Search

BackgroundPatients with cancer may be at high risk of adverse outcomes from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We analyzed a cohort of patients with cancer and coronavirus 2019 (COVID-19) reported to the COVID-19 and Cancer Consortium (CCC19) to identify prognostic clinical factors, including laboratory measurements and anticancer therapies.Patients and methodsPatients with active or historical cancer and a laboratory-confirmed SARS-CoV-2 diagnosis recorded between 17 March and 18 November 2020 were included. The primary outcome was COVID-19 severity measured on an ordinal scale (uncomplicated, hospitalized, admitted to intensive care unit, mechanically ventilated, died within 30 days). Multivariable regression models included demographics, cancer status, anticancer therapy and timing, COVID-19-directed therapies, and laboratory measurements (among hospitalized patients).ResultsA total of 4966 patients were included (median age 66 years, 51% female, 50% non-Hispanic white); 2872 (58%) were hospitalized and 695 (14%) died; 61% had cancer that was present, diagnosed, or treated within the year prior to COVID-19 diagnosis. Older age, male sex, obesity, cardiovascular and pulmonary comorbidities, renal disease, diabetes mellitus, non-Hispanic black race, Hispanic ethnicity, worse Eastern Cooperative Oncology Group performance status, recent cytotoxic chemotherapy, and hematologic malignancy were associated with higher COVID-19 severity. Among hospitalized patients, low or high absolute lymphocyte count; high absolute neutrophil count; low platelet count; abnormal creatinine; troponin; lactate dehydrogenase; and C-reactive protein were associated with higher COVID-19 severity. Patients diagnosed early in the COVID-19 pandemic (January-April 2020) had worse outcomes than those diagnosed later. Specific anticancer therapies (e.g. R-CHOP, platinum combined with etoposide, and DNA methyltransferase inhibitors) were associated with high 30-day all-cause mortality.ConclusionsClinical factors (e.g. older age, hematological malignancy, recent chemotherapy) and laboratory measurements were associated with poor outcomes among patients with cancer and COVID-19. Although further studies are needed, caution may be required in utilizing particular anticancer therapies.Clinical trial identifierNCT04354701.

INTRODUCTION: Aerobic exercise within the habitable volume of small spacecraft needed for space exploration beyond low Earth orbit is expected to challenge the capacity of environmental control systems. Moisture control is a primary concern. Crewmembers will contribute moisture to the cabin environment in the form of sweat while exercising. The effects of continuous aerobic exercise for improving and maintaining aerobic capacity is well characterized. Likewise, evidence suggests that high intensity interval exercise for shorter durations is also effective in building and maintaining aerobic capacity. METHODS: On separate days, measures of sweat and respiratory responses were made for continuous (30 min of steady state exercise at ~75% of aerobic capacity) and two interval (4 × 4 min, 8 × 30 s) exercise protocols. RESULTS: We observed that the 4-min and 30-s interval protocols produce 16% and 66% less metabolic water loss vs. the continuous exercise protocol, respectively. These responses were highly correlated with the amount of work performed (R2 = 0.81) and the amount of energy expenditure (R2 = 0.83) during exercise. DISCUSSION: These results suggest that interval exercise may be a useful alternative to continuous aerobic exercise when metabolic water production is an environmental concern. The results may inform the choices of aerobic exercise countermeasure protocols for use in deep space exploration. [ABSTRACT FROM AUTHOR]

We present experimental and calculated vibration–rotation spectra as a function of temperature for the methoxy species (–OCH3 and –OCD3) chemisorbed on an alumina surface. The axis of rotation is the C–O bond axis. The model for our calculations is that of free rotation, and we describe the methods employed here in full detail. The qualitative agreement between the calculated and experimental spectra suggests that the adsorbed methoxy species is undergoing free rotational motion about the C–O bond axis. [ABSTRACT FROM AUTHOR]

