakover events was quantified using Tracker software. Data were collected for leading and non-leading forelimbs and hindlimbs, at gallop speeds ranging from 23–56 km h−1. Linear mixed-models assessed whether speed, surface, shoeing condition and any interaction between these parameters (fixed factors) significantly affected breakover duration. Day and horse–jockey pair were included as random factors and speed was included as a covariate. The significance threshold was set at p < 0.05. For all limbs, breakover times decreased as gallop speed increased (p < 0.0005), although a greater relative reduction in breakover duration for hindlimbs was apparent beyond approximately 45 km h−1. Breakover duration was longer on turf compared to the artificial surface (p ≤ 0.04). In the non-leading hindlimb only, breakover duration was affected by shoeing condition (p = 0.025) and an interaction between shoeing condition and speed (p = 0.023). This work demonstrates that speed, ground surface and shoeing condition are important factors influencing the galloping gait of the Thoroughbred racehorse.

Introduction: Neighbourhood contextual factors such as accessibility of food shops and green spaces are associated with adult bodyweight but not necessarily weight-related behaviours. Whether these associations are replicated amongst children is unknown.Aim: To understand which aspects of childrens' neighbourhoods are associated with unhealthy weight and weight-related behaviours.Methods: Individual-level data for children from the 2006/7 New Zealand Health Survey (of Body Mass Index (BMI), dietary indicators and socioeconomic variables) were linked with geographic level data on neighbourhood deprivation, rural/urban status, percentage of community engaged in active travel, access to green space, food shops and sports/leisure facilities. Logistic regression models were fitted for measures of BMI and weight-related behaviours; sugar sweetened beverage (SSB) consumption; fast-food consumption; and television viewing. Results:Increased Ccommunity engagement in active transport was, counterintuitively, the only neighbourhood contextual factor associated with unhealthy weight amongst children. After adjustment for socioeconomic and environmental variables, greater access to green space appeared to have a protective effect on SSB consumption and neighbourhood deprivation was associated with all three unhealthy weight-related behaviours (SSB and fast-food consumption and television viewing). Conclusions: Although further research is needed, evidence from the current study suggests that a repertoire of health promotion interventions and policies to change unhealthy weight- related behaviours in high deprivation neighbourhoods may be required to address childhood obesity.

Abstract Objective: To detect spatial clusters of high infant mortality rates in New Zealand for Māori and non‐Māori populations and verify if these clusters are stable over a certain time period (1995–2008) and similar between the two populations. Method: We applied the Kulldorff's spatial scan statistics on data collected by New Zealand Ministry of Health (1995 to 2008) at the territorial local authorities (TLA) level. Kappa coefficient was used to assess the concordance between clusters obtained for Māori and non‐Māori populations. T‐test analyses were conducted to identify associations between spatial clusters and two predictors (population density and deprivation score). Results: There are some significant spatial clusters of infant mortality in New Zealand for both Māori and Non‐Māori. The concordance of the cluster locations between the two populations is strong (kappa=0.77). Unsurprisingly, infant mortality clusters for both Māori and Non‐Māori are associated with the deprivation score. The population density predictor is only significantly and positively associated with clusters obtained for the non‐Māori population. After controlling for deprivation the presence of spatial clusters is all but eliminated. Conclusions: Infant mortality patterns are geographically similar for both Māori and Non‐Māori. However, there are differences geographically between the two populations after accounting for deprivation. Implications: Health services that can affect infant mortality should be aware of the geographical differences across NZ. Deprivation is an important factor in explaining infant mortality rates and policies that ameliorate its effects should be pursued, as it is the major determinant of the geographical pattern of infant mortality in NZ.

