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Formularies are used by payers to optimize access and ensure the appropriate use of medications. Lack of follow-up and re-evaluation can lead to outdated formularies that are not reflective of current evidence. Formulary modernization, an approach to re-align formularies with current evidence has proven successful. The Ontario Drug Policy Research Network (ODPRN) launched a framework for conducting comprehensive drug-class reviews. This commentary describes the individual components of this framework and lessons learned through completion of 12 reviews between 2013 and 2016. We present the ODPRN drug-class review of treatments for chronic hepatitis B as a case example to illustrate the components and impact. The incorporation of foundational health technology assessment components such as economic evaluations and knowledge synthesis with contextualizing evidence such as patient and clinician perspectives (through qualitative studies), real-world evidence (through data analytics), and cross-jurisdictional comparisons (through environmental scans and data analytics), successfully developed jurisdictionally specific policy recommendations grounded in up-to-date evidence. The ODPRN framework for conducting comprehensive drug-class reviews is a robust and feasible approach to conduct formulary modernization. This framework allows for actionable and specific policies which are likely to be considered by decision makers. Adoption of similar frameworks in other jurisdictions may improve uptake of evidence-informed policy recommendations.
To assess whether disparities in energy consumption and insufficient energy intake in India have changed over time across socio-economic status (SES).
This cross-sectional, population-based survey study examines the relationship between several SES indicators (i.e. wealth, education, caste, occupation) and energy consumption in India at two time points almost 20 years apart. Household food intake in the last 30 d was assessed in 1993–94 and in 2011–12. Average dietary energy intake per person in the household (e.g. kilocalories) and whether the household consumed less than 80 % of the recommended energy intake (i.e. insufficient energy intake) were calculated. Linear and relative risk regression models were used to estimate the relationship between SES and average energy consumed per day per person and the relative risk of consuming an insufficient amount of energy.
Rural and urban areas across India.
A nationally representative sample of households.
Among rural households, there was a positive association between SES and energy intake across all four SES indicators during both survey years. Similar results were seen for energy insufficiency vis-à-vis recommended energy intake levels. Among urban households, wealth was associated with energy intake and insufficiency at both time points, but there was no educational patterning of energy insufficiency in 2011–12.
Results suggest little overall change in the SES patterning of energy consumption and percentage of households with insufficient energy intake from 1993–94 to 2011–12 in India. Policies in India need to improve energy intake among low-SES households, particularly in rural areas.
In situ nanomechanical testing in (scanning) transmission electron microscopy provides unique opportunities for studying fundamental deformation processes in materials. New insights have been gained by combining advanced imaging techniques with novel preparation methods and controlled loading scenarios. For instance, by applying in situ high-resolution imaging during tensile deformation of metallic nanostructures, the interplay of dislocation slip and surface diffusion has been identified as the key enabler of superplasticity. Evidence for dislocation pinning by hydrogen defect complexes has been provided by in situ imaging under cyclic pillar compression in a tunable gas environment. And, for the very first time, individual dislocations have been moved around in situ in two-dimensional materials by combining micromanipulation and imaging in a scanning electron microscope.
Lowering dietary protein concentration is known to decrease urinary nitrogen (N) losses and increase milk N efficiency in dairy cows, but it may negatively affect animal productivity. Plant-derived essential oils (EO) may alleviate these negative effects by improving the efficiency of rumen fermentation in cows fed reduced feed protein diets. The experiment was conducted to investigate the effects of lowering crude protein (CP) supply alone or in a combination with an EO product on feed intake, milk production and composition, rumen fermentation, total tract digestibility and N utilization in dairy cows. Twenty-one Holstein cows were used in a replicated 3 × 3 Latin square design experiment. Each period consisted of 14 days for adaptation and 14 days for data collection and sampling. Cows were randomly assigned to one of three experimental diets: a 165 g/kg CP diet (control), a 155 g/kg CP diet (LCP) and LCP supplemented with 35 g/day per cow EO (LCPEO). The dry matter (DM) intake was decreased by LCP and LCPEO compared with the control; there was no effect of EO on DM intake. Milk yield and composition and feed efficiency were similar among treatments. Ruminal pH, lactate, ammonia and volatile fatty acids concentrations were not affected by treatment, except increased valerate concentration by LCPEO compared with LCP. The supplementation of EO tended to decrease protozoal counts. The LCP and LCPEO increased total tract digestibility of DM and organic matter and decreased CP digestibility compared with the control. Supplementation with EO did not affect total tract digestibility of dietary nutrients compared with the control or LCP. The LCP and LCPEO decreased urinary and fecal N excretions and increased milk N efficiency; nitrogen losses were not affected by EO. In this study, lowering dietary CP by 10 g/kg decreased urinary and fecal N excretion without affecting productivity. The supplementation of EO to LCP had only minor effects on rumen fermentation and did not affect productivity, digestibility and N excretion in lactating dairy cows.
