Low-Grade Appendiceal Mucinous Neoplasm Involving the Endometrium and Presenting with Mucinous Vaginal Discharge.

Primary appendiceal mucinous lesions are uncommon and represent a spectrum from nonneoplastic mucous retention cysts to invasive adenocarcinoma. Low-grade appendiceal mucinous neoplasms (LAMNs) represent an intermediate category on this spectrum and can be classified according to whether or not they are confined to the appendix. Although LAMNs are frequently confined to the appendix, they can also spread to the peritoneum and clinically progress as pseudomyxoma peritonei (i.e., mucinous ascites). Thus, the appropriate classification of appendiceal primary neoplasia is essential for prognosis and influences clinical management. In addition, the precise classification, management, and clinical outcome of patients with disseminated peritoneal disease remain controversial. Here, we report an unusual case of LAMN with pseudomyxoma peritonei that initially presented with mucinous and bloody vaginal discharge. Pathological evaluation revealed low-grade appendiceal mucinous neoplasm with secondary involvement of the peritoneum, ovaries, and endometrial surface. Therefore, LAMN should be considered in the differential diagnosis of mucinous vaginal discharge

Are self-identified "disadvantaged" students less likely to enter surgical residencies? A single-institution study.

BackgroundGiven more emphasis on training primary care physicians for underserved areas, we hypothesized that students self-identifying as "disadvantaged" would be less likely to pursue surgical training.MethodsWe retrospectively reviewed medical school data on students graduating 2005-2014. Students were stratified into "disadvantaged" and "nondisadvantaged". Data were recorded on age, grade point average, Medical College Admission Test (MCAT), gender, surgery grade, United States Medical Licensing Examination step 1 score, and residency match into a surgical field. A comparison of the proportion of students matching into a surgical field was assessed with chi-square test. Multivariate logistic regression was performed to assess the factors that predict the choice of general surgery versus another surgical field.ResultsOf the 1140 students who graduated during the study period, 219 (19.2%) students self-identified as "disadvantaged". Of all students, 158 (13.9%) chose a surgical field. The disadvantaged group was older at entry and had lower grade point average and total MCAT scores. Twenty-seven (12.3%) disadvantaged students chose a surgical residency versus 130 (14.1%) nondisadvantaged students (P = 0.56). On multivariate logistic regression, female gender (odds ratio [OR] = 3.9; 95% confidence interval = [1.9-8.3], P < 0.01), disadvantaged status (OR = 2.8 [1.1-7.1], P = 0.03), and United States Medical Licensing Examination step 1 score ≥ 227 (OR = 0.43 [0.21-0.88], P = 0.02) were significantly associated with matching into general surgery versus another surgical specialty.DiscussionAlthough the disadvantaged cohort was older and had lower undergraduate GPAs and MCAT scores, the proportion of disadvantaged students matching into a surgical residency was not statistically different. To address the future shortage of general surgeons in underserved areas, increasing enrollment of "disadvantaged" students may alleviate the "surgical desert"

A Novel Tool for Predicting Major Complications After Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy

ABSTRACT Background. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) has an emerging role in the treatment of peritoneal malignancies. The CRS-HIPEC approach has known treatment-related toxicities. This study sought to determine the predictors of major postoperative complications after CRS-HIPEC in a high-volume center. Methods. From a single-institution database, this study investigated complications experienced by patients undergoing CRS-HIPEC. Multiple preoperative and operative factors were analyzed for their ability to predict 60-day Clavien grade 3 and greater (major) complications by logistic regression. A predictive model was created from preoperative factors using multivariate logistic regression. The model was tested by Akaike's information criterion, the Hosmer and Lemeshow Goodness-of-Fit Test, the receiver operating characteristic, and the Youden Index. Results. The study evaluated 247 patients undergoing CRS-HIPEC. The primary tumor site was the appendix in 166 cases (67.2 %), the colorectal area in 51 cases (20.6 %), the peritoneum (mesothelioma) in 22 cases (8.9 %), the ovary in 5 cases (2 %), and the small bowel in 3 cases Patients with peritoneal metastases have historically been considered as having incurable disease. In select patients, the peritoneum may represent the sole site of metastatic disease, prompting the use of cytoreductive surgery (CRS) and regional chemotherapy in the form of hyperthermic intraperitoneal chemotherapy (HIPEC). Mounting evidence points to the efficacy of CRS-HIPEC in the treatment of select patients with peritoneal metastases from cancers of the appendix, 1-3 colon and rectum, 4-6 small bowel, 7,8 ovary, 9 and peritoneum (mesothelioma). 10,11 Whereas the magnitude of the benefit from CRS-HIPEC for peritoneal metastases is being better defined, treatmentrelated toxicities are well-known. Large series in the modern era have found a major morbidity rate of 24-34 % and a mortality rate of 2-4 % after CRS-HIPEC

