Demography of Global Aging

Individuals aged 65 years and older currently make up a larger share of the population than ever before, and this group is predicted to continue growing both in absolute terms and relative to the rest of the population. This chapter begins by introducing the facts, figures, and forecasts surrounding the aging of populations across different countries at varying levels of development. In light of these trends, we examine challenges facing graying societies through the lenses of health, economics, and policy development. The chapter concludes with a selection of adaptable strategies that countries might consider to mitigate the strain – and to harness the full potential – of aging populations worldwide

Cross-checking to reduce adverse events resulting from medical errors in the emergency department: study protocol of the CHARMED cluster randomized study

International audienceBackgroundMedical errors and preventable adverse events are a major cause of concern, especially in the emergency department (ED) where its prevalence has been reported to be roughly of 5–10 % of visits. Due to a short length of stay, emergency patients are often managed by a sole physician – in contrast with other specialties where they can benefit from multiples handover, ward rounds and staff meetings. As some studies report that the rate and severity of errors may decrease when there is more than one physician involved in the management in different settings, we sought to assess the impact of regular systematic cross-checkings between physicians in the ED.DesignThe CHARMED (Cross-checking to reduce adverse events resulting from medical errors in the emergency department) study is a multicenter cluster randomized study that aim to evaluate the reduction of the rate of severe medical errors with implementation of systematic cross checkings between emergency physician, compared to a control period with usual care. This study will evaluate the effect of this intervention on the rate of severe medical errors (i.e. preventable adverse events or near miss) using a previously described two-level chart abstraction. We made the hypothesis that implementing frequent and systematic cross checking will reduce the rate of severe medical errors from 10 to 6 % - 1584 patients will be included, 140 for each period in each center.DiscussionThe CHARMED study will be the largest study that analyse unselected ED charts for medical errors. This could provide evidence that frequent systematic cross-checking will reduce the incidence of severe medical errors

Parents' perceived obstacles to pediatric clinical trial participation: Findings from the clinical trials transformation initiative.

Enrollment of children into pediatric clinical trials remains challenging. More effective strategies to improve recruitment of children into trials are needed. This study used in-depth qualitative interviews with parents who were approached to enroll their children in a clinical trial in order to gain an understanding of the barriers to pediatric clinical trial participation. Twenty-four parents whose children had been offered the opportunity to participate in a clinical trial were interviewed: 19 whose children had participated in at least 1 clinical trial and 5 who had declined participation in any trial. Each study aspect, from the initial explanation of the study to the end of the study, can affect the willingness of parents to consent to the proposed study and future studies. Establishing trust, appropriate timing, a transparent discussion of risks and benefits oriented to the layperson, and providing motivation for children to participate were key factors that impacted parents' decisions. In order for clinical trial accrual to be successful, parents' priorities and considerations must be a central focus, beginning with initial trial design. The recommendations from the parents who participated in this study can be used to support budget allocations that ensure adequate training of study staff and improved staffing on nights and weekends. Studies of parent responses in outpatient settings and additional inpatient settings will provide valuable information on the consent process from the child's and parent's perspectives. Further studies are needed to explore whether implementation of such strategies will result in improved recruitment for pediatric clinical trials

The New Normal: Families, Caretakers, and Adults with Autism

Over the last several decades, the clinical prevalence of autism has increased considerably, as has the amount of popular and scientific attention directed towards the condition. However, discussions of autism tend to focus on children and finding a cause and a cure, while the growing numbers of adults diagnosed with autism have received relatively little attention. This dissertation begins with the argument that popular representations of autism are shaped by the idealism of modern medicine, and its overriding search to discover etiologies and treatments for all forms of biological difference that fall within its purview. And yet, for those responsible for adults with autism, management, care, and support are more relevant concerns to everyday experience than are cause and cure. In order to describe and analyze this everyday experience, this dissertation features a three-year ethnographic study of thirteen families with adult members with severe forms of autism. After reviewing pertinent historical and demographic information, the body of the manuscript explores: 1) the process by which caretakers negotiate between different definitions of problem behavior in the face of persistent situational complexity and ambiguity; 2) the contextual dynamics that make it possible for caretakers to perceive as innocent and/or humorous behaviors that are often viewed as atypical by others; and 3) the ways in which the experience of continued atypicality and dependency comes into conflict with popular representations of autism while at the same time highlighting the reality of the ever-looming future and the care and support required after primary caretakers are gone. At the end of the dissertation, I return to the argument that modern medical idealism discourages popular recognition that, in the case of autism, continued atypicality and dependency constitute the condition\u27s usual prognosis. I conclude with a short consideration of how the themes explored in this thesis resonate with the experiences of those living with or alongside other forms of biological difference (e.g. disability, mental illness, Alzehemier\u27s) that are currently incurable

Secondary emotional labor: Supervisor support vs. non-support of the emotional labor of hospice nurses

