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To identify priorities for future research into the treatment of bullous pemphigoid, mucous membrane pemphigoid and pemphigus vulgaris, we conducted a Priority Setting Partnership using James Lind Alliance methodology. The top 10 priorities identified in this PSP represent the key questions that patients, carers and healthcare professionals have about the treatment of these diseases and which future research will hopefully address.

PURPOSE The Groningen International Study on Sentinel nodes in Vulvar cancer (GROINSS-V)-II investigated whether inguinofemoral radiotherapy is a safe alternative to inguinofemoral lymphadenectomy (IFL) in vulvar cancer patients with a metastatic sentinel node (SN). METHODS GROINSS-V-II was a prospective multicenter phase-II single-arm treatment trial, including patients with early-stage vulvar cancer (diameter < 4 cm) without signs of lymph node involvement at imaging, who had primary surgical treatment (local excision with SN biopsy). Where the SN was involved (metastasis of any size), inguinofemoral radiotherapy was given (50 Gy). The primary end point was isolated groin recurrence rate at 24 months. Stopping rules were defined for the occurrence of groin recurrences. RESULTS From December 2005 until October 2016, 1,535 eligible patients were registered. The SN showed metastasis in 322 (21.0%) patients. In June 2010, with 91 SN-positive patients included, the stopping rule was activated because the isolated groin recurrence rate in this group went above our predefined threshold. Among 10 patients with an isolated groin recurrence, nine had SN metastases > 2 mm and/or extracapsular spread. The protocol was amended so that those with SN macrometastases (> 2 mm) underwent standard of care (IFL), whereas patients with SN micrometastases (≤ 2 mm) continued to receive inguinofemoral radiotherapy. Among 160 patients with SN micrometastases, 126 received inguinofemoral radiotherapy, with an ipsilateral isolated groin recurrence rate at 2 years of 1.6%. Among 162 patients with SN macrometastases, the isolated groin recurrence rate at 2 years was 22% in those who underwent radiotherapy, and 6.9% in those who underwent IFL ( P = .011). Treatment-related morbidity after radiotherapy was less frequent compared with IFL. CONCLUSION Inguinofemoral radiotherapy is a safe alternative for IFL in patients with SN micrometastases, with minimal morbidity. For patients with SN macrometastasis, radiotherapy with a total dose of 50 Gy resulted in more isolated groin recurrences compared with IFL.

On March 11, 2020 the COVID-19 outbreak was declared a ‘pandemic’ by the World Health Organization. COVID-19 is associated with higher surgical morbidity and mortality. An array of guidelines on the management of cancer during this pandemic have been published since the first reports of the outbreak. This narrative review brings all the relevant information from the guidelines together into one document, to support patient care. We present a detailed review of published guidelines, statements, comments from peer-reviewed journals, and nationally/internationally recognized professional bodies and societies' web pages (in English or with English translation available) between December 1, 2019 and May 27, 2020. Search terms included combinations of COVID, SARS-COV-2, guideline, gynecology, oncology, gynecological, cancer. Recommendations for surgical and oncological prioritization of gynecological cancers are discussed and summarized. The role of minimally invasive surgery, patient perspectives, medico-legal aspects, and clinical trials during the pandemic are also discussed. The consensus is that elective benign surgery should cease and cancer surgery, chemotherapy, and radiotherapy should continue based on prioritization. Patient and staff face-to-face interactions should be limited, and health resources used efficiently using prioritization strategies. This review and the guidelines on which it is based support the difficult decisions currently facing us in gynecological cancer. It is a balancing act: limited resources and a hostile environment pitted against the time-sensitive nature of cancer treatment. We can only hope to do our best for our patients with the resources available to us.

For those with certain recurrent gynaecological cancers where primary management such as chemo-radiotherapy has failed, or in cases of recurrence following primary surgery, pelvic exenteration (PE) is considered the only curative option. Whilst initially considered a morbid procedure, improved surgical techniques, advancing technology, and nuanced reconstructive options have facilitated more radical resections and improved morbidity and mortality. Open PE remains the gold standard approach, however, minimally invasive techniques for PE may lessen morbidity whilst achieving the same oncological outcomes. The objective of this study was to assess the feasibility and safety of minimally invasive PE with a laparoscopic or robot-assisted approach. We also performed a review of the literature on robot-assisted PE which has not been widely reported for cases of recurrent gynaecological malignancy. Between 2015 and 2021six minimally invasive PE were performed. All patients underwent extensive multi-disciplinary assessment and counselling pre-operatively. Patient characteristics, treatment indication, perioperative data, short-term complications, and histological outcomes were recorded. There were two anterior exenterations, three posterior exenterations and one total exenteration performed. The primary cancer stage varied from stage 1a-3b. Five out of six patients had pre-operative chemo-radiotherapy. The average operative time (including surgical docking) was 600 min. Mean blood loss was 400 mL and the average length of stay was eight days. Enhanced recovery practices were used where possible. There were no intraoperative complications and one major post-operative complicationwhich was breakdown of an inferior gluteal artery perforator flap perineal reconstruction. All patients had negative margins at post-operative histopathology. All patients are alive and recurrence free at follow-up, but long-term outcome data is needed. This initial case series suggest that minimally invasive pelvic exenterationcan feasibly be performed in place of open pelvic exenteration. Furthermore, our findings suggest this may be a safe alternative as we report similar findings to the existing literature, however no firm conclusions can be drawn at such an early stage. Long term follow-up data and a larger cohort study will be needed to establish non-inferiority to open PE.

