The effect of statin therapy on heart failure events: a collaborative meta-analysis of unpublished data from major randomized trials

The effect of statins on risk of heart failure (HF) hospitalization and HF death remains uncertain. We aimed to establish whether statins reduce major HF events.We searched Medline, EMBASE, and the Cochrane Central Register of Controlled Trials for randomized controlled endpoint statin trials from 1994 to 2014. Collaborating trialists provided unpublished data from adverse event reports. We included primary- and secondary-prevention statin trials with >1000 participants followed for >1 year. Outcomes consisted of first non-fatal HF hospitalization, HF death and a composite of first non-fatal HF hospitalization or HF death. HF events occurring <30 days after within-trial myocardial infarction (MI) were excluded. We calculated risk ratios (RR) with fixed-effects meta-analyses. In up to 17 trials with 132 538 participants conducted over 4.3 [weighted standard deviation (SD) 1.4] years, statin therapy reduced LDL-cholesterol by 0.97 mmol/L (weighted SD 0.38 mmol/L). Statins reduced the numbers of patients experiencing non-fatal HF hospitalization (1344/66 238 vs. 1498/66 330; RR 0.90, 95% confidence interval, CI 0.84-0.97) and the composite HF outcome (1234/57 734 vs. 1344/57 836; RR 0.92, 95% CI 0.85-0.99) but not HF death (213/57 734 vs. 220/57 836; RR 0.97, 95% CI 0.80-1.17). The effect of statins on first non-fatal HF hospitalization was similar whether this was preceded by MI (RR 0.87, 95% CI 0.68-1.11) or not (RR 0.91, 95% CI 0.84-0.98).In primary- and secondary-prevention trials, statins modestly reduced the risks of non-fatal HF hospitalization and a composite of non-fatal HF hospitalization and HF death with no demonstrable difference in risk reduction between those who suffered an MI or not

Moving towards a population health approach to the primary prevention of common mental disorders

There is a need for the development of effective universal preventive approaches to the common mental disorders, depression and anxiety, at a population level. Poor diet, physical inactivity and smoking have long been recognized as key contributors to the high prevalence noncommunicable diseases. However, there are now an increasing number of studies suggesting that the same modifiable lifestyle behaviors are also risk factors for common mental disorders. In this paper we point to the emerging data regarding lifestyle risk factors for common mental disorders, with a particular focus on and critique of the newest evidence regarding diet quality. On the basis of this most recent evidence, we consequently argue for the inclusion of depression and anxiety in the ranks of the high prevalence noncommunicable diseases influenced by habitual lifestyle practices. We believe that it is both feasible and timely to begin to develop effective, sustainable, population-level prevention initiatives for the common mental illnesses that build on the established and developing approaches to the noncommunicable somatic diseases.<br /

The effects of stimulus complexity on the preattentive processing of self-generated and nonself voices: an ERP study

The ability to differentiate one's own voice from the voice of somebody else plays a critical role in successful verbal self-monitoring processes and in communication. However, most of the existing studies have only focused on the sensory correlates of self-generated voice processing, whereas the effects of attentional demands and stimulus complexity on self-generated voice processing remain largely unknown. In this study, we investigated the effects of stimulus complexity on the preattentive processing of self and nonself voice stimuli. Event-related potentials (ERPs) were recorded from 17 healthy males who watched a silent movie while ignoring prerecorded self-generated (SGV) and nonself (NSV) voice stimuli, consisting of a vocalization (vocalization category condition: VCC) or of a disyllabic word (word category condition: WCC). All voice stimuli were presented as standard and deviant events in four distinct oddball sequences. The mismatch negativity (MMN) ERP component peaked earlier for NSV than for SGV stimuli. Moreover, when compared with SGV stimuli, the P3a amplitude was increased for NSV stimuli in the VCC only, whereas in the WCC no significant differences were found between the two voice types. These findings suggest differences in the time course of automatic detection of a change in voice identity. In addition, they suggest that stimulus complexity modulates the magnitude of the orienting response to SGV and NSV stimuli, extending previous findings on self-voice processing.This work was supported by Grant Numbers IF/00334/2012, PTDC/PSI-PCL/116626/2010, and PTDC/MHN-PCN/3606/2012, funded by the Fundacao para a Ciencia e a Tecnologia (FCT, Portugal) and the Fundo Europeu de Desenvolvimento Regional through the European programs Quadro de Referencia Estrategico Nacional and Programa Operacional Factores de Competitividade, awarded to A.P.P., and by FCT Doctoral Grant Number SFRH/BD/77681/2011, awarded to T.C.info:eu-repo/semantics/publishedVersio

