Showing papers by "University of Rochester published in 2008"

The CMS experiment at the CERN LHC

Abstract: The Compact Muon Solenoid (CMS) detector is described. The detector operates at the Large Hadron Collider (LHC) at CERN. It was conceived to study proton-proton (and lead-lead) collisions at a centre-of-mass energy of 14 TeV (5.5 TeV nucleon-nucleon) and at luminosities up to 10(34)cm(-2)s(-1) (10(27)cm(-2)s(-1)). At the core of the CMS detector sits a high-magnetic-field and large-bore superconducting solenoid surrounding an all-silicon pixel and strip tracker, a lead-tungstate scintillating-crystals electromagnetic calorimeter, and a brass-scintillator sampling hadron calorimeter. The iron yoke of the flux-return is instrumented with four stations of muon detectors covering most of the 4 pi solid angle. Forward sampling calorimeters extend the pseudo-rapidity coverage to high values (vertical bar eta vertical bar <= 5) assuring very good hermeticity. The overall dimensions of the CMS detector are a length of 21.6 m, a diameter of 14.6 m and a total weight of 12500 t.

Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS): scale presentation and clinimetric testing results.

Abstract: We present a clinimetric assessment of the Movement Disorder Society (MDS)-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS). The MDS-UDPRS Task Force revised and expanded the UPDRS using recommendations from a published critique. The MDS-UPDRS has four parts, namely, I: Non-motor Experiences of Daily Living; II: Motor Experiences of Daily Living; III: Motor Examination; IV: Motor Complications. Twenty questions are completed by the patient/caregiver. Item-specific instructions and an appendix of complementary additional scales are provided. Movement disorder specialists and study coordinators administered the UPDRS (55 items) and MDS-UPDRS (65 items) to 877 English speaking (78% non-Latino Caucasian) patients with Parkinson's disease from 39 sites. We compared the two scales using correlative techniques and factor analysis. The MDS-UPDRS showed high internal consistency (Cronbach's alpha = 0.79-0.93 across parts) and correlated with the original UPDRS (rho = 0.96). MDS-UPDRS across-part correlations ranged from 0.22 to 0.66. Reliable factor structures for each part were obtained (comparative fit index > 0.90 for each part), which support the use of sum scores for each part in preference to a total score of all parts. The combined clinimetric results of this study support the validity of the MDS-UPDRS for rating PD.

Self-Determination Theory: A Macrotheory of Human Motivation, Development and Health.

Abstract: Self-determination theory (SDT) is an empirically based theory of human motivation, development, and wellness. The theory focuses on types, rather than just amount, of motivation, paying particular attention to autonomous motivation, controlled motivation, and amotivation as predictors of performance, relational, and well-being outcomes. It also addresses the social conditions that enhance versus diminish these types of motivation, proposing and finding that the degrees to which basic psychological needs for autonomy, competence, and relatedness are supported versus thwarted affect both the type and strength of motivation. SDT also examines people’s life goals or aspirations, showing differential relations of intrinsic versus extrinsic life goals to performance and psychological health. In this introduction we also briefly discuss recent developments within SDT concerning mindfulness and vitality, and highlight the applicability of SDT within applied domains, including work, relationships, parenting, education, virtual environments, sport, sustainability, health care, and psychotherapy.

Growth factors and cytokines in wound healing.

Abstract: Wound healing is an evolutionarily conserved, complex, multicellular process that, in skin, aims at barrier restoration. This process involves the coordinated efforts of several cell types including keratinocytes, fibroblasts, endothelial cells, macrophages, and platelets. The migration, infiltration, proliferation, and differentiation of these cells will culminate in an inflammatory response, the formation of new tissue and ultimately wound closure. This complex process is executed and regulated by an equally complex signaling network involving numerous growth factors, cytokines and chemokines. Of particular importance is the epidermal growth factor (EGF) family, transforming growth factor beta (TGF-beta) family, fibroblast growth factor (FGF) family, vascular endothelial growth factor (VEGF), granulocyte macrophage colony stimulating factor (GM-CSF), platelet-derived growth factor (PDGF), connective tissue growth factor (CTGF), interleukin (IL) family, and tumor necrosis factor-alpha family. Currently, patients are treated by three growth factors: PDGF-BB, bFGF, and GM-CSF. Only PDGF-BB has successfully completed randomized clinical trials in the Unites States. With gene therapy now in clinical trial and the discovery of biodegradable polymers, fibrin mesh, and human collagen serving as potential delivery systems other growth factors may soon be available to patients. This review will focus on the specific roles of these growth factors and cytokines during the wound healing process.