Introduction/Background* MIRRORS (Minimally Invasive Robotic surgery, Role in optimal debulking Ovarian cancer, Recovery & Survival) is the largest prospective cohort study of robotic interval debulking surgery (IDS) in women with advanced-stage epithelial ovarian cancer (EOC) to date. MIRRORS has investigated the feasibility of obtaining consent from women, the acceptability and success of robotic IDS and its impact on short-term surgical outcomes and quality of life. Methodology Eligibility Women with FIGO IIIc-IVb EOC undergoing neo-adjuvant chemotherapy and suitable for IDS. Exclusions: pelvic mass >8cm, extensive HPB and/or extensive bowel involvement. Surgery commenced with an initial laparoscopic assessment, for all women recruited, followed by a decision to proceed immediately to robotic or open IDS. Result(s)* 23/24 eligible women recruited. Following initial diagnostic laparoscopy, 20 women proceeded directly to robotic IDS, 3 women received open IDS. All patients were debulked with maximal surgical effort to R Conclusion* MIRRORS has shown significantly enhanced recovery with short LOS, reduced blood loss and reduced HDU/ITU demands, enabling faster re-commencement of chemotherapy in women with FIGO IIIc-IVb EOC. This proved to be greatly beneficial during the COVID-19 pandemic. In experienced hands robotic IDS proved feasible in cases with a pelvic mass up to 8cm. Robotic surgery is not suitable for peritoneal disease covering the anterior abdominal wall close to port sites but does facilitate pelvic and diaphragmatic stripping and arguably provides better visualisation of these peritoneal surfaces in women with high BMI. The planned multicentre MIRRORS-RCT will assess whether robotic IDS offers improved quality of life and recovery with non-inferior progression-free and overall survival. We present the evolution of our surgical technique with illustrative surgical videos and qualitative patient feedback, supported by the objective surgical outcomes for this trial. Trial Registration ClinicalTrials gov: NCT04402333 ( https://clinicaltrials.gov/ct2/show/study/NCT04402333) ISRCTN ISRCTN74222598 (https://www.isrctn.com/ISRCTN74222598)

Royal Surrey NHS Foundation Trust introduced robotic surgery for uterine corpus cancer in 2010 to support increased access to minimally invasive surgery, a central element of an enhanced recovery after surgery (ERAS) pathway. More than 1750 gynaecological oncology robotic procedures have now been performed at Royal Surrey NHS Foundation Trust. A retrospective cohort study was performed of patients undergoing surgery for uterine corpus cancer between the 1 January 2010 and the 31 December 2019 to evaluate its success. Data was extracted from the dedicated gynaecological oncology database and a detailed notes review performed. During this time; 952 patients received primary surgery for uterine corpus cancer; robotic: n = 734; open: n = 164; other minimally invasive surgery: n = 54. The introduction of the Da VinciTM robot to Royal Surrey NHS Foundation Trust was associated with an increase in the minimally invasive surgery rate. Prior to the introduction of robotic surgery in 2008 the minimally invasive surgery (MIS) rate was 33% for women with uterine corpus cancer undergoing full surgical staging. In 2019, 10 years after the start of the robotic surgery program 91.3% of women with uterine corpus cancer received robotic surgery. Overall the MIS rate increased from 33% in 2008 to 92.9% in 2019. Robotic surgery is associated with a low 30-day mortality (0.1%), low return to theatre (0.5%), a low use of blood transfusion and intensive care (1.8% & 7.2% respectively), low conversion to open surgery (0.5%) and a reduction in median length of stay from 6 days (in 2008) to 1 day, regardless of age/BMI. Robotic survival is consistent with published data. Introduction of the robotic program for the treatment of uterine cancer increased productivity and was associated with a highly predicable patient pathway of care, for high-risk patients, with reduced demands on health services. Future health care commissioning should further expand access to robotic surgery nationally for women with uterine corpus cancer.

