Evaluating the Effectiveness of Child Safety Seats and Seat Belts in Protecting Children from Injury

Young children are required to use child safety seats, and the age threshold at which children can legally graduate to seat belts has steadily increased. This paper tests the relative effectiveness of child safety seats, lap-and-shoulder seat belts, and lap belts in preventing injuries among motor vehicle passengers aged 2-6. We analyze three large, representative samples of crashes reported to police, as well as linked hospital data. We find no apparent difference in the two most serious injury categories for children in child safety seats versus lap-and-shoulder belts. Child safety seats provide a statistically significant 25% reduction in the least serious injury category. Lap belts are somewhat less effective than the two other types of restraints, but far superior to riding unrestrained.

Modeling the Tripartite Role of Cyclin C in Cellular Stress Response Coordination

For normal cellular function, exogenous signals must be interpreted and careful coordination must take place to ensure desired fates are achieved. Mitochondria are key regulatory nodes of cellular fate, undergoing fission/fusion cycles depending on the needs of the cell, and help mediate cell death fates. The CKM or Cdk8 kinase module, is composed of cyclin C (CC), Cdk8, Med12/12L, and Med13/13L. The CKM controls RNA polymerase II, acting as a regulator of stress-response and growth-control genes. Following stress, CC translocates to the mitochondria and interacts with both fission and iRCD apoptotic mediators. We hypothesize that CC represents a key mediator, linking transcription to mitochondrial fission and RCD. A more in-depth analysis of the roles of CC and the protein interactions that mediate them encompasses the focus of this dissertation. To mediate individual functions, CC uses distinct binding partners. We revealed the presence two separable/discrete cyclin box domains. To determine the residues mediating these functions, rigid body protein-protein docking simulations were performed using human cyclin C, Drp1, and Bax. These analyses revealed specific residues which support distinct functions of the CB1 and CB2 domains. Results indicate that modeled Bax-interacting residues are concentrated to the first half of the CB2 domain, while Drp1-interacting residues span the entirety of the CB2 domain. Interestingly, we determined that CC contains a unique BH2-like domain, normally only found in Bcl-2 protein family members, which appears to mediate interactions with Bax. Results from human protein modeling simulations were then applied to yeast homologous proteins. As presented here, yeast studies have confirmed residues that mediate interaction between CC and fission machinery. The results support the model that CB1 and CB2 are distinct, mediating independent functionalities. We suggest a model that CC possesses three distinct interaction domains and acts to bridge fission and apoptotic machinery, either in a mutually exclusive or trimeric manner. In conclusion, CC is shown to mediate each of its unique functions through distinct interacting residues and interfaces. With CC implicated in many human disorders, this will serve as a tool to study disease pathogeneses and treatments, taking into account unique interfaces governing the tripartite functions

Modeling the Role of Cyclin C in Connecting Stress-Induced Mitochondrial Fission to Apoptosis

For normal cell function, exogenous signals must be correctly interpreted, and the proper response executed. The mitochondria are key regulatory nodes of cellular fate. For example, mitochondria undergo fission and fusion cycles depending on the energetic needs of the cell. Additionally, regulated cell death pathways also function at the mitochondria. Cyclin C is a transcriptional regulator of stress response and growth control genes. Following stress, a portion of cyclin C translocates to the cytoplasm, where it interacts with both the mitochondrial fission and apoptotic machinery. Based on these findings, we hypothesize that Cyclin C represents a key mediator linking transcription to mitochondrial fission and intrinsic regulated cell death (iRCD). Cyclin C has two conserved cyclin box domains each composed of five alpha-helices, termed CB1 and CB2, which mediate protein-protein interactions with regards to transcriptional regulation (Cdk8) and mitochondrial fission (Drp1), respectively. Pull down studies show that both pro-apoptotic protein Bax and fission machinery protein Drp1 interact directly with cyclin C. Cyclin C interaction is required for Bax activation and efficient iRCD; however, Drp1 is required for this interaction to occur, suggesting a role for the interaction of all three proteins. Docking simulations show cyclin C and Bax interact directly through multiple sites within amino acids 160-170 of cyclin C. Inspection of this region shows a homologous BH2 sequence, similar to that of Bcl-2 protein family members. Prior work has demonstrated that while this sequence is required for Bax binding, it is not required for binding Drp1. To further support this, preliminary modeling data suggests Drp1 interaction is mediated through the latter half of CB2, which is downstream of this sequence. Taken together, these results suggest a model that cyclin C possesses three distinct interaction domains, leading cyclin C to physically bridge the fission and apoptotic machinery and allowing the cell to properly coordinate mitochondrial dynamics with iRCD pathways