Although injuries have been linked to worse mental health, little is known about this association among the general population in low- and middle-income countries (LAMICs). This study examined the association between injuries and depression in 40 LAMICs that participated in the World Health Survey.
Cross-sectional information was obtained from 212 039 community-based adults on the past 12-month experience of road traffic and other (non-traffic) injuries and depression, which was assessed using questions based on the World Mental Health Survey version of the Composite International Diagnostic Interview. Multivariable logistic regression analysis and meta-analysis were used to examine associations.
The overall prevalence (95% CI) of past 12-month traffic injury, other injury, and depression was 2.8% (2.6–3.0%), 4.8% (4.6–5.0%) and 7.4% (7.1–7.8%), respectively. The prevalence of traffic injuries [range 0.1% (Ethiopia) to 5.1% (Bangladesh)], and other (non-traffic) injuries [range 0.9% (Myanmar) to 12.1% (Kenya)] varied widely across countries. After adjusting for demographic variables, alcohol consumption and smoking, the pooled OR (95%CI) for depression among individuals experiencing traffic injury based on a meta-analysis was 1.72 (1.48–1.99), and 2.04 (1.85–2.24) for those with other injuries. There was little between-country heterogeneity in the association between either form of injury and depression, although for traffic injuries, significant heterogeneity was observed between groups by country-income level (p = 0.043) where the pooled association was strongest in upper middle-income countries (OR = 2.37) and weakest in low-income countries (OR = 1.46).
Alerting health care providers in LAMICs to the increased risk of worse mental health among injury survivors and establishing effective trauma treatment systems to reduce the detrimental effects of injury should now be prioritised.
Cognitive deficits are an important factor in the pathogenesis of psychosis. Subjective cognitive complaints (SCCs) are often considered to be a precursor of objective cognitive deficits, but there are no studies specifically on SCC and psychotic experiences (PE). Thus, we assessed the association between SCC and PE using data from 48 low- and middle-income countries.
Community-based cross-sectional data of the World Health Survey were analysed. Two questions on subjective memory and learning complaints in the past 30 days were used to create a SCC scale ranging from 0 to 10 with higher scores representing more severe SCC. The Composite International Diagnostic Interview was used to identify past 12-month PE. Multivariable logistic regression and mediation analyses were performed.
The final sample consisted of 224 842 adults aged ⩾18 years [mean (SD) age 38.3 (16.0) years; 49.3% males]. After adjustment for sociodemographic factors, a one-unit increase in the SCC scale was associated with a 1.17 (95% CI 1.16–1.18) times higher odds for PE in the overall sample, with this association being more pronounced in younger individuals: age 18–44 years OR = 1.19 (95% CI 1.17–1.20); 45–64 years OR = 1.15 (95% CI 1.12–1.17); ⩾65 years OR = 1.14 (95% CI 1.09–1.19). Collectively, other mental health conditions (perceived stress, depression, anxiety, sleep problems) explained 43.4% of this association, and chronic physical conditions partially explained the association but to a lesser extent (11.8%).
SCC were associated with PE. Future longitudinal studies are needed to understand temporal associations and causal inferences, while the utility of SCC as a risk marker for psychosis especially for young adults should be scrutinised.
