To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure firstname.lastname@example.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Excess sleep is associated with higher risk of stroke, but whether the risk is modified by age and if it remains elevated after accounting for the competing risk of death is not well understood.
We used nine years of the Canadian Community Health Survey between 2000 to 2016 to obtain self-reported sleep duration and created a cohort of individuals without prior stroke, heart disease, or cancer. We linked to hospital records to determine subsequent admissions or emergency department visits for acute stroke until December 31, 2017. We used Cox proportional hazard models to determine the association between sleep duration and risk of stroke, assessing for modification by age and sex and adjusting for demographic, vascular, and social factors. We obtained cumulative incidence of stroke accounting for the competing risk of death.
There were 82,795 individuals in our cohort who met inclusion criteria and had self-reported sleep duration, with 1705 stroke events in follow-up. There was an association between excess sleep (≥10 h/night) and risk of stroke in those <70 years (fully adjusted hazard ratio 2.29, 95% CI 1.04–5.06), but not ≥70 years of age, with a similar association after accounting for the competing risk of death.
Sleep duration ≥10 h/night is associated with increased risk of stroke in those <70 years of age. The findings support current guidelines for 7–9 h of sleep per night. Further research is needed to elucidate the relationship between sleep and cerebrovascular disease.
Mass vaccination campaigns have been used effectively to limit the impact of communicable disease on public health. However, the scale of the coronavirus disease (COVID-19) vaccination campaign is unprecedented. Mass vaccination sites consolidate resources and experience into a single entity and are essential to achieving community (“herd”) immunity rapidly, efficiently, and equitably. Health care systems, local and regional public health entities, emergency medical services, and private organizations can rapidly come together to solve problems and achieve success. As medical directors at several mass vaccination sites across the United States, we describe key mass vaccination site concepts, including site selection, operational models, patient flow, inventory management, staffing, technology, reporting, medical oversight, communication, and equity. Lessons learned from experience operating a diverse group of mass vaccination sites will help inform not only sites operating during the current pandemic, but also may serve as a blueprint for future outbreaks of highly infectious communicable disease.
Health utility instruments are increasingly being used to measure impairment in health-related quality of life (HRQoL) after stroke. Population-based studies of HRQoL after stroke and assessment of differences by age and functional domain are needed.
We used the Canadian Community Health Survey linked with administrative databases to determine HRQoL using the Health Utilities Index Mark 3 (HUI3) among those with prior hospitalization or emergency department visit for stroke and compared to controls without stroke. We used multivariable linear regression to determine the difference in HUI3 between those with stroke and controls for the global index and individual attributes, with assessment for modification by age (<60, 60–74, and 75+ years) and sex, and we combined estimates across survey years using random effects meta-analysis.
Our cohort contained 1240 stroke survivors and 123,765 controls and was weighted to be representative of the Canadian household population. Mean health utility was 0.63 (95% confidence interval [CI] 0.58, 0.68) for those with stroke and 0.83 (95% CI 0.82, 0.84) for controls. There was significant modification by age, but not sex, with the greatest adjusted reduction in HUI3 among stroke respondents aged 60–74 years. Individual HUI3 attributes with the largest reductions in utility among stroke survivors compared to controls were mobility, cognition, emotion, and pain.
In this population-based study, the reduction in HUI3 among stroke survivors compared to controls was greatest among respondents aged 60–74, and in attributes of mobility, cognition, emotion, and pain. These results highlight the persistent impairment of HRQoL in the chronic phase of stroke and potential targets for community support.
To understand the long-term climate and glaciological evolution of the ice sheet in the region bordering the Weddell Sea, the British Antarctic Survey has undertaken a series of successful ice core projects drilling to bedrock on Berkner Island, James Ross Island and the Fletcher Promontory. A new project, WACSWAIN, seeks to increase this knowledge by further drilling to bedrock on two further ice rises in this region. In a single-season project, an ice core was recovered to bedrock at 651 m on Skytrain Ice Rise using an ice core drill in a fluid-filled borehole. In a second season, a rapid access drill was used to recover ice chips to 323 m on Sherman Island in a dry borehole, though failing to reach the bedrock which was at an estimated depth of 428 m.