Beyond association: How employees want to participate in their firms\u27 corporate social performance

© 2015 Center for Business Ethics at Bentley University. Although many studies have found a positive relationship between corporate social performance and employer attractiveness, few have examined how different forms of responsibility might mediate that attraction, particularly when those social practices afford different degrees of employee participation. The current study undertook this line of inquiry by examining prospective employees\u27 attraction to three common approaches to corporate social performance (CSP) that offer increasing levels of participation: donation, volunteerism, and operational integration. Unexpectedly, findings from an empirical investigation challenged the study\u27s main hypothesis; that is, prospective employees were least attracted to firms that integrated their social and financial goals. Consequently, important implications and questions remain for both employers and business educators

Astrometric Discovery of GJ 164B

We discovered a low-mass companion to the M-dwarf GJ 164 with the CCD-based imaging system of the Stellar Planet Survey (STEPS) astrometric program. The existence of GJ 164B was confirmed with Hubble Space Telescope NICMOS imaging observations. A high-dispersion spectral observation in V sets a lower limit of delta m> 2.2 mag between the two components of the system. Based upon our parallax value of 0.082 +/- 0.008, we derive the following orbital parameters: P = 2.04 +/- 0.03 y, a = 1.03 +/- 0.03 AU, and Mtotal = 0.265 +/- 0.020 MSun. The component masses are MA = 0.170 +/- 0.015 MSun and MB = 0.095 +/- 0.015 MSun. Based on its mass, colors, and spectral properties, GJ 164B has spectral type M6-8 V.Comment: pdf file 14 pages with 6 fig

Returns to Physician Human Capital: Analyzing Patients Randomized to Physician Teams

Patient sorting can confound estimates of the returns to physician human capital. This paper compares nearly 30,000 patients who were randomly assigned to clinical teams from one of two academic institutions. One institution is among the top medical schools in the country, while the other institution is ranked lower in the quality distribution. Patients treated by the two teams have identical observable characteristics and have access to a single set of facilities and ancillary staff. Those treated by physicians from the higher-ranked institution have 10-25% shorter and less expensive stays than patients assigned to the lower-ranked institution. Health outcomes are not related to the physician team assignment, and the estimates are precise. Procedure differences across the teams are consistent with the ability of physicians in the lower-ranked institution to substitute time and diagnostic tests for the faster judgments of physicians from the top-ranked institution.

A Multinational Pharmacoeconomic Evaluation of Acute Major Depressive Disorder (MDD): a Comparison of Cost-Effectiveness Between Venlafaxine, SSRIs and TCAs

AbstractMethodsWe conducted a multinational pharmacoeconomic evaluation comparing the immediate release form of a new class of serotonin norepinephrine reuptake inhibitor (SNRI), venlafaxine IR to the selective serotonin reuptake inhibitors (SSRIs) and the tricyclic antidepressants (TCAs) in the treatment of acute major depressive disorder (MDD) in 10 countries (Germany, Italy, Netherlands, Poland, Spain, Sweden, Switzerland, United Kingdom, United States, and Venezuela). We designed a decision analytic model assessing the acute phase of MDD treatment within a 6-month time horizon. Six decision tree models were customized with country-specific estimates from a clinical management analysis, meta-analytic rates from two published meta-analyses, and a resource valuation of treatment costs representing the inpatient and outpatient settings within each country. The meta-analyses provided the clinical rates of success defined as a 50% reduction in depression scores on the Hamilton Depression Scale (HAM-D) or the Montgomery-Asberg Depression Rating Scale (MADRS). Treatment regimen costs were determined from standard lists, fee schedules, and communication with local health economists in each country. The meta-analytic rates were applied to the decision analytic model to calculate the expected cost and expected outcomes for each antidepressant comparator. Cost-effectiveness was determined using the expected values for both a successful outcome, and a composite measure of outcome termed symptom-free days. A policy analysis was conducted to examine the health system budget impact in each country of increasing the utilization of the most effective antidepressant found in our study.ResultsInitiating treatment of MDD with venlafaxine IR yielded a lower expected cost compared to the SSRIs and TCAs in all countries except Poland in the inpatient setting, and Italy and Poland within the outpatient settings. The weighted average expected cost per patient varied from US$632 (Poland) to US$5647 (US) in the six-month acute phase treatment of MDD. The estimated total budgetary impact for each 1% of venlafaxine utilization, assuming a population of one million MDD patients, ranged from US$1600 (Italy) to US$29,049 (US).ConclusionsWithin the inpatient and outpatient treatment settings, venlafaxine IR was a more cost-effective treatment of MDD compared to the SSRIs and TCAs. Additionally, the results of this investigation indicate that increased utilization of venlafaxine in most settings across Europe and the Americas will have favorable impact on health care payer budgets.ADR, adverse drug reaction; CMA, clinical management analysis; ECT, electroconvulsive therapy; HAM-D, Hamilton Depression Scale; MADRS, Montgomery-Asberg depression rating scale; MDD, major depressive disorder; SFD, symptom-free day; SNRI, serotonin-norepinephrine reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor; TCA, tricyclic antidepressant; WHO, world health organization

