801 research outputs found
Observations on African elephants (Loxodonta africana), including possible urine drinking, during a severe drought in Zimbabwe
Visual and tactile displays in African elephants, Loxodonta africana: a progress report (1991-1997)
The debris disk - terrestrial planet connection
The eccentric orbits of the known extrasolar giant planets provide evidence
that most planet-forming environments undergo violent dynamical instabilities.
Here, we numerically simulate the impact of giant planet instabilities on
planetary systems as a whole. We find that populations of inner rocky and outer
icy bodies are both shaped by the giant planet dynamics and are naturally
correlated. Strong instabilities -- those with very eccentric surviving giant
planets -- completely clear out their inner and outer regions. In contrast,
systems with stable or low-mass giant planets form terrestrial planets in their
inner regions and outer icy bodies produce dust that is observable as debris
disks at mid-infrared wavelengths. Fifteen to twenty percent of old stars are
observed to have bright debris disks (at wavelengths of ~70 microns) and we
predict that these signpost dynamically calm environments that should contain
terrestrial planets.Comment: Contribution to proceedings of IAU 276: Astrophysics of Planetary
System
Robotic proctectomy for rectal cancer: analysis of 71 patients from a single institution
BackgroundDespite increasing use of robotic surgery for rectal cancer, few series have been published from the practice of generalizable US surgeons.MethodsA retrospective chart review was performed for 71 consecutive patients who underwent robotic low anterior resection (LAR) or abdominoperineal resection (APR) for rectal adenocarcinoma between 2010 and 2014.Results46 LARs (65%) and 25 APRs (35%) were identified. Median procedure time was 219 minutes (IQR 184–275) and mean blood loss 164.9 cc (SD 155.9 cc). Radial margin was negative in 70/71 (99%) patients. Total mesorectal excision integrity was complete/near complete in 38/39 (97%) of graded specimens. A mean of 16.8 (SD+/− 8.9) lymph nodes were retrieved. At median follow‐up of 21.9 months, there were no local recurrences.ConclusionsRobotic proctectomy for rectal cancer was introduced into typical colorectal surgery practice by a single surgeon, with a low conversion rate, low complication rate, and satisfactory oncologic outcomes.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139933/1/rcs1841_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139933/2/rcs1841.pd
Uniqueness Typing for Resource Management in Message-Passing Concurrency
We view channels as the main form of resources in a message-passing
programming paradigm. These channels need to be carefully managed in settings
where resources are scarce. To study this problem, we extend the pi-calculus
with primitives for channel allocation and deallocation and allow channels to
be reused to communicate values of different types. Inevitably, the added
expressiveness increases the possibilities for runtime errors. We define a
substructural type system which combines uniqueness typing and affine typing to
reject these ill-behaved programs
Vacancy enhanced oxygen redox reversibility in P3-type magnesium doped sodium manganese oxide Na0.67Mg0.2Mn0.8O2
EJK would like to thank the Alistore ERI for the award of a studentship. This work was supported by the Faraday Institution (grant number FIRG018).Lithium-rich layered oxides and sodium layered oxides represent attractive positive electrode materials exhibiting excess capacity delivered by additional oxygen redox activity. However, structural degradation in the bulk and detrimental reactions with the electrolyte on the surface often occur, leading to limited reversibility of oxygen redox processes. Here we present the properties of P3-type Na0.67Mg0.2Mn0.8O2 synthesized under both air and oxygen. Both materials exhibit stable cycling performance in the voltage range 1.8-3.8 V where the Mn3+/Mn4+ redox couple entirely dominates the electrochemical reaction. Oxygen redox activity is triggered for both compounds in the wider voltage window 1.8-4.3 V with typical large voltage hysteresis from non-bonding O 2p states generated by substituted Mg. Interestingly, for the compound prepared under oxygen, an additional reversible oxygen redox activity is shown with exceptionally small voltage hysteresis (20 mV). The presence of vacancies in the transition metal layers is shown to play a critical role not only in forming unpaired O 2p states independent of substituted elements but also in stabilising the P3 structure during charge with reduced structural transformation to the O’3 phase at the end of discharge. This study reveals the important role of vacancies in P3-type sodium layered oxides to increase energy density using both cationic and anionic redox processes.PostprintPostprintPeer reviewe
Real-world outcomes of sipuleucel-T treatment in PROCEED, a prospective registry of men with metastatic castration-resistant prostate cancer.
