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Background: Severe hypertriglyceridemia is often caused by variants in genes of triglyceride metabolism. These variants include rare, heterozygous pathogenic variants (PVs), or multiple common, small-effect single nucleotide polymorphisms that can be quantified using a polygenic risk score (PRS). The role of genetic testing to examine PVs and PRS in predicting risk for pancreatitis and severity of hypertriglyceridemia is unknown. Methods: We examined the relationship of PVs and PRSs associated with hypertriglyceridemia with the highest recorded plasma triglyceride level and risk for acute pancreatitis in 363 patients from 3 academic lipid clinics who underwent genetic testing (GBinsight’s Dyslipidemia Comprehensive Panel). Categories of hypertriglyceridemia included: normal triglyceride ( Results: PVs and high PRSs were identified in 37 (10%) and 59 (16%) individuals, respectively. Patients with both had increased risk for very severe hypertriglyceridemia compared with those with neither genetic risk factor. Risk for acute pancreatitis was also increased in individuals with both genetic risk factors (odds ratio, 5.1 [ P =0.02] after controlling for age, race, sex, body mass index, and highest triglyceride level), but not in individuals with PV or high PRS alone. Conclusions: The presence of both PV and high PRS significantly increased risk for very severe hypertriglyceridemia and acute pancreatitis, whereas PV or PRS alone only modestly increased risk. Genetic testing may help identify patients with hypertriglyceridemia who have the greatest risk for developing pancreatitis and may derive the greatest benefit from novel triglyceride-lowering therapies.

The extent of intervention effects on carotid intima-media thickness (CIMT) can predict the degree of atherosclerotic cardiovascular risk-reduction. We hypothesized that regular lipoprotein apheresis over the course of 10 years might slow down progression of CIMT in patients with severe hypercholesterolemia. This case series describes 10 Caucasian patients (mean age 60 ± 9 years, 70% female, 80% statin intolerant) with a severe hypercholesterolemia phenotype treated with lipoprotein apheresis between 2005 and 2020 (mean duration, 10 ± 4 years). The median pretreatment low-density lipoprotein cholesterol (LDL-C) level was 214 mg/100 ml (95% confidence interval, 145 to 248), lipoprotein(a) (Lp[a]), 26 mg/100 ml (15 to 109; 40% with Lp(a)60 mg/100 ml). Three patients were diagnosed with a monogenic cause. The baseline mean CIMT was 850 ± 170 µm, and maximum CIMT was 1,040 ± 220 µm across the age range of 46 to 70 years. Acute effects of lipoprotein apheresis determined as a difference before and immediately after the procedure were estimated as a median of 72 ± 8% and 75 ± 7% reduction in the LDL-C and Lp(a) levels, respectively. Using the imputed trajectories, period-specific on-treatment time-weighted averages for LDL-C and Lp(a) were 141 mg/100 ml (interquartile range, 89 to 152; 38% reduction from the baseline) and 24 mg/100 ml (interquartile range, 12 to 119; 19% reduction from baseline), respectively. The number of patients with CIMT above their "vascular age" decreased from 80% to 30% over the treatment course. In conclusion, an increase in CIMT seen with advanced age and severe hypercholesterolemia was halted with lipoprotein apheresis with an estimated annual rate of change in mean common CIMT of -4 µm/y and maximum CIMT of -3 µm/y.

Adult women require routine care for the acute and chronic health problems found in both sexes, and they require specialized care for women's health problems, including disease prevention, disease screening, and disease management. Internists should direct primary care and participate in specialized care and to the extent possible follow guidelines published by various professional organizations. They should understand the use of ultrasound in breast cancer screening, the management of pregnancy, and other gynecologic problems, including vaginal bleeding, pelvic pain, and investigation for pelvic malignancy. Finally, all management decisions need discussions on the potential benefit or harm in each step of a woman's care with an emphasis on personal preferences.

Women’s political underrepresentation in right-wing parties remains a global phenomenon. Despite their rejection of “identity politics,” the United Kingdom’s Conservative Party and the United State...

Objective Niraparib is a poly (ADP-ribose) polymerase inhibitor (PARP) approved for use in maintenance therapy for ovarian cancer that is associated with the unpredictable grade 3/4 thrombocytopenia. This study was conducted to refine patient dosing recommendations for niraparib based upon clinical practice observations of grade 3/4 thrombocytopenia. Methods and materials Six patient cases were reviewed to identify similarities in patient factors. An in vitro study was conducted using healthy volunteer blood spiked with Niraparib concentrations ranging from 0 ng/mL to 5000 ng/mL. Manual platelet counts were evaluated at different time intervals for each concentration and compared to untreated controls. Data was then analyzed based on percent change in platelet count versus untreated control for each concentration/time point. Results In three patients with body weight > 80 kg and platelet count >200 × 109/L, decreased creatinine clearance (CrCl) Conclusion The data suggests that renal insufficiency and hypoalbuminemia may be associated with the development of niraparib-induced thrombocytopenia. Moreover, the preliminary in vitro studies also demonstrated a concentration-dependent relationship between niraparib and direct toxicity to platelets.

