Medical Protective

This report describes the public health impact of Alzheimer's disease, including incidence and prevalence, mortality rates, costs of care, and the overall impact on caregivers and society. It also examines in detail the financial impact of Alzheimer's on families, including annual costs to families and the difficult decisions families must often make to pay those costs. An estimated 5.4 million Americans have Alzheimer's disease. By mid-century, the number of people living with Alzheimer's disease in the United States is projected to grow to 13.8 million, fueled in large part by the aging baby boom generation. Today, someone in the country develops Alzheimer's disease every 66 seconds. By 2050, one new case of Alzheimer's is expected to develop every 33 seconds, resulting in nearly 1 million new cases per year. In 2013, official death certificates recorded 84,767 deaths from Alzheimer's disease, making it the sixth leading cause of death in the United States and the fifth leading cause of death in Americans age ≥ 65 years. Between 2000 and 2013, deaths resulting from stroke, heart disease, and prostate cancer decreased 23%, 14%, and 11%, respectively, whereas deaths from Alzheimer's disease increased 71%. The actual number of deaths to which Alzheimer's disease contributes is likely much larger than the number of deaths from Alzheimer's disease recorded on death certificates. In 2016, an estimated 700,000 Americans age ≥ 65 years will die with Alzheimer's disease, and many of them will die because of the complications caused by Alzheimer's disease. In 2015, more than 15 million family members and other unpaid caregivers provided an estimated 18.1 billion hours of care to people with Alzheimer's and other dementias, a contribution valued at more than $221 billion. Average per-person Medicare payments for services to beneficiaries age ≥ 65 years with Alzheimer's disease and other dementias are more than two and a half times as great as payments for all beneficiaries without these conditions, and Medicaid payments are 19 times as great. Total payments in 2016 for health care, long-term care and hospice services for people age ≥ 65 years with dementia are estimated to be $236 billion. The costs of Alzheimer's care may place a substantial financial burden on families, who often have to take money out of their retirement savings, cut back on buying food, and reduce their own trips to the doctor. In addition, many family members incorrectly believe that Medicare pays for nursing home care and other types of long-term care. Such findings highlight the need for solutions to prevent dementia-related costs from jeopardizing the health and financial security of the families of people with Alzheimer's and other dementias.

CONTEXT: Survival estimates help individualize goals of care for geriatric patients, but life tables fail to account for the great variability in survival. Physical performance measures, such as gait speed, might help account for variability, allowing clinicians to make more individualized estimates. OBJECTIVE: To evaluate the relationship between gait speed and survival. DESIGN, SETTING, AND PARTICIPANTS: Pooled analysis of 9 cohort studies (collected between 1986 and 2000), using individual data from 34,485 community-dwelling older adults aged 65 years or older with baseline gait speed data, followed up for 6 to 21 years. Participants were a mean (SD) age of 73.5 (5.9) years; 59.6%, women; and 79.8%, white; and had a mean (SD) gait speed of 0.92 (0.27) m/s. MAIN OUTCOME MEASURES: Survival rates and life expectancy. RESULTS: There were 17,528 deaths; the overall 5-year survival rate was 84.8% (confidence interval [CI], 79.6%-88.8%) and 10-year survival rate was 59.7% (95% CI, 46.5%-70.6%). Gait speed was associated with survival in all studies (pooled hazard ratio per 0.1 m/s, 0.88; 95% CI, 0.87-0.90; P < .001). Survival increased across the full range of gait speeds, with significant increments per 0.1 m/s. At age 75, predicted 10-year survival across the range of gait speeds ranged from 19% to 87% in men and from 35% to 91% in women. Predicted survival based on age, sex, and gait speed was as accurate as predicted based on age, sex, use of mobility aids, and self-reported function or as age, sex, chronic conditions, smoking history, blood pressure, body mass index, and hospitalization. CONCLUSION: In this pooled analysis of individual data from 9 selected cohorts, gait speed was associated with survival in older adults.

