Characterization of Rock Types at Meridiani Planum, Mars using MER 13-Filter Pancam Spectra

The Mars Exploration Rover Opportunity has traversed more than 13 km across Meridiani Planum, finding evidence of ancient aqueous environments that, in the past, may have been suitable for life. Meridiani bedrock along the rover traverse is a mixture in composition and bulk mineralogy between a sulfate-rich sedimentary rock and hematite spherules ("blueberries"). On top of the bedrock, numerous loose rocks exist. These rocks consist of both local bedrock and "cobbles" of foreign origin. The cobbles provide a window into lithologic diversity and a chance to understand other types of martian rocks and meteorites. This study was also an attempt to establish a method to expand upon those of Mini-TES to remotely identify rocks of interest to make efficient use of the rover s current resources

The complete conformal spectrum of a sl(2∣1)sl(2|1) invariant network model and logarithmic corrections

We investigate the low temperature asymptotics and the finite size spectrum of a class of Temperley-Lieb models. As reference system we use the spin-1/2 Heisenberg chain with anisotropy parameter $\Delta$ and twisted boundary conditions. Special emphasis is placed on the study of logarithmic corrections appearing in the case of $\Delta=1/2$ in the bulk susceptibility data and in the low-energy spectrum yielding the conformal dimensions. For the $sl(2|1)$ invariant 3-state representation of the Temperley-Lieb algebra with $\Delta=1/2$ we give the complete set of scaling dimensions which show huge degeneracies.Comment: 18 pages, 5 figure

Discharge Identity of Medullary Inspiratory Neurons is Altered during Repetitive Fictive Cough

This study investigated the stability of the discharge identity of inspiratory decrementing (I-Dec) and augmenting (I-Aug) neurons in the caudal (cVRC) and rostral (rVRC) ventral respiratory column during repetitive fictive cough in the cat. Inspiratory neurons in the cVRC (n = 23) and rVRC (n = 17) were recorded with microelectrodes. Fictive cough was elicited by mechanical stimulation of the intrathoracic trachea. Approximately 43% (10 of 23) of I-Dec neurons shifted to an augmenting discharge pattern during the first cough cycle (C1). By the second cough cycle (C2), half of these returned to a decrementing pattern. Approximately 94% (16 of 17) of I-Aug neurons retained an augmenting pattern during C1 of a multi-cough response episode. Phrenic burst amplitude and inspiratory duration increased during C1, but decreased with each subsequent cough in a series of repetitive coughs. As a step in evaluating the model-driven hypothesis that VRC I-Dec neurons contribute to the augmentation of inspiratory drive during cough via inhibition of VRC tonic expiratory neurons that inhibit premotor inspiratory neurons, cross-correlation analysis was used to assess relationships of tonic expiratory cells with simultaneously recorded inspiratory neurons. Our results suggest that reconfiguration of inspiratory-related sub-networks of the respiratory pattern generator occurs on a cycle-by-cycle basis during repetitive coughing

Mineralogy and chemistry of cobbles at Meridiani Planum, Mars, investigated by the Mars Exploration Rover Opportunity

Numerous loose rocks with dimensions of a few centimeters to tens of centimeters and with no obvious physical relationship to outcrop rocks have been observed along the traverse of the Mars Exploration Rover Opportunity. To date, about a dozen of these rocks have been analyzed with Opportunity’s contact instruments, providing information about elemental chemistry (Alpha Particle X‐ray Spectrometer), iron mineralogy and oxidation states (Mössbauer Spectrometer) and texture (Microscopic Imager). These “cobbles” appear to be impact related, and three distinct groups can be identified on the basis of chemistry and mineralogy. The first group comprises bright fragments of the sulfate‐rich bedrock that are compositionally and texturally indistinguishable from outcrop rocks. All other cobbles are dark and are divided into two groups, referred to as the “Barberton group” and the “Arkansas group,” after the first specimen of each that was encountered by Opportunity. Barberton group cobbles are interpreted as meteorites with an overall chemistry and mineralogy consistent with a mesosiderite silicate clast composition. Arkansas group cobbles appear to be related to Meridiani outcrop and contain an additional basaltic component. They have brecciated textures, pointing to an impact‐related origin during which local bedrock and basaltic material were mixed

Efficacy and safety of trimodulin, a novel polyclonal antibody preparation, in patients with severe community-acquired pneumonia: a randomized, placebo-controlled, double-blind, multicenter, phase II trial (CIGMA study)