There is substantial evidence that voters’ choices are shaped by assessments of the state of the economy and that these assessments, in turn, are influenced by the news. But how does the economic news track the welfare of different income groups in an era of rising inequality? Whose economy does the news cover? Drawing on a large new dataset of US news content, we demonstrate that the tone of the economic news strongly and disproportionately tracks the fortunes of the richest households, with little sensitivity to income changes among the non-rich. Further, we present evidence that this pro-rich bias emerges not from pro-rich journalistic preferences but, rather, from the interaction of the media’s focus on economic aggregates with structural features of the relationship between economic growth and distribution. The findings yield a novel explanation of distributionally perverse electoral patterns and demonstrate how distributional biases in the economy condition economic accountability.
ABSTRACT IMPACT: This work will help to understand a novel therapeutic approach to a common type of acute myeloid leukemia. OBJECTIVES/GOALS: FMS-like tyrosine kinase 3 (or FLT3) mutations occur in ˜30% of acute myeloid leukemia (AML) cases. FLT3 tyrosine kinase domain (TKD) mutations are particularly important in relapsed/refractory FLT3 mutant AML, which portends poor prognosis. This study describes a therapeutic approach to overcoming resistance conferred by FLT3-TKD mutations. METHODS/STUDY POPULATION: To understand the efficacy of a novel type 1 FLT3 inhibitor (NCGC1481), as a monotherapy and combination therapy, several assays were utilized to interrogate functionality of these therapies. Cell lines and patient samples containing aspartate 835 to tyrosine mutations (D835Y, the most common TKD alteration) and phenylalanine 691 to leucine (F691L) were utilized to examine the effects of NCGC1481 with and without other targeted therapies like MEK inhibitors. Specifically, assays measuring viability, cell death using flow cytometry, in vitro clonogenicity, cellular signaling, and xenograft survival were examined in these FLT3-TKD AML models. Synergy was also measured using well described methods, which also allowed for appropriate dose finding for drug combination experiments. RESULTS/ANTICIPATED RESULTS: Our novel type 1 FLT3 inhibitor (NCGC1481) was particularly effective in the most common FLT3 TKD mutant, D835Y. NCGC1481 reduced viability and cell signaling, while also inducing cell death and prolonging xenograft survival in the FLT3-D835Y model system. In contrast, clinically approved FLT3 inhibitors were less effective at suppressing AML cells expressing FLT3-D835Y. In the case of FLT3-F691L, most of the FLT3 inhibitors tested, including NCGC1481, suppressed canonical FLT3 signaling, but did not significantly reduce viability or leukemic clonogenicity. However, when NCGC1481 was combined with other targeted agents like MEK inhibitors, at synergistic doses, eradication of the FLT3-F691L AML clone was substantially increased. DISCUSSION/SIGNIFICANCE OF FINDINGS: In AML, response to FLT3 inhibitor therapy is often short-lived, with resistance sometimes occurring via FLT3-TKD mutations. Given the dismal prognosis of relapsed FLT3 mutant AML, novel therapies are necessary. This study describes efficacy of a novel FLT3 inhibitor, along with its synergistic activity when combined with other targeted agents.
Nearly three times as many people detained in a jail have a serious mental illness (SMI) when compared to community samples. Once an individual with SMI gets involved in the criminal justice system, they are more likely than the general population to stay in the system, face repeated incarcerations, and return to prison more quickly when compared to their nonmentally ill counterparts.
The Cal-DSH Diversion Guidelines provide 10 general guidelines that jurisdictions should consider when developing diversion programs for individuals with a serious mental illness (SMI) who become involved in the criminal justice system. Screening for SMI in a jail setting is reviewed. In addition, important treatment interventions for SMI and substance use disorders are highlighted with the need to address criminogenic risk factors highlighted.
The World Health Organization (WHO; Geneva, Switzerland) recommends lay first responder (LFR) programs as a first step toward establishing formal Emergency Medical Services (EMS) in low- and middle-income countries (LMICs) to address injury. There is a scarcity of research investigating LFR program development in predominantly rural settings of LMICs.
A pilot LFR program was launched and assessed over 12 months to investigate the feasibility of leveraging pre-existing transportation providers to scale up prehospital emergency care in rural, low-resource settings of LMICs.