In the quest for dynamic multimodal probing of a material’s structure and functionality, it is critical to be able to quantify the chemical state on the atomic-/nanoscale using element-specific electronic and structurally sensitive tools such as electron energy-loss spectroscopy (EELS). Ultrafast EELS, with combined energy, time, and spatial resolution in a transmission electron microscope, has recently enabled transformative studies of photoexcited nanostructure evolution and mapping of evanescent electromagnetic fields. This article aims to describe state-of-the-art experimental techniques in this emerging field and its major uses and future applications.
Group-3 medulloblastoma (MBL) is highly resistant to radiation (IR) and chemotherapy and has the worst prognosis. Hence, there is an urgent need to elucidate targets that sensitize these tumors to chemotherapy and IR. Employing standard assays for viability and sensitization to IR, we identified PRDX1 as a therapeutic target in Group-3 MBL. Specifically, targeting PRDX1 by RNAi or inhibition by Adenanthin led to specific killing and sensitization to IR of Group-3 MBL cells. We rescued sensitization of Daoy and UW228 cells by hypermorphic expression of PRDX1. PRDX1 knockdown caused oxidative DNA damage and induced apoptosis. We correlated PRDX1 expression to patient outcomes in a validated MBL tumor-microarray. Whole genome sequencing identified pathways/genes that were dysregulated with PRDX1 inhibition or silencing. Our in vivo studies in mice employing flank/orthotopic tumors from patient derived xenografts/Group-3 MBL cells confirmed in vitro observations. Animals with tumors in which PRDX1 was targeted by RNAi or Adenanthin (using mini osmotic pumps) showed decreased tumor burden and increased survival when compared to controls. Since, Adenanthin does not cross the blood brain barrier (BBB) we used HAV6 peptide to transiently disrupt the BBB and deliver Adenanthin to the tumor. Immunohistochemistry confirmed that targeting PRDX1 resulted in increased oxidative DNA damage, apoptosis and decreased proliferation. In summary, we have validated PRDX1 as a therapeutic target in group-3 MBL, identified Adenanthin as a potent chemical inhibitor of PRDX1 and confirmed the role of HAV peptide (in the transient modulation of BBB permeability) in an orthotopic model of group-3 MBL.
Background: NEDA is a composite measure that may ultimately influence clinical decisions concerning switches of disease modifying therapy (DMT) for relapsing remitting multiple sclerosis (RRMS) patients. Cohort studies from MS clinics suggest NEDA is not sustained over time in most patients despite DMT but may be limited by referral bias. We investigated NEDA in a population-based RRMS cohort. Methods: We identified all incident cases of RRMS in Olmsted County from 01/01/2000-12/31/2011. Retrospective chart review was conducted to determine persistence of NEDA -following RRMS diagnosis. NEDA failure was defined as new MRI activity, relapse, or expanded disability status scale (EDSS) -worsening. Results: There were 93 incident cases of RRMS with 82 individuals having sufficient follow-up to determine persistence of NEDA. Prior to NEDA failure 44 were not on DMT, 37 were on first-tier, injectable DMT, and 1 received mitoxantrone. NEDA was maintained by 63% at 1 year, 38% at 2 years, 19% at 5 years, and 12% at 10 years. Disability measured by EDSS was no different at 10 years in patients maintaining NEDA versus those that failed NEDA at one year (p=0.3). Conclusions: Maintenance of NEDA beyond 2 years is infrequent among a population-based cohort of newly diagnosed RRMS patients and similar to prior clinic-based cohorts.
The present study aimed to examine the correlates of fruit and vegetable intake (FVI) separately among parents and their adolescents.
Parents and adolescents completed the Family Life, Activity, Sun, Health, and Eating (FLASHE) survey through the National Cancer Institute. The survey assessed daily intake frequencies of food/beverage groups, psychosocial, parenting and sociodemographic factors. Generalized linear models were run for both parents and adolescents, for a total of six models (three each): (i) sociodemographic characteristics; (ii) psychosocial factors; (iii) parent/caregiver factors.