Purpose The CIGMA study investigated a novel human polyclonal antibody preparation (trimodulin) containing ~ 23% immunoglobulin (Ig) M, ~ 21% IgA, and ~ 56% IgG as add-on therapy for patients with severe community-acquired pneumonia (sCAP). Methods In this double-blind, phase II study (NCT01420744), 160 patients with sCAP requiring invasive mechanical ventilation were randomized (1:1) to trimodulin (42 mg IgM/kg/day) or placebo for five consecutive days. Primary endpoint was ventilator-free days (VFDs). Secondary endpoints included 28-day all-cause and pneumonia-related mortality. Safety and tolerability were monitored. Exploratory post hoc analyses were performed in subsets stratified by baseline C-reactive protein (CRP; ≥ 70 mg/L) and/or IgM (≤ 0.8 g/L). Results Overall, there was no statistically significant difference in VFDs between trimodulin (mean 11.0, median 11 [n = 81]) and placebo (mean 9.6; median 8 [n = 79]; p = 0.173). Twenty-eight-day all-cause mortality was 22.2% vs. 27.8%, respectively (p = 0.465). Time to discharge from intensive care unit and mean duration of hospitalization were comparable between groups. Adverse-event incidences were comparable. Post hoc subset analyses, which included the majority of patients (58–78%), showed significant reductions in all-cause mortality (trimodulin vs. placebo) in patients with high CRP, low IgM, and high CRP/low IgM at baseline. Conclusions No significant differences were found in VFDs and mortality between trimodulin and placebo groups. Post hoc analyses supported improved outcome regarding mortality with trimodulin in subsets of patients with elevated CRP, reduced IgM, or both. These findings warrant further investigation

Neurogenic mechanisms in bladder and bowel ageing

The prevalence of both urinary and faecal incontinence, and also chronic constipation, increases with ageing and these conditions have a major impact on the quality of life of the elderly. Management of bladder and bowel dysfunction in the elderly is currently far from ideal and also carries a significant financial burden. Understanding how these changes occur is thus a major priority in biogerontology. The functions of the bladder and terminal bowel are regulated by complex neuronal networks. In particular neurons of the spinal cord and peripheral ganglia play a key role in regulating micturition and defaecation reflexes as well as promoting continence. In this review we discuss the evidence for ageing-induced neuronal dysfunction that might predispose to neurogenic forms of incontinence in the elderly

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Large-scale genome-wide analysis identifies genetic variants associated with cardiac structure and function

BACKGROUND: Understanding the genetic architecture of cardiac structure and function may help to prevent and treat heart disease. This investigation sought to identify common genetic variations associated with inter-individual variability in cardiac structure and function. METHODS: A GWAS meta-analysis of echocardiographic traits was performed, including 46,533 individuals from 30 studies (EchoGen consortium). The analysis included 16 traits of left ventricular (LV) structure, and systolic and diastolic function. RESULTS: The discovery analysis included 21 cohorts for structural and systolic function traits (n = 32,212) and 17 cohorts for diastolic function traits (n = 21,852). Replication was performed in 5 cohorts (n = 14,321) and 6 cohorts (n = 16,308), respectively. Besides 5 previously reported loci, the combined meta-analysis identified 10 additional genome-wide significant SNPs: rs12541595 near MTSS1 and rs10774625 in ATXN2 for LV end-diastolic internal dimension; rs806322 near KCNRG, rs4765663 in CACNA1C, rs6702619 near PALMD, rs7127129 in TMEM16A, rs11207426 near FGGY, rs17608766 in GOSR2, and rs17696696 in CFDP1 for aortic root diameter; and rs12440869 in IQCH for Doppler transmitral A-wave peak velocity. Findings were in part validated in other cohorts and in GWAS of related disease traits. The genetic loci showed associations with putative signaling pathways, and with gene expression in whole blood, monocytes, and myocardial tissue. CONCLUSION: The additional genetic loci identified in this large meta-analysis of cardiac structure and function provide insights into the underlying genetic architecture of cardiac structure and warrant follow-up in future functional studies. FUNDING: For detailed information per study, see Acknowledgments.This work was supported by a grant from the US National Heart, Lung, and Blood Institute (N01-HL-25195; R01HL 093328 to RSV), a MAIFOR grant from the University Medical Center Mainz, Germany (to PSW), the Center for Translational Vascular Biology (CTVB) of the Johannes Gutenberg-University of Mainz, and the Federal Ministry of Research and Education, Germany (BMBF 01EO1003 to PSW). This work was also supported by the research project Greifswald Approach to Individualized Medicine (GANI_MED). GANI_MED was funded by the Federal Ministry of Education and Research and the Ministry of Cultural Affairs of the Federal State of Mecklenburg, West Pomerania (contract 03IS2061A). We thank all study participants, and the colleagues and coworkers from all cohorts and sites who were involved in the generation of data or in the analysis. We especially thank Andrew Johnson (FHS) for generation of the gene annotation database used for analysis. We thank the German Center for Cardiovascular Research (DZHK e.V.) for supporting the analysis and publication of this project. RSV is a member of the Scientific Advisory Board of the DZHK. Data on CAD and MI were contributed by CARDIoGRAMplusC4D investigators. See Supplemental Acknowledgments for consortium details. PSW, JFF, AS, AT, TZ, RSV, and MD had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis

