On 2011 May 31 UT a supernova (SN) exploded in the nearby galaxy M51 (the Whirlpool Galaxy). We discovered this event using small telescopes equipped with CCD cameras and also detected it with the ...Palomar Transient Factory survey, rapidly confirming it to be a Type II SN. Here, we present multi-color ultraviolet through infrared photometry which is used to calculate the bolometric luminosity and a series of spectra. Our early-time observations indicate that SN 2011dh resulted from the explosion of a relatively compact progenitor star. Rapid shock-breakout cooling leads to relatively low temperatures in early-time spectra, compared to explosions of red supergiant stars, as well as a rapid early light curve decline. Optical spectra of SN 2011dh are dominated by H lines out to day 10 after explosion, after which He I lines develop. This SN is likely a member of the cIIb (compact IIb) class, with progenitor radius larger than that of SN 2008ax and smaller than the eIIb (extended IIb) SN 1993J progenitor. Our data imply that the object identified in pre-explosion Hubble Space Telescope images at the SN location is possibly a companion to the progenitor or a blended source, and not the progenitor star itself, as its radius (~1013 cm) would be highly inconsistent with constraints from our post-explosion spectra.
Key points
Many mammals are born with immature motor systems that develop through a critical period of postnatal development.
In rodents, postnatal maturation of movement occurs from rostral to ...caudal, correlating with maturation of descending supraspinal and local spinal circuits.
We asked whether development of fundamental electrophysiological properties of spinal motoneurons follows the same rostro‐caudal sequence.
We show that in both regions, repetitive firing parameters increase and excitability decreases with development; however, these characteristics mature earlier in cervical motoneurons.
We suggest that in addition to autonomous mechanisms, motoneuron development depends on activity resulting from their circuit milieu.
Altricial mammals are born with immature nervous systems comprised of circuits that do not yet have the neuronal properties and connectivity required to produce future behaviours. During the critical period of postnatal development, neuronal properties are tuned to participate in functional circuits. In rodents, cervical motoneurons are born prior to lumbar motoneurons, and spinal cord development follows a sequential rostro‐caudal pattern. Here we asked whether birth order is reflected in the postnatal development of electrophysiological properties. We show that motoneurons of both regions have similar properties at birth and follow the same developmental profile, with maximal firing increasing and excitability decreasing into the third postnatal week. However, these maturative processes occur in cervical motoneurons prior to lumbar motoneurons, correlating with the maturation of premotor descending and local spinal systems. These results suggest that motoneuron properties do not mature by cell autonomous mechanisms alone, but also depend on developing premotor circuits.
Key points
Many mammals are born with immature motor systems that develop through a critical period of postnatal development.
In rodents, postnatal maturation of movement occurs from rostral to caudal, correlating with maturation of descending supraspinal and local spinal circuits.
We asked whether development of fundamental electrophysiological properties of spinal motoneurons follows the same rostro‐caudal sequence.
We show that in both regions, repetitive firing parameters increase and excitability decreases with development; however, these characteristics mature earlier in cervical motoneurons.
We suggest that in addition to autonomous mechanisms, motoneuron development depends on activity resulting from their circuit milieu.
Severe symptomatic degenerative mitral regurgitation (DMR) has a poor prognosis in the absence of treatment, and new transcatheter options are emerging.
The CLASP IID (Edwards PASCAL Transcatheter ...Valve Repair System Pivotal Clinical Trial) randomized trial (NCT03706833) is the first to evaluate the safety and effectiveness of the PASCAL system compared with the MitraClip system in patients with significant symptomatic DMR. This report presents the primary safety and effectiveness endpoints for the trial.
Patients with 3+ or 4+ DMR at prohibitive surgical risk were assessed by a central screening committee and randomized 2:1 (PASCAL:MitraClip). Study oversight also included an echocardiography core laboratory and a clinical events committee. The primary safety endpoint was the composite major adverse event rate at 30 days. The primary effectiveness endpoint was the proportion of patients with mitral regurgitation (MR) ≤2+ at 6 months.
A prespecified interim analysis in 180 patients demonstrated noninferiority of the PASCAL system vs the MitraClip system for the primary safety and effectiveness endpoints of major adverse event rate (3.4% vs 4.8%) and MR ≤2+ (96.5% vs 96.8%), respectively. Functional and quality-of-life outcomes significantly improved in both groups (P < 0.05). The proportion of patients with MR ≤1+ was durable in the PASCAL group from discharge to 6 months (PASCAL, 87.2% and 83.7% P = 0.317 vs discharge; MitraClip, 88.5% and 71.2% P = 0.003 vs discharge).
The CLASP IID trial demonstrated safety and effectiveness of the PASCAL system and met noninferiority endpoints, expanding transcatheter treatment options for prohibitive surgical risk patients with significant symptomatic DMR.