Parent participants (n 1542) were predominantly 35–59 years old (86 %), female (73 %), non-Hispanic White (71 %) or non-Hispanic Black (17 %), with household income <$US 100 000 (79 %). Adolescents (n 805) were aged 12–14 years (50 %), non-Hispanic White (66 %) and non-Hispanic Black (15 %). Parents consumed 2·9 cups fruits and vegetables (F&V) daily, while adolescents consumed 2·2 cups daily. Educational attainment (higher education had greater FVI) and sex (men consumed more than women; all P<0·001) were significant FVI predictors. Parents with greater autonomous and controlled motivation, self-efficacy and preferences for fruit reported higher FVI (all P<0·001). Similarly, adolescents with greater autonomous and controlled motivation, self-efficacy and knowledge reported higher FVI (all P<0·001). Parenting factors of importance were co-deciding how many F&V teens should have, rules, having F&V in the home and cooking meals from scratch (all P<0·05).
Findings suggest factors that impact FVI among parents and their adolescent(s), which highlight the importance of the role of parent behaviour and can inform tailored approaches for increasing FVI in various settings.
This study aimed to examine a range of factors influencing the long-term recovery of New York City residents affected by Hurricane Sandy.
In a series of logistic regressions, we analyzed data from a survey of New York City residents to assess self-reported recovery status from Hurricane Sandy.
General health, displacement from home, and household income had substantial influences on recovery. Individuals with excellent or fair health were more likely to have recovered than were individuals with poor health. Those with high and middle income were more likely to have recovered than were those with low income. Also, individuals who had not experienced a decrease in household income following Hurricane Sandy had higher odds of recovery than the odds for those with decreased income. Additionally, displacement from the home decreased the odds of recovery. Individuals who applied for assistance from the Build it Back program and the Federal Emergency Management Agency had lower odds of recovering than did those who did not apply.
The study outlines the critical importance of health and socioeconomic factors in long-term disaster recovery and highlights the need for increased consideration of those factors in post-disaster interventions and recovery monitoring. More research is needed to assess the effectiveness of state and federal assistance programs, particularly among disadvantaged populations. (Disaster Med Public Health Preparedness. 2018;12:172–175)
Theory predicts that capping brokers’ compensation exacerbates the exploitation of retail investors. We show that regulated caps on mutual fund 12b-1 fees, effectively sales commissions, are associated with negative equity fund performance, but only after a structural shift toward maximum permitted levels of the fees around 2000. Past this break point, flow–performance sensitivity shifts from the middle- to the highest-performing funds, suggesting that the fee cap increases performance-chasing behavior by constraining brokers’ incentives to learn about lower-ranked funds. The policy implication is that regulators must reevaluate the efficacy of caps on brokerage fees.
Victimisation by the police is purported to be widespread in cities in the USA, but there is limited data on police–public encounters from community samples. This is partly due to an absence of measures for assessing police violence exposure from the standpoint of civilians. As such, the demographic distribution and mental health correlates of police victimisation are poorly understood. The aims of this study were to present community-based prevalence estimates of positive policing and police victimisation based on assessment with two novel measures, and to test the hypotheses that (1) exposure to police victimisation would vary across demographic groups and (2) would be associated with depression and psychological distress.
The Survey of Police–Public Encounters study surveyed adults residing in four US cities to examine the prevalence, demographic distribution and psychological correlates of police victimisation. Participants (N = 1615) completed measures of psychological distress (K-6 scale), depression (Patient Health Questionnaire 9) and two newly constructed measures of civilian-reported police–public encounters. Both measures were developed to assess police victimisation based on the WHO domains of violence, which include physical violence (with and without a weapon, assessed separately), sexual violence (inappropriate sexual contact, including public strip searches), psychological violence (e.g., threatening, intimidating, stopping without cause, or using discriminatory slurs) and neglect (police not responding when called or responding too late). The Police Practices Inventory assesses lifetime history of exposure to positive policing and police victimisation, and the Expectations of Police Practices Scale assesses the perceived likelihood of future incidents of police victimisation. Linear regression models were used to test for associations between police–public encounters and psychological distress and depression.