An LFR program was established in rural Chad to evaluate curriculum efficacy, using a validated 15-question pre-/post-test to measure participant knowledge improvement. Pre-/post-test score distributions were compared using a Wilcoxon Signed-Rank test. For test evaluation, each pre-test question was mapped to its corresponding post-test analog and compared using McNemar’s Chi-Squared Test to examine knowledge acquisition on a by-question basis. Longitudinal prehospital care was evaluated with incident reports, while program cost was tracked using a one-way sensitivity analysis. Qualitative follow-up surveys and semi-interviews were conducted at 12 months, with initial participants and randomly sampled motorcycle taxi drivers, and used a constructivist grounded theory approach to understand the factors motivating continued voluntary participation to inform future program continuity. The consolidated criteria for reporting qualitative research (COREQ) checklist was used to guide design, analysis, and reporting the qualitative results.
A total of 108 motorcycle taxi participants demonstrated significant knowledge improvement (P <.001) across three of four curricular categories: scene safety, airway and breathing, and bleeding control. Lay first responders treated 71 patients over six months, encountering five deaths, and provided patient transport in 82% of encounters. Lay first responders reported an average confidence score of 8.53/10 (n = 38). In qualitative follow-up surveys and semi-structured interviews, the ability to care for the injured, new knowledge/skills, and the resultant gain in social status and customer acquisition motivated continued involvement as LFRs. Ninety-six percent of untrained, randomly sampled motorcycle taxi drivers reported they would be willing to pay to participate in future training courses.
Lay first responder programs appear feasible and cost-effective in rural LMIC settings. Participants demonstrate significant knowledge acquisition, and after 12 months of providing emergency care, report sustained voluntary participation due to social and financial benefits, suggesting sustainability and scalability of LFR programs in low-resource settings.
There is a continual need for invasive plant science to develop approaches for cost-effectively benefiting native over nonnative species in dynamic management and biophysical contexts, including within predominantly nonnative plant landscapes containing only small patches of native plants. Our objective was to test the effectiveness of a minimal-input strategy for enlarging native species patches within a nonnative plant matrix. In Pecos National Historical Park, New Mexico, USA, we identified 40 native perennial grass patches within a matrix of the nonnative annual forb kochia [Bassia scoparia (L.) A.J. Scott]. We mechanically cut B. scoparia in a 2-m-wide ring surrounding the perimeters of half the native grass patches (with the other half as uncut controls) and measured change in native grass patch size (relative to pretreatment) for 3 yr. Native grass patches around which B. scoparia was cut grew quickly the first posttreatment year and by the third year had increased in size four times more than control patches. Treated native grass patches expanded by an average of 25 m2, from 4 m2 in October 2015 before treatment to 29 m2 in October 2018. The experiment occurred during a dry period, conditions that should favor B. scoparia and contraction of the native grasses, suggesting that the observed increase in native grasses occurred despite suboptimal climatic conditions. Strategically treating around native patches to enlarge them over time showed promise as a minimal-input technique for increasing the proportion of the landscape dominated by native plants.
Glyphosate-resistant (GR) kochia has been reported across the western and midwestern United States. From 2011 to 2014, kochia seed was collected from agronomic regions across Colorado to evaluate the frequency and distribution of glyphosate-, dicamba-, and fluroxypyr-resistant kochia, and to assess the frequency of multiple resistance. Here we report resistance frequency as percent resistance within a population, and resistance distribution as the percentage and locations of accessions classified as resistant to a discriminating herbicide dose. In 2011, kochia accessions were screened with glyphosate only, whereas from 2012 to 2014 kochia accessions were screened with glyphosate, dicamba, and fluroxypyr. From 2011 to 2014, the percentages of GR kochia accessions were 60%, 45%, 39%, and 52%, respectively. The percentages of dicamba-resistant kochia accessions from 2012 to 2014 were 33%, 45%, and 28%, respectively. No fluroxypyr-resistant accessions were identified. Multiple-resistant accessions (low resistance or resistant to both glyphosate and dicamba) from 2012 to 2014 were identified in 14%, 15%, and 20% of total sampled accessions, respectively. This confirmation of multiple glyphosate and dicamba resistance in kochia accessions emphasizes the importance of diversity in herbicide site of action as critical to extend the usefulness of remaining effective herbicides such as fluroxypyr for management of this weed.
