Explaining differential socioeconomic effects in population health interventions: development and application of a new tool to classify intervention agentic demand.

BACKGROUND: The agentic demand of population health interventions (PHIs) might influence how interventions work. Highly agentic interventions (eg, information campaigns) rely on recipients noticing and responding to the intervention. Resources required for individuals to benefit from highly agentic interventions have a socioeconomical pattern, thus agentic demand might affect intervention effectiveness and equity. Systematic evidence exploring these associations is missing due to the absence of adequate tools to classify agentic demands. We aimed to develop such a tool and test its application. METHODS: Our iterative development process involved: (1) systematic identification of diet and physical activity PHIs; (2) coding of intervention actors and actions; (3) data synthesis; (4) expert qualitative feedback; and (5) reliability assessment. We searched nine databases for articles published between Jan 1, 2010, and Aug 17, 2020. For all included articles, we coded the actors (people required to act within an intervention) and their actions (what they were required to do for the intervention to have its intended effects). We combined these codes for similar intervention types to develop overarching schematic flow chart diagrams used to identify concepts, and we organised these into a draft tool. After expert feedback, and we assessed inter-rater reliability of the final version. We applied the final tool in a proof-of-concept review, extracting studies from three existing equity-focused systematic reviews on tool category, overall intervention effect, and differential socioeconomic effects and visualised findings. FINDINGS: We identified three concepts affecting agentic demands of intervention components: exposure, two levels (how recipients encounter the intervention); mechanism of action, five levels; and engagement, two levels (how recipients respond to the intervention). We then combined these concepts to form 20 categories that grouped together interventions with similar agentic demands. In the review, we applied the tool to 26 PHIs that included 163 components. Intervention components were concentrated in a small number of categories, and their categorisation was related to intervention equity but not to effectiveness. INTERPRETATION: We present a novel tool to classify the agentic demand of PHIs and demonstrate its feasibility within a systematic review. Linking intervention types to their effect on inequalities enables these factors to be considered when designing or selecting interventions. Users of the tool can avoid implementing intervention types that are likely to widen inequalities or implement them alongside counter-strategies to minimise any adverse equity effects. Applying this tool within future research, policy, and practice to design, select, evaluate, and synthesise evidence from PHIs has the potential to advance our understanding of how interventions work and their effect on socioeconomic inequalities. FUNDING: Public Health Policy Research Unit (PH-PRU), National Institute for Health and Care Research (NIHR) Policy Research Programme.

The physical activity implications of retirement across occupational activity groups.

Retirement is an important later life transition which may represent a critical period for physical activity in older age. Past findings on the association between retirement and physical activity are inconclusive and there is some evidence that the physical activity implications of retirement may differ by occupational activity level. This study used data from waves 4-9 (June 2008-July 2019) of the English Longitudinal Study on Aging to evaluate whether there is an association between retirement and physical activity, and whether this varies across occupational activity groups. Retirement was associated with a significant increase in physical activity (n = 10,693; ß: 0.602 METhrs/wk. [95% CI: 0.490, 0.713], p < 0.001). There were significant interactions between retirement and past occupational activity level (n = 5109; X2 (3)=32.59, p < 0.001), such that people retiring from sedentary or standing occupations experienced a significant increase in physical activity with retirement but retirement from an occupation involving heavy manual labour was associated with a decrease in physical activity. This study quantified the importance of retirement for later life physical activity. With demographic aging, the population health importance of later life physical activity will likely become more important. These findings should inform the design of public health interventions to increase physical activity around the retirement transition.

Associations of Public Transportation Use With Cardiometabolic Health: A Systematic Review and Meta-Analysis.

Public transportation provides an opportunity to incorporate physical activity into journeys, but potential health impacts have not been systematically examined. We searched the literature for articles on public transportation and health published through December 2017 using Google (Google Inc., Mountain View, California), 5 medical databases, and 1 transportation-related database. We identified longitudinal studies which examined associations between public transportation and cardiometabolic health (including adiposity, type 2 diabetes mellitus, and cardiovascular disease). We assessed study quality using the Newcastle-Ottawa Scale for cohort studies and performed meta-analyses where possible. Ten studies were identified, 7 investigating use of public transportation and 3 examining proximity to public transportation. Seven studies used individual-level data on changes in body mass index (BMI; weight (kg)/height (m)2), with objective outcomes being measured in 6 studies. Study follow-up ranged from 1 year to 10 years, and 3 studies adjusted for nontransportation physical activity. We found a consistent association between use of public transportation and lower BMI. Meta-analysis of data from 5 comparable studies found that switching from automobile use to public transportation was associated with lower BMI (-0.30 units, 95% confidence interval: -0.47, -0.14). Few studies have investigated associations between public transportation use and nonadiposity outcomes. These findings suggest that sustainable urban design which promotes public transportation use may produce modest reductions in population BMI.