Study Objective To compare the accuracy of frozen section diagnosis of borderline ovarian tumors among 3 distinct types of hospital—academic hospital with gynecologic pathologists, academic hospital with nongynecologic pathologists, and community hospital with nongynecologic pathologists—and to determine if surgical staging alters patient care or outcomes for women with a frozen section diagnosis of borderline ovarian tumor. Design Retrospective study (Canadian Task Force classification II-1). Setting Tertiary care, academic, and community hospitals. Patients Women with an intraoperative frozen section diagnosis of borderline ovarian tumor at 1 of 3 types of hospital from April 1998 through June 2016. Interventions Comparison of final pathology with intraoperative frozen section diagnosis. Measurements and Main Results Two hundred twelve women met the inclusion criteria. The frozen section diagnosis of borderline ovarian tumor correlated with the final pathologic diagnosis in 192 of 212 cases (90.6%), and the rate of correlation did not differ among the 3 hospital types (p = .82). Seven tumors (3.3%) were downgraded to benign on final pathologic analysis and 13 (6.1%) upgraded to invasive carcinoma. The 3 hospital types did not differ with respect to the proportion of tumors upgraded to invasive carcinoma (p = .62). Mucinous (odds ratio, 7.1; 95% confidence interval, 2.1–23.7; p = .002) and endometrioid borderline ovarian tumors (odds ratio, 32.4; 95% confidence interval, 1.8–595.5; p = .02) were more likely than serous ovarian tumors to be upgraded to carcinoma. Only 88 patients (41.5%) underwent lymphadenectomy, and only 1 (1.1%) had invasive carcinoma in a lymph node. Conclusions A frozen section diagnosis of borderline ovarian tumor correlates with the final pathologic diagnosis in a variety of hospital types.

The recent approval of olaparib and niraparib as maintenance therapy can significantly affect the management of ovarian cancer. Clinical benefits, however, come with trade-offs in adverse events and costs.To evaluate the cost-effectiveness of new ovarian cancer poly-ADP ribose polymerase (PARP) inhibitor therapies, olaparib and niraparib, as maintenance therapy for patients with platinum-sensitive recurrent ovarian cancer.A decision tree model was constructed to evaluate the costs and effectiveness of olaparib and niraparib compared with placebo from a U.S. health care sector perspective. Costs included drug costs and costs of disease monitoring and management of adverse events throughout the treatment course. Costs were estimated from RED BOOK, Medicare reimbursement rates, and the literature and reported in 2017 U.S. dollars. Clinical effectiveness was measured in progression-free survival (PFS) life-years based on clinical trial results (NCT00753545, NCT01874353, and NCT01847274). The incremental cost-effectiveness ratio (ICER) was computed by dividing the incremental cost by the incremental effectiveness.At base case, niraparib was the more effective treatment option with slightly higher PFS, followed by olaparib. The ICERs for niraparib and olaparib compared with common baseline placebo were $235K and $287K per PFS life-year, respectively, with olaparib extended-dominated by niraparib. Both drugs were associated with lower ICERs in patients with a gBRCA mutation than in patients without a gBRCA mutation. One-way sensitivity analysis suggested that drug prices and PFS could affect ICERs significantly, but the ICERs remained above $100K per PFS life-year within the plausible ranges of all parameters. Probabilistic sensitivity analysis suggested that niraparib was associated with higher net benefits compared with placebo only when willingness-to-pay (WTP) values were above $210K per PFS life-year thresholds.PARP inhibitors niraparib and olaparib will extend PFS in platinum-sensitive recurrent ovarian cancer patients but are also associated with high drug acquisition costs. The base case ICERs were around or above $250K per PFS life-year in this model. No formal cost-effectiveness WTP threshold for health technology assessment exists in the United States. At a reference WTP of $100K per PFS life-year, the PARP inhibitors may not be cost-effective options.This study was unfunded. The authors have nothing to disclose.

