John Chalmers DaCosta (1863-1933): restoration of the old operating table.

John Chalmers DaCosta was an influential chairman and the first Samuel D. Gross Professor of Surgery at Jefferson Medical College in Philadelphia. He was well known throughout the field as a skilled surgeon, passionate speaker, and exceptional writer. In addition to countless accomplishments during his career, DaCosta was deeply dedicated to the preservation and commemoration of surgical history. This ideology was exemplified when he set out on a mission to recover the old wooden operating table used by many of his iconic mentors including Samuel D. Gross, Joseph Pancoast, and William W. Keen. This table was originally used for surgical demonstrations and anatomy lessons in a lecture room of the Ely Building and later in the great amphitheater of the Jefferson Sansom Street Hospital. It was found forgotten in the basement of the College Building and was promptly refurbished, donned with dedicatory plaques, and returned to its honored position in the medical college. Dr. DaCosta also contributed a detailed article recalling the history of the table and the notable leaders in surgery who taught and practiced on its surface. The old table currently stands proudly in the entranceway of the Department of Surgery where it will remain as a cherished symbol of the early beginnings of surgical practice and education

Clinical Validation of Fragile X Syndrome Screening by DNA Methylation Array

Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability. It is most frequently caused by an abnormal expansion of the CGG trinucleotide repeat (\u3e200 repeats) located in the promoter of the fragile X mental retardation gene (FMR1), resulting in promoter DNA hypermethylation and gene silencing. Current clinical tests for FXS are technically challenging and labor intensive, and may involve use of hazardous chemicals or radioisotopes. We clinically validated the Illumina Infinium HumanMethylation450 DNA methylation array for FXS screening. We assessed genome-wide and FMR1-specific DNA methylation in 32 males previously diagnosed with FXS, including nine with mosaicism, as well as five females with full mutation, and premutation carrier males (n = 11) and females (n = 11), who were compared to 300 normal control DNA samples. Our findings demonstrate 100% sensitivity and specificity for detection of FXS in male patients, as well as the ability to differentiate patients with mosaic methylation defects. Full mutation and premutation carrier females did not show FMR1 methylation changes. We have clinically validated this genome-wide DNA methylation assay as a cost- and labor-effective alternative for sensitive and specific screening for FXS, while ruling out the most common differential diagnoses of FXS, Prader-Willi syndrome, and Sotos syndrome in the same assay

Phase 1b safety study of farletuzumab, carboplatin and pegylated liposomal doxorubicin in patients with platinum-sensitive epithelial ovarian cancer

Farletuzumab is a humanized monoclonal antibody that binds to folate receptor alpha, over-expressed in epithelial ovarian cancer (EOC) but largely absent in normal tissue. Previously, carboplatin plus pegylated liposomal doxorubicin showed superior progression-free survival and an improved therapeutic index compared with carboplatin/paclitaxel in relapsed platinum-sensitive EOC. This study assessed safety of farletuzumab/carboplatin/pegylated liposomal doxorubicin in women with platinum-sensitive recurrent EOC

Influence of high pressure hydrogen environment on creep deformation of Mo-Re, Haynes 188, and NARloy-Z alloys

The present study focuses on the investigation of the influence of hydrogen on the mechanical properties of three types of alloys at elevated temperatures. The reasons for the consideration of hydrogen effects are the potential use of hydrogen as a coolant in gas-cooled reactors and fuel in advanced hypersonic vehicles. The materials used in hydrogen atmosphere must not be embrittled by hydrogen at ambient temperature and should have good strength in hydrogen atmosphere at elevated temperature. The paucity of information concerning the mechanical performance in hydrogen atmosphere at elevated temperature has been a limiting factor in the selection and design of structural components for operation in hydrogen environment

Peripheral Blood Epi-Signature of Claes-Jensen Syndrome Enables Sensitive and Specific Identification of Patients and Healthy Carriers with Pathogenic Mutations in KDM5C.