Sedentary behaviour and risk of all-cause, cardiovascular and cancer mortality, and incident type 2 diabetes: a systematic review and dose response meta-analysis.

PURPOSE:  To estimate the strength and shape of the dose-response relationship between sedentary behaviour and all-cause, cardiovascular disease (CVD) and cancer mortality, and incident type 2 diabetes (T2D), adjusted for physical activity (PA). Data Sources: Pubmed, Web of Knowledge, Medline, Embase, Cochrane Library and Google Scholar (through September-2016); reference lists. Study Selection: Prospective studies reporting associations between total daily sedentary time or TV viewing time, and ≥ one outcome of interest. Data Extraction: Two independent reviewers extracted data, study quality was assessed; corresponding authors were approached where needed. Data Synthesis: Thirty-four studies (1,331,468 unique participants; good study quality) covering 8 exposure-outcome combinations were included. For total sedentary behaviour, the PA-adjusted relationship was non-linear for all-cause mortality (RR per 1 h/day: were 1.01 (1.00-1.01) ≤ 8 h/day; 1.04 (1.03-1.05) > 8 h/day of exposure), and for CVD mortality (1.01 (0.99-1.02) ≤ 6 h/day; 1.04 (1.03-1.04) > 6 h/day). The association was linear (1.01 (1.00-1.01)) with T2D and non-significant with cancer mortality. Stronger PA-adjusted associations were found for TV viewing (h/day); non-linear for all-cause mortality (1.03 (1.01-1.04) ≤ 3.5 h/day; 1.06 (1.05-1.08) > 3.5 h/day) and for CVD mortality (1.02 (0.99-1.04) ≤ 4 h/day; 1.08 (1.05-1.12) > 4 h/day). Associations with cancer mortality (1.03 (1.02-1.04)) and T2D were linear (1.09 (1.07-1.12)). CONCLUSIONS:  Independent of PA, total sitting and TV viewing time are associated with greater risk for several major chronic disease outcomes. For all-cause and CVD mortality, a threshold of 6-8 h/day of total sitting and 3-4 h/day of TV viewing was identified, above which the risk is increased.

Parasagittal vertex clots on head CT in infants with subdural hemorrhage as a predictor for abusive head trauma.

BACKGROUND: Abusive head trauma (AHT) is the most common cause of subdural hemorrhage (SDH) in infants younger than 12 months old. Clot formation in the parasagittal vertex seen on imaging has been associated with SDH due to AHT. There have been very few studies regarding these findings; to our knowledge, no studies including controls have been performed. OBJECTIVE: To describe parasagittal vertex clots on head computed tomography (CT) in infants with SDH and AHT compared to patients with SDH and accidental trauma, and to evaluate for parasagittal vertex clots in the absence of SDH in the setting of known accidental head trauma. MATERIALS AND METHODS: All infants younger than 12 months old with SDH present on CT scan were retrospectively identified from 2004 to 2014. Blinded, independent review of all CT scans for clot formation at the parasagittal vertex was performed by a pediatric neuroradiologist. RESULTS: Ninety-nine patients were eligible for analysis. Mean age was 4 months. Fifty-seven (57.6%) were male. Fifty-five (55.6%) patients were identified as having AHT and 22 (22.2%) had accidental trauma. Forty-five (81.2%) patients with AHT had parasagittal vertex clots present on CT scan compared to 8 (36.4%) patients with accidental trauma. Compared to patients without parasagittal vertex clots, those with parasagittal vertex clots were more likely to have AHT (66.2% vs. 32.3%, P=0.001), no known mechanism of injury (69.1% vs. 32.3%, P=0.015), retinal hemorrhage (75% vs. 35.5%, P=0.002) and hypoxic-ischemic changes (25% vs. 0%, P=0.002). Patients with parasagittal vertex clots have eight times the odds of AHT compared to patients without parasagittal vertex clots. Age-matched control patients who underwent head CT scan due to a history of accidental head injury without SDH were identified (n=87); no patient in the control group had parasagittal vertex clots. CONCLUSION: The finding of parasagittal vertex clots on CT scans should raise suspicion for abuse and prompt further investigation, especially in the setting of no known, uncertain or inconsistent mechanism of injury.

