Caregiving experiences predict changes in spiritual well-being among family caregivers of cancer patients

OBJECTIVE: Although enhanced spiritual well-being has been linked to positive mental health outcomes among family caregivers of cancer patients, little is known regarding predictors of spiritual well-being in this population. The current study aimed to examine caregiving experiences as predictors of change in family caregivers' spiritual well-being during the initial months following the patient's cancer diagnosis. METHODS: Seventy family caregivers of newly diagnosed cancer patients (74% female, mean age = 59 years) participated in this longitudinal survey. Caregivers completed baseline questionnaires shortly before staying with the patient at an American Cancer Society Hope Lodge. Baseline questionnaires assessed caregiving experiences (i.e., self-esteem related to caregiving, family support for providing care, impact of caregiving on finances, and impact of caregiving on one's schedule). In addition, caregivers' spiritual well-being (i.e., meaning in life, peace, and faith) was assessed at baseline and 4-month follow-up. RESULTS: In univariate analyses, all caregiving experiences studied were associated with one or more aspects of spiritual well-being at 4-month follow-up. However, in the multivariate analysis, the only caregiving experience associated with aspects of spiritual well-being at 4-month follow-up was caregivers' perceptions of family support. Specifically, lack of family support was associated with lower levels of meaning and peace. CONCLUSIONS: Findings point to the importance of family support in facilitating the search for meaning and peace shortly after a loved one's cancer diagnosis and suggest that interventions targeting caregivers' support system may enhance their spiritual well-being

CYP-mediated drug-drug interactions with evacetrapib, an investigational CETP inhibitor: in vitro prediction and clinical outcome

AIMS Evacetrapib is a cholesteryl ester transfer protein (CETP) inhibitor under development for reducing cardiovascular events in patients with high risk vascular disease. CETP inhibitors are likely to be utilized as ‘add-on’ therapy to statins in patients receiving concomitant medications, so the potential for evacetrapib to cause clinically important drug–drug interactions (DDIs) with cytochromes P450 (CYP) was evaluated. METHODS The DDI potential of evacetrapib was investigated in vitro, followed by predictions to determine clinical relevance. Potential DDIs with possible clinical implications were then investigated in the clinic. RESULTS In vitro, evacetrapib inhibited all of the major CYPs, with inhibition constants (Ki) ranging from 0.57 μM (CYP2C9) to 7.6 μM (CYP2C19). Evacetrapib was a time-dependent inhibitor and inducer of CYP3A. The effects of evacetrapib on CYP3A and CYP2C9 were assessed in a phase 1 study using midazolam and tolbutamide as probe substrates, respectively. After 14 days of daily dosing with evacetrapib (100 or 300 mg), midazolam exposures (AUC) changed by factors (95% CI) of 1.19 (1.06, 1.33) and 1.44 (1.28, 1.62), respectively. Tolbutamide exposures (AUC) changed by factors of 0.85 (0.77, 0.94) and 1.06 (0.95, 1.18), respectively. In a phase 2 study, evacetrapib 100 mg had minimal impact on AUC of co-administered simvastatin vs. simvastatin alone with a ratio of 1.25 (1.03, 1.53) at steady-state, with no differences in reported hepatic or muscular adverse events. CONCLUSIONS Taken together, the extent of CYP-mediated DDI with the potential clinical dose of evacetrapib is weak and clinically important DDIs are not expected to occur in patients taking concomitant medications.Ellen A. Cannady, Jeffrey G. Suico, Ming-Dauh Wang, Stuart Friedrich, Jessica R. F. Rehmel, Stephen J. Nicholls, Kathryn A. Kruege

Space power distribution system technology. Volume 2: Autonomous power management

Electrical power subsystem requirements, power management system functional requirements, algorithms, power management subsystem, hardware development, and trade studies and analyses are discussed

Space power distribution system technology. Volume 1: Reference EPS design

The multihundred kilowatt electrical power aspects of a mannable space platform in low Earth orbit is analyzed from a cost and technology viewpoint. At the projected orbital altitudes, Shuttle launch and servicing are technically and economically viable. Power generation is specified as photovoltaic consistent with projected planning. The cost models and trades are based upon a zero interest rate (the government taxes concurrently as required), constant dollars (1980), and costs derived in the first half of 1980. Space platform utilization of up to 30 years is evaluated to fully understand the impact of resupply and replacement as satellite missions are extended. Such lifetimes are potentially realizable with Shuttle servicing capability and are economically desirable

