Medical Protective

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.

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.

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.

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.

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.

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.

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.

Given the rapid expansion of narrative approaches in management and organization theory in recent years, this paper investigates the contribution of this literature to the understanding of organizations and processes of organizing. The paper tells the story of the development of narrative approaches in organizational theory. Narrative's contribution to substantive areas of organization theory is evaluated. These developments are then reviewed in relation to an ongoing tension between story and science. We conclude by contemplating some of the criticisms, and the future, of narrative research.

A new set of broad-host-range promoter-probe vectors has been constructed. One subset contains the pVS1 and p15a replicons and confers resistance to either gentamicin or kanamycin. The other set contains the broad-host-range replicon from pBBR1 and confers resistance to kanamycin, tetracycline, ampicillin, or spectinomycin/streptomycin. Both plasmid sets are highly stable and are maintained without selection for more than 30 generations in several bacterial taxa. Each plasmid contains a promoter-probe cassette that consists of a multicloning site, containing several unique restriction sites, and gfp or inaZ as a reporter gene. The cassette is bound by transcriptional terminators to permit the insertion of strong promoters and to insulate the cassette from external transcription enabling the detection of weak or moderate promoters. The vector suite was augmented with derivatives of the kanamycin-resistant gfp promoter-probe plasmids that encode Gfp variants with different half-life times.

In Brief OBJECTIVE: To review the biology and the pathophysiology of uterine myomas, focus on options for management, and emphasize principles that will render the decision-making process as logical as possible. DESIGN: Literature review and synthesis of the authors’ experience and philosophy. RESULTS: Uterine myomas are the most common solid pelvic tumors in women. There is increasing evidence that they have a genetic basis and that their growth is related to genetic predisposition, hormonal influences, and various growth factors. Treatment choices are wide and include pharmacologic, surgical, and radiographically directed intervention. Most myomas can be followed serially with surveillance for development of symptoms or progressive growth. CONCLUSION: The past century has witnessed development of highly sophisticated diagnostic and therapeutic technology for myomas. The tools currently at our disposal permit greater management flexibility with safe options, which must be tailored to the individual clinical situation. The past century has witnessed development of highly sophisticated diagnostic and therapeutic technology for leiomyomata; current tools permit greater management flexibility with safe options that must be tailored to each individual clinical situation.

Author Affiliation: Senior Nurse Scientist and Clinical Nurse Specialist, Office of Nursing Research & Innovation, Nursing Institute, Cleveland Clinic, Ohio. The author reports no conflicts of interest. Correspondence: Sandra L. Siedlecki, PhD, RN, APRN-CNS, 3271 Stillwater Dr, Medina, OH 44256 ([email protected]).

Nicotiana benthamiana is a widely used model plant species for the study of fundamental questions in molecular plant-microbe interactions and other areas of plant biology. This popularity derives from its well-characterized susceptibility to diverse pathogens and, especially, its amenability to virus-induced gene silencing and transient protein expression methods. Here, we report the generation of a 63-fold coverage draft genome sequence of N. benthamiana and its availability on the Sol Genomics Network for both BLAST searches and for downloading to local servers. The estimated genome size of N. benthamiana is 3 Gb (gigabases). The current assembly consists of approximately 141,000 scaffolds, spanning 2.6 Gb with 50% of the genome sequence contained within scaffolds >89 kilobases. Of the approximately 16,000 N. benthamiana unigenes available in GenBank, >90% are represented in the assembly. The usefulness of the sequence was demonstrated by the retrieval of N. benthamiana orthologs for 24 immunity-associated genes from other species including Ago2, Ago7, Bak1, Bik1, Crt1, Fls2, Pto, Prf, Rar1, and mitogen-activated protein kinases. The sequence will also be useful for comparative genomics in the Solanaceae family as shown here by the discovery of microsynteny between N. benthamiana and tomato in the region encompassing the Pto and Prf genes.

Abstract The child directed speech of twelve English‐speaking motherswas analyzed in terms of utterance‐level constructions. First, the mothers' utterances were categorized in terms of general constructional categories such as Wh‐questions, copulas and transitives. Second, mothers' utterances within these categories were further specified in terms of the initial words that framed the utterance, item‐based phrases such as Are you …, I'll …, It's …, Let's …, What did … The findings were: (i) overall, only about 15% of all maternal utterances had SVO form (most were questions, imperatives, copulas, and fragments); (ii) 51% of all maternal utterances began with one of 52 item‐based phrases, mostly consisting of two words or morphemes (45% began with one of just 17 words); and (iii) children used many of these same item‐based phrases, in some cases at a rate that correlated highly with their own mother's frequency of use. We suggest that analyses of adult–child linguistic interaction should take into account not just general constructional categories, but also the item‐based constructions that adults and children use and the frequency with which they use them.