This essay elaborates a critical geographical perspective on neoliberalism that emphasizes (a) the path–dependent character of neoliberal reform projects and (b) the strategic role of cities in the contemporary remaking of political–economic space. We begin by presenting the methodological foundations for an approach to the geographies of what we term “actually existing neoliberalism.” In contrast to neoliberal ideology, in which market forces are assumed to operate according to immutable laws no matter where they are “unleashed,” we emphasize the contextual embeddedness of neoliberal restructuring projects insofar as they have been produced within national, regional, and local contexts defined by the legacies of inherited institutional frameworks, policy regimes, regulatory practices, and political struggles. An adequate understanding of actually existing neoliberalism must therefore explore the path–dependent, contextually specific interactions between inherited regulatory landscapes and emergent neoliberal, market–oriented restructuring projects at a broad range of geographical scales. These considerations lead to a conceptualization of contemporary neoliberalization processes as catalysts and expressions of an ongoing creative destruction of political–economic space at multiple geographical scales. While the neoliberal restructuring projects of the last two decades have not established a coherent basis for sustainable capitalist growth, it can be argued that they have nonetheless profoundly reworked the institutional infrastructures upon which Fordist–Keynesian capitalism was grounded. The concept of creative destruction is presented as a useful means for describing the geographically uneven, socially regressive, and politically volatile trajectories of institutional/spatial change that have been crystallizing under these conditions. The essay concludes by discussing the role of urban spaces within the contradictory and chronically unstable geographies of actually existing neoliberalism. Throughout the advanced capitalist world, we suggest, cities have become strategically crucial geographical arenas in which a variety of neoliberal initiatives—along with closely intertwined strategies of crisis displacement and crisis management—have been articulated.

We are interested in estimating the average effect of a binary treatment on a scalar outcome. If assignment to the treatment is exogenous or unconfounded, that is, independent of the potential outcomes given covariates, biases associated with simple treatment-control average comparisons can be removed by adjusting for differences in the covariates. Rosenbaum and Rubin (1983) show that adjusting solely for differences between treated and control units in the propensity score removes all biases associated with differences in covariates. Although adjusting for differences in the propensity score removes all the bias, this can come at the expense of efficiency, as shown by Hahn (1998), Heckman, Ichimura, and Todd (1998), and Robins, Mark, and Newey (1992). We show that weighting by the inverse of a nonparametric estimate of the propensity score, rather than the true propensity score, leads to an efficient estimate of the average treatment effect. We provide intuition for this result by showing that this estimator can be interpreted as an empirical likelihood estimator that efficiently incorporates the information about the propensity score.

The recommendations listed in this document are, whenever possible, evidence based. An extensive evidence review was conducted for the period beginning March 2008 through April 2010. Searches were limited to studies, reviews, and other evidence conducted in human subjects and published in English. Key search words included, but were not limited to, African Americans, Asian Americans, albuminuria, asymptomatic, asymptomatic screening and brachial artery reactivity, atherosclerosis imaging, atrial fibrillation, brachial artery testing for atherosclerosis, calibration, cardiac tomography, compliance, carotid intima-media thickness (IMT), coronary calcium, coronary computed tomography angiography (CCTA), C-reactive protein (CRP), detection of subclinical atherosclerosis, discrimination, endothelial function, family history, flow-mediated dilation, genetics, genetic screening, guidelines, Hispanic Americans, hemoglobin A, glycosylated, meta-analysis, Mexican Americans, myocardial perfusion imaging (MPI), noninvasive testing, noninvasive testing and type 2 diabetes, outcomes, patient compliance, peripheral arterial tonometry (PAT), peripheral tonometry and atherosclerosis, lipoprotein-associated phospholipase A2, primary prevention of coronary artery disease (CAD), proteinuria, cardiovascular risk, risk scoring, receiver operating characteristics (ROC) curve, screening for brachial artery reactivity, stress echocardiography, subclinical atherosclerosis, subclinical and Framingham, subclinical and Multi-Ethnic Study of Atherosclerosis (MESA), and type 2 diabetes. Additionally, the writing committee reviewed documents related to the subject matter previously published by the ACCF and AHA, American Diabetes Association (ADA), European Society of Cardiology, and the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC) 7. References selected and published in this document are representative and not all-inclusive.