Cardiopulmonary exercise testing and cardiopulmonary morbidity in patients undergoing major head and neck surgery

Cardiopulmonary exercise testing (CPET) is used as a risk stratification tool for patients undergoing major surgery. In this study, we investigated the role of CPET in predicting day five cardiopulmonary morbidity in patients undergoing head and neck surgery. This observational cohort study included 230 adults. We recorded preoperative CPET variables and day five postoperative cardiopulmonary morbidity. Full data from 187 patients were analysed; 43 patients either had incomplete data sets or declined surgery/CPET. One hundred and nineteen patients (63.6%) developed cardiopulmonary morbidity at day five. Increased preoperative heart rate and duration of surgery were independently associated with day five cardiopulmonary morbidity. Those with such morbidity also had lower peak V̇O2 11.4 (IQR 8.4-18.0) vs 16.0 (IQR 14.0-19.7) ml.kg-1.min-1, P<0.0001 and V̇O2 at AT 10.6 (IQR 9.1-13.1) vs 11.5 (IQR 10.5-13.0) ml.kg-1.min-1, p=0.03. Logistic regression model containing peak V̇O2 and duration of surgery demonstrated that increased peak V̇O2 was associated with a reduction in the likelihood of cardiopulmonary complications OR 0.92 (95%CI 0.87 to 0.96), p=0.001. The area under the receiver operating characteristic curve for this model was 0.75(95%CI 0.68 to 0.82), p<0.0001, 64% sensitivity, 81% specificity. CPET can help to predict day five cardiopulmonary morbidity in the patients undergoing head and neck surgery. A model containing peak V̇O2 allowed identification of those with such complications

Search for GeV Gamma-ray Counterparts of Gravitational Wave Events by CALET

We present results on searches for gamma-ray counterparts of the LIGO/Virgo gravitational-wave events using CALorimetric Electron Telescope ({\sl CALET}) observations. The main instrument of {\sl CALET}, CALorimeter (CAL), observes gamma-rays from $\sim1$ GeV up to 10 TeV with a field of view of nearly 2 sr. In addition, the {\sl CALET} gamma-ray burst monitor (CGBM) views $\sim$3 sr and $\sim2\pi$ sr of the sky in the 7 keV -- 1 MeV and the 40 keV -- 20 MeV bands, respectively, by using two different crystal scintillators. The {\sl CALET} observations on the International Space Station started in October 2015, and here we report analyses of events associated with the following gravitational wave events: GW151226, GW170104, GW170608, GW170814 and GW170817. Although only upper limits on gamma-ray emission are obtained, they correspond to a luminosity of $10^{49}\sim10^{53}$ erg s$^{-1}$ in the GeV energy band depending on the distance and the assumed time duration of each event, which is approximately the order of luminosity of typical short gamma-ray bursts. This implies there will be a favorable opportunity to detect high-energy gamma-ray emission in further observations if additional gravitational wave events with favorable geometry will occur within our field-of-view. We also show the sensitivity of {\sl CALET} for gamma-ray transient events which is the order of $10^{-7}$~erg\,cm$^{-2}$\,s$^{-1}$ for an observation of 100~s duration.Comment: 12 pages, 8 figures, 1 table. Accepted for publication in Astrophysical Journa

Prognostic factors for outcomes after whole-brain irradiation of brain metastases from relatively radioresistant tumors: a retrospective analysis

<p>Abstract</p> <p>Background</p> <p>This study investigated potential prognostic factors in patients treated with whole-brain irradiation (WBI) alone for brain metastases from relatively radioresistant tumors such as malignant melanoma, renal cell carcinoma, and colorectal cancer. Additionally, a potential benefit from escalating the radiation dose was investigated.</p> <p>Methods</p> <p>Data from 220 patients were retrospectively analyzed for overall survival and local control. Nine potential prognostic factors were evaluated: tumor type, WBI schedule, age, gender, Karnofsky performance score, number of brain metastases, extracerebral metastases, interval from diagnosis of cancer to WBI, and recursive partitioning analysis (RPA) class.</p> <p>Results</p> <p>Survival rates at 6 and 12 months were 32% and 19%, respectively. In the multivariate analysis, WBI doses >30 Gy (p = 0.038), KPS ≥70 (p < 0.001), only 1-3 brain metastases (p = 0.007), no extracerebral metastases (p < 0.001), and RPA class 1 (p < 0.001) were associated with improved survival. Local control rates at 6 and 12 months were 37% and 15%, respectively. In the multivariate analyses, KPS ≥70 (p < 0.001), only 1-3 brain metastases (p < 0.001), and RPA class 1 (p < 0.001) were associated with improved local control. In RPA class 3 patients, survival rates at 6 months were 10% (35 of 39 patients) after 10 × 3 Gy and 9% (2 of 23 patients) after greater doses, respectively (p = 0.98).</p> <p>Conclusions</p> <p>Improved outcomes were associated with WBI doses >30 Gy, better performance status, fewer brain metastases, lack of extracerebral metastases, and lower RPA class. Patients receiving WBI alone appear to benefit from WBI doses >30 Gy. However, such a benefit is limited to RPA class 1 or 2 patients.</p