Cranial Rhabdomyosarcoma Masquerading as Infectious Mastoiditis: Case Report and Literature Review.

BACKGROUND: Rhabdomyosarcoma originating in the mastoid is rare and may be misdiagnosed as an infectious mastoiditis due to overlapping clinical and imaging features. We aimed to identify distinguishing characteristics to facilitate earlier diagnosis and treatment. METHOD: Here we describe a case report and a systematic review of 23 reports describing previous cases of mastoid rhabdomyosarcoma. We compare these patients to a systematic review of patients with infectious mastoiditis and identify distinguishing clinical features. RESULTS: A total of 43 patients with rhabdomyosarcoma of the mastoid were identified and compared with patients with mastoiditis. Rhabdomyosarcoma patients were more likely to present with a mass (86%) or cranial nerve dysfunction (83.7%), while mastoiditis patients were more likely to have fever (72.4%), pain (48.2%), and present at a younger age (4.4 vs. 6.1 years). The average lifespan with rhabdomyosarcoma of the mastoid was 7.1 months after diagnosis, with 41.7% of patients alive at the time of report. CONCLUSIONS: Based on abstracted and aggregated information, we identified unique features observed more frequently in each of rhabdomyosarcoma and mastoiditis. These predictive features allow for the differentiation of each diagnosis and avoid the delay of proper treatment.

Neuroradiographic findings in 22q11.2 deletion syndrome.

22q11.2 deletion syndrome (22q11.2DS) is a common genetic disorder with enormous phenotypic heterogeneity. Despite the established prevalence of developmental and neuropsychiatric issues in this syndrome, its neuroanatomical correlates are not as well understood. A retrospective chart review was performed on 111 patients diagnosed with 22q11.2DS. Of the 111 patients, 24 with genetically confirmed 22q11.2 deletion and brain MRI or MRA were included in this study. The most common indications for imaging were unexplained developmental delay (6/24), seizures of unknown etiology (5/24), and unilateral weakness (3/24). More than half (13/24) of the patients had significant radiographic findings, including persistent cavum septi pellucidi and/or cavum vergae (8/24), aberrant cortical veins (6/24), polymicrogyria or cortical dysplasia (4/24), inner ear deformities (3/24), hypoplastic internal carotid artery (2/24), and hypoplastic cerebellum (1/24). These findings reveal the types and frequencies of brain malformations in this case series, and suggest that the prevalence of neuroanatomical abnormalities in 22q11.2DS may be underestimated. Understanding indications for imaging and frequently encountered brain malformations will result in early diagnosis and intervention in an effort to optimize patient outcomes.

PD0332991 (palbociclib) for treatment of pediatric intracranial growing teratoma syndrome.

Growing teratoma syndrome is characterized by growth of mature teratoma elements of a mixed germ cell tumor despite resolution of immature/malignant elements with administration of chemotherapy. Surgical resection is the only known cure for growing teratoma syndrome but in the brain, complete resection may be impossible. In these instances, mature teratoma, although histologically benign, may be fatal. In this report, we present the case of a child with a large, rapidly growing, unresectable pineal region growing teratoma. PD0332991 was administered with stabilization of the solid, enhancing components of the mass. Minimal adverse effects were noted.

The Effects of TMR® Fab 6 on Hamstring Flexibility in Healthy Subjects; An Exploratory Observational Investigation.

