Public transit infrastructure and heat perceptions in hot and dry climates.

Many cities aim to progress toward their sustainability and public health goals by increasing use of their public transit systems. However, without adequate protective infrastructure that provides thermally comfortable conditions for public transit riders, it can be challenging to reach these goals in hot climates. We took micrometeorological measurements and surveyed riders about their perceptions of heat and heat-coping behaviors at bus stops with a variety of design attributes in Phoenix, AZ, USA, during the summer of 2018. We identified the design attributes and coping behaviors that made riders feel cooler. We observed that current infrastructure standards and material choices for bus stops in Phoenix are insufficient to provide thermal comfort, and can even expose riders to health risks. Almost half of the study participants felt hot or very hot at the time they were surveyed, and more than half reported feeling thermally uncomfortable. On average, shade reduced the physiological equivalent temperature (PET) by 19 °C. Moreover, we found significant diurnal differences in PET reductions from the shade provided by various design attributes. For instance, all design attributes were effective in reducing PET in the morning; however, a vegetated awning did not provide statistically significant shade reductions in the afternoon. Temperatures of sun-exposed surfaces of man-made materials exceeded skin burn thresholds in the afternoon, but shade was effective in bringing the same surfaces to safe levels. Aesthetically pleasing stops were rated as cooler than stops rated as less beautiful. We conclude that cities striving to increase public transit use should prioritize thermal comfort when designing public transit stops in hot climates.

The Impact of COVID-19 Pandemic on Screening Programs for Cervical Cancer Prevention Across Europe.

OBJECTIVE: The aim of the study was to estimate the impact of COVID-19 pandemic on the practice of cervical cancer screening in European countries. MATERIALS AND METHODS: A 3 rounds e-survey was conducted among the 31 European Federation for Colposcopy member countries during 2020. Each representative was asked to answer to each questionnaire for their own country. Questionnaires were not anonymous. The first questionnaire was sent in April 2020 and second and third in June and December 2020, respectively. RESULTS: Twenty five of the 31 European countries solicited responded. A total of 19 countries (70.4%) reported that screening for cervical cancer was suspended at least once during the 3 rounds of questionnaires. In addition, 11 countries reported stopping colposcopy and treatments for cervical precancerous lesions at least once during the 3 rounds of questionnaires. These situations evolved with time, with the highest rate of countries recommending suspension of screening, colposcopy, and treatments during the second round of the survey. At round 3, no country recommended screening, colposcopy, and treatment, and 12 countries (57.5%) reported normal screening was fully implemented. CONCLUSIONS: Our results suggest massive disruption in cervical cancer screening programs across Europe resulting from COVID-19 pandemic. Increase in the incidence of cervical cancer is to be expected.

Incomplete excision of cervical precancer as a predictor of treatment failure: a systematic review and meta-analysis.