BackgroundThe large registry, PROVENGE Registry for the Observation, Collection, and Evaluation of Experience Data (PROCEED)(NCT01306890), evaluated sipuleucel-T immunotherapy for asymptomatic/minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC).MethodsPROCEED enrolled patients with mCRPC receiving 3 biweekly sipuleucel-T infusions. Assessments included overall survival (OS), serious adverse events (SAEs), cerebrovascular events (CVEs), and anticancer interventions (ACIs). Follow-up was for ≥3 years or until death or study withdrawal.ResultsIn 2011-2017, 1976 patients were followed for 46.6 months (median). The median age was 72 years, and the baseline median prostate-specific antigen level was 15.0 ng/mL; 86.7% were white, and 11.6% were African American. Among the patients, 1902 had 1 or more sipuleucel-T infusions. The median OS was 30.7 months (95% confidence interval [CI], 28.6-32.2 months). Known prognostic factors were independently associated with OS in a multivariable analysis. Among the 1255 patients who died, 964 (76.8%) died of prostate cancer (PC) progression. The median time from the first infusion to PC death was 42.7 months (95% CI, 39.4-46.2 months). The incidence of sipuleucel-T-related SAEs was 3.9%. The incidence of CVEs was 2.8%, and the rate per 100 person-years was 1.2 (95% CI, 0.9-1.6). The CVE incidence among 11,972 patients with mCRPC from the Surveillance, Epidemiology, and End Results-Medicare database was 2.8%; the rate per 100 person-years was 1.5 (95% CI, 1.4-1.7). One or more ACIs (abiraterone, enzalutamide, docetaxel, cabazitaxel, or radium 223) were received by 77.1% of the patients after sipuleucel-T; 32.5% and 17.4% of the patients experienced 1- and 2-year treatment-free intervals, respectively.ConclusionsPROCEED provides contemporary survival data for sipuleucel-T-treated men in a real-world setting of new life-prolonging agents, which will be useful in discussing treatment options with patients and in powering future trials with sipuleucel-T. The safety and tolerability of sipuleucel-T in PROCEED were consistent with previous findings
Glucagon-like peptide 1 decreases lipotoxicity in non-alcoholic steatophepatitis
OBJECTIVE: Insulin resistance and lipotoxicity are pathognomonic in non-alcoholic steatohepatitis (NASH). Glucagon-like peptide-1 (GLP-1) analogues are licensed for type 2 diabetes, but no prospective experimental data exists in NASH. This study determined the effect of a long-acting GLP-1 analogue, liraglutide, on organ-specific insulin sensitivity, hepatic lipid handling and adipose dysfunction in biopsy-proven NASH.DESIGN: 14 patients were randomised to 1.8mg liraglutide or placebo for 12-weeks of the mechanistic component of a double-blind, randomized, placebo-controlled trial (ClinicalTrials.gov-NCT01237119). Patients underwent paired hyperinsulinaemic euglycaemic clamps, stable isotope tracers, adipose microdialysis and serum adipocytokine/metabolic profiling. In vitro isotope experiments on lipid flux were performed on primary human hepatocytes.RESULTS: Liraglutide reduced BMI (-1.9 vs. +0.04 kg/m2;p<0.001), HbA1c (-0.3 vs. +0.3%;p<0.01), cholesterol-LDL (-0.7 vs. +0.05 mmol/L;p<0.01), ALT (-54 vs -4.0 IU/L;p<0.01) and serum leptin, adiponectin, and CCL-2 (all p<0.05). Liraglutide increased hepatic insulin sensitivity (-9.36 vs. -2.54% suppression of hepatic endogenous glucose production with low-dose insulin;p<0.05). Liraglutide increased adipose tissue insulin sensitivity enhancing the ability of insulin to suppress lipolysis both globally (-24.9 vs. +54.8 pmol/L insulin required to ½ maximally suppress serum NEFA; p<0.05), and specifically within subcutaneous adipose tissue (p<0.05). In addition, liraglutide decreased hepatic DNL in-vivo (-1.26 vs. +1.30%; p<0.05); a finding endorsed by the effect of GLP-1 receptor agonist on primary human hepatocytes (24.6% decrease in lipogenesis vs. untreated controls; p<0.01).CONCLUSIONS: Liraglutide reduces metabolic dysfunction, insulin resistance and lipotoxicity in the key metabolic organs in the pathogenesis of NASH. Liraglutide may offer the potential for a disease-modifying intervention in NASH.</p