The Society of Academic Emergency Medicine Disaster Medicine Interest Group, the Office of the Assistant Secretary for Preparedness and Response – Technical Resources, Assistance Center, and Information Exchange (ASPR TRACIE) team, and the National Institutes of Health Library searched disaster medicine peer-reviewed and gray literature to identify, review, and disseminate the most important new research in this field for academics and practitioners.
MEDLINE/PubMed and Scopus databases were searched with key words. Additional gray literature and focused hand search were performed. A Level I review of titles and abstracts with inclusion criteria of disaster medicine, health care system, and disaster type concepts was performed. Eight reviewers performed Level II full-text review and formal scoring for overall quality, impact, clarity, and importance, with scoring ranging from 0 to 20. Reviewers summarized and critiqued articles scoring 16.5 and above.
Articles totaling 1176 were identified, and 347 were screened in a Level II review. Of these, 193 (56%) were Original Research, 117 (34%) Case Report or other, and 37 (11%) were Review/Meta-Analysis. The average final score after a Level II review was 11.34. Eighteen articles scored 16.5 or higher. Of the 18 articles, 9 (50%) were Case Report or other, 7 (39%) were Original Research, and 2 (11%) were Review/Meta-Analysis.
This first review highlighted the breadth of disaster medicine, including emerging infectious disease outbreaks, terror attacks, and natural disasters. We hope this review becomes an annual source of actionable, pertinent literature for the emerging field of disaster medicine.
The USA is currently enduring an opioid crisis. Identifying cost-effective, easy-to-implement behavioral measures that predict treatment outcomes in opioid misusers is a crucial scientific, therapeutic, and epidemiological goal.
The current study used a mixed cross-sectional and longitudinal design to test whether a behavioral choice task, previously validated in stimulant users, was associated with increased opioid misuse severity at baseline, and whether it predicted change in opioid misuse severity at follow-up. At baseline, data from 100 prescription opioid-treated chronic pain patients were analyzed; at follow-up, data were analyzed in 34 of these participants who were non-misusers at baseline. During the choice task, participants chose under probabilistic contingencies whether to view opioid-related images in comparison with affectively pleasant, unpleasant, and neutral images. Following previous procedures, we also assessed insight into choice behavior, operationalized as whether (yes/no) participants correctly self-reported the image category they chose most often.
At baseline, the higher choice for viewing opioid images in direct comparison with pleasant images was associated with opioid misuse and impaired insight into choice behavior; the combination of these produced especially elevated opioid-related choice behavior. In longitudinal analyses of individuals who were initially non-misusers, higher baseline opioid v. pleasant choice behavior predicted more opioid misuse behaviors at follow-up.
These results indicate that greater relative allocation of behavior toward opioid stimuli and away from stimuli depicting natural reinforcement is associated with concurrent opioid misuse and portends vulnerability toward future misuse. The choice task may provide important medical information to guide opioid-prescribing practices.
Drawing on a landscape analysis of existing data-sharing initiatives, in-depth interviews with expert stakeholders, and public deliberations with community advisory panels across the U.S., we describe features of the evolving medical information commons (MIC). We identify participant-centricity and trustworthiness as the most important features of an MIC and discuss the implications for those seeking to create a sustainable, useful, and widely available collection of linked resources for research and other purposes.
Inflammation of the mammary gland following bacterial infection, commonly known as mastitis, affects all mammalian species. Although the aetiology and epidemiology of mastitis in the dairy cow are well described, the genetic factors mediating resistance to mammary gland infection are not well known, due in part to the difficulty in obtaining robust phenotypic information from sufficiently large numbers of individuals. To address this problem, an experimental mammary gland infection experiment was undertaken, using a Friesian-Jersey cross breed F2 herd. A total of 604 animals received an intramammary infusion of Streptococcus uberis in one gland, and the clinical response over 13 milkings was used for linkage mapping and genome-wide association analysis. A quantitative trait locus (QTL) was detected on bovine chromosome 11 for clinical mastitis status using micro-satellite and Affymetrix 10 K SNP markers, and then exome and genome sequence data used from the six F1 sires of the experimental animals to examine this region in more detail. A total of 485 sequence variants were typed in the QTL interval, and association mapping using these and an additional 37 986 genome-wide markers from the Illumina SNP50 bovine SNP panel revealed association with markers encompassing the interleukin-1 gene cluster locus. This study highlights a region on bovine chromosome 11, consistent with earlier studies, as conferring resistance to experimentally induced mammary gland infection, and newly prioritises the IL1 gene cluster for further analysis in genetic resistance to mastitis.
