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Introduction: Children diagnosed with medulloblastoma (MB) who are refractory to upfront therapy or experience recurrence have very poor prognoses. Although phase I and phase II trials exist, these treatments bear significant treatment-related morbidity and mortality. Methods: A retrospective review of children diagnosed with a recurrence of MB from 2002 to 2015 at McMaster University was undertaken. Results: Recurrent disease in 10 patients involved leptomeningeal dissemination, with 3 experiencing local recurrence. In three recurrent patients the disease significantly progressed, and the children were palliated. The remaining 10 children underwent some form of salvage therapy, including surgical re-resection, radiation, and chemotherapy, either in isolation or in varying combinations. Of the 13 children experiencing treatment-refractory or recurrent disease, 4 are currently alive with a median follow-up of 38.5 months (75.5 months). Of the eight patients with molecular subgrouping data, none of the Wnt MB experienced recurrence. Conclusion: Recurrent MB carried a poor prognosis with a 5-year overall survival (OS) of 18.2% despite the administration of salvage therapy. The upfront therapy received, available treatment, and tolerability of the proposed salvage therapy resulted in significant heterogeneity in the treatment of our recurrent cohort.
The role that vitamin D plays in pulmonary function remains uncertain. Epidemiological studies reported mixed findings for serum 25-hydroxyvitamin D (25(OH)D)–pulmonary function association. We conducted the largest cross-sectional meta-analysis of the 25(OH)D–pulmonary function association to date, based on nine European ancestry (EA) cohorts (n 22 838) and five African ancestry (AA) cohorts (n 4290) in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Data were analysed using linear models by cohort and ancestry. Effect modification by smoking status (current/former/never) was tested. Results were combined using fixed-effects meta-analysis. Mean serum 25(OH)D was 68 (sd 29) nmol/l for EA and 49 (sd 21) nmol/l for AA. For each 1 nmol/l higher 25(OH)D, forced expiratory volume in the 1st second (FEV1) was higher by 1·1 ml in EA (95 % CI 0·9, 1·3; P<0·0001) and 1·8 ml (95 % CI 1·1, 2·5; P<0·0001) in AA (Prace difference=0·06), and forced vital capacity (FVC) was higher by 1·3 ml in EA (95 % CI 1·0, 1·6; P<0·0001) and 1·5 ml (95 % CI 0·8, 2·3; P=0·0001) in AA (Prace difference=0·56). Among EA, the 25(OH)D–FVC association was stronger in smokers: per 1 nmol/l higher 25(OH)D, FVC was higher by 1·7 ml (95 % CI 1·1, 2·3) for current smokers and 1·7 ml (95 % CI 1·2, 2·1) for former smokers, compared with 0·8 ml (95 % CI 0·4, 1·2) for never smokers. In summary, the 25(OH)D associations with FEV1 and FVC were positive in both ancestries. In EA, a stronger association was observed for smokers compared with never smokers, which supports the importance of vitamin D in vulnerable populations.
Schneider and Ingram introduced the pivotal theory of social construction of target populations in the American Political Science Review nearly 25 years ago. There, they developed four ideal type groups: advantaged, contenders, dependents, and deviants. They noted that there may be contention around the construction of the groups but implied an expectation of consensus. There has not been, however, a systematic categorization of politically salient target groups based on these categories, nor has there been an empirical assessment of whether or the extent to which consensus around the social constructions of salient target groups exists. We revisit this theory to offer a novel perspective and do so by leveraging advances in technology and methodological strategies. By crowdsourcing the task of evaluating the social construction of various target populations, we are able to assess underlying assumptions of theory as well as outline avenues for future research on policy design.
The widespread use of smartphones makes effective therapies such as cognitive–behavioural therapy (CBT) potentially accessible to large numbers of people.
This paper reports the usage data of the first trial of Catch It, a new CBT smartphone app.
Uptake and usage rates, fidelity of user responses to CBT principles, and impact on reported negative and positive moods were assessed.
A relatively modest proportion of people chose to download the app. Once used, the app tended to be used more than once, and 84% of the user-generated content was consistent with the basic concepts of CBT. There were statistically significant reductions in negative mood intensity and increases in positive mood intensity.
Smartphone apps have potential beneficial effects in mental health through the application of basic CBT principles. More research with randomised controlled trial designs should be conducted.
Use of ketamine in the prehospital setting may be advantageous due to its potent analgesic and sedative properties and favorable risk profile. Use in the military setting has demonstrated both efficacy and safety for pain relief. The purpose of this study was to assess ketamine training, use, and perceptions in the civilian setting among nationally certified paramedics (NRPs) in the United States.
A cross-sectional survey of NRPs was performed. The electronic questionnaire assessed paramedic training, authorization, use, and perceptions of ketamine. Included in the analysis were completed surveys of paramedics who held one or more state paramedic credentials, indicated “patient care provider” as their primary role, and worked in non-military settings. Descriptive statistics were calculated.
