NUT midline carcinoma (NMC) is a poorly differentiated squamous cancer characterized by rearrangement of the NUT gene. Research advances have provided opportunities for targeted therapy in NMC, yet ...the clinical features of this rare disease have not been systematically characterized. We report on a large population of such patients to identify the disease characteristics and treatments, correlate them with outcome, and to consider clinical recommendations.
A clinical database was established using retrospective demographic and outcomes data available on all known cases of NMC. Questionnaires were completed by treating physicians. Pathologic, demographic, and clinical variables were assessed for 63 patients, the largest cohort of patients with NMC studied to date. Outcome data from 54 patients were available for survival analyses.
The diagnosis of NMC has increased annually since 2007. Since 2009, there has been an observed increase in the age at diagnosis (P < 0.05). Geographic distribution of patients with NMC has been concentrated in the United States (n = 41, 65%). The median overall survival for patients with NMC was 6.7 months. The 2-year progression-free survival (PFS) was 9% with a 95% confidence interval (CI) of 1% to 17% 1-year PFS 15% (5-24%) and 2-year overall survival (OS) was 19% with a 95% CI of 7%-31% (1-year OS: 30% (27-34%). Multivariate analysis suggested that extent of surgical resection and initial radiotherapy were independent predictors of PFS and OS. Notably, no chemotherapeutic regimen was associated with improved outcome.
NMC portends a poor prognosis among all squamous cell neoplasms and seems to be frequently unrecognized. The finding that conventional chemotherapy has been inadequate indicates a pressing need for the development of targeted therapeutics. Intensive local therapies such as gross total resection and radiotherapy might be associated with enhanced survival.
Objective To investigate clinical trialists’ opinions and experiences of sharing of clinical trial data with investigators who are not directly collaborating with the research team.Design and setting ...Cross sectional, web based survey.Participants Clinical trialists who were corresponding authors of clinical trials published in 2010 or 2011 in one of six general medical journals with the highest impact factor in 2011.Main outcome measures Support for and prevalence of data sharing through data repositories and in response to individual requests, concerns with data sharing through repositories, and reasons for granting or denying requests.Results Of 683 potential respondents, 317 completed the survey (response rate 46%). In principle, 236 (74%) thought that sharing de-identified data through data repositories should be required, and 229 (72%) thought that investigators should be required to share de-identified data in response to individual requests. In practice, only 56 (18%) indicated that they were required by the trial funder to deposit the trial data in a repository; of these 32 (57%) had done so. In all, 149 respondents (47%) had received an individual request to share their clinical trial data; of these, 115 (77%) had granted and 56 (38%) had denied at least one request. Respondents’ most common concerns about data sharing were related to appropriate data use, investigator or funder interests, and protection of research subjects.Conclusions We found strong support for sharing clinical trial data among corresponding authors of recently published trials in high impact general medical journals who responded to our survey, including a willingness to share data, although several practical concerns were identified.
We describe a muon track reconstruction algorithm for the reactor anti-neutrino experiment Double Chooz. The Double Chooz detector consists of two optically isolated volumes of liquid scintillator ...viewed by PMTs, and an Outer Veto above these made of crossed scintillator strips. Muons are reconstructed by their Outer Veto hit positions along with timing information from the other two detector volumes. In the ideal case of a through-going muon intersecting the center of the detector, the resolution is ∼40mm in each transverse dimension.
Using the Double Chooz reactor neutrino detector, we have measured the products of µ − capture on 12C, 13C, 14N and 16O. Over a period of 490 days, we collected 2.3 × 106 stopping cosmic µ −, of ...which 1.8 × 105 captured on these nuclei in the inner detector. The resulting isotopes were tagged using prompt neutron emission (when applicable), the subsequent beta decays, and, in some cases, β-delayed neutrons. Production of these βn isotopes, primarily 9Li, which are ν ¯ e backgrounds, was found at a significance of 5.5σ. The probability of 9Li production per capture on natC is (2.4 ± 0.9(stat) ± 0.1(syst)) × 10−4. We have made the most precise measurement of the rate of 12C(µ −, ν)12B to date, 6.57 − 0.21 + 0.11 × 10 3 s − 1 , or ( 17.35 − 0.59 + 0.35 ) % of nuclear captures. By tagging excited states emitting gammas, the ground state transition rate to 12B is found to be 5.68 − 0.23 + 0.14 × 10 3 s − 1 .
