In the primary analysis of the Aspirin in Reducing Events in the Elderly (ASPREE) trial, now published in the Journal, we report that the daily use of aspirin did not provide a benefit with regard to ...the primary end point of disability-free survival among older adults. A numerically higher rate of the secondary end point of death from any cause was observed with aspirin than with placebo.
From 2010 through 2014, we enrolled community-dwelling persons in Australia and the United States who were 70 years of age or older (or ≥65 years of age among blacks and Hispanics in the United States) and did not have cardiovascular disease, dementia, or disability. Participants were randomly assigned to receive 100 mg of enteric-coated aspirin or placebo. Deaths were classified according to the underlying cause by adjudicators who were unaware of trial-group assignments. Hazard ratios were calculated to compare mortality between the aspirin group and the placebo group, and post hoc exploratory analyses of specific causes of death were performed.
Of the 19,114 persons who were enrolled, 9525 were assigned to receive aspirin and 9589 to receive placebo. A total of 1052 deaths occurred during a median of 4.7 years of follow-up. The risk of death from any cause was 12.7 events per 1000 person-years in the aspirin group and 11.1 events per 1000 person-years in the placebo group (hazard ratio, 1.14; 95% confidence interval CI, 1.01 to 1.29). Cancer was the major contributor to the higher mortality in the aspirin group, accounting for 1.6 excess deaths per 1000 person-years. Cancer-related death occurred in 3.1% of the participants in the aspirin group and in 2.3% of those in the placebo group (hazard ratio, 1.31; 95% CI, 1.10 to 1.56).
Higher all-cause mortality was observed among apparently healthy older adults who received daily aspirin than among those who received placebo and was attributed primarily to cancer-related death. In the context of previous studies, this result was unexpected and should be interpreted with caution. (Funded by the National Institute on Aging and others; ASPREE ClinicalTrials.gov number, NCT01038583 .).
Many patients show no or incomplete responses to current pharmacological or psychological therapies for depression. Here we explored the feasibility of a new brain self-regulation technique that ...integrates psychological and neurobiological approaches through neurofeedback with functional magnetic resonance imaging (fMRI). In a proof-of-concept study, eight patients with depression learned to upregulate brain areas involved in the generation of positive emotions (such as the ventrolateral prefrontal cortex (VLPFC) and insula) during four neurofeedback sessions. Their clinical symptoms, as assessed with the 17-item Hamilton Rating Scale for Depression (HDRS), improved significantly. A control group that underwent a training procedure with the same cognitive strategies but without neurofeedback did not improve clinically. Randomised blinded clinical trials are now needed to exclude possible placebo effects and to determine whether fMRI-based neurofeedback might become a useful adjunct to current therapies for depression.
‘Perytons’ are millisecond-duration transients of terrestrial origin, whose frequency-swept emission mimics the dispersion of an astrophysical pulse that has propagated through tenuous cold plasma. ...In fact, their similarity to FRB 010724 had previously cast a shadow over the interpretation of ‘fast radio bursts’ (FRBs), which otherwise appear to be of extragalactic origin. Until now, the physical origin of the dispersion-mimicking perytons had remained a mystery. We have identified strong out-of-band emission at 2.3–2.5 GHz associated with several peryton events. Subsequent tests revealed that a peryton can be generated at 1.4 GHz when a microwave oven door is opened prematurely and the telescope is at an appropriate relative angle. Radio emission escaping from microwave ovens during the magnetron shut-down phase neatly explains all of the observed properties of the peryton signals. Now that the peryton source has been identified, we furthermore demonstrate that the microwave ovens on site could not have caused FRB 010724. This and other distinct observational differences show that FRBs are excellent candidates for genuine extragalactic transients.
To systematically review evidence bearing on the management of patients with amyotrophic lateral sclerosis (ALS).
The authors analyzed studies from 1998 to 2007 to update the 1999 practice parameter. ...Topics covered in this section include breaking the news, multidisciplinary clinics, symptom management, cognitive and behavioral impairment, communication, and palliative care for patients with ALS.
The authors identified 2 Class I studies, 8 Class II studies, and 30 Class III studies in ALS, but many important areas have been little studied. More high-quality, controlled studies of symptomatic therapies and palliative care are needed to guide management and assess outcomes in patients with ALS.
Multidisciplinary clinic referral should be considered for managing patients with ALS to optimize health care delivery and prolong survival (Level B) and may be considered to enhance quality of life (Level C). For the treatment of refractory sialorrhea, botulinum toxin B should be considered (Level B) and low-dose radiation therapy to the salivary glands may be considered (Level C). For treatment of pseudobulbar affect, dextromethorphan and quinidine should be considered if approved by the US Food and Drug Administration (Level B). For patients who develop fatigue while taking riluzole, withholding the drug may be considered (Level C). Because many patients with ALS demonstrate cognitive impairment, which in some cases meets criteria for dementia, screening for cognitive and behavioral impairment should be considered in patients with ALS (Level B). Other management strategies all lack strong evidence.