Introduction/Background The European Society of Gynaecological Oncology(ESGO) and The British Gynaecological Cancer Society(BGCS) recommend laparoscopic surgery for treatment of endometrial cancer. Conversion rates to open can be high when performing surgical staging, particularly in patients with high BMI. The Royal Surrey in Guildford has been performing laparoscopic surgery for endometrial cancer since 2002 and introduced robotic assistance in January 2010. Since then >1400 gynaecological oncology robotic procedures have been performed: the greatest experience in the UK. Objective Assess surgical outcomes and survival for endometrial cancer since robotic surgery was introduced. Methodology Retrospective cohort study of surgical treatment for corpus cancer using data collected prospectively on a dedicated database between 1st January 2010 and 31st December 2019. Conversation rate to laparotomy(%), estimated blood loss in ml(EBL), mean and median length of stay(LOS) and 30-day mortality rate(n,%) were calculated. Results 952 patients received primary surgery for corpus cancer between 2010–2019 Robotic: 734 operations, conversion rate 0.54% Median EBL 50 ml. Median LOS 1 day, 30-day Mortality 1/734(0.14%) Open: 164 operations, Median EBL 500 ml, Median LOS 6 days, 30-day Mortality 5/164(3.05%). In 2019 115/126(91%) of all operations performed for corpus cancer were performed using the Da Vinci Robot with 9 open. Between 2008 and 2019 the median length of stay for patients with corpus cancer fell, from 6 days to 1 day. The rate performed by minimal access surgery(MAS) increased from 33% to 93% despite an increasingly obese population. Conclusion In 2019, 93% of women treated in Guildford for endometrial cancer, received MAS. Since 2008 our conversion rate to open has fallen from 18% to 1.7%, median EBL from 300 ml to 50 ml and our median LOS from 6 days to 1 night. In our experience, Robotic surgery is extremely well tolerated, safe and predictable. Increasingly, we are performing palliative procedures for women with advanced endometrial cancer with minimal negative impact. Robotic surgery is particularly well suited to high BMI patients; allowing surgical staging to be performed without undue difficulty or surgical compromise. This study demonstrates the lowest 30-day mortality (0.14%) within our robotic cohort. Introduction of the Da Vinci robot in our Centre has led to a revolutionary change in practice with significant patient benefit. Many cases previously thought not fit for surgery at all, are now recommended robotic surgery. Disclosures Anil Tailor: Proctor for Intuitive Surgical Jayanta Chatterjee: paid-lectures on behalf of pharmaceutical companies Agnieszka Michael: Educational-grants: Clovis, GSK, Ipsen, Novartis, Pfizer, and Tesaro Simon Butler-Manuel: Proctor for Intuitive Surgical, Plasma Surgical & Ethicon

Introduction/Background MIRRORS is a UK based prospective feasibility study opened June 2020, following ethics approval. Its purpose is to establish the feasibility of launching a randomised control trial (RCT) of Robotic interval debulking surgery for ovarian cancer (including cancer of the fallopian tube & peritoneum) MIRRORS-RCT in the future. MIRRORS will focus on the feasibility of obtaining consent from women and the acceptability of Robotic interval debulking surgery for advanced ovarian cancer. Methodology Women will be identified through the Gynaecological Oncology multi-disciplinary team meeting. Inclusion Criteria adult women ≥18 years with stage IIIc–IVb ovarian cancer (including cancer of the fallopian tube & peritoneum) undergoing neo–adjuvant chemotherapy considered suitable for interval debulking surgery (IDS). ≤8 cm pelvic mass on CT Exclusion Criteria Pelvic Mass >8 cm open surgical approach considered necessary following MDT review. Women lacking capacity to the extent they are unable to understand or complete trial documentation/questionnaires will be excluded from the trial. MIRRORS inclusion criteria are intentionally wide, not restricting by Body Mass Index (BMI), patient comorbidity or Ca125 values. Surgery will commence with an initial laparoscopic assessment followed by a decision to proceed to robotic or open interval debulking surgery. The aim of surgery is to remove all visible disease safely by whichever route. If conversion to open surgery is required to complete this, then it will be done. Results All women recruited to MIRRORS, whether eventually undergoing robotic or open surgery, will be followed up to assess recovery, complication rate, pain and quality of life. If the following Success Criteria are met, we will progress to MIRRORS-RCT: ≥20% of women eligible for the study accept inclusion in MIRRORS. Robotic IDS Complication rate is not higher than for open interval debulking surgery Conversion to open surgery rate not greater than 50% in patient group deemed suitable for Robotic IDS following initial diagnostic laparoscopy. Conclusion Robotic surgery is unlikely to be suitable in all cases of ovarian cancer, particularly those with large pelvic masses or extensive disease around the upper part of the abdomen, however, it has the potential to provide significant recovery and quality of life benefits. Ultimately we would like to determine whether, in selected women, robotic surgery offers improved quality of life and recovery with equivalent overall and progression free survival. Disclosures Anil Tailor: Proctor for Intuitive Surgical Jayanta Chatterjee: paid-lectures on behalf of pharmaceutical companies Agnieszka Michael: Educational-grants: Clovis, GSK, Ipsen, Novartis, Pfizer, and Tesaro Simon Butler-Manuel: Proctor for Intuitive Surgical, Plasma Surgical & Ethicon