A Common Ca2+-Driven Interdomain Module Governs Eukaryotic NCX Regulation

Na+/Ca2+ exchanger (NCX) proteins mediate Ca2+-fluxes across the cell membrane to maintain Ca2+ homeostasis in many cell types. Eukaryotic NCX contains Ca2+-binding regulatory domains, CBD1 and CBD2. Ca2+ binding to a primary sensor (Ca3-Ca4 sites) on CBD1 activates mammalian NCXs, whereas CALX, a Drosophila NCX ortholog, displays an inhibitory response to regulatory Ca2+. To further elucidate the underlying regulatory mechanisms, we determined the 2.7 Å crystal structure of mammalian CBD12-E454K, a two-domain construct that retains wild-type properties. In conjunction with stopped-flow kinetics and SAXS (small-angle X-ray scattering) analyses of CBD12 mutants, we show that Ca2+ binding to Ca3-Ca4 sites tethers the domains via a network of interdomain salt-bridges. This Ca2+-driven interdomain switch controls slow dissociation of “occluded” Ca2+ from the primary sensor and thus dictates Ca2+ sensing dynamics. In the Ca2+-bound conformation, the interdomain angle of CBD12 is very similar in NCX and CALX, meaning that the interdomain distances cannot account for regulatory diversity in NCX and CALX. Since the two-domain interface is nearly identical among eukaryotic NCXs, including CALX, we suggest that the Ca2+-driven interdomain switch described here represents a general mechanism for initial conduction of regulatory signals in NCX variants

Exploring movement patterns and changing distributions of baleen whales in the western North Atlantic using a decade of passive acoustic data