Blending Video Therapy and Digital Self-Help for Individuals With Suicidal Ideation: Intervention Design and a Qualitative Study Within the Development Process

BackgroundDigital formats have the potential to enhance accessibility to care for individuals with suicidal ideation. However, digital self-help interventions have faced limitations, including small effect sizes in reducing suicidal ideation, low adherence, and safety concerns. ObjectiveTherefore, we aimed to develop a remote blended cognitive behavioral therapy intervention that specifically targets suicidal ideation by blending video therapy with web-based self-help modules. The objective of this paper is to describe the collaborative development process and the resulting intervention and treatment rationale. MethodsFirst, we compiled intervention components from established treatment manuals designed for people with suicidal ideation or behavior, resulting in the development of 11 drafts of web-based modules. Second, we conducted a qualitative study, involving 5 licensed psychotherapists and 3 lay counselors specialized in individuals with suicidal ideation who reviewed these module drafts. Data were collected using the think-aloud method and semistructured interviews, and a qualitative content analysis was performed. The 4 a priori main categories of interest were blended care for individuals with suicidal ideation, contents of web-based modules, usability of modules, and layout. Subcategories emerged inductively from the interview transcripts. Finally, informed by previous treatment manuals and qualitative findings, we developed the remote blended treatment program. ResultsThe participants suggested that therapists should thoroughly prepare the web-based therapy with patients to tailor the therapy to each individual’s needs. Participants emphasized that the web-based modules should explain concepts in a simple manner, convey empathy and validation, and include reminders for the safety plan. In addition, participants highlighted the need for a simple navigation and layout. Taking these recommendations into account, we developed a fully remote blended cognitive behavioral therapy intervention comprising 12 video therapy sessions and up to 31 web-based modules. The treatment involves collaboratively developing a personalized treatment plan to address individual suicidal drivers. ConclusionsThis remote treatment takes advantage of the high accessibility of digital formats while incorporating full sessions with a therapist. In a subsequent pilot trial, we will seek input from individuals with lived experience and therapists to test the feasibility of the treatment

Functional Connectivity in Raphé-Pontomedullary Circuits Supports Active Suppression of Breathing During Hypocapnic Apnea