Background: Stretching programs are designed to improve hamstring flexibility by attempting to mechanically increase the length of the target tissue. However, other manual treatment approaches such as those utilized in Total Motion Release (TMR®), could be beneficial by identifying body asymmetries to assess and treat soft tissue impairments leading to diminished extensibility. Purpose: The purpose of this study was to determine the effectiveness of the TMR® Fab 6 assessment and treatment to increase hamstring flexibility in healthy participants following one session of TMR®. Study Design: Observational Cohort study. Methods: A convenience sample of 20 healthy participants (10 males, 10 females) were recruited from three institutions. Following collection of demographic information and a brief medical history, each participant performed a five minute warm-up on the stationary bike at a moderate intensity (80-90 RPMs) followed immediately by the bilateral performance of the Active Knee Extension Test (AKET) and Passive Straight Leg Raise (PSLR) to assess hamstring muscle length. Participants were randomly placed in the TMR® or control group. The TMR® group completed the "Fab 6" evaluation and treatment, while the control group performed one repetition of standing active hip flexion every 30-seconds for 15-minutes with both knees in full extension. Upon completion of treatment, control and TMR® groups were immediately re-evaluated on the AKET and the PSLR in the same order and fashion as baseline testing. Participants were asked to return in 24-hours for the same objective measurements as previously described. Results: A significant time by group interaction was identified across all variables (p ≤ 0.001) for AKET and PSLR except the PSLR preferred leg from post-treatment to 24hr follow-up. The most significant increase in the AKET occurred in the TMR® group between baseline and post-treatment of the non-preferred leg (12.15°±2.94) when compared to the control group (7.15°±1.56). Conclusion: The results of the study suggest that implementing a regionally interdependent treatment approach like TMR® results in significant improvements in hamstring extensibility and hip ROM compared to the control group. Level of evidence: 3.

Equity impacts of cycling investment in England: A natural experimental study using longitudinally linked individual-level Census data.

Background: Cycling is beneficial for health and the environment but the evidence on the overall and differential impacts of interventions to promote cycling is limited. Here we assess the equity impacts of funding awarded to support cycling in 18 urban areas between 2005 and 2011. Methods: We used longitudinally linked 2001 and 2011 census data from 25,747 individuals in the Office for National Statistics Longitudinal Study of England and Wales. Logistic regression was used to assess the impacts of funding on commute mode as the interaction between time and area (intervention/comparison) in individual-level difference-in-difference analyses, adjusting for a range of potential confounding factors. Differential impacts were examined by age, gender, education and area-level deprivation, and uptake and maintenance of cycling were examined separately. Results: Difference-in-difference analyses showed no intervention impact on cycle commuting prevalence in the whole sample (AOR = 1.08; 95% CI 0.92, 1.26) or among men (AOR = 0.91; 95% CI 0.76, 1.10) but found an intervention effect among women (AOR = 1.56; 95% CI 1.16, 2.10). The intervention promoted uptake of cycling commuting in women (AOR = 2.13; 95% CI 1.56, 2.91) but not men (AOR = 1.19; 95% CI 0.93, 1.51). Differences in intervention effects by age, education and area-level deprivation were less consistent and more modest in magnitude. Conclusions: Living in an intervention area was associated with greater uptake of cycle commuting among women but not men. Potential gender differences in the determinants of transport mode choice should be considered in the design and evaluation of future interventions to promote cycling.

Pornography, religion, and the happiness gap: does pornography impact the actively religious differently?

Club good models developed by economists suggest that the club provides a benefit to members by fostering the provision of semi-public goods. In the case of religion, churches create enforcement mechanisms to reduce free riding. Consequently, the psychic costs of deviant activity should be higher for individuals who belong to religious groups with strong social norms. Data from the General Social Survey are used to examine whether the cost of using pornography is greater for the more religiously involved. We measure the cost of using pornography as the happiness gap or the gap between the average happiness reported by individuals who do and individuals who do not report using pornography. The happiness gap is larger for individuals who regularly attend church and who belong to religious groups with strong attitudes against pornography.

Shifting towards healthier transport: carrots or sticks? Systematic review and meta-analysis of population-level interventions.

