Showing papers by "Dartmouth College published in 2008"

Community Resilience as a Metaphor, Theory, Set of Capacities, and Strategy for Disaster Readiness

Abstract: Communities have the potential to function effectively and adapt successfully in the aftermath of disasters. Drawing upon literatures in several disciplines, we present a theory of resilience that encompasses contemporary understandings of stress, adaptation, wellness, and resource dynamics. Community resilience is a process linking a network of adaptive capacities (resources with dynamic attributes) to adaptation after a disturbance or adversity. Community adaptation is manifest in population wellness, defined as high and non-disparate levels of mental and behavioral health, functioning, and quality of life. Community resilience emerges from four primary sets of adaptive capacities—Economic Development, Social Capital, Information and Communication, and Community Competence—that together provide a strategy for disaster readiness. To build collective resilience, communities must reduce risk and resource inequities, engage local people in mitigation, create organizational linkages, boost and protect social supports, and plan for not having a plan, which requires flexibility, decision-making skills, and trusted sources of information that function in the face of unknowns.

The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2

Abstract: Cancer progression has similarities with the process of epithelial-to-mesenchymal transition (EMT) found during embryonic development, during which cells down-regulate E-cadherin and up-regulate Vimentin expression. By evaluating the expression of 207 microRNAs (miRNAs) in the 60 cell lines of the drug screening panel maintained by the Nation Cancer Institute, we identified the miR-200 miRNA family as an extraordinary marker for cells that express E-cadherin but lack expression of Vimentin. These findings were extended to primary ovarian cancer specimens. miR-200 was found to directly target the mRNA of the E-cadherin transcriptional repressors ZEB1 (TCF8/δEF1) and ZEB2 (SMAD-interacting protein 1 [SIP1]/ZFXH1B). Ectopic expression of miR-200 caused up-regulation of E-cadherin in cancer cell lines and reduced their motility. Conversely, inhibition of miR-200 reduced E-cadherin expression, increased expression of Vimentin, and induced EMT. Our data identify miR-200 as a powerful marker and determining factor of the epithelial phenotype of cancer cells.

The Economic Consequences of Legal Origins

Abstract: In the last decade, economists have produced a considerable body of research suggesting that the historical origin of a country's laws is highly correlated with a broad range of its legal rules and regulations, as well as with economic outcomes. We summarize this evidence and attempt a unified interpretation. We also address several objections to the empirical claim that legal origins matter. Finally, we assess the implications of this research for economic reform.

The Dartmouth Stellar Evolution Database

Abstract: The ever-expanding depth and quality of photometric and spectroscopic observations of stellar populations increase the need for theoretical models in regions of age-composition parameter space that are largely unexplored at present. Stellar evolution models that employ the most advanced physics and cover a wide range of compositions are needed to extract the most information from current observations of both resolved and unresolved stellar populations. The Dartmouth Stellar Evolution Database is a collection of stellar evolution tracks and isochrones that spans a range of [Fe/H] from –2.5 to +0.5, [α/Fe] from –0.2 to +0.8 (for [Fe/H] ≤ 0) or +0.2 (for [Fe/H] > 0), and initial He mass fractions from Y = 0.245 to 0.40. Stellar evolution tracks were computed for masses between 0.1 and 4 M☉, allowing isochrones to be generated for ages as young as 250 Myr. For the range in masses where the core He flash occurs, separate He-burning tracks were computed starting from the zero age horizontal branch. The tracks and isochrones have been transformed to the observational plane in a variety of photometric systems including standard UBV(RI)C, Stromgren uvby, SDSS ugriz, 2MASS JHKs, and HST ACS/WFC and WFPC2. The Dartmouth Stellar Evolution Database is accessible through a Web site at http://stellar.dartmouth.edu/~models/ where all tracks, isochrones, and additional files can be downloaded.

Identification of RIP1 kinase as a specific cellular target of necrostatins.