Abstract Objective: To investigate whether travel time or distance to the nearest general practitioner (GP) and/or cancer centre accounts for the ethnic differences in cervical cancer screening, stage at diagnosis and mortality in New Zealand (NZ). Methods: The study involved 1,594 cervical cancer cases registered between 1994 and 2005. Travel time and distance to the GP and cancer centre were estimated using a Geographical Information System. Results: Adjustment for travel time or distance made almost no difference to ethnic differences in screening rates. Adjustment for travel time reduced the excess risk for late‐stage diagnosis in Māori (the odds ratio (OR) reduced from 2.71 (95%CI 1.98–3.72) to 2.59 (1.88–3.56), a 7% decrease) and 33% in Pacific (the OR reduced from 1.39 (0.76–2.54) to 1.26 (0.68–2.33)) women. Adjustment for travel time reduced the excess risk for mortality by 3% in Māori (the hazard ratio (HR) reduced from 1.59 (1.21–2.08) to 1.57 (1.19–2.06)) and 13% in Pacific (the HR reduced from 1.92 (1.20–3.08) to 1.80 (1.11–2.91)) women. Similar findings were observed when using travel distance rather than travel time. Conclusions: Travel time and distance are only weakly associated with cervical cancer screening, stage at diagnosis and mortality in NZ. However, travel time may account for a small proportion of the ethnic differences in stage at diagnosis, and to a lesser extent mortality, particularly for Pacific women. Implications: The findings suggest that there may be ethnic variations in access to treatment or treatment quality, which may be related to travel time.

Abstract Objective: To examine the association between geographic access to alcohol outlets and serious violent crime in New Zealand. Methods: A national study of alcohol outlet access and serious violent crime used a cross‐sectional ecological analysis. Serious violence offences recorded between 2005 and 2007 were aggregated for 286 police station areas. Using Geographical Information Systems (GIS), 9,320 licensed premises were geocoded and road travel distances to the closest alcohol outlet type/category were calculated for each area. Negative binomial regression models measured the association between the distance to the closest alcohol outlet and the number of serious violent offences in each police station area, controlling for area‐level measures of social deprivation, Māori population, young males 15–29 years and population density. Results: There were significant negative associations between distance (access) to licensed outlets and the incidence of serious violent offences with greater levels of violent offending recorded in areas with close access to any licensed premises compared to those areas with least access (IRR 1.5, 95% CI 1.10–2.03); with on‐licensed premises (IRR 1.6, 95% CI 1.16–2.08); and off‐licensed premises (IRR 1.4, 95% CI 1.05–1.93). Conclusion: Having greater geographic access to alcohol outlets was associated with increased levels of serious violent offending across study areas. Implications: Alcohol availability and access promoted under the current liberalised licensing regime are important contextual determinants of alcohol‐related harm within New Zealand communities.

The relationship between achievement and feedback and the fact that effective feedback improves achievement is well documented (Taylor and McCormack, 2004; Hattie, 2007). This is especially true of written feedback.àHowever in art and design education feedback will take place in an often emotionally charged face-to-face meeting where verbal criticism, both negative and positive, takes place in front of an audience. The forum for this feedback in art education is the Group Crit (Crit, Art Crit, or Group Critique) at which students are expected to present and perform. It is the studentsââ¬â¢ reception and perception of this oral feedback in todayââ¬â¢s quality-focused context, which is at the heart of this study. This article presents a study into the impact of verbal feedback on achievement in art and design education via a survey taken amongst 60 undergraduate art and design students, at the University of Institution in 2009/10. The survey collected both quantitative and qualitative responses and identified a fundamentally emotional and fear-focused perception of the Group Crit, one opposed to its supportive and bespoke dynamic intentions. A stress factor (Pope, 2005; Anthony, 1991) is created when personalised feedback is perceived as a negative (critical) reflection on the student performance (at the Crit), their self worth and esteem and not the work presented. Criticism, and by implication feedback, is perceived as negative, personal and subjective and fraught with contradiction and loss of ââ¬Ërespectââ¬â¢ - in opposition to the studentsââ¬â¢ previous prescriptive and ââ¬Ëobjectiveââ¬â¢ educational experiences.

