An olivine cumulate outcrop on the floor of Jezero crater, Mars.

The geological units on the floor of Jezero crater, Mars, are part of a wider regional stratigraphy of olivine-rich rocks, which extends well beyond the crater. We investigated the petrology of olivine and carbonate-bearing rocks of the Séítah formation in the floor of Jezero. Using multispectral images and x-ray fluorescence data, acquired by the Perseverance rover, we performed a petrographic analysis of the Bastide and Brac outcrops within this unit. We found that these outcrops are composed of igneous rock, moderately altered by aqueous fluid. The igneous rocks are mainly made of coarse-grained olivine, similar to some martian meteorites. We interpret them as an olivine cumulate, formed by settling and enrichment of olivine through multistage cooling of a thick magma body.

Aqueously altered igneous rocks sampled on the floor of Jezero crater, Mars.

The Perseverance rover landed in Jezero crater, Mars, to investigate ancient lake and river deposits. We report observations of the crater floor, below the crater's sedimentary delta, finding that the floor consists of igneous rocks altered by water. The lowest exposed unit, informally named Séítah, is a coarsely crystalline olivine-rich rock, which accumulated at the base of a magma body. Magnesium-iron carbonates along grain boundaries indicate reactions with carbon dioxide-rich water under water-poor conditions. Overlying Séítah is a unit informally named Máaz, which we interpret as lava flows or the chemical complement to Séítah in a layered igneous body. Voids in these rocks contain sulfates and perchlorates, likely introduced by later near-surface brine evaporation. Core samples of these rocks have been stored aboard Perseverance for potential return to Earth.

Effects and moderators of exercise on sleep in adults with cancer: Individual patient data and aggregated meta-analyses.

OBJECTIVES: To evaluate the effects of exercise interventions on sleep disturbances and sleep quality in patients with mixed cancer diagnoses, and identify demographic, clinical, and intervention-related moderators of these effects. METHODS: Individual patient data (IPD) and aggregated meta-analyses of randomized controlled trials (RCTs). Using data from the Predicting OptimaL cAncer RehabIlitation and Supportive care project, IPD of 2173 adults (mean age = 54.8) with cancer from 17 RCTs were analyzed. A complementary systematic search was conducted (until November 2018) to study the overall effects and test the representativeness of analyzed IPD. Effect sizes of exercise effects on self-reported sleep outcomes were calculated for all included RCTs. Linear mixed-effect models were used to evaluate the effects of exercise on post-intervention outcome values, adjusting for baseline values. Moderator effects were studied by testing interactions for demographic, clinical and intervention-related characteristics. RESULTS: For all 27 eligible RCTs from the updated search, exercise interventions significantly decreased sleep disturbances in adults with cancer (g = -0.09, 95% CI [-0.16; -0.02]). No significant effect was obtained for sleep quality. RCTs included in IPD analyses constituted a representative sample of the published literature. The intervention effects on sleep disturbances were not significantly moderated by any demographic, clinical, or intervention-related factor, nor by sleep disturbances. CONCLUSIONS: This meta-analysis provides some evidence that, compared to control conditions, exercise interventions may improve sleep disturbances, but not sleep quality, in cancer patients, although this effect is of a small magnitude. Among the investigated variables, none was found to significantly moderate the effect of exercise interventions on sleep disturbances.

Validation of inflammatory genetic variants associated with long-term cancer related fatigue in a large breast cancer cohort.