An Examination of Not-For-Profit Stakeholder Networks for Relationship Management: A Small-Scale Analysis on Social Media

Using a small-scale descriptive network analysis approach, this study highlights the importance of stakeholder networks for identifying valuable stakeholders and the management of existing stakeholders in the context of mental health not-for-profit services. We extract network data from the social media brand pages of three health service organizations from the U.S., U.K., and Australia, to visually map networks of 579 social media brand pages (represented by nodes), connected by 5,600 edges. This network data is analyzed using a collection of popular graph analysis techniques to assess the differences in the way each of the service organizations manage stakeholder networks. We also compare node meta-information against basic topology measures to emphasize the importance of effectively managing relationships with stakeholders who have large external audiences. Implications and future research directions are also discussed

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Skillful long-range prediction of European and North American winters

This is the final version. Available from AGU via the DOI in this recordUntil recently, long-range forecast systems showed only modest levels of skill in predicting surface winter climate around the Atlantic Basin and associated fluctuations in the North Atlantic Oscillation at seasonal lead times. Here we use a new forecast system to assess seasonal predictability of winter North Atlantic climate. We demonstrate that key aspects of European and North American winter climate and the surface North Atlantic Oscillation are highly predictable months ahead. We demonstrate high levels of prediction skill in retrospective forecasts of the surface North Atlantic Oscillation, winter storminess, near-surface temperature, and wind speed, all of which have high value for planning and adaptation to extreme winter conditions. Analysis of forecast ensembles suggests that while useful levels of seasonal forecast skill have now been achieved, key sources of predictability are still only partially represented and there is further untapped predictability. Key Points The winter NAO can be skilfully predicted months ahead The signal-to-noise ratio of the predictable signal is anomalously low Predictions of the risk of regional winter extremes are possibleThis work was supported by the Joint DECC/Defra Met Office Hadley Centre Climate Programme (GA01101), the UK Public Weather Service research program, and the European Union Framework 7 SPECS project. Leon Hermanson was funded as part of his Research Fellowship by Willis as part of Willis Research Network (WRN)

Physiological Properties of Cholinergic and Non-Cholinergic Magnocellular Neurons in Acute Slices from Adult Mouse Nucleus Basalis

The basal forebrain is a series of nuclei that provides cholinergic input to much of the forebrain. The most posterior of these nuclei, nucleus basalis, provides cholinergic drive to neocortex and is involved in arousal and attention. The physiological properties of neurons in anterior basal forebrain nuclei, including medial septum, the diagonal band of Broca and substantia innominata, have been described previously. In contrast the physiological properties of neurons in nucleus basalis, the most posterior nucleus of the basal forebrain, are unknown.Here we investigate the physiological properties of neurons in adult mouse nucleus basalis. We obtained cell-attached and whole-cell recordings from magnocellular neurons in slices from P42-54 mice and compared cholinergic and non-cholinergic neurons, distinguished retrospectively by anti-choline acetyltransferase immunocytochemistry. The majority (70-80%) of cholinergic and non-cholinergic neurons were silent at rest. Spontaneously active cholinergic and non-cholinergic neurons exhibited irregular spiking at 3 Hz and at 0.3 to 13.4 Hz, respectively. Cholinergic neurons had smaller, broader action potentials than non-cholinergic neurons (amplitudes 64+/-3.4 and 75+/-2 mV; half widths 0.52+/-0.04 and 0.33+/-0.02 ms). Cholinergic neurons displayed a more pronounced slow after-hyperpolarization than non-cholinergic neurons (13.3+/-2.2 and 3.6+/-0.5 mV) and were unable to spike at high frequencies during tonic current injection (maximum frequencies of approximately 20 Hz and >120 Hz).Our results indicate that neurons in nucleus basalis share similar physiological properties with neurons in anterior regions of the basal forebrain. Furthermore, cholinergic and non-cholinergic neurons in nucleus basalis can be distinguished by their responses to injected current. To our knowledge, this is the first description of the physiological properties of cholinergic and non-cholinergic neurons in the posterior aspects of the basal forebrain complex and the first study of basal forebrain neurons from the mouse