Wolbachia: master manipulators of invertebrate biology.

Abstract: Wolbachia are common intracellular bacteria that are found in arthropods and nematodes. These alphaproteobacteria endosymbionts are transmitted vertically through host eggs and alter host biology in diverse ways, including the induction of reproductive manipulations, such as feminization, parthenogenesis, male killing and sperm-egg incompatibility. They can also move horizontally across species boundaries, resulting in a widespread and global distribution in diverse invertebrate hosts. Here, we review the basic biology of Wolbachia, with emphasis on recent advances in our understanding of these fascinating endosymbionts.

Facilitating Optimal Motivation and Psychological Well- Being Across Life's Domains

Abstract: Self-determination theory (SDT) differentiates motivation, with autonomous and controlled motivations constituting the key, broad distinction. Research has shown that autonomous motivation predicts persistence and adherence and is advantageous for effective performance, especially on complex or heuristic tasks that involve deep information processing or creativity. Autonomous motivation is also reliably related to psychological health. Considerable research has found interpersonal contexts that facilitate satisfaction of the basic psychological needs for competence, autonomy, and relatedness to enhance autonomous motivation, which comprises intrinsic motivation and well-internalized extrinsic motivation. SDT has been applied in varied cultures and in many life domains, and research is reviewed that has related autonomous and controlled motivation to education, parenting, work, health care, sport, and close relationships.

Environmental niche equivalency versus conservatism: quantitative approaches to niche evolution.

Abstract: Environmental niche models, which are generated by combining species occurrence data with environmental GIS data layers, are increasingly used to answer fundamental questions about niche evolution, speciation, and the accumulation of ecological diversity within clades. The question of whether environmental niches are conserved over evolutionary time scales has attracted considerable attention, but often produced conflicting conclusions. This conflict, however, may result from differences in how niche similarity is measured and the specific null hypothesis being tested. We develop new methods for quantifying niche overlap that rely on a traditional ecological measure and a metric from mathematical statistics. We reexamine a classic study of niche conservatism between sister species in several groups of Mexican animals, and, for the first time, address alternative definitions of "niche conservatism" within a single framework using consistent methods. As expected, we find that environmental niches of sister species are more similar than expected under three distinct null hypotheses, but that they are rarely identical. We demonstrate how our measures can be used in phylogenetic comparative analyses by reexamining niche divergence in an adaptive radiation of Cuban anoles. Our results show that environmental niche overlap is closely tied to geographic overlap, but not to phylogenetic distances, suggesting that niche conservatism has not constrained local communities in this group to consist of closely related species. We suggest various randomization tests that may prove useful in other areas of ecology and evolutionary biology.

Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection

Abstract: The precise identification of the HIV-1 envelope glycoprotein (Env) responsible for productive clinical infection could be instrumental in elucidating the molecular basis of HIV-1 transmission and in designing effective vaccines. Here, we developed a mathematical model of random viral evolution and, together with phylogenetic tree construction, used it to analyze 3,449 complete env sequences derived by single genome amplification from 102 subjects with acute HIV-1 (clade B) infection. Viral env genes evolving from individual transmitted or founder viruses generally exhibited a Poisson distribution of mutations and star-like phylogeny, which coalesced to an inferred consensus sequence at or near the estimated time of virus transmission. Overall, 78 of 102 subjects had evidence of productive clinical infection by a single virus, and 24 others had evidence of productive clinical infection by a minimum of two to five viruses. Phenotypic analysis of transmitted or early founder Envs revealed a consistent pattern of CCR5 dependence, masking of coreceptor binding regions, and equivalent or modestly enhanced resistance to the fusion inhibitor T1249 and broadly neutralizing antibodies compared with Envs from chronically infected subjects. Low multiplicity infection and limited viral evolution preceding peak viremia suggest a finite window of potential vulnerability of HIV-1 to vaccine-elicited immune responses, although phenotypic properties of transmitted Envs pose a formidable defense.