BACKGROUND: Studies to date have reported several associations between single nucleotide polymorphisms (SNPs) and cancer related fatigue (CRF), but have been limited by small sample sizes, missing adjustment for relevant covariates or multiple testing, as well as varying CRF definitions, i.e. time and method of assessment. This study aimed to validate previously reported associations using the largest independent breast cancer sample to date and to evaluate further functional cytokine variants in relation to total CRF and all relevant CRF subdomains (physical, cognitive, and affective CRF). METHOD: 45 candidate SNPs in inflammatory pathway genes were selected based on previous reports (16 SNPs) or regulatory function (29 SNPs). Breast cancer patients recruited between 2002 and 2005 provided information on CRF at first follow-up (FU1) (N = 1389) and second follow-up (FU2) (N = 950), a median of 6.2 years and 11.7 years respectively after diagnosis. SNP associations were assessed using linear regression models on CRF scores separately for FU1 and FU2. Additionally, patients with persistent fatigue (fatigued at both time-points) were compared to those never fatigued using logistic regression models (N = 684). All analyses were adjusted for relevant covariates. Secondary analyses were conducted for CRF subdomains. RESULTS: For total CRF none of the previously reported associations were confirmed after correction for multiple testing. The p-value distribution of all SNPs was not different than the one expected by chance. Analyses of CRF subdomains yielded a significant association between TNF-α rs3093662 and persistent physical CRF (Odds Ratio (OR) = 3.23, 95% Confidence Interval (CI) = 1.71-6.10, p = 0.0003). CONCLUSION: We were unable to confirm previously reported findings, suggesting that individual SNPs are unlikely to be of clinical utility. Further investigations in well powered studies are warranted, which consider genetic heterogeneity according to subdomains of CRF.

Redox stratification of an ancient lake in Gale crater, Mars.

In 2012, NASA's Curiosity rover landed on Mars to assess its potential as a habitat for past life and investigate the paleoclimate record preserved by sedimentary rocks inside the ~150-kilometer-diameter Gale impact crater. Geological reconstructions from Curiosity rover data have revealed an ancient, habitable lake environment fed by rivers draining into the crater. We synthesize geochemical and mineralogical data from lake-bed mudstones collected during the first 1300 martian solar days of rover operations in Gale. We present evidence for lake redox stratification, established by depth-dependent variations in atmospheric oxidant and dissolved-solute concentrations. Paleoclimate proxy data indicate that a transition from colder to warmer climate conditions is preserved in the stratigraphy. Finally, a late phase of geochemical modification by saline fluids is recognized.

Effects of 12-week resistance training during radiotherapy in breast cancer patients.

Exercise is considered to be an effective supportive treatment approach in breast cancer (BC) patients. We conducted a randomized controlled trial to assess the efficacy of a 12-week PRT during radiotherapy. Strength performance was assessed by maximal isokinetic peak torque (MIPT) in two different angular velocities (60°/s and 180°/s) and maximal voluntary isometric contraction for shoulder external and internal rotation, as well as for knee extension and flexion were assessed pre- and post-intervention in 146 patients randomized to PRT or a control group. Statistical analyses were based on analysis of covariance models for the individual changes from baseline to week 13. Intention-to-treat analyses showed significant between-group differences favoring the exercise group (EX) for MIPT in knee flexion and shoulder internal and external rotation (P < 0.05). Subgroup analyses showed borderline significant differences with regard to pretreatment history, revealing that pretreated chemotherapy patients tend to benefit more from PRT than patients without chemotherapy (P = 0.06). Strength gain at the operated arm was significantly higher than at the non-operated arm in EX. PRT was efficacious in increasing upper and lower limb strength in BC patients undergoing adjuvant radiotherapy. Patients with restrictions due to breast cancer-related surgery and pretreated with chemotherapy might benefit the most.

Determining best practices in reconnoitering sites for habitability potential on Mars using a semi-autonomous rover: A GeoHeuristic Operational Strategies Test.

We tested science operations strategies developed for use in remote mobile spacecraft missions, to determine whether reconnoitering a site of potential habitability prior to in-depth study (a walkabout-first strategy) can be a more efficient use of time and resources than the linear approach commonly used by planetary rover missions. Two field teams studied a sedimentary sequence in Utah to assess habitability potential. At each site one team commanded a human "rover" to execute observations and conducted data analysis and made follow-on decisions based solely on those observations. Another team followed the same traverse using traditional terrestrial field methods, and the results of the two teams were compared. Test results indicate that for a mission with goals similar to our field case, the walkabout-first strategy may save time and other mission resources, while improving science return. The approach enabled more informed choices and higher team confidence in choosing where to spend time and other consumable resources. The walkabout strategy may prove most efficient when many close sites must be triaged to a smaller subset for detailed study or sampling. This situation would arise when mission goals include finding, identifying, characterizing or sampling a specific material, feature or type of environment within a certain area.