BACKGROUND: Incomplete excision of cervical precancer is associated with therapeutic failure and is therefore considered as a quality indicator of clinical practice. Conversely, the risk of preterm birth is reported to correlate with size of cervical excision and therefore balancing the risk of adequate treatment with iatrogenic harm is challenging. We reviewed the literature with an aim to reveal whether incomplete excision, reflected by presence of precancerous tissue at the section margins, or post-treatment HPV testing are accurate predictors of treatment failure. METHODS: We did a systematic review and meta-analysis to assess the risk of therapeutic failure associated with the histological status of the margins of the tissue excised to treat cervical precancer. We estimated the accuracy of the margin status to predict occurrence of residual or recurrent high-grade cervical intraepithelial neoplasia of grade two or worse (CIN2+) and compared it with post-treatment high-risk human papillomavirus (HPV) testing. We searched for published systematic reviews and new references from PubMed-MEDLINE, Embase, and CENTRAL and did also a new search spanning the period Jan 1, 1975, until Feb 1, 2016. Studies were eligible if women underwent treatment by excision of a histologically confirmed CIN2+ lesion, with verification of presence or absence of CIN at the resection margins; were tested by cytology or HPV assay between 3 months and 9 months after treatment; and had subsequent follow-up of at least 18 months post-treatment including histological confirmation of the occurrence of CIN2+. Primary endpoints were the proportion of positive section margins and the occurrence of treatment failure associated with the marginal status, in which treatment failure was defined as occurrence of residual or recurrent CIN2+. Information about positive resection margins and subsequent treatment failure was pooled using procedures for meta-analysis of binomial data and analysed using random-effects models. FINDINGS: 97 studies were eligible for inclusion in the meta-analysis and included 44 446 women treated for cervical precancer. The proportion of positive margins was 23·1% (95% CI 20·4-25·9) overall and varied by treatment procedure (ranging from 17·8% [12·9-23·2] for laser conisation to 25·9% [22·3-29·6] for large loop excision of the transformation zone) and increased by the severity of the treated lesion. The overall risk of residual or recurrent CIN2+ was 6·6% (95% CI 4·9-8·4) and was increased with positive compared with negative resection margins (relative risk 4·8, 95% CI 3·2-7·2). The pooled sensitivity and specificity to predict residual or recurrent CIN2+ was 55·8% (95% CI 45·8-65·5) and 84·4% (79·5-88·4), respectively, for the margin status, and 91·0% (82·3-95·5) and 83·8% (77·7-88·7), respectively, for high-risk HPV testing. A negative high-risk HPV test post treatment was associated with a risk of CIN2+ of 0·8%, whereas this risk was 3·7% when margins were free. INTERPRETATION: The risk of residual or recurrent CIN2+ is significantly greater with involved margins on excisional treatment; however, high-risk HPV post-treatment predicts treatment failure more accurately than margin status. FUNDING: European Federation for Colposcopy and Institut national du Cancer (INCA).

Psycho-social influences upon older women's decision to attend cervical screening: A review of current evidence.

Cervical cancer is the fourth most common cancer in women worldwide (WHO, 2016). In many developed countries the incidence of cervical cancer has been significantly reduced by the introduction of organised screening programmes however, in the UK, a fall in screening coverage is becoming a cause for concern. Much research attention has been afforded to younger women but age stratified mortality and incidence data suggest that older women's screening attendance is also worthy of study. This paper provides a review of current evidence concerning the psycho-social influences that older women experience when deciding whether to attend cervical screening. Few studies have focussed on older women and there are significant methodological issues with those that have included them in their samples. Findings from these studies indicate several barriers which may deter older women from screening, such as embarrassment and logistical issues. Drivers to screening include reassurance and a sense of obligation. Physical, social and emotional changes that occur as women age may also have an impact on attendance. This review concludes that there is a clear need for better understanding of the perceptions of older women specifically with regard to cervical cancer and screening. Future research should inform the design of targeted interventions and provision of information to enable informed decision-making regarding cervical screening among older women.

Defining the Cervical Transformation Zone and Squamocolumnar Junction: Can We Reach a Common Colposcopic and Histologic Definition?

Quality assurance and research in colposcopy and cervical pathology require standardized terminologies and reporting. However, clinical and histologic definitions of the cervical transformation zone (TZ) and squamocolumnar junction (SCJ) vary considerably. We aimed to identify areas of agreement and areas where work is required to standardize the definitions of the TZ and the SCJ. We conducted a survey among the board members of the European Federation of Colposcopy member societies and members of the International Society of Gynecological Pathologists. Overall, 22 expert colposcopists and 34 gynecologic pathologists responded. There was broad agreement that the TZ is the area where squamous metaplasia has occurred. There was consensus that the original SCJ can appear colposcopically indistinct in cases of maturation of the metaplastic squamous epithelium but can be identified histologically by the presence of the so-called last cervical gland. It was agreed that the border between the metaplastic squamous epithelium and the columnar epithelium on the surface of the cervix is called the new SCJ. Areas where work is required include the questions as to whether the cervical crypts lined by columnar epithelium in the field of squamous metaplasia are an integral part of the TZ or not and whether the individual microscopic borders between the metaplastic squamous epithelium of glandular crypts and the residual columnar epithelium of glandular crypts should be considered as part of the new SCJ or not. This paper is a step in an attempt to standardize colposcopic and histologic definitions among colposcopists and pathologists.