Lung cancer is the 3rd most common cancer in the UK and the numbers of new cases increase every year. In contrast to gastrointestinal tumours and breast cancer, lung cancer, metastases to the female genital tract are incredibly rare with only five cases reported with uterine metastases on review of the published English literature. We report an interesting case of successful ongoing management of metastatic lung cancer to the pelvis along with an extensive literature review. A 47-year-old lady with recurrent respiratory tract symptoms and chest pain was diagnosed with advanced stage non-small-cell lung cancer (Stage T4N2M1A). Five years following diagnosis and several cycles of chemotherapy and radiotherapy, aged 52, she complained of post-menopausal bleeding and pelvic discomfort. An endometrial biopsy confirmed a malignancy morphologically and immunohistochemically similar to her lung adenocarcinoma, in keeping with metastatic disease. She underwent robotic surgery to excise the pelvic organs and successfully gain local disease control. The patient remains clinically stable 3 years following hysterectomy. Although metastases of lung cancer to uterus are very rare, any patient with abnormal uterine bleeding with known cancer should be investigated thoroughly to rule out metastatic disease. Combined multimodal treatment as in this case may increase overall survival.

BACKGROUND We present the largest UK single institute robotic radical hysterectomy (RRH) case series for the management of cervical cancer (CC). METHODS Data were collected on women who had a RRH as primary treatment for stage 1b1 CC between December 2009 and December 2018. RESULTS Ninty women had a robotic hysterectomy. Five-year follow-up data were available for 30%. The disease-free survival at 5 years was 89.6%. Overall survival at 3 and 5 years for death from any cause was 96.1% and 91.4%, respectively. The overall 5-year survival for death from disease only was 92.8%. Overall survival by tumour size alone showed that women with tumours less than 2 cm had a 98.3% 5-year survival compared to 83.4% for tumour size greater than 2 cm. Irrespective of tumour size, those that had no evidence of lymphovascular space invasion had a 100% 5-year survival. CONCLUSION Our preliminary data supports the oncological safety of RRH in a selective cohort of patients with stage 1b1 CC.

Background Hypotension following major abdominal surgery is common, and once hypovolaemia has been optimally treated, is often due to vasodilation which can be treated with vasopressor infusions. There is unpredictability in the dose and duration of post-operative vasopressor infusions, and factors associated with this have not been determined. Methods We present a case series of consecutive patients who received major gynae-oncology surgery delivered within an Enhanced Recovery After Surgery (ERAS) pathway at a single institution. Patients were electively admitted from theatre directly to the intensive care unit (ICU). Data was collected prospectively into electronic databases (Philips ICCA, Wardwatcher) and then retrospectively collated and appropriate statistical analyses were performed. In the absence of a consensus definition of vasoplegia, we, necessarily arbitrarily, chose a noradrenaline dose of > 0.1 mcg/kg/min at 08:00 on the first post-operative day. The rationale is that this would be more than would typically be expected to counteract the vasodilatory effects of epidural analgesia, which is commonly used at our institution. Results Data was collected from 324 patients, all treated between February 2014 and July 2016. The average age was 67 years and 39% received neoadjuvant chemotherapy. The commonest tumour type was ovarian (58%). The median estimated blood loss was 800 ml and epidural analgesia was used in 71%. Fifty per cent received post-operative vasopressor infusions: factors associated with this included epidural use and estimated blood loss. Nineteen per cent met our criteria for vasoplegia: factors associated with this included CRP on post-operative day 1 and P-POSSUM morbidity score. Hospital and ICU length of stay was prolonged in those who had vasoplegia. Conclusions Patients commonly receive vasopressors following major gynae-oncologic surgery, and this can be at relatively high doses. Clinical factors only accounted for a minority of the variability in vasopressor usage—suggesting considerable biological variability. Optimal care of patients having major abdomino-pelvic surgery may include advanced haemodynamic monitoring and ready availability of infused vasopressors, in a suitable environment.

ObjectiveTo identify and prioritise research questions concerning the elective surgical management of children with conditions affecting the lower limb by engaging patients, carers and healthcare professionals.DesignA modified nominal group technique.SettingUK.Participants388 individuals (29 patients, 155 parents/carers, 204 healthcare professionals) were recruited through hospital clinics, patient charities and professional organisations and participated in the initial prioritisation survey; 234 individuals took part in the interim prioritisation survey. 33 individuals (3 patients, 9 parents/carers, 11 healthcare professionals, 7 individuals representing the project’s steering group and 3 James Lind Alliance (JLA) facilitators) attended the final face-to-face workshop to rank the top 10 research priorities.InterventionsSurveys were distributed using various media resources such as newsletters, internet messaging boards and the ‘Paediatric Lower Limb Surgery Priority Setting Partnership (PSP) website. Printed copies of the questionnaire were also made available to families in outpatient clinics.Outcome measuresSurvey results, top 10 and top 26 priority rankingsResultsThe process took 18 months to complete (July 2017–January 2019); 388 people generated 1023 questions; a total of 801 research questions were classified as true uncertainties. Following the JLA methodology, 75 uncertainties were developed from the initial 801 questions. Twenty six of those were selected through a second survey and were taken to the final face-to-face workshop where the top 10 research priorities were selected. The top10 priorities included questions on cerebral palsy, common hip conditions (ie, Perthes’ disease and developmental dysplasia of the hip) as well as rehabilitation techniques and methods to improve shared decision-making between clinicians and patients/families.ConclusionsThis is the first JLA PSP in children’s orthopaedic surgery, a particularly under-researched and underfunded area. We have identified important research topics which will guide researchers and funders and direct their efforts in future research.