Humans need to be on their toes when interacting with competitive others to avoid being taken advantage of. Too much caution out of context can, however, be detrimental and produce false beliefs of intended harm. Here, we offer a formal account of this phenomenon through the lens of Theory of Mind. We simulate agents of different depths of mentalizing within a simple game theoretic paradigm and show how, if aligned well, deep recursive mentalization gives rise to both successful deception as well as reasonable skepticism. However, we also show that if a self is mentalizing too deeply – hyper-mentalizing – false beliefs arise that a partner is trying to trick them maliciously, resulting in a material loss to the self. Importantly, we show that this is only true when hypermentalizing agents believe observed actions are generated intentionally. This theory offers a potential cognitive mechanism for suspiciousness, paranoia, and conspiratorial ideation. Rather than a deficit in Theory of Mind, paranoia may arise from the application of overly strategic thinking to ingenuous behaviour. Author Summary Interacting competitively requires vigilance to avoid deception. However, excessive caution can have adverse effects, stemming from false beliefs of intentional harm. So far there is no formal cognitive account of what may cause this suspiciousness. Here we present an examination of this phenomenon through the lens of Theory of Mind – the cognitive ability to consider the beliefs, intentions, and desires of others. By simulating interacting computer agents we illustrate how well-aligned agents can give rise to successful deception and justified skepticism. Crucially, we also reveal that overly cautious agents develop false beliefs that an ingenuous partner is attempting malicious trickery, leading to tangible losses. As well as formally defining a plausible mechanism for suspiciousness, paranoia, and conspiratorial thinking, our theory indicates that rather than a deficit in Theory of Mind, paranoia may involve an over-application of strategy to genuine behaviour.

Abstract Unavoidable stress can lead to perceived lack of control and learned helplessness, a risk factor for depression. Avoiding punishment and gaining rewards involve updating the values of actions based on experience. Such updating is however useful only if action values are sufficiently stable, something that a lack of control may impair. We examined whether self-reported stress uncontrollability during the first wave of the COVID-19 pandemic predicted impaired reward-learning. In a preregistered study during the first-wave of the COVID-19 pandemic, we used self-reported measures of depression, anxiety, uncontrollable stress, and COVID-19 risk from 427 online participants to predict performance in a three-armed-bandit probabilistic reward learning task. As hypothesised, uncontrollable stress predicted impaired learning, and a greater proportion of probabilistic errors following negative feedback for correct choices, an effect mediated by state anxiety. A parameter from the best-fitting hidden Markov model that estimates expected beliefs that the identity of the optimal choice will shift across images, mediated effects of state anxiety on probabilistic errors and learning deficits. Our findings show that following uncontrollable stress, anxiety promotes an overly volatile representation of the reward-structure of uncertain environments, impairing reward attainment, which is a potential path to anhedonia in depression.

Some aspects of cognition are more taxing than others. Accordingly, many people will avoid cognitively demanding tasks in favor of simpler alternatives. Which components of these tasks are costly, and how much, remains unknown. Here, we use a novel task design in which subjects request wages for completing cognitive tasks and a computational modeling procedure that decomposes their wages into the costs driving them. Using working memory as a test case, our approach revealed that gating new information into memory and protecting against interference are costly. Critically, other factors, like memory load, appeared less costly. Other key factors which may drive effort costs, such as error avoidance, had minimal influence on wage requests. Our approach is sensitive to individual differences, and could be used in psychiatric populations to understand the true underlying nature of apparent cognitive deficits.

Summary: In social environments, survival can depend upon inferring and adapting to other agents’ goal-directed behavior. However, it remains unclear how humans achieve this, despite the fact that many decisions must account for complex, dynamic agents acting according to their own goals. Here, we use a predator-prey task (total n = 510) to demonstrate that humans exploit an interactive cognitive map of the social environment to infer other agents’ preferences and simulate their future behavior, providing for flexible, generalizable responses. A model-based inverse reinforcement learning model explained participants’ inferences about threatening agents’ preferences, with participants using this inferred knowledge to enact generalizable, model-based behavioral responses. Using tree-search planning models, we then found that behavior was best explained by a planning algorithm that incorporated simulations of the threat’s goal-directed behavior. Our results indicate that humans use a cognitive map to determine other agents’ preferences, facilitating generalized predictions of their behavior and effective responses.