Psychological violence (18.6%) and police neglect (18.8%) were commonly reported in this sample and a substantial minority of respondents also reported more severe forms of violence, specifically physical (6.1%), sexual (2.8%) and physical with a weapon (3.3%). Police victimisation was more frequently reported by racial/ethnic minorities, males, transgender respondents and younger adults. Nearly all forms of victimisation (but not positive policing) were associated with psychological distress and depression in adjusted linear regression models.
Victimisation by police appears to be widespread, inequitably distributed across demographic groups and psychologically impactful. These findings suggest that public health efforts to both reduce the prevalence of police violence and to alleviate its psychological impact may be needed, particularly in disadvantaged urban communities.
The co-existence of depression and psychotic experiences (PEs) is associated with more pronounced adverse health outcomes compared to depression alone. However, data on its prevalence and correlates are lacking in the general adult population, and there is no published data on its association with chronic physical conditions.
Cross-sectional, community-based data from 201 337 adults aged ⩾18 years from 47 low- and middle-income countries from the World Health Survey were analyzed. The presence of past 12-month PE and DSM-IV depression was assessed with the Composite International Diagnostic Interview (CIDI). Information on six chronic medical conditions (chronic back pain, edentulism, arthritis, angina, asthma, diabetes) were obtained by self-report. Multivariable logistic regression analysis was performed.
The crude overall prevalence of co-morbid depression/PEs was 2.5% [95% confidence interval (CI) 2.3–2.7%], with the age- and sex-adjusted prevalence ranging from 0.1% (Sri Lanka, Vietnam) to 9.03% (Brazil). Younger age, urban setting, current smoking, alcohol consumption, and anxiety were significant correlates of co-existing depression/PEs. Co-occurring depression/PEs was associated with significantly higher odds for arthritis, angina, and diabetes beyond that of depression alone after adjusting for sociodemographics, anxiety, and country, with odds ratios (depression/PEs v. depression only) being: arthritis 1.30 (95% CI 1.07–1.59, p = 0.0086); angina 1.40 (95% CI 1.18–1.67, p = 0.0002); diabetes 1.65 (95% CI 1.21–2.26, p = 0.0017).
The prevalence of co-existing depression/PEs was non-negligible in most countries. Our study suggests that when depression/PE or a chronic condition (e.g. arthritis, angina, diabetes) is detected, screening for the other may be important to improve clinical outcomes.
Studies on whether the co-occurrence of psychotic experiences (PEs) and depression confers a more pronounced decrement in health status and function compared with depression alone are scarce in the general adult population.
Data on 195 479 adults aged ⩾18 years from the World Health Survey were analysed. Using the World Mental Health Survey version of the Composite International Diagnostic Interview (CIDI), depression in the past 12 months was categorized into four groups: depressive episode, brief depressive episode, subsyndromal depression, and no depression. Past 12-month psychotic symptoms were assessed using four questions on positive symptoms from the CIDI. Health status across seven domains (cognition, interpersonal activities, sleep/energy, self-care, mobility, pain/discomfort, vision) and interviewer-rated presence of a mental health problem were assessed. Multivariable logistic and linear regression analyses were performed to assess the associations.
When compared with those with no depression, individuals with depression had higher odds of reporting at least one PE, and this was seen across all levels of depression severity: subsyndromal depression [odds ratio (OR) 2.38, 95% confidence interval (CI) 2.02–2.81], brief depressive episode (OR 3.84, 95% CI 3.31–4.46) and depressive episode (OR 3.75, 95% CI 3.24–4.33). Having coexisting PEs and depression was associated with a higher risk for observable illness behavior and a significant decline in health status in the cognition, interpersonal activities and sleep/energy domains, compared with those with depression alone.
This coexistence of depression and PEs is associated with more severe social, cognitive and sleep disturbances, and more outwardly apparent illness behavior. Detecting this co-occurrence may be important for treatment planning.
We present recent observation results of Sgr A* at millimeter obtained with VLBI arrays in Korea and Japan.