© The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Davis, G. E., Baumgartner, M. F., Corkeron, P. J., Bell, J., Berchok, C., Bonnell, J. M., Thornton, J. B., Brault, S., Buchanan, G. A., Cholewiak, D. M., Clark, C. W., Delarue, J., Hatch, L. T., Klinck, H., Kraus, S. D., Martin, B., Mellinger, D. K., Moors-Murphy, H., Nieukirk, S., Nowacek, D. P., Parks, S. E., Parry, D., Pegg, N., Read, A. J., Rice, A. N., Risch, D., Scott, A., Soldevilla, M. S., Stafford, K. M., Stanistreet, J. E., Summers, E., Todd, S., & Van Parijs, S. M. Exploring movement patterns and changing distributions of baleen whales in the western North Atlantic using a decade of passive acoustic data. Global Change Biology, (2020): 1-30, doi:10.1111/gcb.15191.Six baleen whale species are found in the temperate western North Atlantic Ocean, with limited information existing on the distribution and movement patterns for most. There is mounting evidence of distributional shifts in many species, including marine mammals, likely because of climate‐driven changes in ocean temperature and circulation. Previous acoustic studies examined the occurrence of minke (Balaenoptera acutorostrata ) and North Atlantic right whales (NARW; Eubalaena glacialis ). This study assesses the acoustic presence of humpback (Megaptera novaeangliae ), sei (B. borealis ), fin (B. physalus ), and blue whales (B. musculus ) over a decade, based on daily detections of their vocalizations. Data collected from 2004 to 2014 on 281 bottom‐mounted recorders, totaling 35,033 days, were processed using automated detection software and screened for each species' presence. A published study on NARW acoustics revealed significant changes in occurrence patterns between the periods of 2004–2010 and 2011–2014; therefore, these same time periods were examined here. All four species were present from the Southeast United States to Greenland; humpback whales were also present in the Caribbean. All species occurred throughout all regions in the winter, suggesting that baleen whales are widely distributed during these months. Each of the species showed significant changes in acoustic occurrence after 2010. Similar to NARWs, sei whales had higher acoustic occurrence in mid‐Atlantic regions after 2010. Fin, blue, and sei whales were more frequently detected in the northern latitudes of the study area after 2010. Despite this general northward shift, all four species were detected less on the Scotian Shelf area after 2010, matching documented shifts in prey availability in this region. A decade of acoustic observations have shown important distributional changes over the range of baleen whales, mirroring known climatic shifts and identifying new habitats that will require further protection from anthropogenic threats like fixed fishing gear, shipping, and noise pollution.We thank Chris Pelkie, David Wiley, Michael Thompson, Chris Tessaglia‐Hymes, Eric Matzen, Chris Tremblay, Lance Garrison, Anurag Kumar, John Hildebrand, Lynne Hodge, Russell Charif, Kathleen Dudzinski, and Ann Warde for help with project planning, field work support, and data management. For all the support and advice, thanks to the NEFSC Protected Species Branch, especially the passive acoustics group, Josh Hatch, and Leah Crowe. We thank the field and crew teams on all the ships that helped in the numerous deployments and recoveries. This research was funded and supported by many organizations, specified by projects as follows: data recordings from region 1 were provided by K. Stafford (funding: National Science Foundation #NSF‐ARC 0532611). Region 2 data: D. K. Mellinger and S. Nieukirk, National Oceanic and Atmospheric Administration (NOAA) PMEL contribution #5055 (funding: NOAA and the Office of Naval Research #N00014–03–1–0099, NOAA #NA06OAR4600100, US Navy #N00244‐08‐1‐0029, N00244‐09‐1‐0079, and N00244‐10‐1‐0047). Region 3A data: D. Risch (funding: NOAA and Navy N45 programs). Region 3 data: H. Moors‐Murphy and Fisheries and Oceans Canada (2005–2014 data), and the Whitehead Lab of Dalhousie University (eastern Scotian Shelf data; logistical support by A. Cogswell, J. Bartholette, A. Hartling, and vessel CCGS Hudson crew). Emerald Basin and Roseway Basin Guardbuoy data, deployment, and funding: Akoostix Inc. Region 3 Emerald Bank and Roseway Basin 2004 data: D. K. Mellinger and S. Nieukirk, NOAA PMEL contribution #5055 (funding: NOAA). Region 4 data: S. Parks (funding: NOAA and Cornell University) and E. Summers, S. Todd, J. Bort Thornton, A. N. Rice, and C. W. Clark (funding: Maine Department of Marine Resources, NOAA #NA09NMF4520418, and #NA10NMF4520291). Region 5 data: S. M. Van Parijs, D. Cholewiak, L. Hatch, C. W. Clark, D. Risch, and D. Wiley (funding: National Oceanic Partnership Program (NOPP), NOAA, and Navy N45). Region 6 data: S. M. Van Parijs and D. Cholewiak (funding: Navy N45 and Bureau of Ocean and Energy Management (BOEM) Atlantic Marine Assessment Program for Protected Species [AMAPPS] program). Region 7 data: A. N. Rice, H. Klinck, A. Warde, B. Martin, J. Delarue, and S. Kraus (funding: New York State Department of Environmental Conservation, Massachusetts Clean Energy Center, and BOEM). Region 8 data: G. Buchanan, and K. Dudzinski (funding: New Jersey Department of Environmental Protection and the New Jersey Clean Energy Fund) and A. N. Rice, C. W. Clark, and H. Klinck (funding: Center for Conservation Bioacoustics at Cornell University and BOEM). Region 9 data: J. E. Stanistreet, J. Bell, D. P. Nowacek, A. J. Read, and S. M. Van Parijs (funding: NOAA and US Fleet Forces Command). Region 10 data: L. Garrison, M. Soldevilla, C. W. Clark, R. A. Chariff, A. N. Rice, H. Klinck, J. Bell, D. P. Nowacek, A. J. Read, J. Hildebrand, A. Kumar, L. Hodge, and J. E. Stanistreet (funding: US Fleet Forces Command, BOEM, NOAA, and NOPP). Region 11 data: C. Berchok as part of a collaborative project led by the Fundacion Dominicana de Estudios Marinos, Inc. (Dr. Idelisa Bonnelly de Calventi; funding: The Nature Conservancy [Elianny Dominguez]) and D. Risch (funding: World Wildlife Fund, NOAA, and Dutch Ministry of Economic Affairs)

Abrupt Ice Age Shifts in Southern Westerlies and Antarctic Climate Forced from the North