BACKGROUND: Promoting active travel can be beneficial for both health and the environment. However, evidence about the most effective strategies is inconsistent. We aimed to compare the effectiveness of interventions with positive (ie, carrot), negative (ie, stick), or a combination of strategies on changing population-level travel behaviour. We also aimed to identify which intervention functions, or mechanisms of how interventions seek to alter behaviour (eg, by addressing safety or accessibility), affect transport outcomes. METHODS: For this systematic review and meta-analysis, we searched eight online databases for studies published before March 28, 2022: Web of Science, MEDLINE, Scopus, Applied Social Sciences Index and Abstracts, Global Health, PsycINFO, CINAHL, and Transport Research International Documentation. We did not restrict searches by language or publication date. We included controlled before-and-after studies of population-level interventions and travel behaviours (ie, driving, public transport, walking, and cycling) from adults in the general population. We categorised interventions according to their function. Depending on whether gains or losses due to intervention function could occur, we classified interventions as carrot (eg, new bike-share programmes), stick (eg, congestion charging), or combined carrot-and-stick interventions (eg, pedestrianising areas by use of reallocated parking space). We used harvest plots to summarise the findings and guide narrative synthesis. Where possible, we converted outcomes into standardised mean differences and did random-effects meta-analyses. FINDINGS: From 38 916 records screened, 102 reports describing 121 interventions met the inclusion criteria. 79 interventions were carrots, 22 were carrot-and-sticks, and 20 were sticks. Results for carrot interventions were less consistent than for stick or combined interventions. Findings from the meta-analysis (64 reports describing 67 interventions) agreed with those in the narrative synthesis; although effects were statistically non-significant, for driving outcomes, interventions with stick strategies (standardised mean difference [SMD] -0·17, 95% CI -0·36 to 0·02) and combined carrot-and-stick strategies (-0·13, -0·47 to 0·20) had point estimates of greater magnitude than those for interventions with carrot strategies (-0·10, -0·23 to 0·03). Likewise, for active travel outcomes, combined carrot-and-stick strategies had a higher point estimate (0·33, -0·01 to 0·68) compared with carrot interventions (0·08, -0·05 to 0·21). Functions thought to change behaviour using financial means were effective at decreasing driving behaviour, whereas those improving access, safety, and space were effective for increasing active travel outcomes. INTERPRETATION: This Article found that, although transport interventions with only positive strategies are more commonly evaluated, interventions that combine both positive and negative strategies might be more effective at encouraging alternatives to driving at the population level. Further research is needed for interventions involving a stick strategy, which remain less widely implemented or well studied than those with only carrot strategies. FUNDING: Medical Research Council, Cambridge Trust.

Evaluation of a Pharmacist-Driven Pediatric Dose Rounding Protocol.

OBJECTIVE: Medication errors are 3 times more likely to occur in pediatric populations due to calculation and rounding errors. The objective of this study was to determine the effect of a pharmacist-driven pediatric dose rounding protocol on the dose rounding of medications, measurable volumes of inpatient and discharge prescriptions, and potential cost savings. METHODS: This single center, quasi-experimental study evaluated patients younger than or equal to 18 years of age prescribed intravenous or enteral liquid medications during an inpatient, observation, or emergency department encounter. The primary outcome of rate of measurable dose volumes was evaluated pre- and post-implementation of the protocol. Secondary outcomes, including the number of discharge prescriptions affected by pharmacist dose rounding, an evaluation of protocol effect, and prescriptions dose rounded to limit the number of packages per dose, were evaluated using a cross-sectional analysis of the post-group. RESULTS: Four hundred seventy-seven patients and 1060 medications were evaluated in a 1-month period. The rate of measurable volumes increased from 72% to 93% in the post-group (p = 0.0001). In the post-group, 197 patients had 313 medications dose rounded by pharmacists per protocol. Of the 55 discharge medications in the post-group, 21 prescriptions (38%) matched inpatient orders that had been dose rounded by pharmacists. Twenty-four medications were rounded down to a whole package size resulting in an estimated cost savings of $117 (approximately $1400 per year). CONCLUSIONS: Implementation of a pharmacist-driven dose rounding protocol significantly increased the rate of measurable volumes administered to pediatric patients at our institution.

N3-alkylation during formation of quinazolin-4-ones from condensation of anthranilamides and orthoamides.