Elevated sodium (Na(+)) decreases plant growth and, thereby, agricultural productivity. The ion transporter high-affinity K(+) transporter (HKT)1 controls Na(+) import in roots, yet dysfunction or overexpression of HKT1 fails to increase salt tolerance, raising questions as to HKT1's role in regulating Na(+) homeostasis. Here, we report that tissue-specific regulation of HKT1 by the soil bacterium Bacillus subtilis GB03 confers salt tolerance in Arabidopsis thaliana. Under salt stress (100 mM NaCl), GB03 concurrently down- and upregulates HKT1 expression in roots and shoots, respectively, resulting in lower Na(+) accumulation throughout the plant compared with controls. Consistent with HKT1 participation in GB03-induced salt tolerance, GB03 fails to rescue salt-stressed athkt1 mutants from stunted foliar growth and elevated total Na(+) whereas salt-stressed Na(+) export mutants sos3 show GB03-induced salt tolerance with enhanced shoot and root growth as well as reduced total Na(+). These results demonstrate that tissue-specific regulation of HKT1 is critical for managing Na(+) homeostasis in salt-stressed plants, as well as underscore the breadth and sophistication of plant-microbe interactions.

BACKGROUND: The discovery of low-frequency coding variants affecting the risk of coronary artery disease has facilitated the identification of therapeutic targets. METHODS: Through DNA genotyping, we tested 54,003 coding-sequence variants covering 13,715 human genes in up to 72,868 patients with coronary artery disease and 120,770 controls who did not have coronary artery disease. Through DNA sequencing, we studied the effects of loss-of-function mutations in selected genes. RESULTS: We confirmed previously observed significant associations between coronary artery disease and low-frequency missense variants in the genes LPA and PCSK9. We also found significant associations between coronary artery disease and low-frequency missense variants in the genes SVEP1 (p.D2702G; minor-allele frequency, 3.60%; odds ratio for disease, 1.14; P=4.2×10(-10)) and ANGPTL4 (p.E40K; minor-allele frequency, 2.01%; odds ratio, 0.86; P=4.0×10(-8)), which encodes angiopoietin-like 4. Through sequencing of ANGPTL4, we identified 9 carriers of loss-of-function mutations among 6924 patients with myocardial infarction, as compared with 19 carriers among 6834 controls (odds ratio, 0.47; P=0.04); carriers of ANGPTL4 loss-of-function alleles had triglyceride levels that were 35% lower than the levels among persons who did not carry a loss-of-function allele (P=0.003). ANGPTL4 inhibits lipoprotein lipase; we therefore searched for mutations in LPL and identified a loss-of-function variant that was associated with an increased risk of coronary artery disease (p.D36N; minor-allele frequency, 1.9%; odds ratio, 1.13; P=2.0×10(-4)) and a gain-of-function variant that was associated with protection from coronary artery disease (p.S447*; minor-allele frequency, 9.9%; odds ratio, 0.94; P=2.5×10(-7)). CONCLUSIONS: We found that carriers of loss-of-function mutations in ANGPTL4 had triglyceride levels that were lower than those among noncarriers; these mutations were also associated with protection from coronary artery disease. (Funded by the National Institutes of Health and others.).

Unforgiveness and forgiveness are distinct. One cannot forgive unless unforgiveness has occurred, but one might reduce unforgiveness by many ways—only one of which is forgiveness. We present a model intended to further assist and guide subsequent empirical exploration. The model explains the personal, relationship, and environmental factors that lead people to either unforgiveness or forgiveness. Related areas are reviewed to stimulate as yet unexplored research and clinical efforts related to forgiveness. Clinical protocols for promoting forgiveness in enrichment, preventative, and therapeutic contexts are described.

Abstract. In writings on the open source software development model, it is often argued that it is successful as a result of the gift economy that embraces activities in online communities. However, the theoretical foundations for this argument are seldom discussed and empirically tested. Starting with the ‘classic’ theories of gift giving, we discuss how they need to be developed in order to explain gift‐giving practices in digital domains. In this paper, we argue that the gift economy is important, not only because it creates openness, but also because it organizes relationships between people in a certain way. Open source software development relies on gift giving as a way of getting new ideas and prototypes out into circulation. This also implies that the giver gets power from giving away. This power is used as a way of guaranteeing the quality of the code. We relate this practice to how gifts, in the form of new scientific knowledge, are given to the research community, and how this is done through peer review processes.