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IMPORTANCE: Guidelines recommend early specialty palliative care for all patients with advanced cancer, but most patients lack access to such services. OBJECTIVE: To assess the effect of CONNECT ...(Care Management by Oncology Nurses to Address Supportive Care Needs), a primary palliative care intervention delivered by oncology nurses, on patient outcomes. DESIGN, SETTING, AND PARTICIPANTS: This cluster randomized clinical trial of the CONNECT intervention vs standard care was conducted from July 25, 2016, to October 6, 2020. Participants were adult patients with metastatic solid tumors who were undergoing oncological care and for whom an oncologist would agree with the statement “would not be surprised if the patient died in the next year.” The trial was conducted at 17 community oncology practices in western Pennsylvania. Data analyses adhered to the intention-to-treat principle. INTERVENTIONS: The CONNECT intervention included 3 monthly visits with an existing infusion room nurse who was trained to address symptoms, provide emotional support, engage in advance care planning, and coordinate care. MAIN OUTCOMES AND MEASURES: The primary outcome was quality of life. At baseline and 3 months, participants completed assessments of quality of life (Functional Assessment of Chronic Illness Therapy-Palliative care: score range, 0-184, with higher scores indicating better quality of life), symptom burden (Edmonton Symptom Assessment Scale: score range, 0-90, with higher scores indicating greater symptom burden), and mood symptoms (Hospital Anxiety and Depression Scale HADS: score range, 0-21, with higher scores indicating substantial anxiety and depression). Linear mixed-effects models were used to estimate adjusted mean differences in 3-month outcomes. Preplanned, intensity-adjusted analyses were conducted. RESULTS: A total of 672 patients were enrolled (mean SD age, 69.3 10.2 years; 360 women 53.6%). The mean (SD) number of CONNECT visits completed was 2.2 (1.0). At 3 months, no difference in mean (SD) quality-of-life score was found between the CONNECT and standard care groups (130.7 28.2 vs 134.1 28.1; adjusted mean difference, 1.20; 95% CI, −2.75 to 5.15; P = .55). Similarly, there was no difference between groups in 3-month mean (SD) symptom burden (23.2 16.6 vs 24.0 16.1; adjusted mean difference, −2.64; 95% CI, −5.85 to 0.58; P = .11) or mood symptoms (HADS depression subscale score: 5.1 3.4 vs 4.8 3.7, adjusted mean difference, −0.08 95% CI, −0.71 to 0.57, P = .82; HADS anxiety subscale score: 5.7 3.9 vs 5.4 4.2, adjusted mean difference, −0.31 95% CI, −0.96 to 0.33, P = .34). Intensity-adjusted analyses revealed a larger estimated treatment effect for patients who received a full dose (3 visits) of the CONNECT intervention. CONCLUSIONS AND RELEVANCE: This cluster randomized clinical trial found that a primary palliative care intervention that was delivered by oncology nurses did not improve patient-reported outcomes at 3 months. Primary palliative care interventions with a higher dose intensity may be beneficial for most patients with advanced cancer who lack access to palliative care specialists. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02712229
We investigate how the prevalence of materialistic bank CEOs has evolved over time, and how risk management policies, non-CEO executives’ behavior and tail risk vary with CEO materialism. We document ...that the proportion of banks run by materialistic CEOs increased significantly from 1994 to 2004, that the strength of risk management functions is significantly lower for banks with materialistic CEOs, and that non-CEO executives in banks with materialistic CEOs insider trade more aggressively around government intervention during the financial crisis. Finally, we find that banks with materialistic CEOs have significantly more downside tail risk relative to banks with non-materialistic CEOs.
Commentary placing genetic ancestry markers and racial difference in HbA1c in the context of more common variations in the HbA1c-average glucose relationship and their clinical implications.
Abstract Caspase-mediated cell death contributes to the pathogenesis of motor neuron degeneration in the mutant SOD1G93A transgenic mouse model of amyotrophic lateral sclerosis (ALS), along with ...other factors such as inflammation and oxidative damage. By screening a drug library, we found that melatonin, a pineal hormone, inhibited cytochrome c release in purified mitochondria and prevented cell death in cultured neurons. In this study, we evaluated whether melatonin would slow disease progression in SOD1G93A mice. We demonstrate that melatonin significantly delayed disease onset, neurological deterioration and mortality in ALS mice. ALS-associated ventral horn atrophy and motor neuron death were also inhibited by melatonin treatment. Melatonin inhibited Rip2/caspase-1 pathway activation, blocked the release of mitochondrial cytochrome c , and reduced the overexpression and activation of caspase-3. Moreover, for the first time, we determined that disease progression was associated with the loss of both melatonin and the melatonin receptor 1A (MT1) in the spinal cord of ALS mice. These results demonstrate that melatonin is neuroprotective in transgenic ALS mice, and this protective effect is mediated through its effects on the caspase-mediated cell death pathway. Furthermore, our data suggest that melatonin and MT1 receptor loss may play a role in the pathological phenotype observed in ALS. The above observations indicate that melatonin and modulation of Rip2/caspase-1/cytochrome c or MT1 pathways may be promising therapeutic approaches for ALS.
