Phase comparison and equation of state for Ta2O5.

Tantalum pentoxide (Ta2O5) is among the most technologically useful heavy transition metal oxides. Unfortunately, its crystal structure is the subject of long-standing and unresolved disagreement. Among other consequences, this uncertainty has made it impossible to formulate a robust high pressure equation of state for Ta2O5. Here, we report the results of high pressure x-ray diffraction experiments indexed against a comprehensive list of proposed Ta2O5phases. Five of the proposed phases produce good matches to experimental observations, and the compressibility parameters for these phases are all consistent within uncertainty. This means that regardless of the particular phase chosen, the Ta2O5equation of state can be described with bulk modulusK0=138±3.68 GPa and pressure derivativeK0'=1.82±0.45. Combining these experimental results with new density-functional theory calculations allows us to identify theλphase as the best structural model of Ta2O5at ambient conditions.

Timing of Martian Core Formation from Models of Hf-W Evolution Coupled with N-body Simulations.

Determining how and when Mars formed has been a long-standing challenge for planetary scientists. The size and orbit of Mars are difficult to reproduce in classical simulations of planetary accretion, and this has inspired models of inner solar system evolution that are tuned to produce Mars-like planets. However, such models are not always coupled to geochemical constraints. Analyses of Martian meteorites using the extinct hafnium-tungsten (Hf-W) radioisotopic system, which is sensitive to the timing of core formation, have indicated that the Martian core formed within a few million years of the start of the solar system itself. This has been interpreted to suggest that, unlike Earth's protracted accretion, Mars grew to its modern size very rapidly. These arguments, however, generally rely on simplified growth histories for Mars. Here, we combine likely accretionary histories from a large number of N-body simulations with calculations of metal-silicate partitioning and Hf-W isotopic evolution during core formation to constrain the range of conditions that could have produced Mars. We find that there is no strong correlation between the final masses or orbits of simulated Martian analogs and their 182W anomalies, and that it is readily possible to produce Mars-like Hf-W isotopic compositions for a variety of accretionary conditions. The Hf-W signature of Mars is very sensitive to the oxygen fugacity (fO2) of accreted material because the metal-silicate partitioning behavior of W is strongly dependent on redox conditions. The average fO2 of Martian building blocks must fall in the range of 1.3-1.6 log units below the iron-wüstite buffer to produce a Martian mantle with the observed Hf/W ratio. Other geochemical properties (such as sulfur content) also influence Martian 182W signatures, but the timing of accretion is a more important control. We find that while Mars must have accreted most of its mass within ~5 million years of solar system formation to reproduce the Hf-W isotopic constraints, it may have continued growing afterwards for over 50 million years. There is a high probability of simultaneously matching the orbit, mass, and Hf-W signature of Mars even in cases of prolonged accretion if giant impactor cores were poorly equilibrated and merged directly with the proto-Martian core.

Core Formation and Geophysical Properties of Mars.

The chemical and physical properties of the interiors of terrestrial planets are largely determined during their formation and differentiation. Modeling a planet's formation provides important insights into the properties of its core and mantle, and conversely, knowledge of those properties may constrain formational narratives. Here, we present a multi-stage model of Martian core formation in which we calculate core-mantle equilibration using parameterizations from high pressure-temperature metal-silicate partitioning experiments. We account for changing core-mantle boundary (CMB) conditions, composition-dependent partitioning, and partial equilibration of metal and silicate, and we evolve oxygen fugacity (fO2) self-consistently. The model successfully reproduces published meteorite-based estimates of most elemental abundances in the bulk silicate Mars, which can be used to estimate core formation conditions and core composition. This composition implies that the primordial material that formed Mars was significantly more oxidized (0.9-1.4 log units below the iron-wüstite buffer) than that of the Earth, and that core-mantle equilibration in Mars occurred at 42-60% of the evolving CMB pressure. On average, at least 84% of accreted metal and at least 40% of the mantle were equilibrated in each impact, a significantly higher degree of metal equilibration than previously reported for the Earth. In agreement with previous studies, the modeled Martian core is rich in sulfur (18-19 wt%), with less than one weight percent O and negligible Si. We have used these core and mantle compositions to produce physical models of the present-day Martian interior and evaluate the sensitivity of core radius to crustal thickness, mantle temperature, core composition, core temperature, and density of the core alloy. Trade-offs in how these properties affect observable physical parameters like planetary mass, radius, moment of inertia, and tidal Love number k2 define a range of likely core radii: 1620-1870 km. Seismic velocity profiles for several combinations of model parameters have been used to predict seismic body-wave travel times and planetary normal mode frequencies. These results may be compared to forthcoming Martian seismic data to further constrain core formation conditions and geophysical properties.

