PAMELA, DAMA, INTEGRAL and Signatures of Metastable Excited WIMPs

Models of dark matter with ~ GeV scale force mediators provide attractive explanations of many high energy anomalies, including PAMELA, ATIC, and the WMAP haze. At the same time, by exploiting the ~ MeV scale excited states that are automatically present in such theories, these models naturally explain the DAMA/LIBRA and INTEGRAL signals through the inelastic dark matter (iDM) and exciting dark matter (XDM) scenarios, respectively. Interestingly, with only weak kinetic mixing to hypercharge to mediate decays, the lifetime of excited states with delta < 2 m_e is longer than the age of the universe. The fractional relic abundance of these excited states depends on the temperature of kinetic decoupling, but can be appreciable. There could easily be other mechanisms for rapid decay, but the consequences of such long-lived states are intriguing. We find that CDMS constrains the fractional relic population of ~100 keV states to be <~ 10^-2, for a 1 TeV WIMP with sigma_n = 10^-40 cm^2. Upcoming searches at CDMS, as well as xenon, silicon, and argon targets, can push this limit significantly lower. We also consider the possibility that the DAMA excitation occurs from a metastable state into the XDM state, which decays via e+e- emission, which allows lighter states to explain the INTEGRAL signal due to the small kinetic energies required. Such models yield dramatic signals from down-scattering, with spectra peaking at high energies, sometimes as high as ~1 MeV, well outside the usual search windows. Such signals would be visible at future Ar and Si experiments, and may be visible at Ge and Xe experiments. We also consider other XDM models involving ~ 500 keV metastable states, and find they can allow lighter WIMPs to explain INTEGRAL as well.Comment: 22 pages, 7 figure

Systematic and detailed analysis of behavioural tests in the rat Middle Cerebral Artery Occlusion (MCAO) model of stroke: tests for long-term assessment

In order to test therapeutics, functional assessments are required. In pre-clinical stroke research, there is little consensus regarding the most appropriate behavioural tasks to assess deficits; especially when testing over extended times in milder models with short occlusion times and small lesion volumes. In this study we comprehensively assessed 16 different behavioural tests, with the aim of identifying those that show robust, reliable and stable deficits for up to 2 months. These tasks are regularly used in stroke research, as well as being useful for examining striatal dysfunction in models of Huntington’s and Parkinson’s disease. Two cohorts of male Wistar rats underwent the intraluminal filament model of MCAO (30min) and were imaged 24hrs later. This resulted in primarily subcortical infarcts, with a small amount of cortical damage. Animals were tested, along with sham and naïve groups at 24hrs, 7 days, and 1 and 2 months. Following behavioural testing, brains were processed and striatal neuronal counts were performed alongside measurements of total brain and white matter atrophy. The staircase, adjusting steps, rotarod and apomorphine induced rotations were the most reliable for assessing long-term deficits in the 30 min transient MCAO model of stroke

Differences in Respiratory Symptoms and Lung Structure Between Hispanic and Non-Hispanic White Smokers: A Comparative Study

Background: Prior studies have demonstrated that U.S. Hispanic smokers have a lower risk of decline in lung function and chronic obstructive pulmonary disease (COPD) compared with non-Hispanic whites (NHW). This suggests there might be racial-ethnic differences in susceptibility in cigarette smoke-induced respiratory symptoms, lung parenchymal destruction, and airway and vascular disease, as well as in extra-pulmonary manifestations of COPD. Therefore, we aimed to explore respiratory symptoms, lung function, and pulmonary and extra-pulmonary structural changes in Hispanic and NHW smokers. Methods: We compared respiratory symptoms, lung function, and computed tomography (CT) measures of emphysema-like tissue, airway disease, the branching generation number (BGN) to reach a 2-mm-lumen-diameter airway, and vascular pruning as well as muscle and fat mass between 39 Hispanic and 39 sex-, age- and smoking exposure-matched NHW smokers. Results: Hispanic smokers had higher odds of dyspnea than NHW after adjustment for COPD and asthma statuses (odds ratio[OR] = 2.96; 95% confidence interval [CI] 1.09-8.04), but no significant differences were found in lung function and CT measurements. Conclusions: While lung function and CT measures of the lung structure were similar, dyspnea is reported more frequently by Hispanic than matched-NHW smokers. It seems to be an impossible puzzle but it's easy to solve a Rubik' Cube using a few algorithms