ObjectiveTo determine research priorities for the management of broken bones of the upper limb in people over 50, which represent the shared priorities of patients, their families, carers and healthcare professionals.Design/settingA national (UK) research priority setting partnership.ParticipantsPeople aged 50 and over who have experienced a fracture of the upper limb, carers involved in their care, family and friends of patients, healthcare professionals involved in the treatment of these patients.MethodsUsing a multiphase methodology in partnership with the James Lind Alliance over 15 months (September 2017 to December 2018), a national scoping survey asked respondents to submit their research uncertainties. These were amalgamated into a smaller number of research questions. The existing evidence was searched to ensure that the questions had not already been answered. A second national survey asked respondents to prioritise the research questions. A final shortlist of 25 questions was taken to a multi-stakeholder workshop where a consensus was reached on the top 10 priorities.ResultsThere were 1898 original uncertainties submitted by 328 respondents to the first survey. These original uncertainties were refined into 51 research questions of which 50 were judged to be true uncertainties following a review of the research evidence. There were 209 respondents to the second (interim prioritisation) survey. The top 10 priorities encompass a broad range of uncertainties in management and rehabilitation of upper limb fractures.ConclusionsThe top 10 UK research priorities highlight uncertainties in how we assess outcomes, provide information, achieve pain control, rationalise surgical intervention, optimise rehabilitation and provide psychological support. The breadth of these research areas highlights the value of this methodology. This work should help to steer research in this area for the next 5–10 years and the challenge for researchers now is to refine and deliver answers to these research priorities.

In 2011, the City of Philadelphia, Pennsylvania; the Southeastern Pennsylvania Transportation Authority (SEPTA); and the Delaware Valley Regional Planning Commission (DVRPC) launched the Route 47 Service Enhancement Pilot Project. This project was conceived within the framework of the Transit First Committee. The pilot presented an opportunity to evaluate the effectiveness of low-cost operational initiatives that might have the ability to improve transit services in dense, urban environments. These strategies included bus stop consolidation, farside stop placement, and the switch from a time point-based scheduling system to a headway-based scheduling system. This joint initiative served as a test of the potential to build community support for a pilot, the impact of the interventions themselves, and the ability of the Transit First Committee to work together collaboratively. Although the pilot initiative did not deliver the time savings expected, the process provided important lessons for the city, SEPTA,...

A number of influences including legislation, industry and academia have encouraged advances in computational toxicology and high-throughput testing to probe more broadly putative toxicity pathways. The aim of the 25th United Kingdom Mutagen Society (UKEMS) Industrial Genotoxicity Group Annual Meeting 2011 was to explore current and upcoming research tools that may provide new cancer risk estimation approaches and discuss the genotoxicity testing paradigm of the future. The meeting considered whether computer modelling, molecular biology systems and/or adverse outcome pathway approaches can provide more accurate toxicity predictions and whether high-content study data, pluripotent stem cells or new scientific disciplines, such as epigenetics and adductomics, could be integrated into the risk assessment process. With close collaboration between industry, academia and regulators next generation predictive models and high-content tools have the potential to transform genetic toxicology testing in the 21st century.

The synthesis of pharmaceutical products often involves the use of reactive starting materials and intermediates. Low levels may be present in the final product as impurities and of particular concern are impurities that have mutagenic and carcinogenic potential. Regulatory guidance documents provide a general framework to minimise human exposure to these impurities; however, compound-specific recommendations are limited. Our practical experience with 11 pharmaceutical impurities is presented. The genotoxicity and carcinogenicity data are summarised and the approach used to derive an acceptable daily intake (ADI) is described for each chemical. We have highlighted the considerations and challenges associated with calculating ADIs based on available carcinogenicity data. This may provide a useful reference to others in the pharmaceutical industry regarding impurity control, where the weight of evidence indicates the chemical is a mutagenic carcinogen.