Ketamine induces a robust whole-brain connectivity pattern that can be differentially modulated by drugs of different mechanism and clinical profile

Ketamine, an N-methyl-D-aspartate receptor (NMDAR) antagonist, has been studied in relation to the glutamate hypothesis of schizophrenia and increases dissociation, positive and negative symptom ratings. Ketamine effects brain function through changes in brain activity; these activity patterns can be modulated by pre-treatment of compounds known to attenuate the effects of ketamine on glutamate release. Ketamine also has marked effects on brain connectivity; we predicted that these changes would also be modulated by compounds known to attenuate glutamate release. Here, we perform task-free pharmacological magnetic resonance imaging (phMRI) to investigate the functional connectivity effects of ketamine in the brain and the potential modulation of these effects by pre-treatment of the compounds lamotrigine and risperidone, compounds hypothesised to differentially modulate glutamate release. Connectivity patterns were assessed by combining windowing, graph theory and multivariate Gaussian process classification. We demonstrate that ketamine has a robust effect on the functional connectivity of the human brain compared to saline (87.5 % accuracy). Ketamine produced a shift from a cortically centred, to a subcortically centred pattern of connections. This effect is strongly modulated by pre-treatment with risperidone (81.25 %) but not lamotrigine (43.75 %). Based on the differential effect of these compounds on ketamine response, we suggest the observed connectivity effects are primarily due to NMDAR blockade rather than downstream glutamatergic effects. The connectivity changes contrast with amplitude of response for which no differential effect between pre-treatments was detected, highlighting the necessity of these techniques in forming an informed view of the mechanistic effects of pharmacological compounds in the human brain

Improved Constraints on the Preferential Heating and Acceleration of Oxygen Ions in the Extended Solar Corona

We present a detailed analysis of oxygen ion velocity distributions in the extended solar corona, based on observations made with the Ultraviolet Coronagraph Spectrometer (UVCS) on the SOHO spacecraft. Polar coronal holes at solar minimum are known to exhibit broad line widths and unusual intensity ratios of the O VI 1032, 1037 emission line doublet. The traditional interpretation of these features has been that oxygen ions have a strong temperature anisotropy, with the temperature perpendicular to the magnetic field being much larger than the temperature parallel to the field. However, recent work by Raouafi and Solanki suggested that it may be possible to model the observations using an isotropic velocity distribution. In this paper we analyze an expanded data set to show that the original interpretation of an anisotropic distribution is the only one that is fully consistent with the observations. It is necessary to search the full range of ion plasma parameters to determine the values with the highest probability of agreement with the UVCS data. The derived ion outflow speeds and perpendicular kinetic temperatures are consistent with earlier results, and there continues to be strong evidence for preferential ion heating and acceleration with respect to hydrogen. At heliocentric heights above 2.1 solar radii, every UVCS data point is more consistent with an anisotropic distribution than with an isotropic distribution. At heights above 3 solar radii, the exact probability of isotropy depends on the electron density chosen to simulate the line-of-sight distribution of O VI emissivity. (abridged abstract)Comment: 19 pages (emulateapj style), 13 figures, ApJ, in press (v. 679; May 20, 2008