The physical adsorption of methyl chloride onto Al2O3 surfaces containing surface OH groups has been studied using transmission infrared spectroscopy. Methyl chloride reversibly bonds via hydrogen bonding to the surface hydroxyl groups with a spectroscopically measured heat of adsorption of -3.37±0.38 kcal mol-1. Physisorption of methyl chloride results in a significant reduction in the intensity of the rotational wings of the methyl chloride absorption bands relative to the gas phase, a small downward frequency shift in their band centers, and substantial effects on the ν(OH) region of the alumina spectrum due to hydrogen bonding of surface OH groups with methyl chloride. Fermi resonances are observed for adsorbed methyl chloride and result in the observation of the overtones of both the symmetric and asymmetric methyl deformation modes. It is postulated that the hydrogen-bonded CH3Cl species possess rotational (or other) degrees of freedom which lead to a high entropy in the adsorbed layer, compared to the liquid. [ABSTRACT FROM AUTHOR]

The adsorption of water on both clean and oxygen-predosed Al(111) has been studied by vibrational spectroscopy using electron energy loss spectroscopy (EELS). At 130 K, adsorption on either surface is competitively associative and dissociative. The dominant dissociation product is a hydroxyl species. On the clean surface, adsorption is predominantly molecular, while in the presence of oxygen, adsorption is predominantly dissociative. In contrast to the low temperature behavior, adsorption of water on clean Al(111) at 300 K is completely dissociative, resulting in oxygen adsorption and surface oxidation. Adsorbed hydroxyl species can be produced at 300 K by prolonged water exposure. Upon heating a low-temperature water layer adsorbed on either surface, molecular water desorption and further decomposition both occur. The production of adsorbed hydroxyl species from water reaches a maximum at 250 K on the clean surface and at 350 K on the oxygen-predosed surface. The hydroxyl species decompose above these temperatures to evolve hydrogen and further oxidize the Al(111) surface. [ABSTRACT FROM AUTHOR]

The adsorption and decomposition of formate and formic acid have been studied on the Al(111) surface using high resolution electron energy loss spectroscopy (EELS) and temperature programmed desorption (TPD). Formic acid reacts with clean Al(111) at 120 K to form a surface formate species. Molecular adsorption of formic acid occurs at 120 K only after saturation of the surface formate layer has been reached. Off-specular vibrational measurements have determined that the formate species is symmetrically bridge bonded through both oxygen atoms with C2v symmetry. A lower symmetry formate species of C1 symmetry is produced upon heating or electron bombardment of a condensed formic acid layer. Thermal or electron induced decomposition of a formate or a condensed formic acid layer is controlled by oxygen incorporation into the aluminum lattice, and results in complete decomposition and production of a carbon and oxygen covered surface. Only hydrogen is evolved from a formate-covered Al(111) surface. [ABSTRACT FROM AUTHOR]

The adsorption of water on a well-characterized Al2O3 film produced by oxidizing an Al(111) surface has been studied using electron energy loss spectroscopy (EELS). Water reacts with this oxide layer to form surface hydroxyl species characterized by a sharp O–H (O–D) stretching vibration at 3720 (2740) cm-1. The assignment of the three-peak vibrational spectrum of Al2O3 to surface and bulk Al–O modes is confirmed by chemical means based on the observation that the 625 cm-1 loss feature assigned to a surface Al–O stretching vibration is preferentially affected upon formation of surface hydroxyl groups. The remaining two bulk modes are uninfluenced by surface hydroxylation. The surface hydroxyl species can be quantitatively removed by electron stimulated desorption (ESD), reversing the spectroscopic changes observed upon exposure of Al2O3 to water, further substantiating the vibrational assignments. [ABSTRACT FROM AUTHOR]