Abstract: Necroptosis is a cellular mechanism of necrotic cell death induced by apoptotic stimuli in the form of death domain receptor engagement by their respective ligands under conditions where apoptotic execution is prevented. Although it occurs under regulated conditions, necroptotic cell death is characterized by the same morphological features as unregulated necrotic death. Here we report that necrostatin-1, a previously identified small-molecule inhibitor of necroptosis, is a selective allosteric inhibitor of the death domain receptor-associated adaptor kinase RIP1 in vitro. We show that RIP1 is the primary cellular target responsible for the antinecroptosis activity of necrostatin-1. In addition, we show that two other necrostatins, necrostatin-3 and necrostatin-5, also target the RIP1 kinase step in the necroptosis pathway, but through mechanisms distinct from that of necrostatin-1. Overall, our data establish necrostatins as the first-in-class inhibitors of RIP1 kinase, the key upstream kinase involved in the activation of necroptosis.

Strategic Leadership: Theory and Research on Executives, Top Management Teams, and Boards

Abstract: TABLE OF CONTENTS PREFACE DEDICATION 1. The Study of Top Executives 2. Do Top Executives Matter? 3. How Individual Differences Affect Executive Action 4. Executive Experiences and Organizational Outcomes 5. Top Management Teams 6. Changes at the Top: The Antecedents of Executive Turnover and Succession 7. Changes at the Top: The Consequences of Executive Turnover and Succession 8. Understanding Board Structure, Composition, and Vigilance 9. The Consequences of Board Involvement and Vigilance 10. The Determinants of Executive Compensation 11. Executive Compensation: Consequences and Distributions REFERENCES LIST OF TABLES ENDNOTES

Screening for colorectal cancer: U.S. Preventive Services Task Force recommendation statement

Abstract: DESCRIPTION Update of the 2002 U.S. Preventive Services Task Force (USPSTF) recommendation statement on screening for colorectal cancer. METHODS To update its recommendation, the USPSTF commissioned 2 studies: 1) a targeted systematic evidence review on 4 selected questions relating to test characteristics and benefits and harms of screening technologies, and 2) a decision analytic modeling analysis using population modeling techniques to compare the expected health outcomes and resource requirements of available screening modalities when used in a programmatic way over time. RECOMMENDATIONS The USPSTF recommends screening for colorectal cancer using fecal occult blood testing, sigmoidoscopy, or colonoscopy in adults, beginning at age 50 years and continuing until age 75 years. The risks and benefits of these screening methods vary. (A recommendation). The USPSTF recommends against routine screening for colorectal cancer in adults 76 to 85 years of age. There may be considerations that support colorectal cancer screening in an individual patient. (C recommendation). The USPSTF recommends against screening for colorectal cancer in adults older than age 85 years. (D recommendation). The USPSTF concludes that the evidence is insufficient to assess the benefits and harms of computed tomographic colonography and fecal DNA testing as screening modalities for colorectal cancer. (I statement).

Sensing meets mobile social networks: the design, implementation and evaluation of the CenceMe application

Abstract: We present the design, implementation, evaluation, and user ex periences of theCenceMe application, which represents the first system that combines the inference of the presence of individuals using off-the-shelf, sensor-enabled mobile phones with sharing of this information through social networking applications such as Facebook and MySpace. We discuss the system challenges for the development of software on the Nokia N95 mobile phone. We present the design and tradeoffs of split-level classification, whereby personal sensing presence (e.g., walking, in conversation, at the gym) is derived from classifiers which execute in part on the phones and in part on the backend servers to achieve scalable inference. We report performance measurements that characterize the computational requirements of the software and the energy consumption of the CenceMe phone client. We validate the system through a user study where twenty two people, including undergraduates, graduates and faculty, used CenceMe continuously over a three week period in a campus town. From this user study we learn how the system performs in a production environment and what uses people find for a personal sensing system.

How biotech can transform biofuels

Abstract: For cellulosic ethanol to become a reality, biotechnological solutions should focus on optimizing the conversion of biomass to sugars.