Purpose or Objective In March 2020, a 1-week hypofractionated adjuvant breast radiotherapy schedule, 26 Gy in 5 fractions was adopted to reduce the risk of COVID 19 exposure for patients and staff without compromising on cancer outcomes. This study aimed to confirm acceptable acute toxicity rates for patients receiving this 1-week schedule (+/- sequential boost) and to quantify the positive impact of implementing this schedule on linac capacity. Materials and Methods This is a multicentre prospective observational study of consecutive patients receiving 26 Gy in 5 fractions adjuvant breast cancer radiotherapy (+/- boost) Mar-Aug 2020. Consensus was obtained on planning procedure protocols which included dose-volume evaluation and mandatory radiation quality assurance objectives. Standardised virtual consultations assessed acute skin toxicity during treatment and at weeks 1, 2, 3 and 4 post treatment using CTCAE V5 scoring criteria. Toxicity was compared between patients who received a boost and those that did not. The total number of linac minutes saved was estimated accounting for boost and DIBH use Results In total, 135 women were included, 33 (24%) received a boost. 128/135 (95%) patients, including 31/33 boost patients, completed at least 3/5 acute toxicity assessments. 0/128 (0%) reported moist desquamation not confined to skin folds or minor bleeding (grade 3 toxicity). 41/128 (31%) reported brisk erythema, moist desquamation confined to skin folds or breast swelling (Grade 2) and 63/128 (50%) reported faint erythema or dry desquamation (Grade 1) as their worst reported acute skin toxicity. The highest prevalence of grade 2 toxicity occurred at week 1 following treatment (19.5%), which reduced to 2.6% by week 4. There was no statistically significant difference in acute toxicity between boost and no boost patients (p= 1.00). Delivering a 1-week schedule to 135 patients over a six month period led to a saving of 21,300 linac minutes and 1485 hospital visits compared to delivering a moderately hypofractionated regimen of 3 weeks duration. 6,300 LINAC minutes were saved and 462 hospital visits avoided for patients > 70 years and cocooning under national guidance $Φg $Φg Conclusion This study demonstrates the feasibility of rapidly implementing a 1-week hypofractionated adjuvant breast radiotherapy schedule in clinical practice and how this landmark change has a considerable impact on linac capacity. This change in practice has ensured ongoing access to treatment for patients during the COVID-19 pandemic and greatly reduced the risks of infection for patients and staff. It further confirms acceptable acute skin toxicity even when followed by boost.

Studies on political knowledge routinely find that women have lower levels of political knowledge than men. This gender gap in political knowledge is usually interpreted as troublesome for democracy, because a lack of political knowledge could imply that women’s participation in politics is less effective and that their interests will be represented less well than those of men. In this short article, we present a direct test of the assumption that women are less effective voters because of this lack of political knowledge. We make use of CSES data to study gender differences in proximity voting and correct voting. Our results do not suggest that women vote less correctly than men—a conclusion that prompts important questions about the role of different forms of political knowledge, and the seemingly gendered nature of the vote choice.

Following the death of George Floyd in May of 2020, many museums and museum professionals reignited long-held discussions surrounding the nature of the museum as an institution and the ethics revolving around their collections. This is a resource guide, in book form, for those inside and outside the museum industry who want to initiate change regarding the way non-Western art is presented and displayed, or for those who want to learn about the history of the colonial museum. This book features Nugent's essay, "A Desire for the Primitive: The Lasting 'Othering' of African Art in Western Museums," as a companion text to the resources provided.