Efficient subpixel image registration algorithms

Abstract: Three new algorithms for 2D translation image registration to within a small fraction of a pixel that use nonlinear optimization and matrix-multiply discrete Fourier transforms are compared. These algorithms can achieve registration with an accuracy equivalent to that of the conventional fast Fourier transform upsampling approach in a small fraction of the computation time and with greatly reduced memory requirements. Their accuracy and computation time are compared for the purpose of evaluating a translation-invariant error metric.

Stromal gene signatures in large-B-cell lymphomas

Abstract: Background The addition of rituximab to combination chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), or R-CHOP, has significantly improved the survival of patients with diffuse large-B-cell lymphoma. Whether gene-expression signatures correlate with survival after treatment of diffuse large-B-cell lymphoma is unclear. Methods We profiled gene expression in pretreatment biopsy specimens from 181 patients with diffuse large-B-cell lymphoma who received CHOP and 233 patients with this disease who received R-CHOP. A multivariate gene-expression–based survival-predictor model derived from a training group was tested in a validation group. Results A multivariate model created from three gene-expression signatures — termed “germinal-center B-cell,” “stromal-1,” and “stromal-2” — predicted survival both in patients who received CHOP and patients who received R-CHOP. The prognostically favorable stromal-1 signature reflected extracellular-matrix deposition and histiocytic infilt...

Hedonia, eudaimonia, and well-being: an introduction

Abstract: Research on well-being can be thought of as falling into two traditions. In one—the hedonistic tradition—the focus is on happiness, generally defined as the presence of positive affect and the absence of negative affect. In the other—the eudaimonic tradition—the focus is on living life in a full and deeply satisfying way. Recognizing that much recent research on well-being has been more closely aligned with the hedonistic tradition, this special issue presents discussions and research reviews from the eudaimonic tradition, making clear how the concept of eudaimonia adds an important perspective to our understanding of well-being.

Optimal Medical Therapy With or Without Percutaneous Coronary Intervention to Reduce Ischemic Burden Results From the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) Trial Nuclear Substudy

Abstract: Background— Extent and severity of myocardial ischemia are determinants of risk for patients with coronary artery disease, and ischemia reduction is an important therapeutic goal. The Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) nuclear substudy compared the effectiveness of percutaneous coronary intervention (PCI) for ischemia reduction added to optimal medical therapy (OMT) with the use of myocardial perfusion single photon emission computed tomography (MPS). Methods and Results— Of the 2287 COURAGE patients, 314 were enrolled in this substudy of serial rest/stress MPS performed before treatment and 6 to 18 months (mean=374±50 days) after randomization using paired exercise (n=84) or vasodilator stress (n=230). A blinded core laboratory analyzed quantitative MPS measures of percent ischemic myocardium. Moderate to severe ischemia encumbered ≥10% myocardium. The primary end point was ≥5% reduction in ischemic myocardium at follow-up. Treatment groups had similar ...