PURPOSE: This longitudinal study was designed to examine changes in medical students' empathy during medical school and to determine when the most significant changes occur. METHOD: Four hundred fifty-six students who entered Jefferson Medical College in 2002 (n = 227) and 2004 (n = 229) completed the Jefferson Scale of Physician Empathy at five different times: at entry into medical school on orientation day and subsequently at the end of each academic year. Statistical analyses were performed for the entire cohort, as well as for the "matched" cohort (participants who identified themselves at all five test administrations) and the "unmatched" cohort (participants who did not identify themselves in all five test administrations). RESULTS: Statistical analyses showed that empathy scores did not change significantly during the first two years of medical school. However, a significant decline in empathy scores was observed at the end of the third year which persisted until graduation. Findings were similar for the matched cohort (n = 121) and for the rest of the sample (unmatched cohort, n = 335). Patterns of decline in empathy scores were similar for men and women and across specialties. CONCLUSIONS: It is concluded that a significant decline in empathy occurs during the third year of medical school. It is ironic that the erosion of empathy occurs during a time when the curriculum is shifting toward patient-care activities; this is when empathy is most essential. Implications for retaining and enhancing empathy are discussed.

Recent molecular studies on endophytic bacterial diversity have revealed a large richness of species. Endophytes promote plant growth and yield, suppress pathogens, may help to remove contaminants, solubilize phosphate, or contribute assimilable nitrogen to plants. Some endophytes are seedborne, but others have mechanisms to colonize the plants that are being studied. Bacterial mutants unable to produce secreted proteins are impaired in the colonization process. Plant genes expressed in the presence of endophytes provide clues as to the effects of endophytes in plants. Molecular analysis showed that plant defense responses limit bacterial populations inside plants. Some human pathogens, such as Salmonella spp., have been found as endophytes, and these bacteria are not removed by disinfection procedures that eliminate superficially occurring bacteria. Delivery of endophytes to the environment or agricultural fields should be carefully evaluated to avoid introducing pathogens.

Abstract. Question: What are the major vegetation units in the Arctic, what is their composition, and how are they distributed among major bioclimate subzones and countries? Location: The Arctic tundra region, north of the tree line. Methods: A photo‐interpretive approach was used to delineate the vegetation onto an Advanced Very High Resolution Radiometer (AVHRR) base image. Mapping experts within nine Arctic regions prepared draft maps using geographic information technology (ArcInfo) of their portion of the Arctic, and these were later synthesized to make the final map. Area analysis of the map was done according to bioclimate subzones, and country. The integrated mapping procedures resulted in other maps of vegetation, topography, soils, landscapes, lake cover, substrate pH, and above‐ground biomass. Results: The final map was published at 1:7 500 000 scale map. Within the Arctic (total area = 7.11 × 106 km 2 ), about 5.05 × 10 6 km 2 is vegetated. The remainder is ice covered. The map legend generally portrays the zonal vegetation within each map polygon. About 26% of the vegetated area is erect shrublands, 18% peaty graminoid tundras, 13% mountain complexes, 12% barrens, 11% mineral graminoid tundras, 11% prostrate‐shrub tundras, and 7% wetlands. Canada has by far the most terrain in the High Arctic mostly associated with abundant barren types and prostrate dwarf‐shrub tundra, whereas Russia has the largest area in the Low Arctic, predominantly low‐shrub tundra. Conclusions: The CAVM is the first vegetation map of an entire global biome at a comparable resolution. The consistent treatment of the vegetation across the circumpolar Arctic, abundant ancillary material, and digital database should promote the application to numerous land‐use, and climate‐change applications and will make updating the map relatively easy.