Background Breast cancer is the most commonly diagnosed cancer in women in Ireland. The 5 year net survival is over 80%. Most women diagnosed with breast cancer do not die from the disease and instead cardiovascular disease (CVD) remains the most frequent cause of death. Many breast cancer patients are older and have established CVD risk factors. They are at further risk of a cardiovasular (CV) event due to exposure to anthracyclines, HER2 targeted agents, endocrine therapy and radiotherapy. In this study, we aimed to compare the 10 year risk of breast cancer mortality versus that of a CV event or death in an oncology day ward population at our centre through the use of online prognostic risk calculators. Furthermore, we sought to investigate the predicted outcome of lifestyle changes on their overall CV risk and level of interest in addressing these risk factors. Methods This was a cross cohort study of all breast cancer patients attending for adjuvant chemotherapy at our institution from September 2015 to September 2016. To calculate patients' 10 year CVD risk, we used the JBS3 online calculator. Using this calculator we could also predict patient's lifetime CV risk. To calculate patients' 10 year mortality risk from breast cancer we used NHS predict! These calculators incorporate several variables which we identified from chart review, the use of questionnaires and the performance of a serum lipid test. Results 101 subjects were identified. All patients (pts) completed questionnaires. Eighteen pts were excluded from CV risk analysis due to lack of lipid profile. Of 83 pts, 83% (n=69) were >50 years of age and 17% (n=14) pts were 50 age group (grp) was 59 and 42 in the 50 and 50 grp were smokers/ex smokers and 49% (n=7) were in the 50 grp were on statins and 25% (n=17) were on antihypertensives. Fifty-two percent (n=36) of pts in the >50 grp and 66% (n=10) received anthracyclines. Fifty percent in both grps received left sided radiotherapy. Ninety five percent (n=63) were on endocrine therapy in the >50 grp and 93% (n=13) in the 50 grp (n=28) and 29% (n=4) of patients in the 50 grp, 13% (n=9) were found to have a high 10 year cardiovascular risk (>20% risk of CV event) and 28% were found to be at moderate risk (n=19). Ten percent of patients were found to have a CV risk that exceeded their breast cancer mortality risk (n=7). Even though the 10 year CV risk was low in patients 50 patients in the high risk group post CV risk modification was 8.8% (+/-5.6) versus 28% (+/-8) at baseline. Conclusion This patient population has significant CV risk factors at baseline. Benefits predicted with CV risk intervention model and significant patient interest indicates that formalised CV risk prevention strategy is needed. Citation Format: Prior L, Featherstone H, Nugent K, Lim M, Kelly C. Competing mortality risks: Cardiovascular risk versus risk of metastatic disease in breast cancer patients receiving adjuvant therapy [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-10-16.

Variant interpretation is a complex process, and classification may vary between sources. This study aimed to determine the practice of cancer genetic counselors regarding discrepancies in variant interpretation and to identify concerns when counseling these discrepancies. An electronic survey was sent to genetic counselors in the NSGC Cancer Special Interest Group. The vast majority of counselors (93%) had seen a variant interpretation discrepancy in practice. A large majority (96%) of respondents indicated that they conducted their own research on reported variants. Most respondents cited variant databases as the most common resource utilized in researching variants. Approximately 33% of counselors spent 45 min or more of extra time researching a discrepancy compared to researching a variant with a single classification. When asked how they approached counseling sessions involving variant interpretation discrepancies, the free responses emphasized that counselors considered family history, clinical information, and psychosocial concerns, showing that genetic counselors tailored the session to each individual. Discrepancies in variant interpretation are an ongoing concern for clinical cancer genetic counselors, as demonstrated by the fact that counselors desired further resources to aid in addressing these discrepancies, including a centralized database (89%), guidelines from a major organization (88%), continuing education about the issue (74%), and functional studies (58%). Additionally, most respondents reported that the ideal database would be owned by a non-profit organization (59%) and obtain information directly from laboratories (91%). This investigation was the first to address these discrepancies from a clinical point of view. The study demonstrates that discrepancies in variant interpretation are a concern for clinical cancer genetic counselors and outlines the need for additional support.

Objectives Surgery is a cornerstone for patients with gynecologic malignancies. Surgical site infections (SSI) remain a source of post-operative morbidity. Consequences range from escalated costs, delay in adjuvant therapy, and increased morbidity. Our primary objective was to evaluate the effectiveness of a cyanoacrylate microbial sealant (CMS) to reduce post-operative SSI following laparotomy for suspected gynecologic malignancy. Methods Patients were randomized using a 1:1 allocation to receive either standard skin preparation or standard preparation with CMS and stratified by BMI. Patients were followed for 6weeks for SSI. Demographic data was collected through the EMR. Associations between SSI, use of CMS, and clinicopathologic factors were explored using descriptive statistics, chi-square and multivariate analysis. Results 300 patients underwent randomization. Median age of the cohort was 58. Arms were matched and there was no difference in rate of medical comorbidities. Mean BMI was 38.8kg/m 2 in patients randomized to BMI≥30 and 26.3kg/m 2 randomized to BMI p =0.18). Multivariate model demonstrated that BMI≥30 ( p p =0.010), transfusion in the OR ( p p =0.0005) were associated with post-operative SSI. Conclusions Patients presenting to a gynecologic oncologist for surgery frequently present with multiple risk factors for SSI and laparotomy is complicated by surgical-site complications in up to 30% of cases. The addition of CMS alone does not appear to reduce risk of overall SSI. Additional risk-reducing strategies including use of antimicrobial agents and optimization of modifiable risk factors prior to surgery should be explored as pathways for reducing this significant post-operative morbidity.