Glucagon-like peptide 1 decreases lipotoxicity in non-alcoholic steatophepatitis
Background & AimsInsulin resistance and lipotoxicity are pathognomonic in non-alcoholic steatohepatitis (NASH). Glucagon-like peptide-1 (GLP-1) analogues are licensed for type 2 diabetes, but no prospective experimental data exists in NASH. This study determined the effect of a long-acting GLP-1 analogue, liraglutide, on organ-specific insulin sensitivity, hepatic lipid handling and adipose dysfunction in biopsy-proven NASH.MethodsFourteen patients were randomised to 1.8mg liraglutide or placebo for 12-weeks of the mechanistic component of a double-blind, randomised, placebo-controlled trial (ClinicalTrials.gov-NCT01237119). Patients underwent paired hyperinsulinaemic euglycaemic clamps, stable isotope tracers, adipose microdialysis and serum adipocytokine/metabolic profiling. In vitro isotope experiments on lipid flux were performed on primary human hepatocytes.ResultsLiraglutide reduced BMI (−1.9 vs. +0.04kg/m2; p<0.001), HbA1c (−0.3 vs. +0.3%; p<0.01), cholesterol-LDL (−0.7 vs. +0.05mmol/L; p<0.01), ALT (−54 vs. −4.0IU/L; p<0.01) and serum leptin, adiponectin, and CCL-2 (all p<0.05). Liraglutide increased hepatic insulin sensitivity (−9.36 vs. −2.54% suppression of hepatic endogenous glucose production with low-dose insulin; p<0.05). Liraglutide increased adipose tissue insulin sensitivity enhancing the ability of insulin to suppress lipolysis both globally (−24.9 vs. +54.8pmol/L insulin required to ½ maximally suppress serum non-esterified fatty acids; p<0.05), and specifically within subcutaneous adipose tissue (p<0.05). In addition, liraglutide decreased hepatic de novo lipogenesis in vivo (−1.26 vs. +1.30%; p<0.05); a finding endorsed by the effect of GLP-1 receptor agonist on primary human hepatocytes (24.6% decrease in lipogenesis vs. untreated controls; p<0.01).ConclusionsLiraglutide reduces metabolic dysfunction, insulin resistance and lipotoxicity in the key metabolic organs in the pathogenesis of NASH. Liraglutide may offer the potential for a disease-modifying intervention in NASH
Baseline Q-Wave Surpasses Time From Symptom Onset as a Prognostic Marker in ST-Segment Elevation Myocardial Infarction Patients Treated With Primary Percutaneous Coronary Intervention
ObjectivesWe assessed the incremental value of baseline Q waves over time from symptom onset as a marker of clinical outcome in ST-segment elevation myocardial infarction (STEMI).BackgroundTime from symptom onset is a central focus in STEMI patients. The presence of Q waves on the baseline electrocardiogram (ECG) has been suggested to be of incremental value to time from symptom onset in evaluating clinical outcomes.MethodsWe evaluated baseline Q waves and ST-segment resolution 30 min after primary percutaneous intervention (PCI) ECGs in 4,530 STEMI patients without prior infarction. Additionally, peak biomarkers; 90-day mortality; and the composite of death, congestive heart failure (CHF), or cardiogenic shock were assessed.ResultsFifty-six percent of patients had baseline Q waves: they were older, more frequently male and diabetic, and had a more advanced Killip class. Patients with baseline Q waves had greater mortality and a higher composite rate of death, CHF, and shock versus patients without baseline Q waves at 90 days (5.3% vs. 2.1% and 12.1% vs. 4.8%, respectively, both p < 0.001). Complete ST-segment resolution was highest, whereas 90-day mortality and the composite outcome were lowest among those randomized ≤3 h without baseline Q waves. After multivariable adjustment, baseline Q-wave but not time from symptom onset was significantly associated with a 78% relative increase in the hazard of 90-day mortality and a 90% relative increase in the hazard of death, shock, and CHF.ConclusionsBaseline Q waves in STEMI patients treated with primary PCI provide an independent prognostic marker of clinical outcome. These data might be useful in designing future clinical trials as well as in evaluating patients for triage and potential transfer for planned primary PCI. (Pexelizumab in Conjunction With Angioplasty in Acute Myocardial Infarction [APEX-AMI]; NCT00091637
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