A total of 14,739 responses were obtained (response rate=23%), of which 10,737 (73%) met inclusion criteria and constituted the study cohort. Over one-half (53%) of paramedics reported learning about ketamine during their initial paramedic training. Meanwhile, 42% reported seeking ketamine-related education on their own. Of all respondents, only 33% (3,421/10,737) were authorized by protocol to use ketamine. Most commonly authorized uses included pain management (55%), rapid sequence intubation (RSI; 72%), and chemical restraint/sedation (72%). One-third of authorized providers (1,107/3,350) had never administered ketamine, with another 32% (1,070/3,350) having administered ketamine less than five times in their career. Ketamine was perceived to be safe and effective as the vast majority reported that they were comfortable with the use of ketamine (94%) and would, in similar situations (95%), use it again.
This was the first large, national survey to assess ketamine training, use, and perceptions among paramedics in the civilian prehospital setting. While training related to ketamine use was commonly reported among paramedics, few were authorized to administer the drug by their agency’s protocols. Of those authorized to use ketamine, most paramedics had limited experience administering the drug. Future research is needed to determine why the prevalence of ketamine use is low and to assess the safety and efficacy of ketamine use in the prehospital setting.
BucklandDM, CroweRP, CashRE, GondekS, MalusoP, SirajuddinS, SmithER, DangerfieldP, ShapiroG, WankaC, PanchalAR, SaraniB. Ketamine in the Prehospital Environment: A National Survey of Paramedics in the United States. Prehosp Disaster Med. 2018;33(1):23–28.
Front-of-package (FOP) marketing strategies of a wide variety of beverages were catalogued to examine the prevalence of each strategy prior to a sweeping Chilean restriction of child-directed marketing aimed at reducing obesity-related disease among Chile’s youth.
Photographs of 1005 beverage packages were quantitatively content-analysed to code whether a variety of child-directed, health-oriented and other marketing strategies (e.g. sales promotions) were present on each product’s FOP. Strategies were then analysed based on beverages’ product category, total sugar, energy and tax status (beverages with added sugars are taxed at different rates).
Photographs were taken in six urban supermarkets in Santiago, Chile, representing five different supermarket chains.
Beverages using child-directed characters or nature/fruit references were higher in total sugar and beverages with child-directed characters or childhood/family references were higher in energy than beverages without these respective strategies. Of the beverages taxed at the highest rate (greatest amount of added sugars), 49 % used nutrition and health appeals and 80 % used nature or fruit appeals. Plain waters and plain milks were less likely than other selected product categories to use health-oriented appeals or multiple FOP strategies in combination.
FOP marketing on beverages varied according to the nutritional quality of the product, with heavier use of health-oriented and child-directed strategies in less healthy products. Marketing activities warrant continued observation to evaluate how industry responds to new marketing restrictions as these restrictions are evaluated in the light of existing taxes and other regulatory efforts to improve diets and reduce obesity-related disease.
Early-onset conduct problems (CP) are a key predictor of adult criminality and poor mental health. While previous studies suggest that both genetic and environmental risks play an important role in the development of early-onset CP, little is known about potential biological processes underlying these associations. In this study, we examined prospective associations between DNA methylation (cord blood at birth) and trajectories of CP (4–13 years), using data drawn from the Avon Longitudinal Study of Parents and Children. Methylomic variation at seven loci across the genome (false discovery rate < 0.05) differentiated children who go on to develop early-onset (n = 174) versus low (n = 86) CP, including sites in the vicinity of the monoglyceride lipase (MGLL) gene (involved in endocannabinoid signaling and pain perception). Subthreshold associations in the vicinity of three candidate genes for CP (monoamine oxidase A [MAOA], brain-derived neurotrophic factor [BDNF], and FK506 binding protein 5 [FKBP5]) were also identified. Within the early-onset CP group, methylation levels of the identified sites did not distinguish children who will go on to persist versus desist in CP behavior over time. Overall, we found that several of the identified sites correlated with prenatal exposures, and none were linked to known genetic methylation quantitative trait loci. Findings contribute to a better understanding of epigenetic patterns associated with early-onset CP.
The objective of this study was to determine the economic value of obtaining timely and more accurate clinical mastitis (CM) test results for optimal treatment of cows. Typically CM is first identified when the farmer observes recognisable outward signs. Further information of whether the pathogen causing CM is Gram-positive, Gram-negative or other (including no growth) can be determined by using on-farm culture methods. The most detailed level of information for mastitis diagnostics is obtainable by sending milk samples for culture to an external laboratory. Knowing the exact pathogen permits the treatment method to be specifically targeted to the causation pathogen, resulting in less discarded milk. The disadvantages are the additional waiting time to receive test results, which delays treating cows, and the cost of the culture test. Net returns per year (NR) for various levels of information were estimated using a dynamic programming model. The Value of Information (VOI) was then calculated as the difference in NR using a specific level of information as compared to more detailed information on the CM causative agent. The highest VOI was observed where the farmer assumed the pathogen causing CM was the one with the highest incidence in the herd and no pathogen specific CM information was obtained. The VOI of pathogen specific information, compared with non-optimal treatment of Staphylococcus aureus where recurrence and spread occurred due to lack of treatment efficacy, was $20.43 when the same incorrect treatment was applied to recurrent cases, and $30.52 when recurrent cases were assumed to be the next highest incidence pathogen and treated accordingly. This indicates that negative consequences associated with choosing the wrong CM treatment can make additional information cost-effective if pathogen identification is assessed at the generic information level and if the pathogen can spread to other cows if not treated appropriately.