Improved Age Estimation for Solar-Type Dwarfs Using Activity-Rotation Diagnostics

Abstract: While the strong anticorrelation between chromospheric activity and age has led to the common use of the Ca II H and K emission index (R'_(HK) = L_(HK)/L_(bol)) as an empirical age estimator for solar-type dwarfs, existing activity-age relations produce implausible ages at both high and low activity levels.We have compiled R'_(HK) HK data from the literature for young stellar clusters, richly populating for the first time the young end of the activity-age relation. Combining the cluster activity data with modern cluster age estimates and analyzing the color dependence of the chromospheric activity age index,we derive an improved activity-age calibration for F7-K2 dwarfs (0:5 mag < B - V < 0.9 mag). We also present a more fundamentally motivated activity-age calibration that relies on conversion of R'_(HK) values through the Rossby number to rotation periods and then makes use of improved gyrochronology relations. We demonstrate that our new activity-age calibration has typical age precision of ~0.2 dex for normal solar-type dwarfs aged between the Hyades and the Sun (~0.6-4.5 Gyr). Inferring ages through activity-rotation-age relations accounts for some color-dependent effects and systematically improves the age estimates (albeit only slightly). We demonstrate that coronal activity as measured through the fractional X-ray luminosity (R_X = L_X/L_(bol)) has nearly the same age- and rotation inferring capability as chromospheric activity measured through R'_(HK). As a first application of our calibrations, we provide new activity-derived age estimates for a volume-limited sample of the 108 solar-type field dwarfs within 16 pc.

Accuracy of body mass index in diagnosing obesity in the adult general population.

Abstract: Body mass index (BMI) is the most widely used measure to diagnose obesity. However, the accuracy of BMI in detecting excess body adiposity in the adult general population is largely unknown. A cross-sectional design of 13 601 subjects (age 20–79.9 years; 49% men) from the Third National Health and Nutrition Examination Survey. Bioelectrical impedance analysis was used to estimate body fat percent (BF%). We assessed the diagnostic performance of BMI using the World Health Organization reference standard for obesity of BF%>25% in men and>35% in women. We tested the correlation between BMI and both BF% and lean mass by sex and age groups adjusted for race. BMI-defined obesity (⩾30 kg m−2) was present in 19.1% of men and 24.7% of women, while BF%-defined obesity was present in 43.9% of men and 52.3% of women. A BMI⩾30 had a high specificity (men=95%, 95% confidence interval (CI), 94–96 and women=99%, 95% CI, 98–100), but a poor sensitivity (men=36%, 95% CI, 35–37 and women=49%, 95% CI, 48–50) to detect BF%-defined obesity. The diagnostic performance of BMI diminished as age increased. In men, BMI had a better correlation with lean mass than with BF%, while in women BMI correlated better with BF% than with lean mass. However, in the intermediate range of BMI (25–29.9 kg m−2), BMI failed to discriminate between BF% and lean mass in both sexes. The accuracy of BMI in diagnosing obesity is limited, particularly for individuals in the intermediate BMI ranges, in men and in the elderly. A BMI cutoff of⩾30 kg m−2 has good specificity but misses more than half of people with excess fat. These results may help to explain the unexpected better survival in overweight/mild obese patients.

How many species are infected with Wolbachia?--A statistical analysis of current data.

Abstract: Wolbachia are intracellular bacteria found in many species of arthropods and nematodes They manipulate the reproduction of their arthropod hosts in various ways, may play a role in host speciation and have potential applications in biological pest control Estimates suggest that at least 20% of all insect species are infected with Wolbachia These estimates result from several Wolbachia screenings in which numerous species were tested for infection; however, tests were mostly performed on only one to two individuals per species The actual percent of species infected will depend on the distribution of infection frequencies among species We present a meta-analysis that estimates percentage of infected species based on data on the distribution of infection levels among species We used a beta-binomial model that describes the distribution of infection frequencies of Wolbachia, shedding light on the overall infection rate as well as on the infection frequency within species Our main findings are that (1) the proportion of Wolbachia-infected species is estimated to be 66%, and that (2) within species the infection frequency follows a ‘most-or-few’ infection pattern in a sense that the Wolbachia infection frequency within one species is typically either very high (>90%) or very low (<10%)

On the measurement of achievement goals: critique, illustration, and application

Abstract: The authors identified several specific problems with the measurement of achievement goals in the current literature and illustrated these problems, focusing primarily on A. J. Elliot and H. A. McGregor's (2001) Achievement Goal Questionnaire (AGQ). They attended to these problems by creating the AGQ-Revised and conducting a study that examined the measure's structural validity and predictive utility with 229 (76 male, 150 female, 3 unspecified) undergraduates. The hypothesized factor and dimensional structures of the measure were confirmed and shown to be superior to a host of alternatives. The predictions were nearly uniformly supported with regard to both the antecedents (need for achievement and fear of failure) and consequences (intrinsic motivation and exam performance) of the 4 achievement goals. In discussing their work, the authors highlight the importance and value of additional precision in the area of achievement goal measurement.

