Beyond epistemic democracy: the identification and pooling of information by groups of political agents.

This thesis addresses the mechanisms by which groups of agents can track the truth, particularly in political situations. I argue that the mechanisms which allow groups of agents to track the truth operate in two stages: firstly, there are search procedures; and secondly, there are aggregation procedures. Search procedures and aggregation procedures work in concert. The search procedures allow agents to extract information from the environment. At the conclusion of a search procedure the information will be dispersed among different agents in the group. Aggregation procedures, such as majority rule, expert dictatorship and negative reliability unanimity rule, then pool these pieces of information into a social choice. The institutional features of both search procedures and aggregation procedures account for the ability of groups to track the truth and amount to social epistemic mechanisms. Large numbers of agents are crucial for the epistemic capacities of both search procedures and aggregation procedures. This thesis makes two main contributions to the literature on social epistemology and epistemic democracy. Firstly, most current accounts focus on the Condorcet Jury Theorem and its extensions as the relevant epistemic mechanism that can operate in groups of political agents. The introduction of search procedures to epistemic democracy is (mostly) new. Secondly, the thesis introduces a two-stage framework to the process of group truth-tracking. In 4 addition to showing how the two procedures of search and aggregation can operate in concert, the framework highlights the complexity of social choice situations. Careful consideration of different types of social choice situation shows that different aggregation procedures will be optimal truth-trackers in different situations. Importantly, there will be some situations in which aggregation procedures other than majority rule will be best at tracking the truth

What have birth cohort studies asked about genetic, pre- and perinatal exposures and child and adolescent onset mental health outcomes? : A systematic review

Peer reviewedPreprin

Exploring the NRO Opportunity for a Hubble-sized Wide-field Near-IR Space Telescope -- NEW WFIRST

We discuss scientific, technical and programmatic issues related to the use of an NRO 2.4m telescope for the WFIRST initiative of the 2010 Decadal Survey. We show that this implementation of WFIRST, which we call "NEW WFIRST," would achieve the goals of the NWNH Decadal Survey for the WFIRST core programs of Dark Energy and Microlensing Planet Finding, with the crucial benefit of deeper and/or wider near-IR surveys for GO science and a potentially Hubble-like Guest Observer program. NEW WFIRST could also include a coronagraphic imager for direct detection of dust disks and planets around neighboring stars, a high-priority science and technology precursor for future ambitious programs to image Earth-like planets around neighboring stars.Comment: 76 pages, 26 figures -- associated with the Princeton "New Telescope Meeting

Observations of Infrared Radiative Cooling in the Thermosphere on Daily to Multiyear Timescales from the TIMED/SABER Instrument

We present observations of the infrared radiative cooling by carbon dioxide (CO2) and nitric oxide (NO) in Earth s thermosphere. These data have been taken over a period of 7 years by the SABER instrument on the NASA TIMED satellite and are the dominant radiative cooling mechanisms for the thermosphere. From the SABER observations we derive vertical profiles of radiative cooling rates (W/cu m), radiative fluxes (W/sq m), and radiated power (W). In the period from January 2002 through January 2009 we observe a large decrease in the cooling rates, fluxes, and power consistent with the declining phase of solar cycle. The power radiated by NO during 2008 when the Sun exhibited few sunspots was nearly one order of magnitude smaller than the peak power observed shortly after the mission began. Substantial short-term variability in the infrared emissions is also observed throughout the entire mission duration. Radiative cooling rates and radiative fluxes from NO exhibit fundamentally different latitude dependence than do those from CO2, with the NO fluxes and cooling rates being largest at high latitudes and polar regions. The cooling rates are shown to be derived relatively independent of the collisional and radiative processes that drive the departure from local thermodynamic equilibrium (LTE) in the CO2 15 m and the NO 5.3 m vibration-rotation bands. The observed NO and CO2 cooling rates have been compiled into a separate dataset and represent a climate data record that is available for use in assessments of radiative cooling in upper atmosphere general circulation models

Adjunctive Glucocorticoid Therapy in Patients with Septic Shock.

Background Whether hydrocortisone reduces mortality among patients with septic shock is unclear. Methods We randomly assigned patients with septic shock who were undergoing mechanical ventilation to receive hydrocortisone (at a dose of 200 mg per day) or placebo for 7 days or until death or discharge from the intensive care unit (ICU), whichever came first. The primary outcome was death from any cause at 90 days. Results From March 2013 through April 2017, a total of 3800 patients underwent randomization. Status with respect to the primary outcome was ascertained in 3658 patients (1832 of whom had been assigned to the hydrocortisone group and 1826 to the placebo group). At 90 days, 511 patients (27.9%) in the hydrocortisone group and 526 (28.8%) in the placebo group had died (odds ratio, 0.95; 95% confidence interval [CI], 0.82 to 1.10; P=0.50). The effect of the trial regimen was similar in six prespecified subgroups. Patients who had been assigned to receive hydrocortisone had faster resolution of shock than those assigned to the placebo group (median duration, 3 days [interquartile range, 2 to 5] vs. 4 days [interquartile range, 2 to 9]; hazard ratio, 1.32; 95% CI, 1.23 to 1.41; P<0.001). Patients in the hydrocortisone group had a shorter duration of the initial episode of mechanical ventilation than those in the placebo group (median, 6 days [interquartile range, 3 to 18] vs. 7 days [interquartile range, 3 to 24]; hazard ratio, 1.13; 95% CI, 1.05 to 1.22; P<0.001), but taking into account episodes of recurrence of ventilation, there were no significant differences in the number of days alive and free from mechanical ventilation. Fewer patients in the hydrocortisone group than in the placebo group received a blood transfusion (37.0% vs. 41.7%; odds ratio, 0.82; 95% CI, 0.72 to 0.94; P=0.004). There were no significant between-group differences with respect to mortality at 28 days, the rate of recurrence of shock, the number of days alive and out of the ICU, the number of days alive and out of the hospital, the recurrence of mechanical ventilation, the rate of renal-replacement therapy, and the incidence of new-onset bacteremia or fungemia. Conclusions Among patients with septic shock undergoing mechanical ventilation, a continuous infusion of hydrocortisone did not result in lower 90-day mortality than placebo. (Funded by the National Health and Medical Research Council of Australia and others; ADRENAL ClinicalTrials.gov number, NCT01448109 .)