Plant defenses against pathogens and insects are regulated differentially by cross-communicating signaling pathways in which salicylic acid (SA), jasmonic acid (JA), and ethylene (ET) play key roles. To understand how plants integrate pathogen- and insect-induced signals into specific defense responses, we monitored the dynamics of SA, JA, and ET signaling in Arabidopsis after attack by a set of microbial pathogens and herbivorous insects with different modes of attack. Arabidopsis plants were exposed to a pathogenic leaf bacterium (Pseudomonas syringae pv. tomato), a pathogenic leaf fungus (Alternaria brassicicola), tissue-chewing caterpillars (Pieris rapae), cell-content-feeding thrips (Frankliniella occidentalis), or phloem-feeding aphids (Myzus persicae). Monitoring the signal signature in each plant-attacker combination showed that the kinetics of SA, JA, and ET production varies greatly in both quantity and timing. Analysis of global gene expression profiles demonstrated that the signal signature characteristic of each Arabidopsis-attacker combination is orchestrated into a surprisingly complex set of transcriptional alterations in which, in all cases, stress-related genes are overrepresented. Comparison of the transcript profiles revealed that consistent changes induced by pathogens and insects with very different modes of attack can show considerable overlap. Of all consistent changes induced by A. brassicicola, Pieris rapae, and E occidentalis, more than 50% also were induced consistently by P. syringae. Notably, although these four attackers all stimulated JA biosynthesis, the majority of the changes in JA-responsive gene expression were attacker specific. All together, our study shows that SA, JA, and ET play a primary role in the orchestration of the plant's defense response, but other regulatory mechanisms, such as pathway cross-talk or additional attacker-induced signals, eventually shape the highly complex attacker-specific defense response.

In nature, plants abundantly form beneficial associations with soilborne microbes that are important for plant survival and, as such, affect plant biodiversity and ecosystem functioning. Classical examples of symbiotic microbes are mycorrhizal fungi that aid in the uptake of water and minerals, and Rhizobium bacteria that fix atmospheric nitrogen for the plant. Several other types of beneficial soilborne microbes, such as plant-growth-promoting rhizobacteria and fungi with biological control activity, can stimulate plant growth by directly suppressing deleterious soilborne pathogens or by priming aboveground plant parts for enhanced defense against foliar pathogens or insect herbivores. The establishment of beneficial associations requires mutual recognition and substantial coordination of plant and microbial responses. A growing body of evidence suggests that beneficial microbes are initially recognized as potential invaders, after which an immune response is triggered, whereas, at later stages of the interaction, mutualists are able to short-circuit plant defense responses to enable successful colonization of host roots. Here, we review our current understanding of how symbiotic and nonsymbiotic beneficial soil microbes modulate the plant immune system and discuss the role of local and systemic defense responses in establishing the delicate balance between the two partners.

Somatic, gain-of-function mutations in ras genes were the first specific genetic alterations identified in human cancer about 3 decades ago. Studies during the last quarter century have characterized the Ras proteins as essential components of signaling networks controlling cellular proliferation, differentiation, or survival. The oncogenic mutations of the H-ras, N-ras, or K-ras genes frequently found in human tumors are known to throw off balance the normal outcome of those signaling pathways, thus leading to tumor development. Oncogenic mutations in a number of other upstream or downstream components of Ras signaling pathways (including membrane RTKs or cytosolic kinases) have been detected more recently in association with a variety of cancers. Interestingly, the oncogenic Ras mutations and the mutations in other components of Ras/MAPK signaling pathways appear to be mutually exclusive events in most tumors, indicating that deregulation of Ras-dependent signaling is the essential requirement for tumorigenesis. In contrast to sporadic tumors, separate studies have identified germline mutations in Ras and various other components of Ras signaling pathways that occur in specific association with a number of different familial, developmental syndromes frequently sharing common phenotypic cardiofaciocutaneous features. Finally, even without being a causative force, defective Ras signaling has been cited as a contributing factor to many other human illnesses, including diabetes and immunological and inflammatory disorders. We aim this review at summarizing and updating current knowledge on the contribution of Ras mutations and altered Ras signaling to development of various tumoral and nontumoral pathologies.