The National Cancer Institute has contracted preclinical mutagenicity, teratology and subchronic toxicity studies of well-characterized isoflavone mixtures in collaboration with Protein Technologies International to support clinical investigations. The battery of mutagenicity studies included bacterial mutagenesis, the mouse micronucleus test and the mouse lymphoma test. The bacterial mutagenesis and mouse micronucleus tests were negative. The mouse lymphoma test was positive; thus, additional tests are being undertaken to characterize the dose-response relationship for topoisomerase inhibition and other effects. Range-finding and segment II teratology tests have been completed in rats and rabbits. In rats, decreased fetal weights occurred at doses of 1 g/kg body weight and increased numbers of fetuses with bent ribs (a skeletal variation) occurred at 300 mg and 1 g/kg body weight. Range-finding and subchronic 13-week oral toxicity tests have also been completed in rats and dogs. In rats, clinical chemistry changes in both sexes and adrenal cortical hyperplasia in female rats occurred at doses of 500 mg/kg body weight. The no-observed adverse effect level in the rats (the more sensitive species) was ~100 mg/kg body weight in both the teratology and subchronic studies. The proprietary mixtures were administered in these tests on the basis of genistein, and correlations across studies have been made between in vitro concentrations and plasma concentrations of free and conjugated isoflavones. Pharmacologic plasma levels in hundreds of nanograms per milliliter of free genistein and tens of micrograms per milliliter of conjugated genistein were achieved. Additional preclinical studies will be conducted as clinical studies progress.

The National Cancer Institute has sponsored an investigational new drug application, in collaboration with Protein Technologies International, to conduct single-dose, phase 1 pharmacokinetic and safety studies of well-characterized isoflavone mixtures in men and women. Before the initiation of the trial, a sensitive analytical method was developed and validated to measure free and conjugated genistein and daidzein in plasma and urine. The proprietary mixtures were administered on the basis of genistein. Five groups of three subjects were administered the mixtures at 1, 2, 4, 8 and 16 mg/kg body weight. Blood and urine samples were collected and analyzed to determine pharmacokinetic parameters. Safety was monitored by clinical signs, clinical chemistry values, hematology and follow-up. Results from the study in men will be presented. Pharmacologic plasma levels of free genistein up to ~100 ng/mL and of conjugated genistein up to ~7500 ng/mL were achieved. The repeat-dose portion of the phase 1 studies is now being initiated.

Objectives: Multiple sclerosis (MS) is a neurological disease that commonly results in physical and cognitive dysfunction. Accordingly, MS might impact the ability to safely cross the street. The purpose of this study was to examine the feasibility of a simulated street-crossing task in persons with MS and to determine differences in street-crossing performance between persons with MS and non-MS controls.Methods: 26 participants with MS (median Expanded Disability Status Scale [EDSS] score = 3.5) and 19 controls completed 40 trials of a virtual street-crossing task. There were 2 crossing conditions (i.e., no distraction and phone conversation), and participants performed 20 trials per condition. Participants were instructed that the goal of the task was to cross the street successfully (i.e., without being hit be a vehicle). The primary outcome was task feasibility, assessed as completion and adverse events. Secondary outcomes were measures of street-crossing performance.Results: Overall, the simulated street-crossing task was feasible (i.e., 90% completion, no adverse events) in participants with MS. Participants with MS waited longer and were less attentive to traffic before entering the street compared with controls (all P < .05). Participants with MS also took longer to cross the street and were closer to oncoming vehicles when exiting the street compared to controls (all P < .05). When distracted, all participants took longer to initiate crossing, took longer to cross the street, and made more head turns while crossing (all P < .05). There were no significant group by condition interaction effects (all P > .05).Conclusions: A virtual street-crossing task is feasible for studying street-crossing behavior in persons with mild MS and most individuals with moderate MS. Virtual street-crossing performance is impaired in persons with MS compared to controls; however, persons with MS do not appear to be more vulnerable to a distracting condition. The virtual reality environment presents a safe and useful setting for understanding pedestrian behavior in persons with MS. [ABSTRACT FROM AUTHOR]