CRT-100.12 Risk of Bleeding Among Cangrelor-Treated Patients Administered Upstream P2Y12 Inhibitor Therapy

Introduction: Little is known about the use of cangrelor in patients with MI who are treated with an oral P2Y12 inhibitor upstream prior to cardiac catheterization. Methods: CAMEO (Cangrelor in Acute MI: Effectiveness and Outcomes) is a 12-hospital observational registry studying platelet inhibition for MI patients undergoing cardiac cath. Upstream oral P2Y12 inhibition was defined as receipt of an oral P2Y12 inhibitor within 24 hours prior to hospitalization or in-hospital prior to cath. Among cangrelor-treated patients, we compared bleeding after cangrelor use through 7 days post-discharge between patients with and w/o upstream oral P2Y12 inhibitor exposure using logistic regression. We examined rates of bleeding among patients with a shorter (\u3c1 hour) vs. longer (1-3 hours or \u3e3 hours) duration between the last oral dose and cangrelor start. Results: Among 1,775 cangrelor-treated MI patients, 433 (24.4%) had upstream oral P2Y12 inhibitor treatment prior to cath. Of these, 165 patients (38%) started cangrelor within 1 hour, 109 (25%) between 1-3 hours, and 134 (31%) \u3e 3 hours after the in-hospital oral P2Y12 inhibitor dose. Cangrelor-treated patients who received upstream treatment were more likely to have a history of prior PCI, MI, PAD, and diabetes and to be clopidogrel-treated (all p\u3c0.01) compared w/o upstream treatment. There was no significant difference in risk of bleeding among cangrelor-treated patients with and w/o upstream oral P2Y12 inhibitor exposure (Table). While bleeding events were higher in patients with longer delays to cangrelor initiation, bleeding risk was not significant after adjustment (Table). Conclusions: Bleeding risk was not observed to be higher in cangrelor-treated patients after upstream oral P2Y12 inhibitor exposure compared with patients treated with cangrelor w/o upstream oral P2Y12 inhibitor exposure

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

Measuring the dynamic photosynthome

Background: Photosynthesis underpins plant productivity and yet is notoriously sensitive to small changes inenvironmental conditions, meaning that quantitation in nature across different time scales is not straightforward. The ‘dynamic’ changes in photosynthesis (i.e. the kinetics of the various reactions of photosynthesis in response to environmental shifts) are now known to be important in driving crop yield. Scope: It is known that photosynthesis does not respond in a timely manner, and even a small temporal “mismatch” between a change in the environment and the appropriate response of photosynthesis toward optimality can result in a fall in productivity. Yet the most commonly measured parameters are still made at steady state or a temporary steady state (including those for crop breeding purposes), meaning that new photosynthetic traits remain undiscovered. Conclusions: There is a great need to understand photosynthesis dynamics from a mechanistic and biological viewpoint especially when applied to the field of ‘phenomics’ which typically uses large genetically diverse populations of plants. Despite huge advances in measurement technology in recent years, it is still unclear whether we possess the capability of capturing and describing the physiologically relevant dynamic features of field photosynthesis in sufficient detail. Such traits are highly complex, hence we dub this the ‘photosynthome’. This review sets out the state of play and describes some approaches that could be made to address this challenge with reference to the relevant biological processes involved