On-orbit Operations and Offline Data Processing of CALET onboard the ISS

The CALorimetric Electron Telescope (CALET), launched for installation on the International Space Station (ISS) in August, 2015, has been accumulating scientific data since October, 2015. CALET is intended to perform long-duration observations of high-energy cosmic rays onboard the ISS. CALET directly measures the cosmic-ray electron spectrum in the energy range of 1 GeV to 20 TeV with a 2% energy resolution above 30 GeV. In addition, the instrument can measure the spectrum of gamma rays well into the TeV range, and the spectra of protons and nuclei up to a PeV. In order to operate the CALET onboard ISS, JAXA Ground Support Equipment (JAXA-GSE) and the Waseda CALET Operations Center (WCOC) have been established. Scientific operations using CALET are planned at WCOC, taking into account orbital variations of geomagnetic rigidity cutoff. Scheduled command sequences are used to control the CALET observation modes on orbit. Calibration data acquisition by, for example, recording pedestal and penetrating particle events, a low-energy electron trigger mode operating at high geomagnetic latitude, a low-energy gamma-ray trigger mode operating at low geomagnetic latitude, and an ultra heavy trigger mode, are scheduled around the ISS orbit while maintaining maximum exposure to high-energy electrons and other high-energy shower events by always having the high-energy trigger mode active. The WCOC also prepares and distributes CALET flight data to collaborators in Italy and the United States. As of August 31, 2017, the total observation time is 689 days with a live time fraction of the total time of approximately 84%. Nearly 450 million events are collected with a high-energy (E>10 GeV) trigger. By combining all operation modes with the excellent-quality on-orbit data collected thus far, it is expected that a five-year observation period will provide a wealth of new and interesting results.Comment: 11 pages, 7 figures, published online 27 February 201

Direct Measurement of the Cosmic-Ray Proton Spectrum from 50 GeV to 10 TeV with the Calorimetric Electron Telescope on the International Space Station

In this paper, we present the analysis and results of a direct measurement of the cosmic-ray proton spectrum with the CALET instrument onboard the International Space Station, including the detailed assessment of systematic uncertainties. The observation period used in this analysis is from October 13, 2015 to August 31, 2018 (1054 days). We have achieved the very wide energy range necessary to carry out measurements of the spectrum from 50 GeV to 10 TeV covering, for the first time in space, with a single instrument the whole energy interval previously investigated in most cases in separate subranges by magnetic spectrometers (BESS-TeV, PAMELA, and AMS-02) and calorimetric instruments (ATIC, CREAM, and NUCLEON). The observed spectrum is consistent with AMS-02 but extends to nearly an order of magnitude higher energy, showing a very smooth transition of the power-law spectral index from-2.81±0.03 (50-500 GeV) neglecting solar modulation effects (or-2.87±0.06 including solar modulation effects in the lower energy region) to-2.56±0.04 (1-10 TeV), thereby confirming the existence of spectral hardening and providing evidence of a deviation from a single power law by more than 3σ

CALET results after three years on the International Space Station

The CALET (CALorimetric Electron Telescope) space experiment, which is currently conducting direct cosmic-ray observations onboard the International Space Station (ISS), is an all-calorimetric instrument optimized for cosmic-ray electron measurements with capability to measure hadrons and gamma-rays. Since the start of observation in October 2015, smooth and continuous operations have taken place. In this paper, we will give a brief summary of the CALET observations ranging from charged cosmic rays, gamma-rays, to space weather, while focusing on the energy spectra of electrons and protons