Randomized, controlled trial of resistance training in breast cancer patients receiving adjuvant radiotherapy: results on cancer-related fatigue and quality of life.

BACKGROUND: Exercise has been reported to decrease cancer-related fatigue and to increase quality of life (QoL) in various breast cancer (BC) populations. However, studies investigating exercise during radiotherapy or resistance training are scarce. We conducted a randomized, controlled trial (BEST study) to assess the efficacy of 12-week resistance training on fatigue beyond possible psychosocial effects of a group-based intervention. PATIENTS AND METHODS: One hundred sixty patients with BC stage 0-III were randomly assigned to a 12-week progressive resistance training (2 times/week) or a 12-week relaxation control (RC, 2 times/week). Both interventions were group-based. The primary end point fatigue was assessed with a 20-item multidimensional questionnaire, QoL with EORTC questionnaires. Statistical analyses were based on analysis of covariance models for the individual changes from baseline to week 13. RESULTS: Adherence to the intervention program as well as the completion rate (97%) for the primary outcome variable fatigue was high. In intention-to-treat analyses for the N = 155 patients, significant between-group mean differences (MD) favoring the exercise group (EX) were observed for general fatigue (P = 0.044), especially for the subscale physical fatigue [MD = -0.8; 95% confidence interval -1.5 to -0.2, P = 0.013], but not for affective (P = 0.91) or cognitive fatigue (P = 0.65). For QoL, significantly larger improvements regarding the role function (P = 0.035) and pain (P = 0.040) were noted among exercisers compared with RCs. Future perspective improved significantly stronger in the RC group compared with the EX group (P = 0.047). CONCLUSIONS: The 12-week resistance training program was a safe, feasible and efficacious strategy to improve cancer-related fatigue and components of QoL in BC patients during adjuvant radiotherapy. As exercise was compared with another group-based intervention, results indicate that resistance training effects on fatigue and QoL go beyond psychosocial benefits, and that the clinically relevant overall benefit of resistance exercise compared with usual care can be assumed to be higher. TRIAL REGISTRATION: ClinicalTrials.gov NCT01468766.

Elemental geochemistry of sedimentary rocks at Yellowknife Bay, Gale crater, Mars.

Sedimentary rocks examined by the Curiosity rover at Yellowknife Bay, Mars, were derived from sources that evolved from an approximately average martian crustal composition to one influenced by alkaline basalts. No evidence of chemical weathering is preserved, indicating arid, possibly cold, paleoclimates and rapid erosion and deposition. The absence of predicted geochemical variations indicates that magnetite and phyllosilicates formed by diagenesis under low-temperature, circumneutral pH, rock-dominated aqueous conditions. Analyses of diagenetic features (including concretions, raised ridges, and fractures) at high spatial resolution indicate that they are composed of iron- and halogen-rich components, magnesium-iron-chlorine-rich components, and hydrated calcium sulfates, respectively. Composition of a cross-cutting dike-like feature is consistent with sedimentary intrusion. The geochemistry of these sedimentary rocks provides further evidence for diverse depositional and diagenetic sedimentary environments during the early history of Mars.

The petrochemistry of Jake_M: a martian mugearite.

"Jake_M," the first rock analyzed by the Alpha Particle X-ray Spectrometer instrument on the Curiosity rover, differs substantially in chemical composition from other known martian igneous rocks: It is alkaline (>15% normative nepheline) and relatively fractionated. Jake_M is compositionally similar to terrestrial mugearites, a rock type typically found at ocean islands and continental rifts. By analogy with these comparable terrestrial rocks, Jake_M could have been produced by extensive fractional crystallization of a primary alkaline or transitional magma at elevated pressure, with or without elevated water contents. The discovery of Jake_M suggests that alkaline magmas may be more abundant on Mars than on Earth and that Curiosity could encounter even more fractionated alkaline rocks (for example, phonolites and trachytes).

Applications of imaging biomarkers in the early clinical development of central nervous system therapeutic agents.

The early clinical drug development process increasingly utilizes imaging biomarkers to provide key information in response to a sequential series of questions about potential therapeutic agents. We present several examples of how imaging can answer some of these questions pertaining to the central nervous system (CNS) during the early phases of development of drugs to treat diseases involving the CNS. We also present an overview of the challenges and the potential of using and further qualifying imaging biomarkers for clinical trials.