Background: Claes-Jensen syndrome is an X-linked inherited intellectual disability caused by mutations in the KDM5C gene. Kdm5c is a histone lysine demethylase involved in histone modifications and chromatin remodeling. Males with hemizygous mutations in KDM5C present with intellectual disability and facial dysmorphism, while most heterozygous female carriers are asymptomatic. We hypothesized that loss of KDM5C function may influence other components of the epigenomic machinery including DNA methylation in affected patients. Results: Genome-wide DNA methylation analysis of 7 male patients affected with Claes-Jensen syndrome and 56 age- and sex-matched controls identified a specific DNA methylation defect (epi-signature) in the peripheral blood of these patients, including 1769 individual CpGs and 9 genomic regions. Six healthy female carriers showed less pronounced but distinctive changes in the same regions enabling their differentiation from both patients and controls. Highly specific computational model using the most significant methylation changes demonstrated 100% accuracy in differentiating patients, carriers, and controls in the training cohort, which was confirmed on a separate cohort of patients and carriers. The 100% specificity of this unique epi-signature was further confirmed on additional 500 unaffected controls and 600 patients with intellectual disability and developmental delay, including other patient cohorts with previously described epi-signatures. Conclusion: Peripheral blood epi-signature in Claes-Jensen syndrome can be used for molecular diagnosis and carrier identification and assist with interpretation of genetic variants of unknown clinical significance in the KDM5Cgene

Limited educational attainment and radiographic and symptomatic knee osteoarthritis: a cross-sectional analysis using data from the Johnston County (North Carolina) Osteoarthritis Project

Abstract Introduction Applying a cross-sectional analysis to a sample of 2,627 African-American and Caucasian adults aged ≥ 45 years from the Johnston County Osteoarthritis Project, we studied the association between educational attainment and prevalence of radiographic knee osteoarthritis and symptomatic knee osteoarthritis. Methods Age- and race-adjusted associations between education and osteoarthritis outcomes were assessed by gender-stratified logistic regression models, with additional models adjusting for body mass index, knee injury, smoking, alcohol use, and occupational factors. Results In an analysis of all participants, low educational attainment (<12 years) was associated with higher prevalence of four knee osteoarthritis outcomes (unilateral and bilateral radiographic and symptomatic osteoarthritis). Women with low educational attainment had 50% higher odds of having radiographic knee osteoarthritis and 65% higher odds of symptomatic knee osteoarthritis compared with those with higher educational attainment (≥ 12 years), by using fully adjusted models. In the subset of postmenopausal women, these associations tended to be weaker but little affected by adjustment for hormone replacement therapy. Men with low educational attainment had 85% higher odds of having symptomatic knee osteoarthritis by using fully adjusted models, but the association with radiographic knee osteoarthritis was explained by age. Conclusions After adjustment for known risk factors, educational attainment, as an indicator of socioeconomic status, is associated with symptomatic knee osteoarthritis in both men and women and with radiographic knee osteoarthritis in women

Breast-Cancer-Specific Mortality in Patients Treated Based on the 21-Gene Assay: A SEER Population-Based Study