The CAS-PEAL Large-Scale Chinese Face Database and Baseline Evaluations

Abstract: In this paper, we describe the acquisition and contents of a large-scale Chinese face database: the CAS-PEAL face database. The goals of creating the CAS-PEAL face database include the following: 1) providing the worldwide researchers of face recognition with different sources of variations, particularly pose, expression, accessories, and lighting (PEAL), and exhaustive ground-truth information in one uniform database; 2) advancing the state-of-the-art face recognition technologies aiming at practical applications by using off-the-shelf imaging equipment and by designing normal face variations in the database; and 3) providing a large-scale face database of Mongolian. Currently, the CAS-PEAL face database contains 99 594 images of 1040 individuals (595 males and 445 females). A total of nine cameras are mounted horizontally on an arc arm to simultaneously capture images across different poses. Each subject is asked to look straight ahead, up, and down to obtain 27 images in three shots. Five facial expressions, six accessories, and 15 lighting changes are also included in the database. A selected subset of the database (CAS-PEAL-R1, containing 30 863 images of the 1040 subjects) is available to other researchers now. We discuss the evaluation protocol based on the CAS-PEAL-R1 database and present the performance of four algorithms as a baseline to do the following: 1) elementarily assess the difficulty of the database for face recognition algorithms; 2) preference evaluation results for researchers using the database; and 3) identify the strengths and weaknesses of the commonly used algorithms.

Caregiver burden among dementia patient caregivers: a review of the literature.

Abstract: Purpose: To identify current evidence of factors influencing dementia-related caregiver burden (CB), describe patient and caregiver characteristics associated with CB, and describe evidence-based interventions designed to lessen the burden of caregiving. Data sources: Comprehensive literature review of Cumulative Index of Nursing and Allied Health Literature, MEDLINE, and Psych Info was performed for the years 1996–2006 of peer-reviewed journals using keywords CB and dementia. Conclusion: Dementia caregiving has been associated with negative effects on caregiver health and early nursing home placement for dementia patients. Many factors influence the impact of the caregiving experience such as gender, relationship to the patient, culture, and personal characteristics. Although various interventions have been developed with the goal of alleviating CB, evidence suggests that individually developed multicomponent interventions including a diversity of services will decrease burden, improve quality of life, and enable caregivers to provide at-home care for longer periods prior to institutionalization. Implications for practice: The ability to properly assess the dementia patient–caregiver dyad related to CB is critical to decreasing its negative physical and psychological health outcomes. Appropriately tailored interventions can improve the health and well-being of both caregiver and patient.

Molecular subtypes of diffuse large B-cell lymphoma arise by distinct genetic pathways.

Abstract: Gene-expression profiling has been used to define 3 molecular subtypes of diffuse large B-cell lymphoma (DLBCL), termed germinal center B-cell-like (GCB) DLBCL, activated B-cell-like (ABC) DLBCL, and primary mediastinal B-cell lymphoma (PMBL). To investigate whether these DLBCL subtypes arise by distinct pathogenetic mechanisms, we analyzed 203 DLBCL biopsy samples by high-resolution, genome-wide copy number analysis coupled with gene-expression profiling. Of 272 recurrent chromosomal aberrations that were associated with gene-expression alterations, 30 were used differentially by the DLBCL subtypes (P < 0.006). An amplicon on chromosome 19 was detected in 26% of ABC DLBCLs but in only 3% of GCB DLBCLs and PMBLs. A highly up-regulated gene in this amplicon was SPIB, which encodes an ETS family transcription factor. Knockdown of SPIB by RNA interference was toxic to ABC DLBCL cell lines but not to GCB DLBCL, PMBL, or myeloma cell lines, strongly implicating SPIB as an oncogene involved in the pathogenesis of ABC DLBCL. Deletion of the INK4a/ARF tumor suppressor locus and trisomy 3 also occurred almost exclusively in ABC DLBCLs and was associated with inferior outcome within this subtype. FOXP1 emerged as a potential oncogene in ABC DLBCL that was up-regulated by trisomy 3 and by more focal high-level amplifications. In GCB DLBCL, amplification of the oncogenic mir-17-92 microRNA cluster and deletion of the tumor suppressor PTEN were recurrent, but these events did not occur in ABC DLBCL. Together, these data provide genetic evidence that the DLBCL subtypes are distinct diseases that use different oncogenic pathways.