The political representation of women and ethnic minorities has received growing attention among political parties around the world. Focusing on the British case, we map data and debates concerning the selection of female and minority candidates, highlighting the simultaneous and interactive role of gender and race in shaping citizens’ opportunities to stand for and win election. Utilizing data from the Labour Party, our analysis illustrates the implications of distinct strategies to include members of politically marginalized groups—as well as provides evidence for the potential of “tandem quotas” to result in positive outcomes for minority women. Taken together, these findings suggest the need for stronger measures on the part of Labour to encourage the selection of minority candidates; a shift from “single-axis” to “multiple-axis” thinking when devising strategies to enhance group representation; and rejection of a “zero-sum” mentality regarding the nomination of female and minority candidates.

Objective: To determine the activity of fucoidan from Undaria pinnatifida (UPF) and Fucus vesiculosus (FVF) when given in combination of chemotherapy drugs using selected human breast or ovarian cancer orthotopic mouse models. Methods: Mice were inoculated with 1 × 10 6 cells of TOV-112d, MCF-7, or ZR-75 subcutaneously or SKOV 3 -GFP-Luc intraperitoneally on day 0. MCF-7 and ZR-75 mice were administered with estradiol valerate 2 mg/kg in 0.2 mL castor oil subcutaneously two days prior to cell inoculation. Mice were randomized to one of six arms (N = 10/arm) paclitaxel, UPF/paclitaxel, FVF/paclitaxel, tamoxifen, UPF/tamoxifen, or FVF/tamoxifen. Tumors were measured three times per week for 28 days. Results: Improved activity was observed with UPF or FVF in combination with tamoxifen in both the MCF-7 and ZR-75D breast cancer mouse models. Decreased activity of paclitaxel was observed when given in combination with UPF or FVF in both breast cancer mouse models. The combination of FVF/tamoxifen in the TOV-112d ovarian cancer mouse model had improved activity but no there was difference observed with the UPF/tamoxifen in either ovarian cancer mouse model. No difference was observed with combination of UPF or FVF with paclitaxel in human ovarian cancer SKOV 3 or TOV-112d orthotopic mouse models. Conclusion: This study did confirm that UPF/FVF in combination with tamoxifen did not decrease tamoxifen activity in both breast and ovarian cancer, with some potential to improve activity compared to tamoxifen alone in breast cancers. Previous in vitro studies had suggested UPF and FVF had overall synergistic activity with paclitaxel; however, in the current in vivo human cancer mouse model studies there was no change in paclitaxel activity when given in combination with UPF or FVF in either of the two human ovarian cancer models. Furthermore, this study demonstrated that UPF or FVF given in combination with paclitaxel had a potential antagonistic effect in breast cancer models. Additional studies are warranted to delineate mechanisms contributing to variation in the in vivo activity when given in combination with paclitaxel. As a first step, a clinical pharmacokinetic study evaluating impact of FVF/UPF given in combination with chemotherapy in patients with solid tumors is underway.

To assess the consistency between human papillomavirus (HPV) mRNA testing in women with a history of previous HPV infections diagnosed by HPV DNA assay and the potential effects on follow-up HPV screening.This was a quality improvement study that used data from a pathology laboratory software database reviewed from November 2014 to June 2016 to identify female patients aged 30 years or older with greater than one HPV-positive result, including one or more HPV mRNA assay results and one or more documented HPV DNA assay results for comparison. Previous correlative cytology and colposcopic histopathology were also documented. American College of Obstetricians and Gynecologists' cervical cancer screening guidelines were used to compare potential differences in follow-up recommendations.Four hundred twenty-five charts for female patients 30 years of age or older were identified with one or more prior high-risk HPV infections by DNA assay. There was a 69.3% difference in HPV mRNA results compared with previous HPV DNA-positive results. There was a potential change in follow-up for 71.7% of patients with one prior high-risk-HPV-positive result and 60.0% of patients with two or more prior high-risk HPV-positive results. There were 231 colposcopy reports evaluated in this study. Of these, 62 (26.8%) were abnormal colposcopy reports, including 45 low-grade squamous intraepithelial lesions, 15 high-grade squamous intraepithelial lesions, and two cancers. Twenty-five (40.3%) abnormal colposcopy findings were in patients with a history of at least than two prior HPV DNA-positive results and a report of currently being HPV-negative with the mRNA assay.The HPV mRNA assays are less sensitive for detection of latent HPV infections compared with HPV DNA assays. Based on these data and the potential change in follow-up care, the HPV mRNA assay should not be used for a primary screening tool for cervical cancer. Many pathology laboratories have shifted to using the HPV mRNA assay without clear discussion with gynecologists about the effects on patient follow-up. The type of HPV assay being used should be documented and any HPV mRNA result confirmed by HPV DNA assay.