Testing Mars-inspired operational strategies for semi-autonomous rovers on the Moon: The GeoHeuristic Operational Strategies Test in New Mexico.

BACKGROUND: We tested the science operational strategy used for the Mars Exploration Rover (MER) mission on Mars to determine its suitability for conducting remote geology on the Moon by conducting a field test at Cerro de Santa Clara, New Mexico. This region contains volcanic and sedimentary products from a variety of provenances, mimicking the variety that might be found at a lunar site such as South Pole-Aitken Basin. METHOD: At each site a Science Team broke down observational "days" into a sequence of observations of features and targets of interest. The number, timing, and sequence of observations was chosen to mimic those used by the MERs when traversing. Images simulating high-resolution stereo and hand lens-scale images were taken using a professional SLR digital camera; multispectral and XRD data were acquired from samples to mimic the availability of geochemical data. A separate Tiger Team followed the Science Team and examined each site using traditional terrestrial field methods, facilitating comparison between what was revealed by human versus rover-inspired methods. LESSONS LEARNED: We conclude from this field test that MER-inspired methodology is not conducive to utilizing all acquired data in a timely manner for the case of any lunar architecture that involves the acquisition of rover data in near real-time. We additionally conclude that a methodology similar to that used for MER can be adapted for use on the Moon if mission goals are focused on reconnaissance. If the goal is to locate and identify a specific feature or material, such as water ice, a different methodology will likely be needed.

Physical activity and postmenopausal breast cancer: effect modification by other breast cancer risk factors.

OBJECTIVES: Epidemiological evidence suggests an inverse association between physical activity (PA) and postmenopausal breast cancer risk. Breast cancer is a heterogeneous disease, influenced by reproductive factors, lifestyle pattern, and predispositions. We investigated whether these risk factors modify the effect of PA on breast cancer risk. METHODS: We analyzed data from 2004 hormone-receptor-positive postmenopausal breast cancer cases and 6569 controls from the population-based MARIE study conducted 2002-2005 in Germany. Interaction was statistically tested using adjusted unconditional logistic regression models. RESULTS: The inverse association between leisure-time PA and risk of postmenopausal hormone-receptor-positive breast cancer was not heterogeneous by family history of breast cancer or by hormone therapy. PA showed a significant interaction with benign breast diseases (p = 0.023) and with breastfeeding (p = 0.045) but not with parity (p = 0.94), with clear risk reductions only for women who ever had breastfed or who ever had a benign breast disease (among ever breastfed: odds ratio = 0.63; 95% confidence interval = (0.52, 0.77), highest vs. lowest PA quartile). Interaction with BMI was weak (p = 0.053). CONCLUSIONS: Breastfeeding and benign breast diseases modified the effect of PA on postmenopausal breast cancer risk. If other studies find similar modifications, increasing knowledge about these risk factors may contribute to a better understanding of the mode of action of PA on breast cancer risk. For women who are at higher risk for breast cancer due to family history or due to hormone therapy use, it is encouraging that they might lower their risk by being physically active.

Detection of silica-rich deposits on Mars.

Mineral deposits on the martian surface can elucidate ancient environmental conditions on the planet. Opaline silica deposits (as much as 91 weight percent SiO2) have been found in association with volcanic materials by the Mars rover Spirit. The deposits are present both as light-toned soils and as bedrock. We interpret these materials to have formed under hydrothermal conditions and therefore to be strong indicators of a former aqueous environment. This discovery is important for understanding the past habitability of Mars because hydrothermal environments on Earth support thriving microbial ecosystems.

Prostate cancer tissue is masked by bicalutamide: a case report.

Prostate cancer is the most common malignant tumor in men. Recently, a slightly decreased frequency of margin positivity following neoadjuvant bicalutamide treatment due to tumor shrinkage was reported. Trials investigating other anti-androgens in the past also reported lower frequencies of surgical margin positivity, but patients outcome has not improved. In this case, local recurrence was confirmed by needle biopsy in a patient five years following radical prostatectomy for prostate adenocarcinoma. After therapy with 50 mg bicalutamide for a month, the tumour was resected. Despite of detailed histological work-up and immunohistochemistry cancer suspicious lesions were not found. We think that bicalutamide may be capable of masking prostate cancer cells.