The Use of the Colposcopically Directed Punch Biopsy in Clinical Practice: A Survey of British Society of Colposcopy and Cervical Pathology (BSCCP)-Accredited Colposcopists.

OBJECTIVES: The colposcopically directed punch biopsy has been an integral component of colposcopic practice. In light of the changing landscape of the cervical screening programme, a study was conducted to investigate the current practice of British Society of Colposcopy and Cervical Pathology-accredited colposcopists on technique and rationale for performing a punch biopsy. MATERIALS AND METHODS: A web-based questionnaire survey was e-mailed to all British Society of Colposcopy and Cervical Pathology-accredited colposcopists. Questions included selection criteria for performing a punch biopsy, number of biopsies, and technique. Results were analyzed by specialty, experience, and workload. RESULTS: A total of 749 colposcopists responded, 50.2% of the 1,493 total. The respondents were obstetrician and gynecologists (42.9%), gynecologists/oncologists (33.6%), and nurse colposcopists (19.8%). Most colposcopists (78.3%) had more than 5-year colposcopy experience and saw in excess of 11 new cases (73.4%) of abnormal cervical cytology/month. Most colposcopists (56%) aimed to take 2 biopsies to diagnose cervical intraepithelial neoplasia, and very few (16.2%) reported routinely taking random biopsies from normal areas of cervix. Looking at the trends in management in the case scenarios, there was a lower threshold for performing punch biopsy before large loop excision of the transformation zone in younger (age, <25 years) or nulliparous women versus older women (age, >40 years; p < .05). Colposcopists were more likely to take biopsies in women with low-grade cytology/colposcopic findings (71.2%, always or most of the times) as compared with high-grade cytology/colposcopic findings (40.3%, never or rarely). CONCLUSIONS: Colposcopically directed punch biopsy is routinely used by colposcopists; however, techniques, number of biopsies taken, and rationale for performing a biopsy vary greatly between colposcopists.

The Effect of Country of Birth on the Pattern of Disease and Survival From Cervical Cancer.

OBJECTIVE: The aim of the study was to investigate the impact of country of birth on the pattern of disease and survival from cervical cancer in women living in the United Kingdom. MATERIALS AND METHODS: A retrospective database evaluation study was performed to review all cases of cervical cancer diagnosed in the Pan-Birmingham Cancer Network between 2005 and 2009. Population characteristics and survival data were obtained from the West Midlands Cancer Registry and National Health Authority Information System, United Kingdom. Women's country of birth was classified as being high- (including patients born in the United Kingdom and Ireland), middle-, or low-income countries according to the World Bank country classification. Screening histories data were obtained from the West Midlands Cancer Screening Quality Assurance Reference Centre. Overall survival data were analyzed using the nonparametric Kaplan-Meier method with log-rank tests to compare between groups. RESULTS: Four hundred eighty-four cases were identified. A country of birth was available for 459 cases (94.8%). Cancers detected through screening or interval cancers accounted for 140 (28.9%) of cases compared with 226 (46.7%) where women had not complied with screening. Of the women born outside of the United Kingdom/Ireland, 40 (59.7%) originated from low-income, 23 (34.3%) from middle-income, and 4 (6.0%) from high-income countries. Multivariate analysis identified age (p < .001) and stage (p < .001) at diagnosis as having a significant effect on survival, but no effect was seen from social deprivation (p = .18) or economic status of country of birth (p = .30). DISCUSSION: Country of birth is not an independent prognostic indicator for cervical cancer survival.

Success rate of cold coagulation for the treatment of cervical intraepithelial neoplasia: a retrospective analysis of a series of cases.