Surgical versus Nonsurgical Therapy for Lumbar Spinal Stenosis

Abstract: Background Surgery for spinal stenosis is widely performed, but its effectiveness as compared with nonsurgical treatment has not been shown in controlled trials. Methods Surgical candidates with a history of at least 12 weeks of symptoms and spinal stenosis without spondylolisthesis (as confirmed on imaging) were enrolled in either a randomized cohort or an observational cohort at 13 U.S. spine clinics. Treatment was decompressive surgery or usual nonsurgical care. The primary outcomes were measures of bodily pain and physical function on the Medical Outcomes Study 36-item Short-Form General Health Survey (SF-36) and the modified Oswestry Disability Index at 6 weeks, 3 months, 6 months, and 1 and 2 years. Results A total of 289 patients were enrolled in the randomized cohort, and 365 patients were enrolled in the observational cohort. At 2 years, 67% of patients who were randomly assigned to surgery had undergone surgery, whereas 43% of those who were randomly assigned to receive nonsurgical care had also...

A Skeptical Appraisal of Asset Pricing Tests

Abstract: It has become standard practice in the cross-sectional asset-pricing literature to evaluate models based on how well they explain average returns on size-B/M portfolios, something many models seem to do remarkably well. In this paper, we review and critique the empirical methods used in the literature. We argue that asset-pricing tests are often highly misleading, in the sense that apparently strong explanatory power (high cross-sectional R2s and small pricing errors) in fact provides quite weak support for a model. We offer a number of suggestions for improving empirical tests and evidence that several proposed models don't work as well as originally advertised.

Classification of Traumatic Brain Injury for Targeted Therapies

Abstract: The heterogeneity of traumatic brain injury (TBI) is considered one of the most significant barriers to finding effective therapeutic interventions. In October, 2007, the National Institute of Neurological Disorders and Stroke, with support from the Brain Injury Association of America, the Defense and Veterans Brain Injury Center, and the National Institute of Disability and Rehabilitation Research, convened a workshop to outline the steps needed to develop a reliable, efficient and valid classification system for TBI that could be used to link specific patterns of brain and neurovascular injury with appropriate therapeutic interventions. Currently, the Glasgow Coma Scale (GCS) is the primary selection criterion for inclusion in most TBI clinical trials. While the GCS is extremely useful in the clinical management and prognosis of TBI, it does not provide specific information about the pathophysiologic mechanisms which are responsible for neurological deficits and targeted by interventions. On th...

Planning and Financial Literacy: How Do Women Fare?

Abstract: Many older US households have done little or no planning for retirement, and there is a substantial population that seems to undersave for retirement. Of particular concern is the relative position of older women, who are more vulnerable to old-age poverty due to their longer longevity. This paper uses data from a special module we devised on planning and financial literacy in the 2004 Health and Retirement Study. It shows that women display much lower levels of financial literacy than the older population as a whole. In addition, women who are less financially literate are also less likely to plan for retirement and be successful planners. These findings have important implications for policy and for programs aimed at fostering financial security at older ages.

Superman or the Fantastic Four? Knowledge Combination and Experience in Innovative Teams

Abstract: We examine how knowledge and experience affect both the mean and variance values of innovations from individuals and teams. We apply and extend theory on innovativeness and creativity to propose that holding multiple knowledge domains produces novel combinations that increase the variance of product performance; and that extensive experience produces outputs with high average performance. We analyzed innovations in the comic book industry, finding that innovations with extreme success and failure are affected by similar factors as high-performing innovations. Multi-member teams and teams with experience working together produced innovations with greater variation in value, but individuals were able to combine knowledge diversity more effectively than teams.

Outcomes for COPD pharmacological trials: From lung function to biomarkers

Abstract: The American Thoracic Society/European Respiratory Society jointly created a Task Force on "Outcomes for COPD pharmacological trials: from lung function to biomarkers" to inform the chronic obstructive pulmonary disease research community about the possible use and limitations of current outcomes and markers when evaluating the impact of a pharmacological therapy. Based on their review of the published literature, the following document has been prepared with individual sections that address specific outcomes and markers, and a final section that summarises their recommendations.