The Texas state gas tax has been 20 cents per gallon since 1991, and the federal gas tax has been 18.4 cents per gallon since 1993. The gas tax is not only stagnant but also depreciating in value because of inflation. Thus, the money needed to maintain the infrastructure and improve roadways is not being adequately generated. One proposed alternative to the gas tax is the creation of a fee for vehicle miles traveled (VMT), with equity being a crucial issue. This research used Texas data from the 2009 National Household Travel Survey to consider the equity impacts of four VMT-fee scenarios. Data were filtered and weighted to reflect results representative of Texas vehicle-owning households in 2008. Each scenario was run both statically and dynamically under the assumption that the VMT fee would replace the state gas tax. On the basis of quantitative measures, the vertical equity of all proposed VMT-fee scenarios and that of the current state gas tax were similar. In terms of horizontal equity, Scenario 4 was designed to be inherently horizontally equitable: charging different rates for travel on urban roadways and rural roadways corresponding to funding needs associated with that roadway type. Scenario 3, which favored fuel-efficient vehicles, was found to be the least horizontally equitable and caused rural households to contribute the highest percentage of revenue of all scenarios considered. All other scenarios were found to be more horizontally equitable than the current state gas tax.

The androgen receptor (AR) is a ligand-dependent transcription factor, expressed in male and female reproductive organs, and essential for normal reproduction in both sexes. The levels of AR are tightly controlled in androgen-responsive cells in which it plays a central role in the regulation of target gene expression. The AR is abundantly expressed in human endometrial stromal cells (HESCs), but levels decline markedly after differentiation into decidual cells in vivo and in primary cultures. Decidualization profoundly down-regulated AR protein levels with no discernible effect on either AR mRNA or protein stability, suggesting that loss of the receptor was a consequence of translational inhibition. Here we show that HESCs express three RNA-binding proteins, Hu antigen R and the poly(C)-binding proteins PCBP1 and PCBP2, that reportedly target the 3′-untranslated region of AR transcripts. Only PCBP1 expression was enhanced in secretory endometrium in vivo and in decidualizing HESCs. Furthermore, knockdown of PCBP1 in decidualizing cells was sufficient to restore AR protein levels, indicating that loss of the AR protein is primarily the consequence of a translational block. PCBP1 also blocked AR translation in a cell-free system, although this did not require binding to the 3′-untranslated region of the receptor mRNA. Furthermore, knockdown of PCBP1 in the prostate cancer LNCaP cell line also increased AR protein. Therefore, PCBP1 plays a major role in the dynamic expression of AR in both male and female androgen-responsive cells.

• The incidence of cancers in young women is rising. • Fertility-saving treatment options are available for cervical, endometrial and ovarian cancer. • Fertility-sparing options are usually more appropriate when the cancer is at an early stage. Learning objectives: • To be able to identify the different fertility-saving surgical options for women diagnosed with cervical, endometrial and ovarian cancer. • To understand the advantages and limitations of fertility-saving surgery in women with gynaecological malignancy. • To understand that fertility-saving surgery is not appropriate in all cases. Ethical issues: • Treatments that save fertility may result in other morbidities such as premature delivery. • Long-term follow-up data on some methods of fertility-saving surgery are limited and, therefore, women may be compromising their survival to preserve fertility. Please cite this article as: Ellis P, Mould T. Fertility-saving treatment in gynaecological oncology. The Obstetrician & Gynaecologist 2009;11:239–244.

Since 1947, the continuing dispute over Kashmir has seen large-scale permanent as well as temporary displacements of sections of the Kashmiri population. The majority of those affected by these events have been Muslims who have sought sanctuary in Azad Kashmir and, subsequently, in Pakistan. These waves of forced migration and the associated hard ships, however, have not appeared in international or regional refugee statistics. This paper details the displacement events and statistics, and explores refugee discourse to locate the reasons behind the non-appearance of these refugees on regional and international agendas. The authors then focus on the ways in which the presence of the Kashmiri refugees, particularly in Azad Kashmir, has contributed to the development of a Kashmiri conscious ness, or Kashmiriyat, within Kashmiri communities in Azad Kashmir and the Kashmiri diaspora. The work presented here is based on documentary analysis, discussions with Kashmiris living in the diaspora, and observations fr...

Despite 20 years of official concern, women scientists in the United Kingdom are still unrepresented in the higher echelons of U.K. science, engineering, and technology and limited in their opportunities for advancement. The author attributes this to the organization and structure of scientific work, together with male “ownership” of science (even where women are a sizeable minority), rather than to the choices women make. Conflict with childbearing and child raising is significant in science more than in law and medicine because external funding sources and large, rigid laboratory organizations disparage and hence disadvantage part-time scientists. Perception is another factor. Women scientists are not seen as equally committed to their work or as eager for advancement. Industrial employment, which should be freer of some of the problems in academic or research science, nevertheless shows restrictions on women’s advancement, too.

The reinvigoration of evolutionary theory over the past two decades has highlighted a number of key findings regarding sex differences that have significant implications for feminist politics. An impartial consideration of biological influences is crucial for proceeding towards the goal of sexual equality within public policy. However, many non-evolutionary feminists claim that evolutionary/biological thinking is fairly useless (or even dangerous) when it comes to most aspects of human social behavior. This paper serves two functions. It (1) traces the history of, and contention surrounding, evolutionary thinking within the field of political science; and (2) examines feminist politics with an evolutionary lens.