Association of the Extent of Resection With Survival in Glioblastoma: A Systematic Review and Meta-analysis.

IMPORTANCE: Glioblastoma multiforme (GBM) remains almost invariably fatal despite optimal surgical and medical therapy. The association between the extent of tumor resection (EOR) and outcome remains undefined, notwithstanding many relevant studies. OBJECTIVE: To determine whether greater EOR is associated with improved 1- and 2-year overall survival and 6-month and 1-year progression-free survival in patients with GBM. DATA SOURCES: Pubmed, CINAHL, and Web of Science (January 1, 1966, to December 1, 2015) were systematically reviewed with librarian guidance. Additional articles were included after consultation with experts and evaluation of bibliographies. Articles were collected from January 15 to December 1, 2015. STUDY SELECTION: Studies of adult patients with newly diagnosed supratentorial GBM comparing various EOR and presenting objective overall or progression-free survival data were included. Pediatric studies were excluded. DATA EXTRACTION AND SYNTHESIS: Data were extracted from the text of articles or the Kaplan-Meier curves independently by investigators who were blinded to each other's results. Data were analyzed to assess mortality after gross total resection (GTR), subtotal resection (STR), and biopsy. The body of evidence was evaluated according to Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria and PRISMA guidelines. MAIN OUTCOME AND MEASURES: Relative risk (RR) for mortality at 1 and 2 years and progression at 6 months and 1 year. RESULTS: The search produced 37 studies suitable for inclusion (41 117 unique patients). The meta-analysis revealed decreased mortality for GTR compared with STR at 1 year (RR, 0.62; 95% CI, 0.56-0.69; P < .001; number needed to treat [NNT], 9) and 2 years (RR, 0.84; 95% CI, 0.79-0.89; P < .001; NNT, 17). The 1-year risk for mortality for STR compared with biopsy was reduced significantly (RR, 0.85; 95% CI, 0.80-0.91; P < .001). The risk for mortality was similarly decreased for any resection compared with biopsy at 1 year (RR, 0.77; 95% CI, 0.71-0.84; P < .001; NNT, 21) and 2 years (RR, 0.94; 95% CI, 0.89-1.00; P = .04; NNT, 593). The likelihood of disease progression was decreased with GTR compared with STR at 6 months (RR, 0.72; 95% CI, 0.48-1.09; P = .12; NNT, 14) and 1 year (RR, 0.66; 95% CI, 0.43-0.99; P < .001; NNT, 26). The quality of the body of evidence by the GRADE criteria was moderate to low. CONCLUSION AND RELEVANCE: This analysis represents the largest systematic review and only quantitative systematic review to date performed on this subject. Compared with STR, GTR substantially improves overall and progression-free survival, but the quality of the supporting evidence is moderate to low.

Differential Association of Niemann-Pick C1 Gene Polymorphisms with Maternal Prepregnancy Overweight and Gestational Diabetes.

A genome-wide association study (GWAS) and subsequent replication studies in diverse ethnic groups indicate that common Niemann-Pick C1 gene (NPC1) polymorphisms are associated with morbid-adult obesity or diabetes independent of body weight. The objectives for this prospective cross-sectional study were to determine allele frequencies for NPC1 polymorphisms (644A>G, 1926C>G, 2572A>G, and 3797G>A) and association with metabolic disease phenotypes in an ethnically diverse New Mexican obstetric population. Allele frequencies for 1926C>G, 2572A>G, and 3797G>A were significantly different between race/ethnic groups (non-Hispanic white, Hispanic, and Native American). The results also indicated a significant pairwise linkage-disequilibrium between each of the four NPC1 polymorphisms in race/ethnic groups. Moreover, the derived and major allele for 1926C>G was associated (OR 2.11, 95% CI 1.10-3.96, P = 0.022) with increased risk for maternal prepregnancy overweight (BMI 25.0-29.9kg/m2) while the ancestral and major allele for 2572A>G was associated (OR 4.68, 95% CI 1.23-17.8, P = 0.024) with increased risk for gestational diabetes in non-Hispanic whites, but not Hispanics or Native Americans. In summary, this is the first transferability study to investigate common NPC1 polymorphisms in a multiethnic population and demonstrate a differential association with increased risk for maternal prepregnancy overweight and gestational diabetes.

Off-label use of cetuximab plus sorafenib and panitumumab plus regorafenib to personalize therapy for a patient with V600E BRAF-mutant metastatic colon cancer.