Dimethylformamide dimethylacetal (DMFDMA) is widely used as a source of electrophilic one-carbon units at the formate oxidation level; however, electrophilic methylation with this reagent is previously unreported. Reaction of anthranilamide with DMFDMA at 150 °C for short periods gives mainly quinazolin-4-one. However, prolonged reaction with dimethylformamide di(primary-alkyl)acetals leads to subsequent alkylation at N(3). 3-Substituted anthranilamides give 8-substituted 3-alkylquinazolin-4-ones. Condensation of anthranilamides with dimethylacetamide dimethylacetal provides 2,3-dimethylquinazolin-4-ones. In these reactions, the source of the N(3)-alkyl group is the O-alkyl group of the orthoamides. By contrast, reaction with the more sterically crowded dimethylformamide di(isopropyl)acetal diverts the alkylation to the oxygen, giving 4-isopropoxyquinazolines, along with N(3)-methylquinazolin-4-ones where the methyl is derived from N-Me of the orthoamides. Reaction of anthranilamide with the highly sterically demanding dimethylformamide di(t-butyl)acetal gives largely quinazolin-4-one, whereas dimethylformamide di(neopentyl)acetal forms a mixture of quinazolin-4-one and N(3)-methylquinazolin-4-one. The observations are rationalised in terms of formation of intermediate cationic electrophiles (alkoxymethylidene-N,N-dimethylammonium) by thermal elimination of the corresponding alkoxide from the orthoamides. These are the first observations of orthoamides as direct alkylating agents.

Cognitive Neuroscience Meets the Community of Knowledge.

Cognitive neuroscience seeks to discover the biological foundations of the human mind. One goal is to explain how mental operations are generated by the information processing architecture of the human brain. Our aim is to assess whether this is a well-defined objective. Our contention will be that it is not because the information processing of any given individual is not contained entirely within that individual's brain. Rather, it typically includes components situated in the heads of others, in addition to being distributed across parts of the individual's body and physical environment. Our focus here will be on cognition distributed across individuals, or on what we call the "community of knowledge," the challenge that poses for reduction of cognition to neurobiology and the contribution of cognitive neuroscience to the study of communal processes.

Integrating neuroimaging biomarkers into the multicentre, high-dose erythropoietin for asphyxia and encephalopathy (HEAL) trial: rationale, protocol and harmonisation.

INTRODUCTION: MRI and MR spectroscopy (MRS) provide early biomarkers of brain injury and treatment response in neonates with hypoxic-ischaemic encephalopathy). Still, there are challenges to incorporating neuroimaging biomarkers into multisite randomised controlled trials. In this paper, we provide the rationale for incorporating MRI and MRS biomarkers into the multisite, phase III high-dose erythropoietin for asphyxia and encephalopathy (HEAL) Trial, the MRI/S protocol and describe the strategies used for harmonisation across multiple MRI platforms. METHODS AND ANALYSIS: Neonates with moderate or severe encephalopathy enrolled in the multisite HEAL trial undergo MRI and MRS between 96 and 144 hours of age using standardised neuroimaging protocols. MRI and MRS data are processed centrally and used to determine a brain injury score and quantitative measures of lactate and n-acetylaspartate. Harmonisation is achieved through standardisation-thereby reducing intrasite and intersite variance, real-time quality assurance monitoring and phantom scans. ETHICS AND DISSEMINATION: IRB approval was obtained at each participating site and written consent obtained from parents prior to participation in HEAL. Additional oversight is provided by an National Institutes of Health-appointed data safety monitoring board and medical monitor. TRIAL REGISTRATION NUMBER: NCT02811263; Pre-result.

The social and physical workplace environment and commute mode: A natural experimental study.

Despite strong evidence for health benefits from active travel, levels remain low in many countries. Changes to the physical and social workplace environment might encourage active travel but evaluation has been limited. We explored associations between changes in the physical and social workplace environment and changes in commute mode over one year among 419 participants in the Commuting and Health in Cambridge study. In adjusted analyses, an increase in the presence of one physical characteristic (e.g. bicycle parking or shower facilities) was associated with a 3.3% (95% confidence interval 1.0-5.6) reduction in the proportion of commutes by private motor vehicle and a 4.4% (95% CI 1.2-7.7) increase in the proportion of trips including active modes among men. These associations were not seen in women. A change to a more favourable social environment for walking or cycling among workplace management was associated with an increased proportion of commutes including active modes in women (4.5%, 95% CI 1.4-7.5) but not men. However, in both genders a change to more a favourable social environment for cycling among colleagues was associated with a reduced proportion of commutes by exclusively active modes (-2.8%, 95% CI -5.0 to -0.6). This study provides longitudinal evidence for gender differences in the associations between workplace environment and commute mode. A more supportive physical environment was associated with more active commuting in men, while the social environment appeared to have more complex associations that were stronger among women.

