Impact of positive cytology in uterine serous carcinoma: A reassessment

Objectives: The aim of this study was to evaluate the prognostic value of peritoneal cytology status among other clinicopathological parameters in uterine serous carcinoma (USC). Methods: A retrospective study of 148 patients diagnosed with uterine serous carcinoma from 1997 to 2016 at two academic medical centers in the Detroit metropolitan area was done. A central gynecologic pathologist reviewed all available slides and confirmed the histologic diagnosis of each case of USC. We assessed the prognostic impact of various clinicopathological parameters on overall survival (OS) and endometrial cancer-specific survival (ECSS). Those parameters included race, body mass index (BMI), stage at diagnosis, tumor size, lymphovascular invasion (LVSI), peritoneal cytology status, receipt of adjuvant treatment, and comorbidity count using the Charlson Comorbidity Index (CCI). We used Cox proportional hazards models and 95% confidence intervals for statistical analysis. Results: Positive peritoneal cytology had a statistically significant effect on OS (HR: 2.09, 95% CI: [1.19, 3.68]) and on ECSS (HR: 2.02, 95% CI: [1.06 - 3.82]). LVSI had a statistically significant effect on both OS (HR: 2.27, 95% CI: [1.14, 4.53]) and ECSS (HR: 3.45, 95% CI: [1.49, 7.99]). Black or African American (AA) race was also found to have a significant effect on both OS (HR: 1.92, 95% CI: [1.07, 3.47]) and ECSS (HR: 2.01, 95% CI: [1.02, 3.98]). Other factors including BMI and tumor size \u3e 1 cm did not show a statistically significant impact on OS or ECSS. Conclusions: Peritoneal washings with positive cytology and LVSI are important prognostic tools that may have a significant impact on overall survival in USC and can be used as independent negative prognosticators to help guide adjuvant treatment

Mechanism, assessment and management of pain in chronic pancreatitis: Recommendations of a multidisciplinary study group

AbstractDescriptionPain in patients with chronic pancreatitis (CP) remains the primary clinical complaint and source of poor quality of life. However, clear guidance on evaluation and treatment is lacking.MethodsPancreatic Pain working groups reviewed information on pain mechanisms, clinical pain assessment and pain treatment in CP. Levels of evidence were assigned using the Oxford system, and consensus was based on GRADE. A consensus meeting was held during PancreasFest 2012 with substantial post-meeting discussion, debate, and manuscript refinement.ResultsTwelve discussion questions and proposed guidance statements were presented. Conference participates concluded: Disease Mechanism: Pain etiology is multifactorial, but data are lacking to effectively link symptoms with pathologic feature and molecular subtypes. Assessment of Pain: Pain should be assessed at each clinical visit, but evidence to support an optimal approach to assessing pain character, frequency and severity is lacking. Management: There was general agreement on the roles for endoscopic and surgical therapies, but less agreement on optimal patient selection for medical, psychological, endoscopic, surgical and other therapies.ConclusionsProgress is occurring in pain biology and treatment options, but pain in patients with CP remains a major problem that is inadequately understood, measured and managed. The growing body of information needs to be translated into more effective clinical care

An Analysis of Enzyme Kinetics Data for Mitochondrial DNA Strand Termination by Nucleoside Reverse Transcription Inhibitors

Nucleoside analogs used in antiretroviral treatment have been associated with mitochondrial toxicity. The polymerase-γ hypothesis states that this toxicity stems from the analogs' inhibition of the mitochondrial DNA polymerase (polymerase-γ) leading to mitochondrial DNA (mtDNA) depletion. We have constructed a computational model of the interaction of polymerase-γ with activated nucleoside and nucleotide analog drugs, based on experimentally measured reaction rates and base excision rates, together with the mtDNA genome size, the human mtDNA sequence, and mitochondrial dNTP concentrations. The model predicts an approximately 1000-fold difference in the activated drug concentration required for a 50% probability of mtDNA strand termination between the activated di-deoxy analogs d4T, ddC, and ddI (activated to ddA) and the activated forms of the analogs 3TC, TDF, AZT, FTC, and ABC. These predictions are supported by experimental and clinical data showing significantly greater mtDNA depletion in cell culture and patient samples caused by the di-deoxy analog drugs. For zidovudine (AZT) we calculated a very low mtDNA replication termination probability, in contrast to its reported mitochondrial toxicity in vitro and clinically. Therefore AZT mitochondrial toxicity is likely due to a mechanism that does not involve strand termination of mtDNA replication

Plasma microRNAs as biomarkers of pancreatic cancer risk in a prospective cohort study