Sorafenib, the first agent developed to target BRAF mutant melanoma, is a multi-kinase inhibitor that was approved by the FDA for therapy of kidney and subsequently liver cancer, and is currently in clinical trials for thyroid, lung and brain cancer. Colorectal cancer with V600E BRAF mutation has shown relative resistance to standard chemotherapy regimens, as well as lack of efficacy to vemurafenib in clinical trials. New treatments are needed for BRAF-mutant colorectal cancer. We report a case of a patient with BRAF-mutant metastatic colon cancer whose disease had progressed on FOLFOX plus bevacizumab and subsequent FOLFIRI plus cetuximab. Based on preclinical data published in Nature in 2012 suggesting that successful therapeutic targeting of BRAF in colorectal cancer may require concomitant targeting of the EGFR, we offered this patient without other attractive options the combination of sorafenib plus cetuximab, in off-label use with informed consent. Sorafenib and cetuximab therapy led to a mixed radiographic response with some areas showing dramatic improvement and other areas showing stable disease over a 7-month period which is a notably long period of progression-free survival for V600E BRAF mutated colon cancer. The cetuximab plus sorafenib therapy was very well-tolerated by the patient who remained on it long enough until another therapy option, regorafenib, was approved in September 2012. The patient was offered single agent regorafenib at the time of progression. At the time of progression on single agent regorafenib, panitumumab was combined with regorafenib and this was also well-tolerated and appeared to slow disease progression. Further study of these approaches in the clinic as personalized treatment of BRAF-mutant advanced colorectal cancer is warranted.

Pulmonary embolism and amniotic fluid embolism in pregnancy.

Amniotic fluid embolism and pulmonary embolism are 2 of the most common causes of maternal mortality in the developed world. Symptoms of pulmonary embolism include tachycardia, tachypnea, and shortness of breath, all of which are common complaints in pregnancy. Heightened awareness leads to rapid diagnosis and institution of therapy. Amniotic fluid embolism is associated with maternal collapse. There are currently no proven therapies, although rapid initiation of supportive care may decrease the risk of mortality.

Attrition rates between residents in obstetrics and gynecology and other clinical specialties, 2000-2009.

BACKGROUND: As resident attrition disrupts educational and workload balance and reduces the number of graduating physicians to care for patients, an ongoing goal of graduate medical education programs is to retain residents. OBJECTIVE: We compared annual rates of resident attrition in obstetrics and gynecology (Ob-Gyn) with other clinical specialties of similar or larger size during a recent 10-year period, and explored the reasons for resident attrition. METHODS: In this observational study, we analyzed annual data from the American Medical Association Graduate Medical Education Census between academic years 2000 and 2009 for residents who entered Ob-Gyn and other core clinical specialties. Our primary outcome was the trend in averaged annual attrition rates. RESULTS: The average annual attrition was 196 ± 12 (SD) residents, representing 4.2% ± 0.5% of all Ob-Gyn residents. Rates of attrition were consistently higher among men (5.3%) and international medical school graduates (7.6%). The annual rate of attrition was similar to that for other clinical specialties (mean: 4.0%; range: from 1.5% in emergency medicine to 7.9% in psychiatry). The attrition rates for Ob-Gyn residents were relatively stable for the 10-year period (range: 3.6% in 2008 to 5.1% in 2006). Common reasons for attrition were transition to another specialty (30.0%), withdrawal/dismissal (28.2%), transfer to another Ob-Gyn program (25.4%), and leave of absence (2.2%). These proportions remained fairly constant during this 10-year period. CONCLUSIONS: The average annual attrition rate of residents in Ob-Gyn was 4.2%, comparable to most other core clinical specialties.

Counseling about risks of congenital anomalies from prescription opioids.

The use of prescription opioids is becoming an increasing problem among women of reproductive age. More than half of pregnancies are unintended; therefore, many first-trimester exposures to opioids occur before pregnancy confirmation. Studies are limited about the fetal risks to opioid exposure in early pregnancy. One large study demonstrated an increased risk of certain heart defects and spina bifida with first-trimester exposure to opioids. It is important to counsel women whose fetuses were exposed to opioids in early pregnancy about the potential risks, encourage them to cease using opioids or seek alternative treatments when appropriate, and use the lowest effective dose when opioid treatment is to be continued. It is also valuable to screen for anatomic abnormalities such as neural tube and cardiac defects with available maternal serum testing and ultrasound imaging in the early second trimester. Birth Defects Research (Part A) 94:620-625, 2012. © 2012 Wiley Periodicals, Inc.