Summary Background Cardiosphere-derived cells (CDCs) reduce scarring after myocardial infarction, increase viable myocardium, and boost cardiac function in preclinical models. We aimed to assess ...safety of such an approach in patients with left ventricular dysfunction after myocardial infarction. Methods In the prospective, randomised CArdiosphere-Derived aUtologous stem CElls to reverse ventricUlar dySfunction (CADUCEUS) trial, we enrolled patients 2–4 weeks after myocardial infarction (with left ventricular ejection fraction of 25–45%) at two medical centres in the USA. An independent data coordinating centre randomly allocated patients in a 2:1 ratio to receive CDCs or standard care. For patients assigned to receive CDCs, autologous cells grown from endomyocardial biopsy specimens were infused into the infarct-related artery 1·5–3 months after myocardial infarction. The primary endpoint was proportion of patients at 6 months who died due to ventricular tachycardia, ventricular fibrillation, or sudden unexpected death, or had myocardial infarction after cell infusion, new cardiac tumour formation on MRI, or a major adverse cardiac event (MACE; composite of death and hospital admission for heart failure or non-fatal recurrent myocardial infarction). We also assessed preliminary efficacy endpoints on MRI by 6 months. Data analysers were masked to group assignment. This study is registered with ClinicalTrials.gov , NCT00893360. Findings Between May 5, 2009, and Dec 16, 2010, we randomly allocated 31 eligible participants of whom 25 were included in a per-protocol analysis (17 to CDC group and eight to standard of care). Mean baseline left ventricular ejection fraction (LVEF) was 39% (SD 12) and scar occupied 24% (10) of left ventricular mass. Biopsy samples yielded prescribed cell doses within 36 days (SD 6). No complications were reported within 24 h of CDC infusion. By 6 months, no patients had died, developed cardiac tumours, or MACE in either group. Four patients (24%) in the CDC group had serious adverse events compared with one control (13%; p=1·00). Compared with controls at 6 months, MRI analysis of patients treated with CDCs showed reductions in scar mass (p=0·001), increases in viable heart mass (p=0·01) and regional contractility (p=0·02), and regional systolic wall thickening (p=0·015). However, changes in end-diastolic volume, end-systolic volume, and LVEF did not differ between groups by 6 months. Interpretation We show intracoronary infusion of autologous CDCs after myocardial infarction is safe, warranting the expansion of such therapy to phase 2 study. The unprecedented increases we noted in viable myocardium, which are consistent with therapeutic regeneration, merit further assessment of clinical outcomes. Funding US National Heart, Lung and Blood Institute and Cedars-Sinai Board of Governors Heart Stem Cell Center.
The determinants of the structure, functioning and resilience of pelagic ecosystems across most of the polar regions are not well known. Improved understanding is essential for assessing the value of ...biodiversity and predicting the effects of change (including in biodiversity) on these ecosystems and the services they maintain. Here we focus on the trophic interactions that underpin ecosystem structure, developing comparative analyses of how polar pelagic food webs vary in relation to the environment. We highlight that there is not a singular, generic Arctic or Antarctic pelagic food web, and, although there are characteristic pathways of energy flow dominated by a small number of species, alternative routes are important for maintaining energy transfer and resilience. These more complex routes cannot, however, provide the same rate of energy flow to highest trophic-level species. Food-web structure may be similar in different regions, but the individual species that dominate mid-trophic levels vary across polar regions. The characteristics (traits) of these species are also different and these differences influence a range of food-web processes. Low functional redundancy at key trophic levels makes these ecosystems particularly sensitive to change. To develop models for projecting responses of polar ecosystems to future environmental change, we propose a conceptual framework that links the life histories of pelagic species and the structure of polar food webs.
ABSTRACT We report on timing, flux density, and polarimetric observations of the transient magnetar and 5.54 s radio pulsar XTE J1810−197 using the Green Bank, Nançay, and Parkes radio telescopes ...beginning in early 2006, until its sudden disappearance as a radio source in late 2008. Repeated observations through 2016 have not detected radio pulsations again. The torque on the neutron star, as inferred from its rotation frequency derivative , decreased in an unsteady manner by a factor of three in the first year of radio monitoring, until approximately mid-2007. By contrast, during its final year as a detectable radio source, the torque decreased steadily by only 9%. The period-averaged flux density, after decreasing by a factor of 20 during the first 10 months of radio monitoring, remained relatively steady in the next 22 months, at an average of 0.7 0.3 mJy at 1.4 GHz, while still showing day-to-day fluctuations by factors of a few. There is evidence that during this last phase of radio activity the magnetar had a steep radio spectrum, in contrast to earlier flat-spectrum behavior. No secular decrease presaged its radio demise. During this time, the pulse profile continued to display large variations; polarimetry, including of a new profile component, indicates that the magnetic geometry remained consistent with that of earlier times. We supplement these results with X-ray timing of the pulsar from its outburst in 2003 up to 2014. For the first 4 years, XTE J1810−197 experienced non-monotonic excursions in frequency derivative by at least a factor of eight. But since 2007, its has remained relatively stable near its minimum observed value. The only apparent event in the X-ray record that is possibly contemporaneous with the radio shutdown is a decrease of 20% in the hot-spot flux in 2008-2009, to a stable, minimum value. However, the permanence of the high-amplitude, thermal X-ray pulse, even after the (unexplained) radio demise, implies continuing magnetar activity.