Few established curricula are available for teaching disaster medicine. We describe a comprehensive, multi-modality approach focused on simulation to teach disaster medicine to emergency medicine residents in a 3-year curriculum.
Residents underwent a 3-year disaster medicine curriculum incorporating a variety of venues, personnel, and roles. The curriculum included classroom lectures, tabletop exercises, virtual reality simulation, high-fidelity simulation, hospital disaster drills, and journal club discussion. All aspects were supervised by specialty emergency medicine faculty and followed a structured debriefing. Residents rated the high-fidelity simulations by using a 10-point Likert scale.
Three classes of emergency medicine residents participated in the 3-year training program. Residents found the exercise to be realistic, educational, and relevant to their practice. After participating in the program, residents felt better prepared for future disasters.
Given the large scope of impact that disasters potentiate, it is understandably difficult to teach these skills effectively. Training programs can utilize this simulation-based curriculum to better prepare the nation’s emergency medicine physicians for future disasters. (Disaster Med Public Health Preparedness. 2016;10:611–614)
Although preschoolers are pervasively underinformative in their actual usage of verbal reference, a number of studies have shown that they nonetheless demonstrate sensitivity to listener informational needs, at least when environmental cues to this are obvious. We investigated two issues. The first concerned the types of visual cues to interlocutor informational needs which children aged 2;6 can process whilst producing complex referring expressions. The second was whether performance in experimental tasks related to naturalistic conversational proficiency. We found that 2;6-year-olds used fewer complex expressions when the objects were dissimilar compared to highly similar objects, indicating that they tailor their verbal expressions to the informational needs of another person, even when the cue to the informational need is relatively opaque. We also found a correlation between conversational skills as rated by the parents and the degree to which 2;6-year-olds could learn from feedback to produce complex referring expressions.
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)
Lifelong learning is believed to have physical, social and emotional benefits for older adults. In recognition of this, numerous programmes encouraging learning in later life exist worldwide. One example is the University of the Third Age (U3A) – a lifelong learning co-operative rooted in peer-support and knowledge sharing. This article is based on a collaborative study conducted by university researchers and members of a U3A in North-East England (United Kingdom) investigating the social inclusivity of the group in light of low attendance levels among those from social housing and non-professional backgrounds. A qualitative approach comprising semi-structured interviews and focus groups was adopted to explore knowledge and experience of lifelong learning and the U3A. Sixty individuals aged 50+ were interviewed. The demographic profile of participants largely reflected the socio-economic make-up of the area, with the majority living in areas of high socio-economic deprivation. Several barriers to lifelong learning were revealed, including: poor health, insufficient transport and caring responsibilities. Regarding U3A participation, three exclusionary factors were outlined: lack of knowledge, organisational name and location. Poor comprehension of the purpose and remit of the U3A can result in the development of ‘middle-class' myths regarding membership, perpetuating poor participation rates among lower socio-economic groups. Such perceptions must be dispelled to allow the U3A to fulfil its potential as a highly inclusive organisation.
Background: Extreme appraisals of internal states correlate with and prospectively predict mood symptoms in adults, and discriminate individuals with bipolar disorder from individuals with unipolar depression and non-clinical controls. Aims: These findings required replication in adolescents. This study sought to investigate the relationships between appraisals of internal states, mood symptoms and risk for bipolar disorder in an adolescent sample. Method: A non-clinical sample (n = 98) of adolescents completed measures of mood symptoms, appraisals, and mania risk, alongside covariates. Results: Appraisals of internal states were associated with analogue bipolar symptoms, independently of impulsivity and responses to positive affect. Positive appraisals of activated mood states were uniquely associated with hypomania, whilst negative appraisals were uniquely associated with depression and irritability symptoms. Individuals who appraised activated states as both extremely positive and extremely negative were more likely to score at high or moderate risk for future mania. Conclusions: This study is the first to demonstrate associations between appraisals of internal states, analogue mood symptoms and mania risk in adolescents. Clinical implications are discussed.
Issues of social and economic inequality are increasingly becoming areas of study for archaeologists; however, little work has been done on the uniform application of analytical methods. Here we assess the use of the Gini index for determining wealth inequality in eight Prehispanic central Mexican contexts. We analyze house size at the Late Postclassic sites of Capilco (village), Cuexcomate (town), and Yautepec (city), all in the state of Morelos. Agricultural field sizes for two communities described in a Nahuatl-language census immediately after the Spanish conquest are also analyzed. Our final context is the Xolalpan phase apartment compounds at Teotihuacan. Using these case studies we discuss methodological issues concerning the use of Gini indices to infer social inequality with archaeological data. We find that the Gini index, when applied following the proposed methodological standards, serves as a useful tool for the quantification of inequality across multiple archaeological case studies.