The 21-gene Recurrence Score assay is validated to predict recurrence risk and chemotherapy benefit in hormone-receptor-positive (HR+) invasive breast cancer. To determine prospective breast-cancer-specific mortality (BCSM) outcomes by baseline Recurrence Score results and clinical covariates, the National Cancer Institute collaborated with Genomic Health and 14 population-based registries in the the Surveillance, Epidemiology, and End Results (SEER) Program to electronically supplement cancer surveillance data with Recurrence Score results. The prespecified primary analysis cohort was 40–84 years of age, and had node-negative, HR+, HER2-negative, nonmetastatic disease diagnosed between January 2004 and December 2011 in the entire SEER population, and Recurrence Score results (N = 38,568). Unadjusted 5-year BCSM were 0.4% (n = 21,023; 95% confidence interval (CI), 0.3–0.6%), 1.4% (n = 14,494; 95% CI, 1.1–1.7%), and 4.4% (n = 3,051; 95% CI, 3.4–5.6%) for Recurrence Score \u3c 18, 18–30, and ≥ 31 groups, respectively (P \u3c 0.001). In multivariable analysis adjusted for age, tumor size, grade, and race, the Recurrence Score result predicted BCSM (P \u3c 0.001). Among patients with node-positive disease (micrometastases and up to three positive nodes; N = 4,691), 5-year BCSM (unadjusted) was 1.0% (n = 2,694; 95% CI, 0.5–2.0%), 2.3% (n = 1,669; 95% CI, 1.3–4.1%), and 14.3% (n = 328; 95% CI, 8.4–23.8%) for Recurrence Score \u3c 18, 18–30, ≥ 31 groups, respectively (P \u3c 0.001). Five-year BCSM by Recurrence Score group are reported for important patient subgroups, including age, race, tumor size, grade, and socioeconomic status. This SEER study represents the largest report of prospective BCSM outcomes based on Recurrence Score results for patients with HR+, HER2-negative, node-negative, or node-positive breast cancer, including subgroups often under-represented in clinical trials

Biodiversity offsets may miss opportunities to mitigate impacts on ecosystem services

© The Ecological Society of America Biodiversity offsets are most commonly used to mitigate the adverse impacts of development on biodiversity, but some offsets are now also designed to support ecosystem services (ES) goals. Here, we assemble a global database of biodiversity offsets (n = 70) to show that 41% already take ES into consideration, with the objective of enhancing cultural, regulating, and provisioning services. We found that biodiversity offsets were more likely to consider ES when (1) development projects reported impacts on services, (2) offsets had voluntary biodiversity goals, and (3) conservation organizations were involved. However, offsets that considered ES were similar in design (eg offsetting approach, extent, and location) to offsets focused solely on biodiversity, suggesting that including ES goals may represent an attempt to strengthen community support for development projects, rather than to offset known ES impacts. We also found that 34% of all offsets displaced people and negatively affected livelihoods. Therefore, when biodiversity and ES are linked, current practices may not actually improve outcomes, instead incurring additional costs to communities and companies

Symptoms of depression and cardiovascular reactions to acute psychological stress: Evidence from a population study

Depression and exaggerated cardiovascular reactivity are considered risk factors for cardiovascular disease, possibly as a result of common antecedents, such as altered autonomic nervous system function. We examined the association between depressive symptomatology and cardiovascular reactions to psychological stress in 1608 adults (875 women) comprising three distinct age cohorts: 24-, 44-, and 63-year olds. Depression was assessed using the Hospital Anxiety and Depression Scale. Blood pressure and heart rate were measured at baseline and during the paced auditory serial arithmetic test. Depression scores were negatively associated with systolic blood pressure and heart rate reactions, after adjustment for likely confounders such as sex, cohort, occupational status, body mass index, stress task performance score, baseline cardiovascular activity, antidepressant and antihypertensive medication. The direction of association was opposite to that which would be expected if excessive reactivity were to mediate the association between depression and cardiovascular disease outcomes or if they shared common antecedents

Boojums and the Shapes of Domains in Monolayer Films

Domains in Langmuir monolayers support a texture that is the two-dimensional version of the feature known as a boojum. Such a texture has a quantifiable effect on the shape of the domain with which it is associated. The most noticeable consequence is a cusp-like feature on the domain boundary. We report the results of an experimental and theoretical investigation of the shape of a domain in a Langmuir monolayer. A further aspect of the investigation is the study of the shape of a ``bubble'' of gas-like phase in such a monolayer. This structure supports a texture having the form of an inverse boojum. The distortion of a bubble resulting from this texture is also studied. The correspondence between theory and experiment, while not perfect, indicates that a qualitative understanding of the relationship between textures and domain shapes has been achieved.Comment: replaced with published version, 10 pages, 13 figures include