OBJECTIVE: To establish the cure rate at 1 year of patients who have undergone cold coagulation for the treatment of cervical intraepithelial neoplasia (CIN). DESIGN: Retrospective review of data for all patients at Shrewsbury and Telford NHS Trust who had undergone cold coagulation as part of their treatment for CIN between 2001 and 2011. Follow-up data up to December 2012 were analyzed. SETTING: Colposcopy Department, Shrewsbury and Telford NHS Trust, United Kingdom. POPULATION: Women undergoing cold coagulation for the treatment of CIN between 2001 and 2011, with cytologic follow-up until December 2012. METHODS: Patients were identified using a local colposcopy database. Data were obtained via the local histopathology reporting systems. Statistical analyses were performed using Stata/IC 10.1 software. MAIN OUTCOME MEASURES: Posttreatment cytology and whether subsequent treatment was required, with histology results. RESULTS: Data on 557 patients were collected and analyzed. Pre-cold coagulation treatment histologic findings were CIN 1 in 156 patients (28.01%), CIN 2 in 260 patients (46.68%), and CIN 3 in 141 patients (25.31%). The median length of time between cold coagulation treatment and first follow-up smear, used to calculate cure rates at around 1 year, was 406 days (interquartile range 123 days, range 169-3,116 days). The cure rate after cold coagulation was 95.7% at around 1 year. CONCLUSIONS: Cold coagulation has a cure rate comparable to that of excisional treatments such as large loop excision of the transformation zone and should be considered more widely in patients undergoing primary treatment for CIN, where there is no suspicion of invasive disease on history, examination and cytologic results.

New strategies for the treatment of ovarian cancer.

Ovarian cancer usually responds well to chemotherapy, but once the disease becomes resistant to chemotherapy, the treatment options available are inadequate. A number of strategies are currently undergoing clinical evaluation, among which angiogenesis and PARP [poly(ADP-ribose) polymerase] inhibitors appear promising. Pre-clinical studies have identified several potential new therapeutic strategies, and we review the potential for use of BH3 (Bcl-2 homology) mimetics, autotaxin inhibitors and statins to treat ovarian cancer.

HPV testing and vaccination in Europe.

Current cytology-based screening has a moderate sensitivity to detect cervical intraepithelial neoplasia grade 3 (CIN 3) and cervical cancer even in those states providing rigorous quality control of their cervical screening programs. The impact of vaccination against human papillomavirus (HPV) types 16 and 18 as well as the incorporation of HPV testing on the detection of CIN 3 and cancer is discussed. HPV testing used as a triage for atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesions, test of cure after treatment, and HPV-based primary screening may improve current cervical screening programs.HPV testing as a triage test for ASCUS seems to offer an improved sensitivity, with a similar specificity as compared to repeat cytology for diagnosing high-grade CIN and has been recommended throughout most EU states. HPV testing as a triage test for low-grade squamous intraepithelial lesions has a low specificity and is not recommended in most member states. HPV test of cure offers an improved sensitivity compared to cytology for women with persistent cervical precancer after treatment. HPV-based cervical cancer screening is more effective than screening with cytology. The effects of HPV-based screening depend on the organization of the program and on adherence to algorithms for screening triage. Otherwise, it is likely that HPV-based screening will increase the referral rate to colposcopy including more women with no detectable cervical lesion. HPV vaccination will require many years to evaluate any beneficial effects on cervical cancer incidence and mortality.

The future role for colposcopy in Europe.

Improvements in the performance of cervical screening may be limited by the diagnostic performance of colposcopy. Nonetheless, colposcopy remains the best available tool to assess women considered at high risk for having or developing cervical cancer. The provision and role of colposcopy across Europe is variable. Introduction of vaccination against human papillomavirus (HPV) types 16 and 18 as well as the possible switch to HPV-based screening is likely to change the profiles of women presenting to colposcopy services and provide management difficulties for the colposcopist.The standard of colposcopy in Europe can be maintained or improved despite a variable availability of screening. The prevalence of cervical intraepithelial neoplasia grade 3 may decrease for women having had HPV vaccination. The incidence of cervical intraepithelial neoplasia grade 3 and cervical cancer in second and subsequent rounds of HPV-based screening are likely to decrease compared to cytology-based screening. In HPV-based screening, the numbers of women with no detectable or minor abnormalities at colposcopy and with screen-detected glandular disease are likely to increase. We have considered how these issues will affect states that have varying implementation of organized cervical screening programs and varying degrees of implementation of HPV testing or vaccination.The development of quality assurance across Europe accompanying these program changes is discussed.

Graduate medical education success coaching for residents and fellows: a single-institution real-world experience.