Although risky/harmful drinking, in the form of binge drinking, remains a national problem, only recently have health services in universities systematically screened for drinking, drug use, and smoking. This article recounts "lessons learned" in two nurse-directed, interdisciplinary health services, which adapted the National College Depression Partnership model to include screening and brief intervention (SBIRT) for risky/harmful alcohol use in the form of binge drinking. Using a planned change model, nurse leaders worked with university administrators, providers, and health service staff to screen all students seeking health services for risky drinking. The outcomes suggest that this process may increase staff and student awareness of the importance of alcohol consumption to health, show the ease of using SBIRT screening along with standard screening tools, and yield information on the normalization of high-risk drinking in collegiate settings. Project findings indicate that common perceptions in college students minimize negative outcomes and stress the importance of additional quality assurance initiatives that review the efficacy of combinations of standardized screening tools.

Glioblastoma multiforme (GBM) is the most common primary intrinsic central nervous system tumor and has an extremely poor overall survival with only 10% patients being alive after 5 years. There has been interesting preliminary evidence suggesting that diabetic patients receiving peroxisome proliferator-activated receptor gamma (PPARγ) agonists, a group of anti-diabetic, thiazolidinedione drugs, have an increased median survival for glioblastoma. Although thiazolidinediones are effective oral medications for type 2 diabetes, certain agonists carry the risk for congestive heart failure, myocardial infarction, cardiovascular disease, bone loss, weight gain, and fluid retention as side-effects. The nuclear receptor transcription factor PPARγ has been found to be expressed in high grade gliomas, and its activation has been shown to have several antineoplastic effects on human and rat glioma cell lines, and in some instances an additional protective increase in antioxidant enzymes has been observed in normal astrocytes. At present, no clinical trials are underway with regards to treating glioma patients using PPARγ agonists. This review presents the case for evaluating the potential of PPARγ agonists as novel adjuvants in the treatment of refractory high grade glioma.

The Kashmiri population in Britain has developed a political presence which has had an influence on British politics and parliamentary activity. This phenomenon not only demonstrates the complexities of ‘ethnic politics’, but also the involvement with issues outside of the domestic arena of British politics. Along with other South Asian populations, the Kashmiris have become a fast growing and concentrated electorate within the older urban areas of Britain, and therefore of importance to the political parties. However, the political activity within this group has been focused primarily on the external situation of the unresolved Kashmir dispute. Kashmiris believe that the past colonial involvement confers a moral obligation upon Britain to take action in this dispute. The oppressive actions by the Indian state in Kashmir over the recent years have increased these political pressures. One significant outcome has been the formation of the All Party Kashmir Parliamentary Group, and the associated ta...

In this article, the writer draws on her extensive experience working in community development, with women in the Caribbean, and with using participatory methodology in training and research to examine the issues related to assessing the impact of development projects on men and women. She uses the example of training, research, and evaluation activities carried out with, and undertaken by, people in rural communities to illustrate how gender-sensitive impact assessment can be done.

We developed a survey to assess the prevalence and use of protocols in college health services, using the college health nurse as the primary focus. Three thousand and twenty copies of the survey were mailed to individual and institutional members of the American College Health Association (ACHA), and 812 surveys were returned, yielding a return rate of 25%. The data, which came from all 50 states, Canada, and Guam, were then compiled and analyzed using computer software dBase III. The generalizability of the results are somewhat limited because some surveys were returned with unanswered questions and because duplicate surveys were received from some facilities.

Objective: To implement a pilot quality improvement project for depression identification and treatment in college health. Participants: Eight college health center teams composed primarily of primary care and counseling service directors and clinicians. Methods: Chronic (Collaborative) Care Model (CCM) used with standardized screening to identify, treat, and track depressed students for 12 weeks to monitor predetermined process and clinical outcomes. Results: Of all students receiving primary medical care services between January 2007 and May 2008, 69% (n = 71,908) were screened for depression. A total of 801 depressed students were treated and tracked; most predetermined treatment process and clinical outcome targets were achieved. Conclusion: The CCM for depression shows promise for improving depression identification and care for college students.

Objectives: The growing prevalence of endometrial cancer has made it necessary to characterize its molecular and clinical properties and to develop new strategies in treating this disease. A number of molecular and genetic events have been observed in endometrial cancers, which have enabled us to have a better understanding of the biology and development of the disease. For example, PTEN/AKT pathway and its downstream targets and the mTOR (mammalian target of rapamycin) pathway have been shown to play an important role in endometrial cancer pathogenesis. Novel therapies, such as drugs that target cellular pathways, for example, mTOR inhibitor deforolimus, an analog of rapamycin, have been developed and used in clinical trials to treat women with progressive endometrial cancer. This review outlines the data on the molecular and translational aspects of endometrial cancers and the risk factors. Methods: A literature search was performed using PubMed and OvidSP entering the words endometrial cancer and molecular characteristics and endometrial cancer and risk factors. Results: An evidence-based summary of the data on the molecular and translational aspects of endometrial cancers and risk factors was obtained. Conclusions: Clear understanding of the cellular and molecular pathways and risk factors involved in endometrial tumorigenesis may allow us to identify women at risk of developing endometrial cancer and possibly intervene to prevent cancer development.