Recommendations for end-of-life care in the intensive care unit: A consensus statement by the American College of Critical Care Medicine

Abstract: Background: These recommendations have been developed to improve the care of intensive care unit (ICU) patients during the dying process. The recommendations build on those published in 2003 and highlight recent developments in the field from a U.S. perspective. They do not use an evidence grading system because most of the recommendations are based on ethical and legal principles that are not derived from empirically based evidence. Principal Findings: Family-centered care, which emphasizes the importance of the social structure within which patients are embedded, has emerged as a comprehensive ideal for managing end-of-life care in the ICU. ICU clinicians should be competent in all aspects of this care, including the practical and ethical aspects of withdrawing different modalities of life-sustaining treatment and the use of sedatives, analgesics, and nonpharmacologic approaches to easing the suffering of the dying process. Several key ethical concepts play a foundational role in guiding end-oflife care, including the distinctions between withholding and withdrawing treatments, between actions of killing and allowing to die, and between consequences that are intended vs. those that are merely foreseen (the doctrine of double effect). Improved communication with the family has been shown to improve patient care and family outcomes. Other knowledge unique to endof-life care includes principles for notifying families of a patient’s death and compassionate approaches to discussing options for organ donation. End-of-life care continues even after the death of the patient, and ICUs should consider developing comprehensive bereavement programs to support both families and the needs of the clinical staff. Finally, a comprehensive agenda for improving end-of-life care in the ICU has been developed to guide research, quality improvement efforts, and educational curricula. Conclusions: End-of-life care is emerging as a comprehensive area of expertise in the ICU and demands the same high level of knowledge and competence as all other areas of ICU practice. (Crit Care Med 2008; 36:953‐963)

Splicing of a novel androgen receptor exon generates a constitutively active androgen receptor that mediates prostate cancer therapy resistance.

Abstract: The standard systemic treatment for prostate cancer (PCa) is androgen ablation, which causes tumor regression by inhibiting activity of the androgen receptor (AR). Invariably, PCa recurs with a fatal androgen-refractory phenotype. Importantly, the growth of androgen-refractory PCa remains dependent on the AR through various mechanisms of aberrant AR activation. Here, we studied the 22Rv1 PCa cell line, which was derived from a CWR22 xenograft that relapsed during androgen ablation. Three AR isoforms are expressed in 22Rv1 cells: a full-length version with duplicated exon 3 and two truncated versions lacking the COOH terminal domain (CTD). We found that CTD-truncated AR isoforms are encoded by mRNAs that have a novel exon 2b at their 3' end. Functionally, these AR isoforms are constitutively active and promote the expression of endogenous AR-dependent genes, as well as the proliferation of 22Rv1 cells in a ligand-independent manner. AR mRNAs containing exon 2b and their protein products are expressed in commonly studied PCa cell lines. Moreover, exon 2b-derived species are enriched in xenograft-based models of therapy-resistant PCa. Together, our data describe a simple and effective mechanism by which PCa cells can synthesize a constitutively active AR and thus circumvent androgen ablation.