Objectives: To evaluate potential hepatic metabolism-mediated drug interactions with fucoidan from Undaria pinnatifida (UPF) or Fucus vesiculosus (FVF) and potential growth inhibition activity with either fucoidan alone or with chemotherapy. In vivo studies were done to confirm safety and investigate fucoidan-mediated immune modulation. Methods: Cytochrome P450 (CYP450) 3A4, 2C8, 2C9, and 2D6 inhibition experiments were conducted in vitro followed by an ex vivo human hepatocytes model to evaluate the CYP450 induction potential of each fucoidan at highest theoretical concentrations. Four hepatic metabolism phase II pathways—glutathione S transferase (GST), quinone oxidoreductase (QOR), catechol-O-methyltransferases (COMT), and uridine di-phosphate (UDP)-glucuronosyltransferase (UGT)—were evaluated with validated immunoassays. Growth inhibition assays were performed with each fucoidan alone and in combination with chemotherapy agents in a panel of human cancer cell lines. In vivo studies evaluated safety and immune modualtion. Results: CYP450 inhibition was observed with FVF. The GST, QOR, and UGT pathways had no changes. UPF and FVF both interacted with COMT. No growth inhibitory activity in cancer cell lines was observed. UPF and FVF had synergistic activity with paclitaxel or tamoxifen and additive activity with topotecan. In vivo, FVF decreased HeLa human cervical tumor growth and both FVF and UPF decreased TOV-112D human ovarian tumor growth. Otherwise, no significant change in tumor growth was observed. FVF immune modulation of IgG and IL-6 was observed (p

ObjectiveThis retrospective study evaluates the influence of serum platelet count on chemotherapy response rates among women with endometrial cancer.MethodsFrom 3 separate cancer centers, a total of 318 patients with endometrial cancer who received postoperative chemotherapy between June 1999 and October 2009 were retrospectively identified. Endometrioid, serous, clear cell, and carcinosarcoma histologies were included. Patients were classified as having an elevated platelet count if their serum platelet count was greater than 400 × 109/L at the time of initial diagnosis. Primary outcome was chemotherapy response, classified as either complete or partial/refractory. Secondary outcomes were disease-free and disease-specific survival. χ2Test and Studentttest were performed as appropriate. Kaplan-Meier curves and Cox proportional hazards models were used to assess serum platelet effect on survival.ResultsThere were 125 deaths, 76 recurrences, and 48 disease progressions. Of the total group, 53 (16.7%) were categorized as having an elevated platelet count. An elevated platelet count was associated with a lower chemotherapy response rate in univariate analysis (hazard ratio [HR], 2.8; 95% 95% confidence interval [CI], 1.46–5.38;P< 0.01). Multivariate analysis showed elevated platelets to be independently associated with decreased disease-free survival (HR, 2.24; 95% CI, 1.26–3.98;P< 0.01) but not disease-specific survival (HR, 1.03; 95% CI, 0.56–1.88,P= 0.93).ConclusionsPatients with endometrial cancer who have an elevated serum platelet count greater than 400 × 109/L may have lower chemotherapy response rates and are at increased risk for recurrence when compared with patients with a count within the reference range.

*Gender quotas have emerged globally as a key solution for improving women’s political representation. Yet in Britain—where they take the form of all-women shortlists (AWS)—they remain contentious, both within and outside political parties. We identify nine common criticisms of AWS in the British context, related to candidate recruitment and selection, party and voter support and the effectiveness of ‘quota women’ as politicians. Using qualitative and quantitative data, we find that these objections do not hold when subjected to rigorous empirical analysis, suggesting that quotas do not pose a threat to ‘merit’ at any stage of the political process.

BACKGROUND AND OBJECTIVE: To characterize the cellular, immunological, and inflammatory response to retinal photocoagulation of intense rupture laser lesions as a model of retinal degenerative diseases. MATERIALS AND METHODS: Seven C57BL/6 mice were irradiated using a 532-nm laser to induce 10 retinal burns per eye that ruptured Bruch’s membrane. Blood was drawn from the saphenous vein before and 2 months after laser treatment. The serum was run on antigen microarrays with 85 molecular markers associated with retinal degenerative diseases. RESULTS: Rupture laser resulted in dramatic changes in the immunoglobulin reactivity of most inflammatory markers 2 months after laser injury. Approximately two-thirds increased expression and one-third decreased expression. Notable markers that were increased included complement C3, CRP, PKM2, and aldolase. CONCLUSION: Rupture laser injury causes a change in the serum inflammatory markers after 2 months similar to macular degeneration, diabetic retinopathy, and cancer-associated retinopathy. This animal model could be used as a biomarker for disease stage and activity in retinal degenerations. [ Ophthalmic Surg Lasers Imaging Retina . 2015;46:362–368.]