To systematically review evidence bearing on the management of patients with amyotrophic lateral sclerosis (ALS).
The authors analyzed studies from 1998 to 2007 to update the 1999 practice parameter. ...Topics covered in this section include slowing disease progression, nutrition, and respiratory management for patients with ALS.
The authors identified 8 Class I studies, 5 Class II studies, and 43 Class III studies in ALS. Important treatments are available for patients with ALS that are underutilized. Noninvasive ventilation (NIV), percutaneous endoscopic gastrostomy (PEG), and riluzole are particularly important and have the best evidence. More studies are needed to examine the best tests of respiratory function in ALS, as well as the optimal time for starting PEG, the impact of PEG on quality of life and survival, and the effect of vitamins and supplements on ALS.
Riluzole should be offered to slow disease progression (Level A). PEG should be considered to stabilize weight and to prolong survival in patients with ALS (Level B). NIV should be considered to treat respiratory insufficiency in order to lengthen survival (Level B) and to slow the decline of forced vital capacity (Level B). NIV may be considered to improve quality of life (Level C) corrected.Early initiation of NIV may increase compliance (Level C), and insufflation/exsufflation may be considered to help clear secretions (Level C).
We present 1201 galaxies at 0.05 < z < 0.45 that host tidal features in the first ∼200 deg2 of imaging from the Hyper Suprime-Cam Subaru Strategic Program (HSC-SSP). We select these galaxies from a ...sample of 21,208 galaxies with spectroscopic redshifts drawn from the Sloan Digital Sky Survey (SDSS) spectroscopic campaigns. Of these galaxies, we identify 214 shell systems and 987 stream systems. For 575 of these systems, we are additionally able to measure the (g−i) colors of the tidal features. We find evidence for star formation in a subset of the streams, with the exception of streams around massive ellipticals, and find that stream host galaxies span the full range of stellar masses in our sample. Galaxies that host shells are predominantly red and massive: we find that observable shells form more frequently around ellipticals than around disk galaxies of the same stellar mass. Although the majority of the shells in our sample are consistent with being formed by minor mergers, 15% 4.4% of shell host galaxies have (g−i) colors as red as their host galaxy, consistent with being formed by major mergers. These "red shell" galaxies are preferentially aligned with the major axis of the host galaxy, as previously predicted from simulations. We suggest that although the bulk of the observable shell population originates from fairly minor mergers, which preferentially form shells that are not aligned with the major axis of the galaxy, major mergers produce a significant number of observable shells.
•Microbes are sensitive to environmental stressors, such as wastewater pollution.•This study combined novel methods of microbial ecotoxicology in the field and lab.•Wastewater effluents caused ...community shifts above moderate (>10%) concentrations.•Riverine community shifts were explained by two potentially globally relevant keystone taxa.•Malikia spp. and hgcI_clade proposed as indicators of changes in trophic status.
Widespread wastewater pollution is one of the greatest challenges threatening the sustainable management of rivers globally. Understanding microbial responses to gradients in environmental stressors, such as wastewater pollution, is crucial to identify thresholds of community change and to develop management strategies that protect ecosystem integrity. This study used multiple lines of empirical evidence, including a novel combination of microbial ecotoxicology methods in the laboratory and field to link pressure-stressor-response relationships. Specifically, community-based whole effluent toxicity (WET) testing and environmental genomics were integrated to determine real-world community interactions, shifts and functional change in response to wastewater pollution. Here we show that wastewater effluents above moderate (>10%) concentrations caused consistent significant shifts in bacterial community structure and function. These thresholds of community shifts were also linked to changes in the trophic state of receiving waters in terms of nutrient concentrations. Differences in the community responses along the effluent concentration gradient were primarily driven by two globally relevant bacterial indicator taxa, namely Malikia spp. (Burkholderiales) and hgcI_clade (Frankiales). Species replacement occurred above moderate effluent concentrations with abundances of Malikia spp. increasing, while abundances of hgcI_clade decreased. The responses of Malikia spp. and hgcI_clade matched gene patterns associated with globally important nitrogen cycling pathways, such as denitrification and nitrogen fixation, which linked the core individual taxa to putative function and ecosystem processes, rarely achieved in previous studies. This study has identified potential indicators of change in trophic status and the functional consequences of wastewater pollution. These findings have immediate implications for both the management of environmental stressors and protection of aquatic ecosystems.
Display omitted
PDF