Tropical deforestation has caused a significant share of carbon emissions and species losses, but historical patterns have rarely been explicitly considered when estimating these impacts 1. A ...deforestation event today leads to a time-delayed future release of carbon, from the eventual decay either of forest products or of slash left at the site 2. Similarly, deforestation often does not result in the immediate loss of species, and communities may exhibit a process of “relaxation” to their new equilibrium over time 3. We used a spatially explicit land cover change model 4 to reconstruct the annual rates and spatial patterns of tropical deforestation that occurred between 1950 and 2009 in the Amazon, in the Congo Basin, and across Southeast Asia. Using these patterns, we estimated the resulting gross vegetation carbon emissions 2, 5 and species losses over time 6. Importantly, we accounted for the time lags inherent in both the release of carbon and the extinction of species. We show that even if deforestation had completely halted in 2010, time lags ensured there would still be a carbon emissions debt of at least 8.6 petagrams, equivalent to 5–10 years of global deforestation, and an extinction debt of more than 140 bird, mammal, and amphibian forest-specific species, which if paid, would increase the number of 20th-century extinctions in these groups by 120%. Given the magnitude of these debts, commitments to reduce emissions and biodiversity loss are unlikely to be realized without specific actions that directly address this damaging environmental legacy.
•Time lags in historical tropical deforestation ensure an emission debt of 8.6 PgC•Tropical deforestation resulted in a debt of more than 140 forest-specific vertebrates•The carbon emissions debt is equivalent to 5–10 years of global deforestation•The extinction debt would increase 20th-century extinctions in vertebrates by 120%
Rosa et al. estimate that historical tropical deforestation has indebted the future with 5–10 years of global deforestation’s worth of carbon emissions and more extinctions than estimated to have already occurred since 1900. Habitat protection alone will do little to avoid paying these debts that have already accumulated from historical habitat loss.
Soil carbon sequestration is being considered as a potential pathway to mitigate climate change. Cropland soils could provide a sink for carbon that can be modified by farming practices; however, ...they can also act as a source of greenhouse gases (GHG), including not only nitrous oxide (N2O) and methane (CH4), but also the upstream carbon dioxide (CO2) emissions associated with agronomic management. These latter emissions are also sometimes termed “hidden” or “embedded” CO2. In this paper, we estimated the net GHG balance for Chinese cropping systems by considering the balance of soil carbon sequestration, N2O and CH4 emissions, and the upstream CO2 emissions of agronomic management from a life cycle perspective during 2000–2017. Results showed that although soil organic carbon (SOC) increased by 23.2 ± 8.6 Tg C per year, the soil N2O and CH4 emissions plus upstream CO2 emissions arising from agronomic management added 269.5 ± 21.1 Tg C‐eq per year to the atmosphere. These findings demonstrate that Chinese cropping systems are a net source of GHG emissions and that total GHG emissions are about 12 times larger than carbon uptake by soil sequestration. There were large variations between different cropping systems in the net GHG balance ranging from 328 to 7,567 kg C‐eq ha−1 year−1, but all systems act as a net GHG source to the atmosphere. The main sources of total GHG emissions are nitrogen fertilization (emissions during production and application), power use for irrigation, and soil N2O and CH4 emissions. Optimizing agronomic management practices, especially fertilization, irrigation, plastic mulching, and crop residues to reduce total GHG emissions from the whole chain is urgently required in order to develop a low‐carbon future for Chinese crop production.
This is important to know what extent are greenhouse gas (GHG) emissions from intensive arable agriculture in China mitigated by sequestration of carbon in soil. We calculated the net GHG balance (kg C‐eq ha−1 year−1) between SOC stock change and emissions of N2O and CH4 and upstream CO2‐eq emissions associated with agronomic management. Despite the soil carbon sink found in Chinese cropland soils, it acted as a net GHG source because the emissions of total GHG are about one order of magnitude larger than the soil carbon sink under current farmers’ practices.
Metformin is the most commonly prescribed medication for type 2 diabetes, owing to its glucose-lowering effects, which are mediated through the suppression of hepatic glucose production (reviewed in ...refs.
). However, in addition to its effects on the liver, metformin reduces appetite and in preclinical models exerts beneficial effects on ageing and a number of diverse diseases (for example, cognitive disorders, cancer, cardiovascular disease) through mechanisms that are not fully understood
. Given the high concentration of metformin in the liver and its many beneficial effects beyond glycemic control, we reasoned that metformin may increase the secretion of a hepatocyte-derived endocrine factor that communicates with the central nervous system
. Here we show, using unbiased transcriptomics of mouse hepatocytes and analysis of proteins in human serum, that metformin induces expression and secretion of growth differentiating factor 15 (GDF15). In primary mouse hepatocytes, metformin stimulates the secretion of GDF15 by increasing the expression of activating transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP; also known as DDIT3). In wild-type mice fed a high-fat diet, oral administration of metformin increases serum GDF15 and reduces food intake, body mass, fasting insulin and glucose intolerance; these effects are eliminated in GDF15 null mice. An increase in serum GDF15 is also associated with weight loss in patients with type 2 diabetes who take metformin. Although further studies will be required to determine the tissue source(s) of GDF15 produced in response to metformin in vivo, our data indicate that the therapeutic benefits of metformin on appetite, body mass and serum insulin depend on GDF15.
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