Estimating Teacher Impacts on Student Achievement: An Experimental Evaluation

Abstract: We used a random-assignment experiment in Los Angeles Unified School District to evaluate various non-experimental methods for estimating teacher effects on student test scores. Estimated teacher effects from a pre-experimental period were used to predict student achievement following random assignment of teachers to classrooms. While all of the teacher effect estimates we considered were significant predictors of student achievement under random assignment, those that controlled for prior student test scores yielded unbiased predictions and those that further controlled for mean classroom characteristics yielded the best prediction accuracy. In both the experimental and nonexperimental data, we found that teacher effects faded out by roughly 50 percent per year in the two years following teacher assignment.

Of lineage and legacy: the development of mammalian hematopoietic stem cells

Abstract: The hematopoietic system is one of the first complex tissues to develop in the mammalian conceptus. Of particular interest in the field of developmental hematopoiesis is the origin of adult bone marrow hematopoietic stem cells. Tracing their origin is complicated because blood is a mobile tissue and because hematopoietic cells emerge from many embryonic sites. The origin of the adult mammalian blood system remains a topic of lively discussion and intense research. Interest is also focused on developmental signals that induce the adult hematopoietic stem cell program, as these may prove useful for generating and expanding these clinically important cell populations ex vivo. This review presents a historical overview of and the most recent data on the developmental origins of hematopoiesis.

An update on randomized controlled trials of evidence-based supported employment.

Abstract: Background: The Individual Placement and Support (IPS) model of supported em - ployment for clients with severe mental illness has been described as a standardi - zation of evidence-based supported employment. Although several reviews on the literature on its effectiveness have been conducted, the completion of several new studies suggests an updated review is warranted. Methods: We conducted a comprehensive literature search for randomized con - trolled trials of IPS, limiting our review to programs with high-fidelity IPS pro - grams, locating 11 studies. We examined the following competitive employment outcomes: employment rates, days to first job, annualized weeks worked, and job tenure in longest job held during the follow-up period. Findings: Across the 11 studies, the competitive employment rate was 61% for IPS compared to 23% for controls. About two-thirds of those who obtained competitive employment worked 20 hours or more per week. Among those who obtained a competitive job, IPS participants obtained their first job nearly 10 weeks earlier than did controls. Among IPS participants who obtained competitive work, dura - tion of employment after the start of the first job averaged 24.2 weeks per year, or 47% of the 52-week year. Conclusions: The current review is consistent with earlier reviews, although the evi - dence for high-fidelity IPS appears to be somewhat stronger here than in reviews evaluating studies with more heterogeneity in the supported employment models examined. The number, consistency, and effect sizes of studies of evidence-based supported employment establish it as one of the most robust interventions avail - able for persons with severe mental illness.

Why It Pays to Get Inside the Head of Your Opponent The Differential Effects of Perspective Taking and Empathy in Negotiations

Abstract: The current research explored whether two re- lated yet distinct social competencies—perspective taking (the cognitive capacity to consider the world from another individual's viewpoint) and empathy (the ability to connect emotionally with another individual)—have differential effects in negotiations. Across three studies, using both individual difference measures and experimental manip- ulations, we found that perspective taking increased in- dividuals' ability to discover hidden agreements and to both create and claim resources at the bargaining table. However, empathy did not prove nearly as advantageous and at times was detrimental to discovering a possible deal and achieving individual profit. These results held re- gardless of whether the interaction was a negotiation in which a prima facie solution was not possible or a multiple- issue negotiation that required discovering mutually ben- eficial trade-offs. Although empathy is an essential tool in many aspects of social life, perspective taking appears to be a particularly critical ability in negotiations.

Customer Channel Migration

Abstract: The authors develop a model of customer channel migration and apply it to a retailer that markets over the Web and through catalogs. The model identifies the key phenomena required to analyze customer migration, shows how these phenomena can be modeled, and develops an approach for estimating the model. The methodology is unique in its ability to accommodate heterogeneous customer responses to a large number of distinct marketing communications in a dynamic context. The results indicate that (1) Web purchasing is associated with lower subsequent purchase volumes than when buying from other outlets; (2) marketing efforts are associated with channel usage and purchase incidence, offsetting negative Web experience effects; and (3) negative interactions occur between like communications (catalog × catalog or e-mail × e-mail) and between different types of communications (catalog × e-mail). The authors find that over the four-year period of their data, a Web-oriented “migration” segment emerged, and t...