Mass gathering events can substantially impact public safety. Analyzing patient presentation and transport rates at various mass gathering events can help inform staffing models and improve preparedness.
A retrospective review of all patients seeking medical attention across a variety of event types at a single venue with a capacity of 68,756 from January 2010 through September 2015.
We examined 232 events with a total of 8,260,349 attendees generating 8157 medical contacts. Rates were 10 presentations and 1.6 transports per 10,000 attendees with a non-significant trend towards increased rates in postseason National Football League games. Concerts had significantly higher rates of presentation and transport than all other event types. Presenting concern varied significantly by event type and gender, and transport rate increased predictably with age. For cold weather events, transport rates increased at colder temperatures. Overall, on-site physicians did not impact rates.
At a single venue hosting a variety of events across a 6-year period, we demonstrated significant variations in presentation and transport rates. Weather, gender, event type, and age all play important roles. Our analysis, while representative only of our specific venue, may be useful in developing response plans and staffing models for similar mass gathering venues. (Disaster Med Public Health Preparedness. 2018;12:752-758).
Objectives: To evaluate prospective and retrospective memory abilities in Operation Enduring Freedom (OEF), Operation Iraqi Freedom (OIF), and Operation New Dawn (OND) Veterans with and without a self-reported history of blast-related mild traumatic brain injury (mTBI). Methods: Sixty-one OEF/OIF/OND Veterans, including Veterans with a self-reported history of blast-related mTBI (mTBI group; n=42) and Veterans without a self-reported history of TBI (control group; n=19) completed the Memory for Intentions Test, a measure of prospective memory (PM), and two measures of retrospective memory (RM), the California Verbal Learning Test-II and the Brief Visuospatial Memory Test-Revised. Results: Veterans in the mTBI group exhibited significantly lower PM performance than the control group, but the groups did not differ in their performance on RM measures. Further analysis revealed that Veterans in the mTBI group with current PTSD (mTBI/PTSD+) demonstrated significantly lower performance on the PM measure than Veterans in the control group. PM performance by Veterans in the mTBI group without current PTSD (mTBI/PTSD-) was intermediate between the mTBI/PTSD+ and control groups, and results for the mTBI/PTSD- group were not significantly different from either of the other two groups. Conclusions: Results suggest that PM performance may be a sensitive marker of cognitive dysfunction among OEF/OIF/OND Veterans with a history of self-reported blast-related mTBI and comorbid PTSD. Reduced PM may account, in part, for complaints of cognitive difficulties in this Veteran cohort, even years post-injury. (JINS, 2018, 24, 324–334)
Intentional insulin overdose may lead to severe and refractory hypoglycemia. Exogenous dextrose administration is the mainstay of therapy for these patients and is effective in most cases. However, in patients with a functional pancreas, exogenous dextrose administration may precipitate endogenous insulin release leading to rebound hypoglycemia. We describe a case report of a 41-year-old woman who injected 300 units of insulin aspart with suicidal intent. Her initial blood glucose was 2.3 mmol/L (41 mg/dL). Over the next 12 hours, she experienced recurrent hypoglycemic episodes despite 10% dextrose infusions and 14 ampoules of 50% dextrose. Our patient experienced complications, including peripheral edema, related to the large volumes of intravenous dextrose required to attempt to maintain euglycemia. Octreotide, a somatostatin analogue, may help prevent dextrose-induced hypoglycemia and improve the management in select insulin overdose patients; large infusion volumes resulted in significant peripheral edema. Treatment with octreotide was initiated 12.5 hours post-injection and was followed by a stabilization of blood glucose concentration in this non-diabetic patient.