Peer Reviewed

The share of the population aged 60 and over is projected to increase in nearly every country in the world during the period 2005–50. Population ageing will tend to lower both labour-force participation and savings rates, thereby raising concerns about a future slowing of economic growth. Our calculations suggest that OECD countries are likely to see modest—but not catastrophic—declines in the rate of economic growth. However, behavioural responses (including greater female labour-force participation) and policy reforms (including an increase in the legal age of retirement) can mitigate the economic consequences of an older population. In most non-OECD countries, declining fertility rates will cause labour-force-to-population ratios to rise as the shrinking share of young people will more than offset the skewing of adults towards the older ages. These factors suggest that population ageing will not significantly impede the pace of economic growth in developing countries.

Worldwide, contamination of soil and ground water is a severe problem. The negative effects of pollutants on the environment and on human health are diverse and depend on the nature of the pollution. The search for alternative methods for excavation and incineration to clean polluted sites resulted in the application of bioremediation techniques. In this review, we describe some generally accepted bioremediation tools and subsequently focus on the combination of two approaches, phytoremediation and bioaugmentation, resulting in rhizoremediation. During rhizoremediation, exudates derived from the plant can help to stimulate the survival and action of bacteria, which subsequently results in a more efficient degradation of pollutants. The root system of plants can help to spread bacteria through soil and help to penetrate otherwise impermeable soil layers. The inoculation of pollutant-degrading bacteria on plant seed can be an important additive to improve the efficiency of phytoremediation or bioaugmentation.

Abstract Physically based deformable models have been widely embraced by the Computer Graphics community. Many problems outlined in a previous survey by Gibson and Mirtich have been addressed, thereby making these models interesting and useful for both offline and real‐time applications, such as motion pictures and video games. In this paper, we present the most significant contributions of the past decade, which produce such impressive and perceivably realistic animations and simulations: finite element/difference/volume methods, mass‐spring systems, mesh‐free methods, coupled particle systems and reduced deformable models‐based on modal analysis. For completeness, we also make a connection to the simulation of other continua, such as fluids, gases and melting objects. Since time integration is inherent to all simulated phenomena, the general notion of time discretization is treated separately, while specifics are left to the respective models. Finally, we discuss areas of application, such as elastoplastic deformation and fracture, cloth and hair animation, virtual surgery simulation, interactive entertainment and fluid/smoke animation, and also suggest areas for future research.

Despite its presumed role as an engine of economic growth, we know surprisingly little about the drivers of scientific creativity. We exploit key differences across funding streams within the academic life sciences to estimate the impact of incentives on the rate and direction of scientific exploration. Specifically, we study the careers of investigators of the Howard Hughes Medical Institute (HHMI), which tolerates early failure, rewards long‐term success, and gives its appointees great freedom to experiment, and grantees from the National Institutes of Health (NIH), who are subject to short review cycles, predefined deliverables, and renewal policies unforgiving of failure. Using a combination of propensity‐score weighting and difference‐in‐differences estimation strategies, we find that HHMI investigators produce high‐impact articles at a much higher rate than a control group of similarly accomplished NIH‐funded scientists. Moreover, the direction of their research changes in ways that suggest the program induces them to explore novel lines of inquiry.

ABSTRACT Despite ambitious efforts in various fields of research over multiple decades, the goal of making academic research relevant to the practitioner remains elusive: theoretical and academic research interests do not seem to coincide with the interests of managerial practice. This challenge is more fundamental than knowledge transfer , it is one of diverging knowledge interests and means of knowledge production . In this article, we look at this fundamental challenge through the lens of design science, which is an approach aimed primarily at discovery and problem solving as opposed to accumulation of theoretical knowledge. We explore in particular the ways in which problem‐solving research and theory‐oriented academic research can complement one another. In operations management (OM) research, recognizing and building on this complementarity is especially crucial, because problem‐solving–oriented research produces the very artifacts (e.g., technologies) that empirical OM research subsequently evaluates in an attempt to build explanatory theory. It is indeed the practitioner—not the academic scientist—who engages in basic research in OM. This idiosyncrasy prompts the question: how can we enhance the cross‐fertilization between academic research and research practice to make novel theoretical insights and practical relevance complementary? This article proposes a design science approach to bridge practice to theory rather than theory to practice.