The Rise of People-Centric Sensing

Abstract: Technological advances in sensing, computation, storage, and communications will turn the near-ubiquitous mobile phone into a global mobile sensing device. People-centric sensing will help drive this trend by enabling a different way to sense, learn, visualize, and share information about ourselves, friends, communities, the way we live, and the world we live in. It juxtaposes the traditional view of mesh sensor networks with one in which people, carrying mobile devices, enable opportunistic sensing coverage. In the MetroSense Project's vision of people-centric sensing, users are the key architectural system component, enabling a host of new application areas such as personal, public, and social sensing.

Nicotinic Acid, Nicotinamide, and Nicotinamide Riboside: A Molecular Evaluation of NAD+ Precursor Vitamins in Human Nutrition

Abstract: Although baseline requirements for nicotinamide adenine dinucleotide (NAD+) synthesis can be met either with dietary tryptophan or with less than 20 mg of daily niacin, which consists of nicotinic acid and/or nicotinamide, there is growing evidence that substantially greater rates of NAD+ synthesis may be beneficial to protect against neurological degeneration, Candida glabrata infection, and possibly to enhance reverse cholesterol transport. The distinct and tissue-specific biosynthetic and/or ligand activities of tryptophan, nicotinic acid, nicotinamide, and the newly identified NAD+ precursor, nicotinamide riboside, reviewed herein, are responsible for vitamin-specific effects and side effects. Because current data suggest that nicotinamide riboside may be the only vitamin precursor that supports neuronal NAD+ synthesis, we present prospects for human nicotinamide riboside supplementation and propose areas for future research.

An extremely luminous X-ray outburst at the birth of a supernova

Abstract: Massive stars end their short lives in spectacular explosions—supernovae—that synthesize new elements and drive galaxy evolution. Historically, supernovae were discovered mainly through their 'delayed' optical light (some days after the burst of neutrinos that marks the actual event), preventing observations in the first moments following the explosion. As a result, the progenitors of some supernovae and the events leading up to their violent demise remain intensely debated. Here we report the serendipitous discovery of a supernova at the time of the explosion, marked by an extremely luminous X-ray outburst. We attribute the outburst to the 'break-out' of the supernova shock wave from the progenitor star, and show that the inferred rate of such events agrees with that of all core-collapse supernovae. We predict that future wide-field X-ray surveys will catch each year hundreds of supernovae in the act of exploding.

Effects of febuxostat versus allopurinol and placebo in reducing serum urate in subjects with hyperuricemia and gout: a 28-week, phase III, randomized, double-blind, parallel-group trial.

Abstract: Objective To compare the urate-lowering efficacy and safety of febuxostat, allopurinol, and placebo in a large group of subjects with hyperuricemia and gout, including persons with impaired renal function. Methods Subjects (n = 1,072) with hyperuricemia (serum urate level ≥8.0 mg/dl) and gout with normal or impaired (serum creatinine level >1.5 to ≤2.0 mg/dl) renal function were randomized to receive once-daily febuxostat (80 mg, 120 mg, or 240 mg), allopurinol (300 or 100 mg, based on renal function), or placebo for 28 weeks. Results Significantly (P ≤ 0.05) higher percentages of subjects treated with febuxostat 80 mg (48%), 120 mg (65%), and 240 mg (69%) attained the primary end point of last 3 monthly serum urate levels <6.0 mg/dl compared with allopurinol (22%) and placebo (0%). A significantly (P < 0.05) higher percentage of subjects with impaired renal function treated with febuxostat 80 mg (4 [44%] of 9), 120 mg (5 [45%] of 11), and 240 mg (3 [60%] of 5) achieved the primary end point compared with those treated with 100 mg of allopurinol (0 [0%] of 10). Proportions of subjects experiencing any adverse event or serious adverse event were similar across groups, although diarrhea and dizziness were more frequent in the febuxostat 240 mg group. The primary reasons for withdrawal were similar across groups except for gout flares, which were more frequent with febuxostat than with allopurinol. Conclusion At all doses studied, febuxostat more effectively lowered and maintained serum urate levels <6.0 mg/dl than did allopurinol (300 or 100 mg) or placebo in subjects with hyperuricemia and gout, including those with mild to moderately impaired renal function.