Objective: To determine the activity of fucoidan from Undaria pinnatifida (UPF) and Fucus vesiculosus (FVF) when given in combination of chemotherapy drugs using selected human breast or ovarian cancer orthotopic mouse models. Methods: Mice were inoculated with 1 × 106 cells of TOV-112d, MCF-7, or ZR-75 subcutaneously or SKOV3-GFP-Luc intraperitoneally on day 0. MCF-7 and ZR-75 mice were administered with estradiol valerate 2 mg/kg in 0.2 mL castor oil subcutaneously two days prior to cell inoculation. Mice were randomized to one of six arms (N = 10/arm) paclitaxel, UPF/paclitaxel, FVF/paclitaxel, tamoxifen, UPF/tamoxifen, or FVF/tamoxifen. Tumors were measured three times per week for 28 days. Results: Improved activity was observed with UPF or FVF in combination with tamoxifen in both the MCF-7 and ZR-75D breast cancer mouse models. Decreased activity of paclitaxel was observed when given in combination with UPF or FVF in both breast cancer mouse models. The combination of FVF/tamoxifen in the TOV-112d ovarian cancer mouse model had improved activity but no there was difference observed with the UPF/tamoxifen in either ovarian cancer mouse model. No difference was observed with combination of UPF or FVF with paclitaxel in human ovarian cancer SKOV3 or TOV-112d orthotopic mouse models. Conclusion: This study did confirm that UPF/FVF in combination with tamoxifen did not decrease tamoxifen activity in both breast and ovarian cancer, with some potential to improve activity compared to tamoxifen alone in breast cancers. Previous in vitro studies had suggested UPF and FVF had overall synergistic activity with paclitaxel; however, in the current in vivo human cancer mouse model studies there was no change in paclitaxel activity when given in combination with UPF or FVF in either of the two human ovarian cancer models. Furthermore, this study demonstrated that UPF or FVF given in combination with paclitaxel had a potential antagonistic effect in breast cancer models. Additional studies are warranted to delineate mechanisms contributing to variation in the in vivo activity when given in combination with paclitaxel. As a first step, a clinical pharmacokinetic study evaluating impact of FVF/UPF given in combination with chemotherapy in patients with solid tumors is underway.

Objective. To determine the impact on antitumor activity when active hexose correlated compound (AHCC) in combination with anticancer hormonal agents in orthotopic mouse models of human estrogen receptor positive breast cancer and evaluate impact of AHCC on aromatase activity. Methods. The study consisted of 7 treatment arms (n=10) conducted in 2 breast cancer mouse models: MCF-7 and ZR-75. Treatment groups included untreated, vehicle, AHCC 50 mg/kg, AHCC 50 mg/kg + tamoxifen 10 mg/kg, tamoxifen 10 mg/kg, AHCC 50 mg/kg + letrozole 10 µg/mouse, or letrozole 10 µg/mouse. All treatments were administered daily by oral gavage for 12 weeks. Tumors were measured 3 times a week. In vitro estrone and 17β-estradiol enzyme immunoassay was used to evaluate aromatase activity. Results. There was no difference in the activity with the combination of AHCC + tamoxifen compared with tamoxifen ( P = 0.29). In the ZR-75 model (catechol- O-methyltransferase [COMT] wild-type), there was no difference in activity with the letrozole + AHCC compared with letrozole. However, in the MCF-7 model (COMT variant), AHCC + letrozole resulted in a decrease in activity compared with letrozole ( P < 0.01). Immunoassay data suggested that AHCC is a potential inducer of aromatase activity. In both tumor models, there was cytotoxicity observed with AHCC compared with untreated ( P < 0.02). Conclusion. AHCC did not change the activity of tamoxifen. AHCC may have some interaction with letrozole in patients with COMT variant genotype. AHCC had cytotoxicity that warrents additional studies to evaluate its potential role for consolidation/prevention of breast cancer.