The Southern Hemisphere (SH) mid-latitude westerly winds play a central role in the global climate system via Southern Ocean upwelling, carbon exchange with the deep ocean, Agulhas Leakage, and Antarctic ice sheet stability. Meridional shifts in the SH westerlies have been hypothesized in response to abrupt North Atlantic Dansgaard-Oeschger (DO) climatic events of the last ice age, in parallel with the well-documented shifts of the intertropical convergence zone. Shifting moisture pathways to West Antarctica are consistent with this view, but may represent a Pacific teleconnection pattern. The full SH atmospheric-circulation response to the DO cycle, as well as its impact on Antarctic temperature, have so far remained unclear. Here we use five volcanically-synchronized ice cores to show that the Antarctic temperature response to the DO cycle can be understood as the superposition of two modes: a spatially homogeneous oceanic “bipolar seesaw” mode that lags Northern Hemisphere (NH) climate by about 200 years, and a spatially heterogeneous atmospheric mode that is synchronous with NH abrupt events. Temperature anomalies of the atmospheric mode are similar to those associated with present-day Southern Annular Mode (SAM) variability, rather than the Pacific South America (PSA) pattern. Moreover, deuterium excess records suggest a zonally coherent migration of the SH westerlies over all ocean basins in phase with NH climate. Our work provides a simple conceptual framework for understanding the circum-Antarctic temperature response to abrupt NH climate change. We provide observational evidence for abrupt shifts in the SH westerlies, with ramifications for global ocean circulation and atmospheric CO₂. These coupled changes highlight the necessity of a global, rather than a purely North Atlantic, perspective on the DO cycle

Hair Cortisol in Twins : Heritability and Genetic Overlap with Psychological Variables and Stress-System Genes

A. Palotie on työryhmän jäsen.Hair cortisol concentration (HCC) is a promising measure of long-term hypothalamus-pituitary-adrenal (HPA) axis activity. Previous research has suggested an association between HCC and psychological variables, and initial studies of inter-individual variance in HCC have implicated genetic factors. However, whether HCC and psychological variables share genetic risk factors remains unclear. The aims of the present twin study were to: (i) assess the heritability of HCC; (ii) estimate the phenotypic and genetic correlation between HPA axis activity and the psychological variables perceived stress, depressive symptoms, and neuroticism; using formal genetic twin models and molecular genetic methods, i.e. polygenic risk scores (PRS). HCC was measured in 671 adolescents and young adults. These included 115 monozygotic and 183 dizygotic twin-pairs. For 432 subjects PRS scores for plasma cortisol, major depression, and neuroticism were calculated using data from large genome wide association studies. The twin model revealed a heritability for HCC of 72%. No significant phenotypic or genetic correlation was found between HCC and the three psychological variables of interest. PRS did not explain variance in HCC. The present data suggest that HCC is highly heritable. However, the data do not support a strong biological link between HCC and any of the investigated psychological variables.Peer reviewe

Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in young children in 2015:a systematic review and modelling study

Background: We have previously estimated that respiratory syncytial virus (RSV) was associated with 22% of all episodes of (severe) acute lower respiratory infection (ALRI) resulting in 55 000 to 199 000 deaths in children younger than 5 years in 2005. In the past 5 years, major research activity on RSV has yielded substantial new data from developing countries. With a considerably expanded dataset from a large international collaboration, we aimed to estimate the global incidence, hospital admission rate, and mortality from RSV-ALRI episodes in young children in 2015. Methods: We estimated the incidence and hospital admission rate of RSV-associated ALRI (RSV-ALRI) in children younger than 5 years stratified by age and World Bank income regions from a systematic review of studies published between Jan 1, 1995, and Dec 31, 2016, and unpublished data from 76 high quality population-based studies. We estimated the RSV-ALRI incidence for 132 developing countries using a risk factor-based model and 2015 population estimates. We estimated the in-hospital RSV-ALRI mortality by combining in-hospital case fatality ratios with hospital admission estimates from hospital-based (published and unpublished) studies. We also estimated overall RSV-ALRI mortality by identifying studies reporting monthly data for ALRI mortality in the community and RSV activity. Findings: We estimated that globally in 2015, 33·1 million (uncertainty range [UR] 21·6–50·3) episodes of RSV-ALRI, resulted in about 3·2 million (2·7–3·8) hospital admissions, and 59 600 (48 000–74 500) in-hospital deaths in children younger than 5 years. In children younger than 6 months, 1·4 million (UR 1·2–1·7) hospital admissions, and 27 300 (UR 20 700–36 200) in-hospital deaths were due to RSV-ALRI. We also estimated that the overall RSV-ALRI mortality could be as high as 118 200 (UR 94 600–149 400). Incidence and mortality varied substantially from year to year in any given population. Interpretation: Globally, RSV is a common cause of childhood ALRI and a major cause of hospital admissions in young children, resulting in a substantial burden on health-care services. About 45% of hospital admissions and in-hospital deaths due to RSV-ALRI occur in children younger than 6 months. An effective maternal RSV vaccine or monoclonal antibody could have a substantial effect on disease burden in this age group