Highlights From the Annual Meeting of the American Epilepsy Society 2022

With more than 6000 attendees between in-person and virtual offerings, the American Epilepsy Society Meeting 2022 in Nashville, felt as busy as in prepandemic times. An ever-growing number of physicians, scientists, and allied health professionals gathered to learn a variety of topics about epilepsy. The program was carefully tailored to meet the needs of professionals with different interests and career stages. This article summarizes the different symposia presented at the meeting. Basic science lectures addressed the primary elements of seizure generation and pathophysiology of epilepsy in different disease states. Scientists congregated to learn about anti-seizure medications, mechanisms of action, and new tools to treat epilepsy including surgery and neurostimulation. Some symposia were also dedicated to discuss epilepsy comorbidities and practical issues regarding epilepsy care. An increasing number of patient advocates discussing their stories were intertwined within scientific activities. Many smaller group sessions targeted more specific topics to encourage member participation, including Special Interest Groups, Investigator, and Skills Workshops. Special lectures included the renown Hoyer and Lombroso, an ILAE/IBE joint session, a spotlight on the impact of Dobbs v. Jackson on reproductive health in epilepsy, and a joint session with the NAEC on coding and reimbursement policies. The hot topics symposium was focused on traumatic brain injury and post-traumatic epilepsy. A balanced collaboration with the industry allowed presentations of the latest pharmaceutical and engineering advances in satellite symposia

Gender Gap in Parental Leave Intentions: Evidence from 37 Countries

Despite global commitments and efforts, a gender-based division of paid and unpaid work persists. To identify how psychological factors, national policies, and the broader sociocultural context contribute to this inequality, we assessed parental-leave intentions in young adults (18–30 years old) planning to have children (N = 13,942; 8,880 identified as women; 5,062 identified as men) across 37 countries that varied in parental-leave policies and societal gender equality. In all countries, women intended to take longer leave than men. National parental-leave policies and women’s political representation partially explained cross-national variations in the gender gap. Gender gaps in leave intentions were paradoxically larger in countries with more gender-egalitarian parental-leave policies (i.e., longer leave available to both fathers and mothers). Interestingly, this cross-national variation in the gender gap was driven by cross-national variations in women’s (rather than men’s) leave intentions. Financially generous leave and gender-egalitarian policies (linked to men’s higher uptake in prior research) were not associated with leave intentions in men. Rather, men’s leave intentions were related to their individual gender attitudes. Leave intentions were inversely related to career ambitions. The potential for existing policies to foster gender equality in paid and unpaid work is discussed.Gender Gap in Parental Leave Intentions: Evidence from 37 CountriespublishedVersio

Virological failure and development of new resistance mutations according to CD4 count at combination antiretroviral therapy initiation

Objectives: No randomized controlled trials have yet reported an individual patient benefit of initiating combination antiretroviral therapy (cART) at CD4 counts > 350 cells/μL. It is hypothesized that earlier initiation of cART in asymptomatic and otherwise healthy individuals may lead to poorer adherence and subsequently higher rates of resistance development. Methods: In a large cohort of HIV-positive individuals, we investigated the emergence of new resistance mutations upon virological treatment failure according to the CD4 count at the initiation of cART. Results: Of 7918 included individuals, 6514 (82.3%), 996 (12.6%) and 408 (5.2%) started cART with a CD4 count ≤ 350, 351-499 and ≥ 500 cells/μL, respectively. Virological rebound occurred while on cART in 488 (7.5%), 46 (4.6%) and 30 (7.4%) with a baseline CD4 count ≤ 350, 351-499 and ≥ 500 cells/μL, respectively. Only four (13.0%) individuals with a baseline CD4 count > 350 cells/μL in receipt of a resistance test at viral load rebound were found to have developed new resistance mutations. This compared to 107 (41.2%) of those with virological failure who had initiated cART with a CD4 count < 350 cells/μL. Conclusions: We found no evidence of increased rates of resistance development when cART was initiated at CD4 counts above 350 cells/μL. HIV Medicin