We present two dynamics among nurses and supervisors in Hospice Interdisciplinary Group Meetings: Supervisors encouraging nurses to process their emotional labor with patients and in contrast, supervisors suppressing these attempts and imposing what we describe as secondary emotional labor. We discuss implications of these dynamics for nurses, patients and organizations

Single block attacks and statistical tests on CubeHash

This paper describes a second preimage attack on the CubeHash cryptographic one-way hash function. The attack finds a second preimage in less time than brute force search for these CubeHash variants: CubeHash $r$/$b$-224 for $b \u3e 100$; CubeHash$r$/$b$-256 for $b \u3e 96$; CubeHash$r$/$b$-384 for $b \u3e 80$; and CubeHash$r$/$b$-512 for $b \u3e 64$. However, the attack does not break the CubeHash variants recommended for SHA-3. The attack requires minimal memory and can be performed in a massively parallel fashion. This paper also describes several statistical randomness tests on CubeHash. The tests were unable to disprove the hypothesis that CubeHash behaves as a random mapping. These results support CubeHash\u27s viability as a secure cryptographic hash function

Deep-coverage whole genome sequences and blood lipids among 16,324 individuals.

Large-scale deep-coverage whole-genome sequencing (WGS) is now feasible and offers potential advantages for locus discovery. We perform WGS in 16,324 participants from four ancestries at mean depth >29X and analyze genotypes with four quantitative traits-plasma total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, and triglycerides. Common variant association yields known loci except for few variants previously poorly imputed. Rare coding variant association yields known Mendelian dyslipidemia genes but rare non-coding variant association detects no signals. A high 2M-SNP LDL-C polygenic score (top 5th percentile) confers similar effect size to a monogenic mutation (~30 mg/dl higher for each); however, among those with severe hypercholesterolemia, 23% have a high polygenic score and only 2% carry a monogenic mutation. At these sample sizes and for these phenotypes, the incremental value of WGS for discovery is limited but WGS permits simultaneous assessment of monogenic and polygenic models to severe hypercholesterolemia

Deep coverage whole genome sequences and plasma lipoprotein(a) in individuals of European and African ancestries.

Lipoprotein(a), Lp(a), is a modified low-density lipoprotein particle that contains apolipoprotein(a), encoded by LPA, and is a highly heritable, causal risk factor for cardiovascular diseases that varies in concentrations across ancestries. Here, we use deep-coverage whole genome sequencing in 8392 individuals of European and African ancestry to discover and interpret both single-nucleotide variants and copy number (CN) variation associated with Lp(a). We observe that genetic determinants between Europeans and Africans have several unique determinants. The common variant rs12740374 associated with Lp(a) cholesterol is an eQTL for SORT1 and independent of LDL cholesterol. Observed associations of aggregates of rare non-coding variants are largely explained by LPA structural variation, namely the LPA kringle IV 2 (KIV2)-CN. Finally, we find that LPA risk genotypes confer greater relative risk for incident atherosclerotic cardiovascular diseases compared to directly measured Lp(a), and are significantly associated with measures of subclinical atherosclerosis in African Americans

Promoter keyholes enable specific and persistent multi-gene expression programs in primary T cells without genome modification

Non-invasive epigenome editing is a promising strategy for engineering gene expression programs, yet potency, specificity, and persistence remain challenging. Here we show that effective epigenome editing is gated at single-base precision via 'keyhole' sites in endogenous regulatory DNA. Synthetic repressors targeting promoter keyholes can ablate gene expression in up to 99% of primary cells with single-gene specificity and can seamlessly repress multiple genes in combination. Transient exposure of primary T cells to keyhole repressors confers mitotically heritable silencing that persists to the limit of primary cultures in vitro and for at least 4 weeks in vivo, enabling manufacturing of cell products with enhanced therapeutic efficacy. DNA recognition and effector domains can be encoded as separate proteins that reassemble at keyhole sites and function with the same efficiency as single chain effectors, enabling gated control and rapid screening for novel functional domains that modulate endogenous gene expression patterns. Our results provide a powerful and exponentially flexible system for programming gene expression and therapeutic cell products

Prediction of visibility and aerosol within the operational Met Office unified model. I: Model formulation and variational assimilation

The formulation and performance of the Met Office visibility analysis and prediction system are described. The visibility diagnostic within the limited-area Unified Model is a function of humidity and a prognostic aerosol content. The aerosol model includes advection, industrial and general urban sources, plus boundary-layer mixing and removal by rain. The assimilation is a 3-dimensional variational scheme in which the visibility observation operator is a very nonlinear function of humidity, aerosol and temperature. A quality control scheme for visibility data is included. Visibility observations can give rise to humidity increments of significant magnitude compared with the direct impact of humidity observations. We present the results of sensitivity studies which show the contribution of different components of the system to improved skill in visibility forecasts. Visibility assimilation is most important within the first 6-12 hours of the forecast and for visibilities below 1 km, while modelling of aerosol sources and advection is important for slightly higher visibilities (1-5 km) and is still significant at longer forecast time