Accepted manuscript version. Published version available in International Journal of Cancer 2017, 141 (5):905–915 .Noninvasive biomarkers for early pancreatic ductal adenocarcinoma (PDAC) diagnosis and disease risk stratification are greatly needed. We conducted a nested case-control study within the Prospective Investigation into Cancer and Nutrition (EPIC) cohort to evaluate prediagnostic microRNAs (miRs) as biomarkers of subsequent PDAC risk. A panel of eight miRs (miR-10a, -10b, -21-3p, -21-5p, -30c, -106b, -155 and -212) based on previous evidence from our group was evaluated in 225 microscopically confirmed PDAC cases and 225 controls matched on center, sex, fasting status and age/date/time of blood collection. MiR levels in prediagnostic plasma samples were determined by quantitative RT-PCR. Logistic regression was used to model levels and PDAC risk, adjusting for covariates and to estimate area under the receiver operating characteristic curves (AUC). Plasma miR-10b, -21-5p, -30c and -106b levels were significantly higher in cases diagnosed within 2 years of blood collection compared to matched controls (all p-values <0.04). Based on adjusted logistic regression models, levels for six miRs (miR-10a, -10b, -21-5p, -30c, -155 and -212) overall, and for four miRs (-10a, -10b, -21-5p and -30c) at shorter follow-up time between blood collection and diagnosis (≤5 yr, ≤2 yr), were statistically significantly associated with risk. A score based on the panel showed a linear dose-response trend with risk (p-value = 0.0006). For shorter follow-up (≤5 yr), AUC for the score was 0.73, and for individual miRs ranged from 0.73 (miR-212) to 0.79 (miR-21-5p)

Do the effects of early childhood education programs differ by gender? A meta-analysis

A meta-analysis was conducted to examine gender differences in the effects of early childhood education programs on children's cognitive, academic, behavioral, and adult outcomes. Significant and roughly equal impacts for boys and girls on cognitive and achievement measures were found, although there were no significant effects for either gender on child behavior and adult outcomes such as employment and educational attainment. Boys benefited significantly more from these programs than girls on other school outcomes such as grade retention and special education classification. We also examined important indicators of program quality that could be associated with differential effects by gender

GCSS Analytics Proof of Concept

Our previous research (TRWG 13-01-016) demonstrated the feasibility and usefulness of ADF (Application Development Framework) to develop a suite of supply analytics to augment GCSS- MC. ADF allows developers to quickly develop data driven web based analytics. This study took the next step by installing the “Analtyics Suite (AS) on NPS virtual servers (using VMware Horizon View). The servers were installed in the .edu domain at NPS. Proper IA procedures were applied to the VMware physical machines. AS (csviewtb.nps.edu) have been made available to selected Marine personnel for evaluation. The goal of this research is to bring this proof of concept as close to a model of a production server as possible. Evaluation of the performance was studied as well. In addition to the above, the research looked at how the GCSS data can be "cleaned up" and an evaluation of the technology needed to deal with dirty or missing data.Naval Research ProgramPrepared for: Topic Sponsor: N2/N6; Research POC: Maj Nic Martinez (LX, DC I&L)NPS-N16-M445-

Patterns of sediment transport and morphologic response on a mixed sand and gravel beach in Rich Passage, Puget Sound

Annual and seasonal patterns of sediment transport and morphologic response are examined for a mixed sand and gravel beach in Rich Passage, Puget Sound, WA exposed to wind waves, vessel wakes, and tidal currents. Gravel transport was measured in three intervals at two sites on Point White, Bainbridge Island, WA using Radio Frequency Identification (RFID) Passive Integrated Transponder (PIT) technology and high resolution laser scanning topographic surveys. The measurements are used to examine the relative influence of mechanisms forcing alongshore and cross-shore transport at the two sites, to characterize seasonal and annual sediment transport rates and compare and contrast transport and morphology change patterns under different vessel operating regimes. During the first interval (2006 to 2007) alongshore transport dominated as a result of wind-wave forcing during the storm intervals (winter condition); cross-shore transport resulted primarily from car ferry wake wash and tidal forcing during non-storm intervals (summer condition) (Curtiss et al. 2009). During the second interval (summer of 2012) a new high speed, low wake ferry, Rich Passage 1 (RP1), was tested in-situ for a 6-month interval (Cote et al, 2013). The third interval (2013-2015) encompasses ongoing beach response monitoring after the completion of in-situ testing of RP1. Alongshore transport rates during the RP1 test interval were larger at both sites compared to similar non-storm intervals in 2006 and 2007, but were lower than rates observed during storm intervals in 2006 and 2013. Transport rates during the non-storm interval in 2013 were similar to baseline rates of transport (2006-2007). Difference maps of beach elevation show cross-shore gravel bar formation and alongshore patterns of northeast oriented shore-oblique gravel bedforms. The almost ten years of measurements have been essential for comparing the beach response observed during the RP1 test interval in relation to seasonal and inter-annual beach response

Multilocus Sequence Typing of Escherichia coli O26:H11 Isolates Carrying stx in Canada Does Not Identify Genetic Diversity

Multilocus sequence typing of 31 stx-carrying Escherichia coli O26:H11 strains isolated in Canada between 1999 and 2003 revealed a high degree of genetic relatedness at 10 loci, suggesting either that this is a clonal serotype (similar to O157:H7) or that additional genetic loci need to be examined