Abstract Objective In the province of Ontario, all women diagnosed with invasive serous ovarian cancer are eligible for genetic testing for mutations in the BRCA1 and BRCA2 genes. This study aimed to ...determine the proportion of these women who are seen for genetic counseling and to identify potential predictors and barriers to having genetic counseling. Methods All women who were diagnosed with invasive serous ovarian cancer and had genetic counseling at Princess Margaret Hospital (PMH) between 2002 and 2009 were identified. Logistic regressions and trend analyses explored age at diagnosis, year at diagnosis, and the time between diagnosis and genetic counseling. Genetic counseling outcomes were also examined. Results Of 623 women diagnosed with invasive serous ovarian cancer, 144 (23%) were seen for genetic counseling. As age at diagnosis increased, the likelihood of genetic counseling decreased (p = 0.005). With a more recent date of diagnosis, the probability of having genetic counseling increased (p = 0.032) while the time to genetic counseling decreased (p = 0.001). Of women who pursued genetic testing, 31% were found to have a BRCA1 or BRCA2 mutation, 16% of whom had no family history of breast or ovarian cancer. Conclusions Despite the availability of genetic testing, only a small proportion of women with invasive serous ovarian cancer were seen for genetic counseling. Over time, an improvement in the proportion of women being seen for genetic counseling was noted; however barriers to seeing women with a later age at diagnosis or those with no family history of breast or ovarian cancer clearly exist.
Treatment of osteoporosis with PTH causes a marked increase in vertebral bone mineral density (BMD). However, this effect is rapidly reversed when the treatment is stopped. The purpose of the present ...study was to determine whether the bisphosphonate alendronate could preserve or enhance bone density in patients previously treated with PTH. Sixty-six postmenopausal osteoporotic women were treated for 1 yr with 50, 75, or 100 microg recombinant human PTH-(1-84) or placebo, and then were given 10 mg alendronate daily for an additional year. BMD was measured in the femoral neck, lumbar spine, and whole body. Markers of bone turnover included skeletal alkaline phosphatase, osteocalcin, and N-telopeptide. During the first year, changes in BMD (mean +/- SD) in women receiving PTH (all doses combined) were 7.1 +/- 5.6% (spine), 0.3 +/- 6.2% (femoral neck), and -2.3 +/- 3.3% (total body). After switching to alendronate for 1 yr in women who previously had received PTH, mean changes in BMD were 13.4 +/- 6.4% (spine), 4.4 +/- 7.2% (femoral neck), and 2.6 +/- 3.1% (whole body). In the subgroup of patients who had received the highest dose of PTH, the mean increase in vertebral BMD was 14.6 +/- 7.9%. All markers of bone turnover increased during treatment with PTH and decreased to below baseline after 1 yr of alendronate. In conclusion, sequential treatment of osteoporosis with PTH and alendronate results in an increase in vertebral bone density that is considerably more than has been reported with alendronate or estrogens alone. This combination of drugs may be a useful approach to maximizing bone density in women with vertebral osteoporosis.
The XMM-Newton spectral-fit database (XMMFITCAT) is a catalogue of spectral fitting results for the source detections within the XMM-Newton serendipitous source catalogue with more than 50 net ...(background-subtracted) counts per detector in the 0.5–10 keV energy band. Its most recent version, constructed from the latest version of the XMM-Newton catalogue, the 3XMM Data Release 4 (3XMM-DR4), contains spectral-fitting results for ≳114 000 detections, corresponding to ≃78 000 unique sources. Three energy bands are defined and used in the construction of XMMFITCAT: Soft (0.5–2 keV), Hard (2–10 keV), and Full (0.5–10 keV) bands. Six spectral models, three simple and three more complex models, were implemented and applied to the spectral data. Simple models are applied to all sources, whereas complex models are applied to observations with more than 500 counts (30%). XMMFITCAT includes best-fit parameters and errors, fluxes, and goodness of fit estimates for all fitted models. XMMFITCAT has been conceived to provide the astronomical community with a tool to construct large and representative samples of X-ray sources by allowing source selection according to spectral properties, as well as characterise the X-ray properties of samples selected in different wavelengths. We present in this paper the main details of the construction of this database, and summarise its main characteristics.
The strength of shock-loaded single crystal tantalum 100 has been experimentally determined using in situ broadband x-ray Laue diffraction to measure the strain state of the compressed crystal, and ...elastic constants calculated from first principles. The inferred strength reaches 35 GPa at a shock pressure of 181 GPa and is in excellent agreement with a multiscale strength model N. R. Barton et al., J. Appl. Phys. 109, 073501 (2011), which employs a hierarchy of simulation methods over a range of length scales to calculate strength from first principles.