Associations between commute mode and cardiovascular disease, cancer, and all-cause mortality, and cancer incidence, using linked Census data over 25 years in England and Wales: a cohort study.

BACKGROUND: Active travel is increasingly recognised as an important source of physical activity. We aimed to describe associations between commute mode and cardiovascular disease, cancer, and all-cause mortality. METHODS: We analysed data from the Office for National Statistics Longitudinal Study of England and Wales (ONS-LS), which linked data from the Census of England and Wales (henceforth referred to as the Census) for 1991, 2001, and 2011 to mortality and cancer registrations. The cohort included individuals traced in the ONS-LS who were economically active (ie, aged ≥16 years, not retired from work, and not a full-time carer). Commuting by private motorised transport, public transport, walking, and cycling were compared in terms of all-cause mortality, cancer mortality, cardiovascular disease mortality, and cancer incidence, using Cox proportional-hazards models with time-varying covariates. Models were adjusted for age, sex, housing tenure, marital status, ethnicity, university education, car access, population density, socioeconomic classification, Carstairs index quintile, long-term illness, and year entered the study, and were additionally stratified by socioeconomic group. FINDINGS: Between the 1991 Census and the 2011 Census, 784 677 individuals contributed data for at least one Census, of whom 394 746 were included in the ONS-LS and were considered to be economically active working-age individuals. 13 983 people died, 3172 from cardiovascular disease and 6509 from cancer, and there were 20 980 incident cancer cases. In adjusted models, compared with commuting by private motorised vehicle, bicycle commuting was associated with a 20% reduced rate of all-cause mortality (hazard ratio [HR] 0·80, 95% CI 0·73-0·89), a 24% decreased rate of cardiovascular disease mortality (0·76, 0·61-0·93), a 16% lower rate of cancer mortality (0·84, 0·73-0·98), and an 11% reduced rate of incident cancer (0·89, 0·82-0·97). Compared with commuting by private motorised vehicle, rail commuters had a 10% lower rate of all-cause mortality (HR 0·90, 95% CI 0·83-0·97) and a 21% decreased rate of cardiovascular disease mortality (0·79, 0·67-0·94), in addition to a 12% reduced rate of incident cancer (0·88, 0·83-0·94). Walk commuting was associated with 7% lower cancer incidence (HR 0·93, 95% CI 0·89-0·97) Stratified analyses did not indicate differences in associations between socioeconomic groups. INTERPRETATION: Our findings augment existing evidence for the beneficial health effects of physically active commute modes, particularly cycling and train use, and suggest that all socioeconomic groups could benefit. FUNDING: National Institute for Health Research.

The Down syndrome critical region protein RCAN1 regulates long-term potentiation and memory via inhibition of phosphatase signaling.

Regulator of calcineurin 1 (RCAN1/MCIP1/DSCR1) regulates the calmodulin-dependent phosphatase calcineurin. Because it is located on human chromosome 21, RCAN1 has been postulated to contribute to mental retardation in Down syndrome and has been reported to be associated with neuronal degeneration in Alzheimer's disease. The studies herein are the first to assess the role of RCAN1 in memory and synaptic plasticity by examining the behavioral and electrophysiological properties of RCAN1 knock-out mice. These mice exhibit deficits in spatial learning and memory, reduced associative cued memory, and impaired late-phase long-term potentiation (L-LTP), phenotypes similar to those of transgenic mice with increased calcineurin activity. Consistent with this, the RCAN1 knock-out mice display increased enzymatic calcineurin activity, increased abundance of a cleaved calcineurin fragment, and decreased phosphorylation of the calcineurin substrate dopamine and cAMP-regulated phosphoprotein-32. We propose a model in which RCAN1 plays a positive role in L-LTP and memory by constraining phosphatase signaling.

Acquired obstructive hydrocephalus in globoid-cell leukodystrophy.

Acquired obstructive hydrocephalus has developed rarely in patients with globoid cell leukodystrophy. This report describes a 21-month-old female with this concurrence.