7 mm monitoring of Sgr A* is part of our AGN large project. The results at 7 epochs during 2013-2014, including high resolution maps, flux density and two-dimensional size measurements are presented. The source shows no significant variation in flux and structure related to the G2 encounter in 2014. According to recent MHD simulations by kawashima et al., flux and magnetic field energy can be expected to increase several years after the encounter; We will keep our monitoring in order to test this prediction.
Astrometric observations of Sgr A* were performed in 2015 at 7 and 3.5 millimeter simultaneously. Source-frequency phase referencing was applied and a combined ”core-shift” of Sgr A* and a nearby calibrator was measured. Future observations and analysis are necessary to determine the core-shift in each source.
Objectives: The purpose of this study was to assess whether age-related differences in white matter microstructure are associated with altered task-related connectivity during episodic recognition. Methods: Using functional magnetic resonance imaging and diffusion tensor imaging from 282 cognitively healthy middle-to-late aged adults enrolled in the Wisconsin Registry for Alzheimer’s Prevention, we investigated whether fractional anisotropy (FA) within white matter regions known to decline with age was associated with task-related connectivity within the recognition network. Results: There was a positive relationship between fornix FA and memory performance, both of which negatively correlated with age. Psychophysiological interaction analyses revealed that higher fornix FA was associated with increased task-related connectivity amongst the hippocampus, caudate, precuneus, middle occipital gyrus, and middle frontal gyrus. In addition, better task performance was associated with increased task-related connectivity between the posterior cingulate gyrus, middle frontal gyrus, cuneus, and hippocampus. Conclusions: The findings indicate that age has a negative effect on white matter microstructure, which in turn has a negative impact on memory performance. However, fornix microstructure did not significantly mediate the effect of age on performance. Of interest, dynamic functional connectivity was associated with better memory performance. The results of the psychophysiological interaction analysis further revealed that alterations in fornix microstructure explain–at least in part–connectivity among cortical regions in the recognition memory network. Our results may further elucidate the relationship between structural connectivity, neural function, and cognition. (JINS, 2016, 22, 191–204)
Oxidation behavior of alumina forming ferritic stainless steel (FeCrAl type stainless steels) grades APM and APMT, which are candidate alloys for fuel cladding, was studied using thermogravimetric analysis under dry air condition, and compared to that of ZIRLO®. In addition to the dry air condition, we also studied the high temperature oxidation behavior of APM and APMT under 100% steam condition in order to compare the effect of environment on the oxidation behavior of these alloys. APM and APMT showed an excellent oxidation resistance at high temperatures compared to ZIRLO® under dry air condition due to a stable Al2O3 oxide scale formed at the surface. Under steam condition, the oxidation rate of APM and APMT was found to be higher compared to that under the dry air condition.
The aim of this study was to examine cross-sectionally whether higher cardiorespiratory fitness (CRF) might favorably modify amyloid-β (Aβ)-related decrements in cognition in a cohort of late-middle-aged adults at risk for Alzheimer’s disease (AD). Sixty-nine enrollees in the Wisconsin Registry for Alzheimer’s Prevention participated in this study. They completed a comprehensive neuropsychological exam, underwent 11C Pittsburgh Compound B (PiB)-PET imaging, and performed a graded treadmill exercise test to volitional exhaustion. Peak oxygen consumption (VO2peak) during the exercise test was used as the index of CRF. Forty-five participants also underwent lumbar puncture for collection of cerebrospinal fluid (CSF) samples, from which Aβ42 was immunoassayed. Covariate-adjusted regression analyses were used to test whether the association between Aβ and cognition was modified by CRF. There were significant VO2peak*PiB-PET interactions for Immediate Memory (p=.041) and Verbal Learning & Memory (p=.025). There were also significant VO2peak*CSF Aβ42 interactions for Immediate Memory (p<.001) and Verbal Learning & Memory (p<.001). Specifically, in the context of high Aβ burden, that is, increased PiB-PET binding or reduced CSF Aβ42, individuals with higher CRF exhibited significantly better cognition compared with individuals with lower CRF. In a late-middle-aged, at-risk cohort, higher CRF is associated with a diminution of Aβ-related effects on cognition. These findings suggest that exercise might play an important role in the prevention of AD. (JINS, 2015, 21, 841–850)