Background The treatment for patients with acute myocardial infarction (AMI) was transformed by the introduction of intensive care units (ICUs), yet we know little about how contemporary hospitals ...use this resource-intensive setting and whether higher use is associated with better outcomes. Methods We identified 114,136 adult hospitalizations for AMI from 307 hospitals in the 2009 to 2010 Premier database using codes from the International Classification of Diseases, Ninth Revision, Clinical Modification . Hospitals were stratified into quartiles by rates of ICU admission for AMI patients. Across quartiles, we examined in-hospital risk-standardized mortality rates and usage rates of critical care therapies for these patients. Results Rates of ICU admission for AMI patients varied markedly among hospitals (median 48%, Q1-Q4 20%-71%, range 0%-98%), and there was no association with in-hospital risk-standardized mortality rates (6% all quartiles, P = .7). However, hospitals admitting more AMI patients to the ICU were more likely to use critical care therapies overall (mechanical ventilation from Q1 with lowest rate of ICU use to Q4 with highest rate 13%-16%, vasopressors/inotropes 17%-21%, intra-aortic balloon pumps 4%-7%, and pulmonary artery catheters 4%-5%; P for trend < .05 in all comparisons). Conclusions Rates of ICU admission for patients with AMI vary substantially across hospitals and were not associated with differences in mortality, but were associated with greater use of critical care therapies. These findings suggest uncertainty about the appropriate use of this resource-intensive setting and a need to optimize ICU triage for patients who will truly benefit.
Aims Despite the benefits of regular physical activity participation following acute myocardial infarction, little is known about gender differences in physical activity among patients after acute ...myocardial infarction. We described, by gender, physical activity trajectories pre- and post-acute myocardial infarction, and determined whether gender was independently associated with physical activity. Methods and results The Variation in Recovery: Role of Gender on Outcomes of Young AMI patients (VIRGO) study, conducted at 103 US, 24 Spanish, and three Australian hospitals, was designed, in part, to evaluate gender differences in lifestyle behaviors following acute myocardial infarction. We used baseline, one-month, and 12-month data collected from patients aged 18-55 years ( n = 3572). Patients were assigned to American Heart Association-defined levels of physical activity. A generalized estimating equation model was used to account for repeated measures within the same individual over time. Men were more active (≥150 min/wk moderate or ≥75 min/wk vigorous activity) than women at baseline (42% vs 34%), one month (45% vs 34%), and 12 months (48% vs 36%) (all p < 0.0001). Men engaged in a significantly longer duration of activity at each time point. When controlling for all other factors, women had 1.37 times the odds of being less active than men from pre-acute myocardial infarction to 12-months post-acute myocardial infarction (95% confidence interval: 1.21-1.55). Non-white race, non-active workplaces, smoking, diabetes, hypertension, and obesity were also associated independently with being less active over time (all p < 0.05). Conclusions Although activity increased modestly over time, women recovering from acute myocardial infarction were less likely to meet physical activity recommendations than were men. By identifying factors associated with low levels of activity during acute myocardial infarction recovery, targeted interventions can be introduced prior to hospital discharge.
•Ejecta from hypervelocity impact cratering results in significant momentum transfer, equaling or exceeding the direct momentum transfer from the projectile.•The momentum transfer from hypervelocity ...cratering decreases with increasing target porosity.•Impact cratering of hydrous targets produces greater momentum transfer than for anhydrous targets of the same porosity, likely resulting from the vaporization of water.
Kinetic impact is regarded as an effective way to divert an asteroid on a collision course with the Earth. However, asteroids show a wide diversity in their mineralogy, porosity, and water content. Asteroids range in composition from primitive undifferentiated objects to differentiated objects. Among the undifferentiated asteroids they range from more reflective, carbon-poor bodies to darker, carbonaceous bodies. Porosities of asteroids range from 0 to >50%, with most >20%, and some asteroids exhibit a 0.7 µm water feature in their reflection spectra. Mineralogy, porosity and hydration are each expected to influence the momentum transferred in hypervelocity collisions. We conducted a series of measurements of the post-impact momentum, which is characterized by a factor β, the ratio of the total linear momentum acquired by the target to the momentum of the impactor. We measured β for anhydrous meteorites, which sample their asteroidal parent bodies, spanning a wide range of porosities: including 7 samples of the CV3 carbonaceous chondrite Northwest Africa (NWA) 4502 (2.1% porosity), 7 samples of the ordinary chondrite NWA 869 (6.4% porosity), 4 samples of the ordinary chondrite Saratov (15.6% porosity), and, to extend our measurements to higher porosity than is found among meteorites, 2 samples of terrestrial pumice (80% porosity). We also measured β for hydrous meteorite analog targets: including 2 samples of terrestrial serpentine (17.9% porosity) and 4 samples of terrestrial montmorillonite (51.5% porosity), the two clay minerals that dominate the composition of the hydrous CI carbonaceous chondrite meteorites, as well as 4 samples of hydrous meteorite analog material prepared by powdering and hydrating an anhydrous carbonaceous chondrite. We found that for both the anhydrous and the hydrous samples β decreased with increasing porosity, consistent with hydrocode modeling. However, the β values we measured for the ∼5 km/s impacts onto these anhydrous samples, with β = 3.55 for NWA 4502, 2.69 for NWA 869, 2.10 for Saratov, and 2.15 for pumice, are larger than results from hydrocode modeling for 10 km/s impacts into relatively strong, porous rock targets. The β values for the moderate porosity (17.9%) hydrous serpentine targets (β = 4.70), the highly porous (51.55%) hydrous montmorillonite targets (β = 2.79), and the moderately porous CI-analog targets (β = 2.99) are each significantly larger than the β value for anhydrous targets of comparable porosities. This is likely due to jetting of water vapor, which could significantly affect the deflection of hydrous asteroids and icy comets in natural or human-induced collisions.