The genome sequence of the obligate chemolithoautotroph Hydrogenovibrio crunogenus paradoxically predicts a complete oxidative citric acid cycle (CAC). This prediction was tested by multiple approaches including whole cell carbon assimilation to verify obligate autotrophy, phylogenetic analysis of CAC enzyme sequences and enzyme assays. Hydrogenovibrio crunogenus did not assimilate any of the organic compounds provided (acetate, succinate, glucose, yeast extract, tryptone). Enzyme activities confirmed that its CAC is mostly uncoupled from the NADH pool. 2-Oxoglutarate:ferredoxin oxidoreductase activity is absent, though pyruvate:ferredoxin oxidoreductase is present, indicating that sequence-based predictions of substrate for this oxidoreductase were incorrect, and that H. crunogenus may have an incomplete CAC. Though the H. crunogenus CAC genes encode uncommon enzymes, the taxonomic distribution of their top matches suggests that they were not horizontally acquired. Comparison of H. crunogenus CAC genes to those present in other 'Proteobacteria' reveals that H. crunogenus and other obligate autotrophs lack the functional redundancy for the steps of the CAC typical for facultative autotrophs and heterotrophs, providing another possible mechanism for obligate autotrophy.

Objectives: To evaluate potential hepatic metabolism-mediated drug interactions with fucoidan from Undaria pinnatifida (UPF) or Fucus vesiculosus (FVF) and potential growth inhibition activity with either fucoidan alone or with chemotherapy. In vivo studies were done to confirm safety and investigate fucoidan-mediated immune modulation. Methods: Cytochrome P450 (CYP450) 3A4, 2C8, 2C9, and 2D6 inhibition experiments were conducted in vitro followed by an ex vivo human hepatocytes model to evaluate the CYP450 induction potential of each fucoidan at highest theoretical concentrations. Four hepatic metabolism phase II pathways—glutathione S transferase (GST), quinone oxidoreductase (QOR), catechol-O-methyltransferases (COMT), and uridine di-phosphate (UDP)-glucuronosyltransferase (UGT)—were evaluated with validated immunoassays. Growth inhibition assays were performed with each fucoidan alone and in combination with chemotherapy agents in a panel of human cancer cell lines. In vivo studies evaluated safety and immune modualtion. Results: CYP450 inhibition was observed with FVF. The GST, QOR, and UGT pathways had no changes. UPF and FVF both interacted with COMT. No growth inhibitory activity in cancer cell lines was observed. UPF and FVF had synergistic activity with paclitaxel or tamoxifen and additive activity with topotecan. In vivo, FVF decreased HeLa human cervical tumor growth and both FVF and UPF decreased TOV-112D human ovarian tumor growth. Otherwise, no significant change in tumor growth was observed. FVF immune modulation of IgG and IL-6 was observed (p

The primary objective of this study was to quantify the impact of treatment delay and dose reductions in an in vivo orthotopic ovarian cancer model. In addition, this study evaluated the role of growth factors in achieving “full dose on time”. HeyA-8 and SKOV3.ip1ovarian cancer orthotopic mouse models were used determine the effect of paclitaxel/carboplatin treatment delays or dose reductions on tumor response and overall survival. The addition of growth factor support with pegfilgrastim and darbepoetin was also evaluated in treatment control arm. The results indicated that full dose of paclitaxel (20 mg/kg) and carboplatin (50 mg/kg) delivered on time (every 21 days) achieved better tumor response in both aggressive (HeyA-8) and metastatic (SKOV3.ip1) human ovarian tumors compared to treatment delay or dose reduction arms. In the HeyA-8 orthotopic model treatment delay (P

BACKGROUND: We reviewed local control (LC) and overall survival (OS) post intracranial SRS to cavity post resection of brain metastases at one institution, and factors affecting LC. MATERIAL AND METHODS: A retrospective review was conducted of adjuvant SRS at one institution from 2013 to 2016. Patient records, treatment plans, and diagnostic images were reviewed. Local failure was MRI defined. Categorical variables were analysed using chi-square and Fisher’s exact tests. Continuous variables were analysed using Mann-Whitney tests. The Kaplan-Meier method was used to estimate survival times and the log-rank test was used to compare differences in survival. RESULTS: 47 patients with 48 cavities were treated with SRS post operatively. LC rate was 69%, and the distant intracranial failure rate was 47%. The 12 month freedom from local recurrence (FFLR) was 77% (63–91%). Median OS (95% CI) was 22.7 (14.6–30.8) months. Patients with a single metastasis had longer FFLR (30.1 vs 14.4 months; p = .014). Median interval from surgery to SRS was 6.3 weeks. Patients with interval > 7 weeks had increased local recurrence (LR) (62%) than < 7 weeks (37%), p = 0.025.Patients with a margin < 2mm were more likely to experience LR (48%) than those with margin equal to 2mm (20%); this approached statistical significance (p = 0.063). The median follow up for all patients was 15.4 months (2–41). CONCLUSION: We determined LC and OS using adjuvant SRS at our institution. Based on the findings of this retrospective review SRS should be given promptly post operatively with a 2mm PTV margin.