Planetary Candidates Observed by Kepler VI: Planet Sample from Q1-Q16 (47 Months)

\We present the sixth catalog of Kepler candidate planets based on nearly 4 years of high precision photometry. This catalog builds on the legacy of previous catalogs released by the Kepler project and includes 1493 new Kepler Objects of Interest (KOIs) of which 554 are planet candidates, and 131 of these candidates have best fit radii <1.5 R_earth. This brings the total number of KOIs and planet candidates to 7305 and 4173 respectively. We suspect that many of these new candidates at the low signal-to-noise limit may be false alarms created by instrumental noise, and discuss our efforts to identify such objects. We re-evaluate all previously published KOIs with orbital periods of >50 days to provide a consistently vetted sample that can be used to improve planet occurrence rate calculations. We discuss the performance of our planet detection algorithms, and the consistency of our vetting products. The full catalog is publicly available at the NASA Exoplanet Archive.Comment: 18 pages, to be published in the Astrophysical Journal Supplement Serie

Calcium-sensing receptor antagonists abrogate airway hyperresponsiveness and inflammation in allergic asthma

Airway hyperresponsiveness and inflammation are fundamental hallmarks of allergic asthma that are accompanied by increases in certain polycations, such as eosinophil cationic protein. Levels of these cations in body fluids correlate with asthma severity. We show that polycations and elevated extracellular calcium activate the human recombinant and native calcium-sensing receptor (CaSR), leading to intracellular calcium mobilization, cyclic adenosine monophosphate breakdown, and p38 mitogen-activated protein kinase phosphorylation in airway smooth muscle (ASM) cells. These effects can be prevented by CaSR antagonists, termed calcilytics. Moreover, asthmatic patients and allergen-sensitized mice expressed more CaSR in ASMs than did their healthy counterparts. Indeed, polycations induced hyperreactivity in mouse bronchi, and this effect was prevented by calcilytics and absent in mice with CaSR ablation from ASM. Calcilytics also reduced airway hyperresponsiveness and inflammation in allergen-sensitized mice in vivo. These data show that a functional CaSR is up-regulated in asthmatic ASM and targeted by locally produced polycations to induce hyperresponsiveness and inflammation. Thus, calcilytics may represent effective asthma therapeutics

Tissue Glucocorticoid Metabolism in Adrenal Insufficiency:A Prospective Study of Dual-release Hydrocortisone Therapy

Background: Patients with adrenal insufficiency (AI) require life-long glucocorticoid (GC) replacement therapy. Within tissues, cortisol (F) availability is under the control of the isozymes of 11β-hydroxysteroid dehydrogenase (11β-HSD). We hypothesize that corticosteroid metabolism is altered in patients with AI because of the nonphysiological pattern of current immediate release hydrocortisone (IR-HC) replacement therapy. The use of a once-daily dual-release hydrocortisone (DR-HC) preparation, (Plenadren®), offers a more physiological cortisol profile and may alter corticosteroid metabolism in vivo.Study Design and Methods: Prospective crossover study assessing the impact of 12 weeks of DR-HC on systemic GC metabolism (urinary steroid metabolome profiling), cortisol activation in the liver (cortisone acetate challenge test), and subcutaneous adipose tissue (microdialysis, biopsy for gene expression analysis) in 51 patients with AI (primary and secondary) in comparison to IR-HC treatment and age- and BMI-matched controls.Results: Patients with AI receiving IR-HC had a higher median 24-hour urinary excretion of cortisol compared with healthy controls (72.1 µg/24 hours [IQR 43.6-124.2] vs 51.9 µg/24 hours [35.5-72.3], P = .02), with lower global activity of 11β-HSD2 and higher 5-alpha reductase activity. Following the switch from IR-HC to DR-HC therapy, there was a significant reduction in urinary cortisol and total GC metabolite excretion, which was most significant in the evening. There was an increase in 11β-HSD2 activity. Hepatic 11β-HSD1 activity was not significantly altered after switching to DR-HC, but there was a significant reduction in the expression and activity of 11β-HSD1 in subcutaneous adipose tissue.Conclusion: Using comprehensive in vivo techniques, we have demonstrated abnormalities in corticosteroid metabolism in patients with primary and secondary AI receiving IR-HC. This dysregulation of pre-receptor glucocorticoid metabolism results in enhanced glucocorticoid activation in adipose tissue, which was ameliorated by treatment with DR-HC