Vocal production learning ("vocal learning") is a convergently evolved trait in vertebrates. To identify brain genomic elements associated with mammalian vocal learning, we integrated genomic, ...anatomical, and neurophysiological data from the Egyptian fruit bat (
) with analyses of the genomes of 215 placental mammals. First, we identified a set of proteins evolving more slowly in vocal learners. Then, we discovered a vocal motor cortical region in the Egyptian fruit bat, an emergent vocal learner, and leveraged that knowledge to identify active cis-regulatory elements in the motor cortex of vocal learners. Machine learning methods applied to motor cortex open chromatin revealed 50 enhancers robustly associated with vocal learning whose activity tended to be lower in vocal learners. Our research implicates convergent losses of motor cortex regulatory elements in mammalian vocal learning evolution.
Methyl triclosan and four halogenated analogues have been identified in extracts of individual whole-body male carp (
Cyprinus carpio) tissue that were collected from Las Vegas Bay, Nevada, and ...Semipermeable Membrane Devices (SPMD) that were deployed in Las Vegas Wash, Nevada. Methyl triclosan is believed to be the microbially methylated product of the antibacterial agent triclosan (2, 4, 4'-trichloro-4-hydroxydiphenyl ether, Chemical Abstract Service Registry Number 3380-34-5, Irgasan DP300). The presence of methyl triclosan and four halogenated analogues was confirmed in SPMD extracts by comparing low- and high-resolution mass spectral data and Kovats retention indices of methyl triclosan with commercially obtained triclosan that was derivatized to the methyl ether with ethereal diazomethane. The four halogenated analogues of methyl triclosan detected in both whole-body tissue and SPMD extracts were tentatively identified by high resolution mass spectrometry. Methyl triclosan was detected in all 29 male common carp from Las Vegas Bay with a mean concentration of 596 μg kg
−
1
wet weight (ww) which is more than an order of magnitude higher than previously reported concentrations in the literature. The halogenated analogs were detected less frequently (21%–76%) and at much lower concentrations (<
51 μg kg
−
1
ww). None of these compounds were detected in common carp from a Lake Mead reference site in Overton Arm, Nevada.
Background
The occurrence of postoperative complications and anastomotic leakage are major drivers of mortality in the immediate phase after colorectal cancer surgery. We trained prediction models ...for calculating patients’ individual risk of complications based only on preoperatively available data in a multidisciplinary team setting. Knowing prior to surgery the probability of developing a complication could aid in improving informed decision-making by surgeon and patient and individualize surgical treatment trajectories.
Methods
All patients over 18 years of age undergoing any resection for colorectal cancer between January 1, 2014 and December 31, 2019 from the nationwide Danish Colorectal Cancer Group database were included. Data from the database were converted into Observational Medical Outcomes Partnership Common Data Model maintained by the Observation Health Data Science and Informatics initiative. Multiple machine learning models were trained to predict postoperative complications of Clavien–Dindo grade ≥ 3B and anastomotic leakage within 30 days after surgery.
Results
Between 2014 and 2019, 23,907 patients underwent resection for colorectal cancer in Denmark. A Clavien–Dindo complication grade ≥ 3B occurred in 2,958 patients (12.4%). Of 17,190 patients that received an anastomosis, 929 experienced anastomotic leakage (5.4%). Among the compared machine learning models, Lasso Logistic Regression performed best. The predictive model for complications had an area under the receiver operating characteristic curve (AUROC) of 0.704 (95%CI 0.683–0.724) and an AUROC of 0.690 (95%CI 0.655–0.724) for anastomotic leakage.
Conclusions
The prediction of postoperative complications based only on preoperative variables using a national quality assurance colorectal cancer database shows promise for calculating patient’s individual risk. Future work will focus on assessing the value of adding laboratory parameters and drug exposure as candidate predictors. Furthermore, we plan to assess the external validity of our proposed model.
The Wiskott-Aldrich syndrome (WAS) is a primary immunodeficiency disorder caused by a mutation in WAS protein (WASp) that results in defective actin polymerization. Although the function of many ...hematopoietic cells requires WASp, the specific expression and function of this molecule in natural killer (NK) cells is unknown. Here, we report that WAS patients have increased percentages of peripheral blood NK cells and that fresh enriched NK cells from two patients with a WASp mutation have defective cytolytic function. In normal NK cells, WASp was expressed and localized to the activating immunologic synapse (IS) with filamentous actin (F-actin). Perforin also localized to the NK cell-activating IS but at a lesser frequency than F-actin and WASp. The accumulation of F-actin and WASp at the activating IS was decreased significantly in NK cells that had been treated with the inhibitor of actin polymerization, cytochalasin D. NK cells from WAS patients lacked expression of WASp and accumulated F-actin at the activating IS infrequently. Thus, WASp has an important function in NK cells. In patients with WASp mutations, the resulting NK cell defects are likely to contribute to their disease.
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