Statistical methods for the validation of questionnaires--discrepancy between theory and practice.

OBJECTIVES: Questionnaires used in epidemiological studies should be validated. However, unclarity exists about the appropriate statistical methods and interpretation of validation studies. Thus, we investigated the theory and practice of statistical evaluation approaches. METHODS: Using three platforms, a literature review, own simulations, and a validation study performed by ourselves, we worked out relevant limitations, advantages, and new important aspects of evaluation methods. RESULTS: Our systematic literature review, based on physical activity questionnaires, revealed that correlation coefficients are still the common approach in validation studies, found in 41 of 46 reviewed publications (89.1%). This practice has been criticized in the theoretically oriented literature for more than 20 years. Appropriate evaluation methods as recommended by Bland and Altman were found in only ten publications (21.7%). We showed that serious bias in questionnaires can be revealed by Bland-Altman plots but may remain undetected by correlation coefficients. With our simulations we refuted the argument that correlation coefficients properly investigate whether a questionnaire ranks the subjects sufficiently well. Further, with Bland-Altman analyses we could evaluate differential errors with respect to case-control status in our validation study. Yet, this was not possible with correlation coefficients, because they generally do not identify systematic bias. In addition, we show a potential pitfall in the interpretation of Bland-Altman plots that might occur in specific rare instances. CONCLUSIONS: The commonly used correlation approach can yield misleading conclusions in validation studies. A more frequent and proper use of the Bland-Altman methods would be desirable to improve epidemiological data quality.

Aggressive angiomyxoma of the prostate mimicking benign prostatic hyperplasia.

Aggressive angiomyxoma (AAM) is a locally invasive soft tissue tumor with a high risk of local recurrence but without metastatic spread. The mesenchymal tumor is relatively site-specific and has a peak incidence in females in their 2nd or 4th decade. Only few cases in males have been reported in the literature. We describe what we think is the first case of an aggressive angiomyxoma arising in the prostate presenting with classical symptoms of benign prostatic hyperplasia.

Central nervous system drug development: an integrative biomarker approach toward individualized medicine.

Drug development for CNS disorders faces the same formidable hurdles as other therapeutic areas: escalating development costs; novel drug targets with unproven therapeutic potential; and health care systems and regulatory agencies demanding more compelling demonstrations of the value of new drug products. Extensive clinical testing remains the core of registration of new compounds; however, traditional clinical trial methods are falling short in overcoming these development hurdles. The most common CNS disorders targeted for drug treatment are chronic, slowly vitiating processes manifested by highly subjective and context dependent signs and symptoms. With the exception of a few rare familial degenerative disorders, they have ill-defined or undefined pathophysiology. Samples selected for treatment trials using clinical criteria are inevitably heterogeneous, and dependence on traditional endpoints results in early proof-of-concept trials being long and large, with very poor signal to noise. It is no wonder that pharmaceutical and biotechnology companies are looking to biomarkers as an integral part of decision-making process supported by new technologies such as genetics, genomics, proteomics, and imaging as a mean of rationalizing CNS drug development. The present review represent an effort to illustrate the integration of such technologies in drug development supporting the path of individualized medicine.

Seed quality QTL in a prominent soybean population.

Soybean [Glycine max (L.) Merr.] is a versatile crop due to its multitude of uses as a high protein meal and vegetable oil. Soybean seed traits such as seed protein and oil concentration and seed size are important quantitative traits. The objective of this study was to identify representative protein, oil, and seed size quantitative trait loci (QTL) in soybean. A recombinant inbred line (RIL) population consisting of 131 F6-derived lines was created from two prominent ancestors of North American soybeans ('Essex' and 'Williams') and the RILs were grown in six environments. One hundred simple sequence repeat (SSR) markers spaced throughout the genome were mapped in this population. There were a total of four protein, six oil, and seven seed size QTL found in this population. The QTL found in this study may assist breeders in marker-assisted selection (MAS) to retain current positive QTL in modern soybeans while simultaneously pyramiding additional QTL from new germplasm.