Podosphaera fusca is the main causal agent of cucurbit powdery mildew in Spain. Four Bacillus subtilis strains, UMAF6614, UMAF6619, UMAF6639, and UMAF8561, with proven ability to suppress the disease on melon in detached leaf and seedling assays, were subjected to further analyses to elucidate the mode of action involved in their biocontrol performance. Cell-free supernatants showed antifungal activities very close to those previously reported for vegetative cells. Identification of three lipopeptide antibiotics, surfactin, fengycin, and iturin A or bacillomycin, in butanolic extracts from cell-free culture filtrates of these B. subtilis strains pointed out that antibiosis could be a major factor involved in their biocontrol ability. The strong inhibitory effect of purified lipopeptide fractions corresponding to bacillomycin, fengycin, and iturin A on P. fusca conidia germination, as well as the in situ detection of these lipopeptides in bacterial-treated melon leaves, provided interesting evidence of their putative involvement in the antagonistic activity. Those results were definitively supported by site-directed mutagenesis analysis, targeted to suppress the biosynthesis of the different lipopeptides. Taken together, our data have allowed us to conclude that the iturin and fengycin families of lipopeptides have a major role in the antagonism of B. subtilis toward P. fusca.

Phytohormone-like acting compounds previously have been suggested to be involved in the phytostimulatory action exerted by the plant-beneficial rhizobacterium Bacillus amyloliquefaciens FZB42. Analyses by high-performance liquid chromatography and gas chromatography-mass spectrometry performed with culture filtrates of FZB42 demonstrated the presence of indole-3-acetic acid (IAA), corroborating it as one of the pivotal plant-growth-promoting substances produced by this bacterium. In the presence of 5 mM tryptophan, a fivefold increase in IAA secretion was registered. In addition, in the trp auxotrophic strains E101 (deltatrpBA) and E102 (deltatrpED), and in two other strains bearing knockout mutations in genes probably involved in IAA metabolism, E103 (deltaysnE, putative IAA transacetylase) and E105 (deltayhcX, putative nitrilase), the concentration of IAA in the culture filtrates was diminished. Three of these mutant strains were less efficient in promoting plant growth, indicating that the Trp-dependent synthesis of auxins and plant growth promotion are functionally related in B. amyloliquefaciens.

OBJECTIVES: To further validate and assess the reliability and validity of the Trust in Physician Scale. METHODS: Consecutive adult patients (n = 414) from 20 community-based, primary care practices were enrolled in a prospective, 6-month study. At enrollment, subjects completed the 11-item Trust in Physician Scale plus measures of demographics, preferences for care, and satisfaction with care received from the physician. Continuity, satisfaction with care, and self-reported adherence to treatment were measured at 6 months. Reliability, construct validity, and predictive validity were assessed using correlation coefficients and analysis of variance techniques. RESULTS: The Trust in Physician Scale showed high internal consistency (Cronbach's alpha = .89) and good 1-month test-retest reliability (intraclass correlation coefficient = .77). As expected, trust increased with the length of the relationship and was higher among patients who actively chose their physician, who preferred more physician involvement, and who expected their physician to care for a larger proportion of their problems (P < 0.001 for all associations). Baseline trust predicted continuity with the physician, self-reported adherence to medication, and satisfaction at 6 months after adjustment for gender, age, education, length of the relationship, active choice of the physician, and preferences for care. After additional adjustment for baseline satisfaction with physician care, trust remained a significant predictor of continuity, adherence, and satisfaction. CONCLUSIONS: The Trust in Physician Scale has desirable psychometric characteristics and demonstrates construct and predictive validity. It appears to be related to, but still distinct from, patient satisfaction with the physician and, thus, provides a valuable additional measure for assessment of the quality of the patient-physician relationship.