Abstract We conducted a pilot study of a potential endoscopic alternative to bariatric surgery. We developed a Natural Orifice Transluminal Endoscopic Surgery (NOTES) gastric bypass with controlled bypass limb length using four new devices including a dedicated lumen-apposing metal stent (GJ-LAMS) and pyloric duodenal exclusion device (DED). We evaluated procedural technical success, weight change from baseline, and adverse events in growing Landrace/Large-White pigs through 38 weeks after GJ-LAMS placement. Six pigs (age 2.5 months, mean baseline weight 26.1 ± 2.7 kg) had initial GJ-LAMS placement with controlled bypass limb length, followed by DED placement at 2 weeks. Technical success was 100%. GJ-LAMS migrated in 3 of 6, and DED migrated in 3 of 5 surviving pigs after mucosal abrasion. One pig died by Day 94. At 38 weeks, necropsy showed 100–240 cm limb length except for one at 760 cm. Weight gain was significantly lower in the pigs that underwent endoscopic bypass procedures compared to expected weight for age. This first survival study of a fully endoscopic controlled bypass length gastrojejunostomy with duodenal exclusion in a growing porcine model showed high technical success but significant adverse events. Future studies will include procedural and device optimizations and comparison to a control group.

Humans can implicitly learn complex perceptuo-motor skills over the course of large numbers of trials. This likely depends on our becoming better able to take advantage of ever richer and temporally deeper predictive relationships in the environment. Here, we offer a novel characterization of this process, fitting a non-parametric, hierarchical Bayesian sequence model to the reaction times of human participants' responses over ten sessions, each comprising thousands of trials, in a serial reaction time task involving higher-order dependencies. The model, adapted from the domain of language, forgetfully updates trial-by-trial, and seamlessly combines predictive information from shorter and longer windows onto past events, weighing the windows proportionally to their predictive power. As the model implies a posterior over window depths, we were able to determine how, and how many, previous sequence elements influenced individual participants' internal predictions, and how this changed with practice. Already in the first session, the model showed that participants had begun to rely on two previous elements (i.e., trigrams), thereby successfully adapting to the most prominent higher-order structure in the task. The extent to which local statistical fluctuations in trigram frequency influenced participants' responses waned over subsequent sessions, as participants forgot the trigrams less and evidenced skilled performance. By the eighth session, a subset of participants shifted their prior further to consider a context deeper than two previous elements. Finally, participants showed resistance to interference and slow forgetting of the old sequence when it was changed in the final sessions. Model parameters for individual participants covaried appropriately with independent measures of working memory and error characteristics. In sum, the model offers the first principled account of the adaptive complexity and nuanced dynamics of humans' internal sequence representations during long-term implicit skill learning.

Humans adapt decision strategies in response to environmental demands. Here the authors show that decisions in a virtual foraging task can be modelled based on perceived patch value, which includes reward, competition and threat, and is associated with activity in ventromedial prefrontal and medial cingulate cortices.

Inferring causes of the good and bad events that we experience is part of the process of building models of our own capabilities and of the world around us. Making such inferences can be difficult because of complex reciprocal relationships between attributions of the causes of particular events, and beliefs about the capabilities and skills that influence our role in bringing them about. Abnormal causal attributions have long been studied in connection with psychiatric disorders, notably depression and paranoia; however, the mechanisms behind attributional inferences and the way they can go awry are not fully understood. We administered a novel, challenging, game of skill to a substantial population of healthy online participants, and collected trial-by-trial time series of both their beliefs about skill and attributions about the causes of the success and failure of real experienced outcomes. We found reciprocal relationships that provide empirical confirmation of the attribution-self representation cycle theory. This highlights the dynamic nature of the processes involved in attribution, and validates a framework for developing and testing computational accounts of attribution-belief interactions.