Surgical versus nonoperative treatment for lumbar disc herniation: four-year results for the Spine Patient Outcomes Research Trial (SPORT).

Abstract: Study design Concurrent prospective randomized and observational cohort studies. Objective To assess the 8-year outcomes of surgery versus nonoperative care. Summary of background data Although randomized trials have demonstrated small short-term differences in favor of surgery, long-term outcomes comparing surgical with nonoperative treatment remain controversial. Methods Surgical candidates with imaging-confirmed lumbar intervertebral disc herniation meeting Spine Patient Outcomes Research Trial eligibility criteria enrolled into prospective randomized (501 participants) and observational cohorts (743 participants) at 13 spine clinics in 11 US states. Interventions were standard open discectomy versus usual nonoperative care. Main outcome measures were changes from baseline in the SF-36 Bodily Pain and Physical Function scales and the modified Oswestry Disability Index-AAOS/Modems version assessed at 6 weeks, 3 months, and 6 months, and annually thereafter. Results Advantages were seen for surgery in intent-to-treat analyses for the randomized cohort for all primary and secondary outcomes other than work status; however, with extensive nonadherence to treatment assignment (49% patients assigned to nonoperative therapy receiving surgery versus 60% of patients assigned to surgery) these observed effects were relatively small and not statistically significant for primary outcomes (bodily pain, physical function, Oswestry Disability Index). Importantly, the overall comparison of secondary outcomes was significantly greater with surgery in the intent-to-treat analysis (sciatica bothersomeness [P > 0.005], satisfaction with symptoms [P > 0.013], and self-rated improvement [P > 0.013]) in long-term follow-up. An as-treated analysis showed significant surgical treatment effects for primary outcome measures (mean change, surgery vs. nonoperative care; treatment effect; 95% confidence interval): bodily pain (45.3 vs. 34.4; 10.9; 7.7 to 14); PF (42.2 vs. 31.5; 10.6; 7.7 to 13.5); and Oswestry Disability Index (-36.2 vs. -24.8; -11.3; -13.6 to -9.1). Conclusion Carefully selected patients who underwent surgery for a lumbar disc herniation achieved greater improvement than nonoperatively treated patients; there was little to no degradation of outcomes in either group (operative and nonoperative) from 4 to 8 years. Level of evidence 2.

Socially-aware routing for publish-subscribe in delay-tolerant mobile ad hoc networks

Abstract: Applications involving the dissemination of information directly relevant to humans (e.g., service advertising, news spreading, environmental alerts) often rely on publish-subscribe, in which the network delivers a published message only to the nodes whose subscribed interests match it. In principle, publish- subscribe is particularly useful in mobile environments, since it minimizes the coupling among communication parties. However, to the best of our knowledge, none of the (few) works that tackled publish-subscribe in mobile environments has yet addressed intermittently-connected human networks. Socially-related people tend to be co-located quite regularly. This characteristic can be exploited to drive forwarding decisions in the interest-based routing layer supporting the publish-subscribe network, yielding not only improved performance but also the ability to overcome high rates of mobility and long-lasting disconnections. In this paper we propose SocialCast, a routing framework for publish-subscribe that exploits predictions based on metrics of social interaction (e.g., patterns of movements among communities) to identify the best information carriers. We highlight the principles underlying our protocol, illustrate its operation, and evaluate its performance using a mobility model based on a social network validated with real human mobility traces. The evaluation shows that prediction of colocation and node mobility allow for maintaining a very high and steady event delivery with low overhead and latency, despite the variation in density, number of replicas per message or speed.