Treatment with a corticotrophin releasing factor 2 receptor agonist modulates skeletal muscle mass and force production in aged and chronically ill animals

<p>Abstract</p> <p>Background</p> <p>Muscle weakness is associated with a variety of chronic disorders such as emphysema (EMP) and congestive heart failure (CHF) as well as aging. Therapies to treat muscle weakness associated with chronic disease or aging are lacking. Corticotrophin releasing factor 2 receptor (CRF2R) agonists have been shown to maintain skeletal muscle mass and force production in a variety of acute conditions that lead to skeletal muscle wasting.</p> <p>Hypothesis</p> <p>We hypothesize that treating animals with a CRF2R agonist will maintain skeletal muscle mass and force production in animals with chronic disease and in aged animals.</p> <p>Methods</p> <p>We utilized animal models of aging, CHF and EMP to evaluate the potential of CRF2R agonist treatment to maintain skeletal muscle mass and force production in aged animals and animals with CHF and EMP.</p> <p>Results</p> <p>In aged rats, we demonstrate that treatment with a CRF2R agonist for up to 3 months results in greater extensor digitorum longus (EDL) force production, EDL mass, soleus mass and soleus force production compared to age matched untreated animals. In the hamster EMP model, we demonstrate that treatment with a CRF2R agonist for up to 5 months results in greater EDL force production in EMP hamsters when compared to vehicle treated EMP hamsters and greater EDL mass and force in normal hamsters when compared to vehicle treated normal hamsters. In the rat CHF model, we demonstrate that treatment with a CRF2R agonist for up to 3 months results in greater EDL and soleus muscle mass and force production in CHF rats and normal rats when compared to the corresponding vehicle treated animals.</p> <p>Conclusions</p> <p>These data demonstrate that the underlying physiological conditions associated with chronic diseases such as CHF and emphysema in addition to aging do not reduce the potential of CRF2R agonists to maintain skeletal muscle mass and force production.</p

Echinocandin Treatment of Pneumocystis Pneumonia in Rodent Models Depletes Cysts Leaving Trophic Burdens That Cannot Transmit the Infection

Fungi in the genus Pneumocystis cause pneumonia (PCP) in hosts with debilitated immune systems and are emerging as co-morbidity factors associated with chronic diseases such as COPD. Limited therapeutic choices and poor understanding of the life cycle are a result of the inability of these fungi to grow outside the mammalian lung. Within the alveolar lumen, Pneumocystis spp., appear to have a bi-phasic life cycle consisting of an asexual phase characterized by binary fission of trophic forms and a sexual cycle resulting in formation of cysts, but the life cycle stage that transmits the infection is not known. The cysts, but not the trophic forms, express β -1,3-D-glucan synthetase and contain abundant β -1,3-D-glucan. Here we show that therapeutic and prophylactic treatment of PCP with echinocandins, compounds which inhibit the synthesis of β -1,3-D-glucan, depleted cysts in rodent models of PCP, while sparing the trophic forms which remained in significant numbers. Survival was enhanced in the echincandin treated mice, likely due to the decreased β -1,3-D-glucan content in the lungs of treated mice and rats which coincided with reductions of cyst numbers, and dramatic remodeling of organism morphology. Strong evidence for the cyst as the agent of transmission was provided by the failure of anidulafungin-treated mice to transmit the infection. We show for the first time that withdrawal of anidulafungin treatment with continued immunosuppression permitted the repopulation of cyst forms. Treatment of PCP with an echinocandin alone will not likely result in eradication of infection and cessation of echinocandin treatment while the patient remains immunosuppressed could result in relapse. Importantly, the echinocandins provide novel and powerful chemical tools to probe the still poorly understood bi-phasic life cycle of this genus of fungal pathogens