An international, multi-lab trial was conducted to evaluate a flow cytometry-based method for scoring micronuclei in mouse lymphoma L5178Y cells [S.L. Avlasevich, S.M. Bryce, S.E. Cairns, S.D. Dertinger, In vitro micronucleus scoring by flow cytometry: differential staining of micronuclei versus apoptotic and necrotic chromatin enhances assay reliability, Environ. Mol. Mutagen. 47 (2006) 56–66]. A reference laboratory investigated the potential of six chemicals to induce micronuclei—the genotoxicants mitomycin C (MMC), etoposide (ETOPO), and vinblastine (VB), and the non-genotoxicants sucrose (SUC), staurosporine (STS), and dexamethasone (DEX). The latter two non-genotoxicants were selected as extreme challenges to the assay because of their potent apoptogenic activity. Three collaborating laboratories were supplied with prototype In Vitro MicroFlow™ kits, and each was assigned one genotoxicant and one non-genotoxicant. Cells were treated continuously for 24 h over a range of concentrations up to 5 mg/ml, or overtly cytotoxic concentrations. Micronuclei were scored via standard microscopy and flow cytometry. In addition to enumerating micronucleus frequencies, a cytotoxicity measurement that is simultaneously acquired with the flow cytometric micronucleus scoring procedure was evaluated (Flow-NBR). With this method, latex particles served as counting beads, and facilitated relative survival measurements that exclude the presence of dead/dying cells. For comparison purposes, additional cytotoxicity endpoints were measured, including several that are based on cell number, and others that reflect compromised membrane integrity, including dye permeability and/or phospholipid distribution. Key findings for this set of compounds include the following: (1) significant discrepancies in top concentration selection were found when cytotoxicity measurements were based on different methods, with the Flow-NBR approach tending to be the most sensitive, (2) both microscopy- and flow cytometry-based scoring methods detected concentration-dependent micronucleus formation for the three genotoxic agents studied, with good agreement between the reference laboratory and the collaborating laboratories, and (3) whereas flow cytometric analyses showed no significant increases for the non-genotoxicants when top concentration selection was based on Flow-NBR, significantly elevated micronucleus frequencies were observed for concentrations that were chosen based on less-sensitive cytotoxicity assays. Collectively, these results indicate that rapid assessment of genotoxicity can be accomplished with a relatively simple flow cytometric technique, and that the scoring system is transferable across laboratories. Furthermore, a concurrent assessment of cytotoxicity, Flow-NBR, may help reduce the occurrence of irrelevant positive results, as it may represent a more appropriate means for choosing top concentration levels. Finally, the data presented herein reinforce concerns about the manner in which cytotoxicity limits are described in guidance documents, since these recommendations tend to cite fixed cut-off values without reference to methodology.

Sixteen coded compounds were blind-tested at 4 laboratories using the recently described GADD45a-GFP genotoxicity assay. The compounds were chosen to include non-genotoxic compounds as well as weak and strong genotoxins. None of the compounds required metabolic activation in order to exhibit genotoxic effects. The participating laboratories included 2 global pharmaceutical companies, a global consumer goods company and the Gentronix laboratory in Manchester. Each compound was tested 4 times on different days following a protocol previously described. The tests were carried out after a 3-day training period from the parent lab (Manchester). Following the exclusion of data from tests with positive control failures and data series with 'spikes', 92% of assays gave the correct result: non-genotoxins giving negative results and genotoxins giving positive results. There were no randomly distributed problems suggesting that differences between the results from different sites reflected the use of different instruments, procedural differences and operator experience. In naive operator laboratories the quality of data improved with operator practice. It was concluded that simple clarification of the protocol would provide the level of reliability required for widespread use of the assay in hazard assessment.

Identity and diversity in all its forms present major challenges to countries seeking to best equip citizens with the skills to participate effectively in their diverse societies. The project on Citizenship education in the Commonwealth is one of the followup activities being undertaken by the Commonwealth Secretariat in response to a mandate from Commonwealth Heads of Government and Ministers of Education. It is a component of the Secretariat’s education programme, examining how values are transmitted in society. These books focus on the outcomes of this project in the respective countries, providing valuable insights into the strengthening of values in a society. They set out the strategies and actions needed to support small states wishing to promote the values of good citizenship.

40 men and 40 women university students responded to a questionnaire in which were assessed their attitudes towards the future of Europe as nations divided along political grounds or ethnicity. Half of the items on the questionnaire assessed the extent to which respondents consider the issue of ethnicity (e.g., language, flag, culture) as a factor important to such a division. The other half were directed to evaluating respondents' views on whether the political gains should be considered were European nations to divide. Analysis showed that respondents considered the issue of ethnicity a more motivating force for division than politics. Moreover, there were significant gender differences, with men showing significantly stronger positive views on both issues of ethnicity and politics than women.