In evaluating our choices, we often suffer from two tragic relativities. First, when our lives change for the better, we rapidly habituate to the higher standard of living. Second, we cannot escape comparing ourselves to various relative standards. Habituation and comparisons can be very disruptive to decision-making and happiness, and till date, it remains a puzzle why they have come to be a part of cognition in the first place. Here, we present computational evidence that suggests that these features might play an important role in promoting adaptive behavior. Using the framework of reinforcement learning, we explore the benefit of employing a reward function that, in addition to the reward provided by the underlying task, also depends on prior expectations and relative comparisons. We find that while agents equipped with this reward function are less happy, they learn faster and significantly outperform standard reward-based agents in a wide range of environments. Specifically, we find that relative comparisons speed up learning by providing an exploration incentive to the agents, and prior expectations serve as a useful aid to comparisons, especially in sparsely-rewarded and non-stationary environments. Our simulations also reveal potential drawbacks of this reward function and show that agents perform sub-optimally when comparisons are left unchecked and when there are too many similar options. Together, our results help explain why we are prone to becoming trapped in a cycle of never-ending wants and desires, and may shed light on psychopathologies such as depression, materialism, and overconsumption. Author summary Even in favorable circumstances, we often find it hard to remain happy with what we have. One might enjoy a newly bought car for a season, but over time it brings fewer positive feelings and one eventually begins dreaming of the next rewarding thing to pursue. Here, we present a series of computational simulations that suggest these presumable “flaws” might play an important role in promoting adaptive behavior. We explore the value of prior expectations and relative comparisons as a useful reward signal and find that across a wide range of environments, these features help an agent learn faster and adapt better to changes in the environment. Our simulations also highlight scenarios when these relative features can be harmful to decision-making and happiness. Together, our results help explain why we have the propensity to keep wanting more, even if it contributes to depression, materialism, and overconsumption.

Individuals prone to anxiety and depression often report beliefs and make judgements about themselves that are more negative than those reported by others. We use computational modeling of a richly naturalistic task to disentangle the role of negative priors versus negatively biased belief updating and to investigate their association with different dimensions of Internalizing psychopathology. Undergraduate participants first provided profiles for a hypothetical tech internship. They then viewed pairs of other profiles and selected the individual they would prefer to work alongside out of each pair. In a subsequent phase of the experiment, participants made judgments about their relative popularity as hypothetical internship partners both before any feedback and after each of 20 items of feedback revealing whether or not they had been selected as the preferred teammate from a given pairing. Scores on latent factors of general negative affect, anxiety-specific affect and depression-specific affect were estimated using participants' self-report scores on standardized measures of anxiety and depression together with factor loadings from a bifactor analysis conducted previously. Higher scores on the depression-specific factor were linked to more negative prior beliefs but were not associated with differences in belief updating. In contrast, higher scores on the anxiety-specific factor were associated with a negative bias in belief updating but no difference in prior beliefs. These findings indicate that, to at least some extent, distinct processes may impact the formation of belief priors and in-the-moment belief updating and that these processes may be differentially disrupted in depression and anxiety. Future directions for enquiry include examination of the possibility that prior beliefs biases in depression might reflect generalization from prior experiences or global schema whereas belief updating biases in anxiety might be more situationally specific.

Psychological and neural distinctions between the technical concepts of “liking” and “wanting” pose important problems for motivated choice for goods. Why could we “want” something that we do not “like,” or “like” something but be unwilling to exert effort to acquire it? Here, we suggest a framework for answering these questions through the medium of reinforcement learning. We consider “liking” to provide immediate, but preliminary and ultimately cancellable, information about the true, long-run worth of a good. Such initial estimates, viewed through the lens of what is known as potential-based shaping, help solve the temporally complex learning problems faced by animals. What is the distinction between ’liking’ and ’wanting’? Why could we ’want’ something that we do not ’like,’ or ’like’ something but be unwilling to exert effort to acquire it? This Essay argues that the primary hedonic phenomenon called ’liking’ might solve the temporal credit assignment problem for learning that arises when true reinforcement values are available slowly or late.