Heart failure as recognized and treated in typical practice may represent a complex condition that defies discrete categorizations. To illuminate this complexity, we examined treatment strategies for ...patients hospitalized and treated for decompensated heart failure. We focused on the receipt of medications appropriate for other acute conditions associated with shortness of breath including acute asthma, pneumonia, and exacerbated chronic obstructive pulmonary disease.
Using Premier Perspective(®), we studied adults hospitalized with a principal discharge diagnosis of heart failure and evidence of acute heart failure treatment from 2009-2010 at 370 US hospitals. We determined treatment with acute respiratory therapies during the initial 2 days of hospitalization and daily during hospital days 3-5. We also calculated adjusted odds of in-hospital death, admission to the intensive care unit, and late intubation (intubation after hospital day 2). Among 164,494 heart failure hospitalizations, 53% received acute respiratory therapies during the first 2 hospital days: 37% received short-acting inhaled bronchodilators, 33% received antibiotics, and 10% received high-dose corticosteroids. Of these 87,319 hospitalizations, over 60% continued receiving respiratory therapies after hospital day 2. Respiratory treatment was more frequent among the 60,690 hospitalizations with chronic lung disease. Treatment with acute respiratory therapy during the first 2 hospital days was associated with higher adjusted odds of all adverse outcomes.
Acute respiratory therapy is administered to more than half of patients hospitalized with and treated for decompensated heart failure. Heart failure is therefore regularly treated as a broader cardiopulmonary syndrome rather than as a singular cardiac condition.
Most asteroids for which porosities have been inferred have porosities from 20% to>50%. To investigate the effects of target porosity on cratering, impact disruption, and momentum transfer we ...performed a series of 17 hypervelocity impact experiments on high-porosity (60% to 85% porous), terrestrial, pumice targets impacted at speeds ranging from 3.5 to 5.2km/s at the NASA Ames Vertical Gun Range. Eleven disruptions demonstrated that pumice targets are significantly stronger, i.e., they require more impactor kinetic energy per unit target mass to produce an equivalent disruption, than non-porous targets. The threshold collisional specific energy, QD⁎, for this pumice is ~2380J/kg, more than 60% greater than the value previously determined for ordinary chondrite meteorites having ~10% porosity, and more than three times the literature value for non-porous terrestrial basalt. As a result, in the same impactor environment non-porous asteroids, with properties similar to terrestrial basalt, and highly porous asteroids with the properties of this pumice are equally likely to be disrupted, possibly explaining the survival of asteroids with moderate or high porosity. The six cratering events produced steep-walled, roughly cylindrical craters, with depth/diameter ratios of ~1 to ~2.7, rather than the bowl-shaped craters with depth/diameter ~0.5 produced in non-porous targets. Computed microtomography shows little or no damage to the pumice outside the excavated crater volume even for impactor energies of approximately one-half QD⁎, an energy shown to produce global damage in non-porous targets. Two large, overlapping craters were produced by successive hypervelocity impacts into one pumice target, a result consistent with the interpretation of the large, overlapping craters on the asteroid 253 Mathilde being a result of its high (>50%) porosity. We measured the post-impact momentum of a pumice target, showing that the recoil from the crater ejecta exceeded the direct momentum transferred by absorption of the projectile by ~30%.
•The disruption probability decreases with increasing asteroid porosity.•Craters in highly-porous targets are steep-walled rather than bowl shaped.•Multiple, overlapping large craters can be produced in rigid, porous targets.•Momentum transferred by crater ejecta is significant for highly-porous targets.
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