Hyperventilation is a common feature of disordered breathing. Apnea ensues if CO2 drive is sufficiently reduced. We tested the hypothesis that medullary raphé, ventral respiratory column (VRC), and pontine neurons have functional connectivity and persistent or evoked activities appropriate for roles in the suppression of drive and rhythm during hyperventilation and apnea. Phrenic nerve activity, arterial blood pressure, end-tidal CO2, and other parameters were monitored in 10 decerebrate, vagotomized, neuromuscularly-blocked, and artificially ventilated cats. Multielectrode arrays recorded spiking activity of 649 neurons. Loss and return of rhythmic activity during passive hyperventilation to apnea were identified with the S-transform. Diverse fluctuating activity patterns were recorded in the raphé-pontomedullary respiratory network during the transition to hypocapnic apnea. The firing rates of 160 neurons increased during apnea; the rates of 241 others decreased or stopped. VRC inspiratory neurons were usually the last to cease firing or lose rhythmic activity during the transition to apnea. Mayer wave-related oscillations (0.04–0.1 Hz) in firing rate were also disrupted during apnea. Four-hundred neurons (62%) were elements of pairs with at least one hyperventilation-responsive neuron and a correlational signature of interaction identified by cross-correlation or gravitational clustering. Our results support a model with distinct groups of chemoresponsive raphé neurons contributing to hypocapnic apnea through parallel processes that incorporate disfacilitation and active inhibition of inspiratory motor drive by expiratory neurons. During apnea, carotid chemoreceptors can evoke rhythm reemergence and an inspiratory shift in the balance of reciprocal inhibition via suppression of ongoing tonic expiratory neuron activity. breathing is a remarkably robust behavior that is activated at birth and continues until death, yet the brain stem neural network controlling it is even more remarkable in its malleability. For example, talking, swallowing, and coughing are motor acts that alter the breathing pattern and, rather than simply inhibiting breathing, the neural substrate for these motor acts transiently appropriates and reconfigures the respiratory pattern generator (Bolser et al. 2011, 2013; Shannon et al. 2004). However, what about conditions when breathing stops? Hyperventilation is a component of dangerous underwater breath-holding behaviors (Boyd et al. 2015; Craig 1961) and a common feature of disordered breathing (for discussion, see Abdala et al. 2014; Dempsey 2005; Laffey and Kavanagh 2002). If the drive from CO2 is sufficiently reduced, hypocapnic apnea, a transient cessation of breathing, ensues with its attendant and potentially adverse consequences (Bitter et al. 2011; Harper et al. 2013; Javaheri and Dempsey 2013; Leung et al. 2012; Sankri-Tarbichi et al. 2009; Sankri-Tarbichi 2012). During the transition from eupneic-like breathing to hyperventilatory apnea, phrenic motoneurons (Prabhakar et al. 1986) and phasic respiratory-modulated brain stem neurons either cease to discharge or assume a tonic pattern of activity (Bainton and Kirkwood 1979; Batsel 1967; Cohen 1968; Haber et al. 1957; Nesland and Plum 1965; Orem and Vidruk 1998; St. John 1998; Sun et al. 2001, 2005). With one exception (Cohen 1968), these studies recorded neurons in the ventral respiratory column (VRC; Smith et al. 2013), one at a time. This approach precludes assessment of local connectivity within the VRC and of distributed interactions with pontine and raphé neurons of the respiratory network (Nuding et al. 2009a; Segers et al. 2008). The circuit mechanisms for hypocapnic apnea remain poorly understood. Both reduced excitatory chemoreceptor drive and active inhibitory processes may contribute to the suspended state of the respiratory central pattern generator. Peripheral chemoreceptors of the carotid body monitor changes in arterial O2 and CO2-pH (Kumar and Prabhakar 2012), and central chemoreceptors, distributed among various brain stem sites, sense brain CO2-pH (Nattie and Li 2012). Mechanisms of their joint and separate influences on pattern-generating circuits are subjects of active research (Duffin and Mateika 2013a,b; Phillipson et al. 1981; Teppema and Smith 2013a,b; Wilson and Day 2013a,b). Central chemoreceptors and their follower neurons, collectively termed chemoresponsive, may be either functionally excited or inhibited by an increase in PaCO2 (e.g., Bochorishvili et al. 2012; Dean et al. 1989; Guyenet et al. 2010; Marina et al. 2010; Nuding et al. 2009b; Ott et al. 2011, 2012; Richerson et al. 2001). Medullary raphé neurons have diverse responses to hypercapnia and acidosis: firing rates of serotonergic neurons increase (Brust et al. 2014; Iceman et al. 2013; Severson et al. 2003; Veasey et al. 1995; Wang et al. 1998, 2001), whereas GABAergic raphé neurons are functionally inhibited (Iceman et al. 2014). These results are consistent with the hypothesis that distinct populations of chemoresponsive raphé neurons produce an additive “push-pull” enhancement of breathing via excitation and disinhibition, respectively (Richerson et al. 2001), a notion similar to that proposed for baroreceptor-evoked modulation of breathing via raphé-mediated excitation and disinhibition of ventral respiratory column expiratory neurons (Lindsey et al. 1998). The distinct chemoresponsive profiles of different raphé neuron populations led us to conjecture that cells effectively excited during hypercapnia would exhibit decreased firing rates during hypocapnia and vice versa for neurons inhibited during hypercapnia. This possibility and gaps in our knowledge of network interactions motivated us to test the hypothesis that medullary raphé, VRC, and pontine neurons have functional connectivity as well as persistent and evoked activities appropriate for roles in the suppression of respiratory drive and rhythm during hyperventilation and hypocapnic apnea. Sears et al. (1982) demonstrated reciprocal tonic activation of inspiratory and expiratory motor neurons during hypocapnic apnea. A PaCO2 drive below the apneic threshold may promote expiratory activity and functionally suppress inspiration. Hypoxia associated with apnea evokes increased peripheral chemoreceptor activity, enhances or elicits tonic inspiratory motor neuron activities, and can reestablish respiratory rhythmogenesis. Fluctuations in this peripheral chemoreceptor-mediated “inspiratory shift,” operating through unknown circuit mechanisms, may contribute to periodic breathing in heart failure and central sleep apnea (Lovering et al. 2012). Our multielectrode arrays allow concurrent single-unit recordings from multiple brain stem nuclei that generate and modulate breathing. This approach is well suited for testing our hypothesis and assessment of the activity patterns of many neurons under the same conditions. Thus we recorded changes in firing rates during different chemoreceptor-evoked perturbations of breathing and evaluated spike trains for correlation features indicative of functional connectivity. Preliminary accounts of this work have been presented (Lindsey et al. 2014; Nuding et al. 2005, 2013)