The replay of task-relevant trajectories is known to contribute to memory consolidation and improved task performance. A wide variety of experimental data show that the content of replayed sequences is highly specific and can be modulated by reward as well as other prominent task variables. However, the rules governing the choice of sequences to be replayed still remain poorly understood. One recent theoretical suggestion is that the prioritization of replay experiences in decision-making problems is based on their effect on the choice of action. We show that this implies that subjects should replay sub-optimal actions that they dysfunctionally choose rather than optimal ones, when, by being forgetful, they experience large amounts of uncertainty in their internal models of the world. We use this to account for recent experimental data demonstrating exactly pessimal replay, fitting model parameters to the individual subjects' choices.

Dopamine is implicated in representing model-free (MF) reward prediction errors a as well as influencing model-based (MB) credit assignment and choice. Putative cooperative interactions between MB and MF systems include a guidance of MF credit assignment by MB inference. Here, we used a double-blind, placebo-controlled, within-subjects design to test an hypothesis that enhancing dopamine levels boosts the guidance of MF credit assignment by MB inference. In line with this, we found that levodopa enhanced guidance of MF credit assignment by MB inference, without impacting MF and MB influences directly. This drug effect correlated negatively with a dopamine-dependent change in purely MB credit assignment, possibly reflecting a trade-off between these two MB components of behavioural control. Our findings of a dopamine boost in MB inference guidance of MF learning highlight a novel DA influence on MB-MF cooperative interactions.

The controllability of our social environment has a profound impact on our behavior and mental health. Nevertheless, neurocomputational mechanisms underlying social controllability remain elusive. Here, 48 participants performed a task where their current choices either did (Controllable), or did not (Uncontrollable), influence partners’ future proposals. Computational modeling revealed that people engaged a mental model of forward thinking (FT; i.e., calculating the downstream effects of current actions) to estimate social controllability in both Controllable and Uncontrollable conditions. A large-scale online replication study (n=1342) supported this finding. Using functional magnetic resonance imaging (n=48), we further demonstrated that the ventromedial prefrontal cortex (vmPFC) computed the projected total values of current actions during forward planning, supporting the neural realization of the forward-thinking model. These findings demonstrate that humans use vmPFC-dependent FT to estimate and exploit social controllability, expanding the role of this neurocomputational mechanism beyond spatial and cognitive contexts.

Summary: Foraging is a common decision problem in natural environments. When new exploitable sites are always available, a simple optimal strategy is to leave a current site when its return falls below a single average reward rate. Here, we examined foraging in a more structured environment, with a limited number of sites that replenished at different rates and had to be revisited. When participants could choose sites, they visited fast-replenishing sites more often, left sites at higher levels of reward, and achieved a higher net reward rate. Decisions to exploit-or-leave a site were best explained with a computational model that included both the average reward rate for the environment and reward information about the unattended sites. This suggests that unattended sites influence leave decisions, in foraging environments where sites can be revisited.

The neurotransmitter Norepinephrine (NE) has been implicated in coding surprise during decision making. Here, the authors demonstrate that this extends to sensory processing: NE release is specific to unexpected events even on extremely rapid time scales and without explicit tracking of probability.

Human confidence tracks current performance, but little is known about the formation of ‘global’ self-performance estimates over longer timescales. Here, the authors show that people use local confidence to form global estimates, but tend to underestimate their performance when feedback is absent.

The reinforcement learning literature suggests decisions are based on a model-free system, operating retrospectively, and a model-based system, operating prospectively. Here, the authors show that a model-based retrospective inference of a reward’s cause, guides model-free credit-assignment.