Oncogenic CARD11 Mutations in Human Diffuse Large B Cell Lymphoma

Abstract: Diffuse large B cell lymphoma (DLBCL) is the most common form of non-Hodgkin's lymphoma. In the least curable (ABC) subtype of DLBCL, survival of the malignant cells is dependent on constitutive activation of the nuclear factor-kappaB (NF-kappaB) signaling pathway. In normal B cells, antigen receptor-induced NF-kappaB activation requires CARD11, a cytoplasmic scaffolding protein. To determine whether CARD11 contributes to tumorigenesis, we sequenced the CARD11 gene in human DLBCL tumors. We detected missense mutations in 7 of 73 ABC DLBCL biopsies (9.6%), all within exons encoding the coiled-coil domain. Experimental introduction of CARD11 coiled-coil domain mutants into lymphoma cell lines resulted in constitutive NF-kappaB activation and enhanced NF-kappaB activity upon antigen receptor stimulation. These results demonstrate that CARD11 is a bona fide oncogenein DLBCL, providing a genetic rationale for the development of pharmacological inhibitors of the CARD11 pathway for DLBCL therapy.

Ambiguity, Information Quality, and Asset Pricing

Abstract: When ambiguity-averse investors process news of uncertain quality, they act as if they take a worst-case assessment of quality. As a result, they react more strongly to bad news than to good news. They also dislike assets for which information quality is poor, especially when the underlying fundamentals are volatile. These effects induce ambiguity premia that depend on idiosyncratic risk in fundamentals as well as skewness in returns. Moreover, shocks to information quality can have persistent negative effects on prices even if fundamentals do not change. FINANCIAL MARKET PARTICIPANTS ABSORB a large amount of news, or signals, every day. Processing a signal involves quality judgments: News from a reliable source should lead to more portfolio rebalancing than news from an obscure source. Unfortunately, judging quality itself is sometimes difficult. For example, stock picks from an unknown newsletter without a track record might be very reliable or entirely useless—it is simply hard to tell. Of course, the situation is different when investors can draw on a lot of experience that helps them interpret signals. This is true especially for “tangible” information, such as earnings reports, that lends itself to quantitative analysis. By looking at past data, investors may become quite confident about how well earnings forecast returns. This paper focuses on information processing when there is incomplete knowledge about signal quality. The main idea is that, when quality is difficult to judge, investors treat signals as ambiguous. They do not update beliefs in standard Bayesian fashion, but behave as if they have multiple likelihoods in mind when processing signals. To be concrete, suppose that θ is a parameter that an investor wants to learn. We assume that a signal s is related to the parameter by a family of likelihoods: s = θ + � , � ∼ N � 0, σ 2 s � , σ 2 s ∈ � σ 2

Detection of Huntington’s disease decades before diagnosis: The Predict HD study

Abstract: Objective: The objective of the Predict-HD study is to use genetic, neurobiological and refined clinical markers to understand the early progression of Huntington’s disease (HD), prior to the point of traditional diagnosis, in persons with a known gene mutation. Here we estimate the approximate onset and initial course of various measurable aspects of HD relative to the time of eventual diagnosis. Methods: We studied 438 participants who were positive for the HD gene mutation, but did not yet meet the diagnostic criteria for HD and had no functional decline. Predictability of baseline cognitive, motor, psychiatric and imaging measures was modelled non-linearly using estimated time until diagnosis (based on CAG repeat length and current age) as the predictor. Results: Estimated time to diagnosis was related to most clinical and neuroimaging markers. The patterns of association suggested the commencement of detectable changes one to two decades prior to the predicted time of clinical diagnosis. The patterns were highly robust and consistent, despite the varied types of markers and diverse measurement methodologies. Conclusions: These findings from the Predict-HD study suggest the approximate time scale of measurable disease development, and suggest candidate disease markers for use in preventive HD trials.

Method for altering the lifespan of eukaryotic organisms

Abstract: A method for altering the lifespan of a eukaryotic organism. The method comprises the steps of providing a lifespan altering compound, and administering an effective amount of the compound to a eukaryotic organism, such that the lifespan of the organism is altered. In one embodiment, the compound is identified using the DeaD assay.