While coaching has been employed as a success strategy in many areas such as athletics and business for decades, its use is relatively new in the medical field despite evidence of its benefits. Implementation and engagement regarding coaching in graduate medical education (GME) for residents and fellows is particularly scarce. We report our three-year experience of a GME success coaching program that aims to help trainees reach their full potential by addressing various areas of medical knowledge, clinical skills, efficiency, interpersonal skills and communication, professionalism, and mental health and well-being. The majority of participants (87%) were identified by themselves, their program director, and/or the GME coaches to have more than one area of need. The majority (79%) of referrals were identified by the coaches to have additional needs to the reasons for referral. We provide a framework for implementation of a GME coaching program and propose that coaching in GME may provide an additional safe environment for learners to reveal areas of concerns or difficulty that otherwise would not be disclosed and/or addressed.

Implementation and Outcomes of an Academic Peer Coaching Program for Pediatric Residents.

Introduction Academic coaching fosters self-directed learning and is growing in popularity within residency programs. Implementation is often limited by available faculty time and funding. Peer coaching is an emerging alternative but is not well studied. This study aims to demonstrate the acceptability, feasibility, and efficacy of a resident peer coaching program. Methodology In the 2021-2022 academic year, within a large pediatric residency program, we selected and trained senior residents as coaches and interns who opted in as coachees. Coaching dyads began meeting in the fall and worked toward individualized goals throughout the year; control interns participated in routine didactics. Outcomes included Accreditation Council for Graduate Medical Education (ACGME) milestone scores and a self-assessment survey (SAS). Results We enrolled 15/42 (36%) interns as coachees, with the remaining 27 (64%) as controls. Narrative feedback from coaches and coachees was overall positive, and time commitment was feasible for program staff (10-12 hours/month), coaches (three to four hours/month), and coachees (one to two hours/month) with minimal financial needs. Post-intervention, more coachees than controls scored ≥4.0 on ACGME milestones systems-based practice 3 (SBP3; 3/15, 20%, vs. 2/27, 7%), SBP4 (4/15, 27%, vs. 5/27, 19%), and practice-based learning and improvement 1 (4/15, 27%, vs. 3/27, 11%). SAS response rate was 8/15 (53%) for coachees and 5/27 (19%) for controls. More coachees than controls reported baseline difficulty with time management often (3/8, 38%, vs. 1/5, 20%); only coachees improved post-intervention, with 0/8 (0%) having difficulty often versus 2/5 (40%) of controls. Conclusions Resident peer coaching is acceptable and feasible to implement. Coachees reported more improvement in time management than controls, and ACGME milestone scores suggest improved use of evidence-based medicine and interprofessional care coordination among coachees.

Navitoclax augments the activity of carboplatin and paclitaxel combinations in ovarian cancer cells.

OBJECTIVES: To evaluate the efficacy of combination of navitoclax, carboplatin and paclitaxel in ovarian cancer. METHODS: 8 ovarian cancer cell lines were treated with either doublet or triplet combinations of navitoclax, carboplatin and paclitaxel. Interactions were assessed by determining a combination index or measuring caspase activity. The effect of the combinations was also evaluated by measuring the inhibition of cells grown as spheroids. RESULTS: Navitoclax exhibited modest (IC(50)=3-8 µM) single agent potency. Antagonism between carboplatin and paclitaxel was evident in Ovcar-4, Ovcar-8 and Skov-3 cells. Drug combinations including navitoclax with carboplatin and/or paclitaxel showed significantly less antagonism, or even synergy, in several cell lines than carboplatin/paclitaxel alone. Navitoclax enhanced the activation of caspase 3/7 induced by carboplatin and/or paclitaxel in Igrov-1 cells. Combinations of navitoclax, carboplatin and paclitaxel showed more than additive activity against Igrov-1 spheroids. CONCLUSIONS: Navitoclax improves the activity of combinations of carboplatin and paclitaxel in vitro. Our observations, taken with other published data, provide a rationale for clinical trials of navitoclax in ovarian cancer in combination with chemotherapy.

Added value of electrical impedance spectroscopy in adjunction of colposcopy: a prospective cohort study.

OBJECTIVE: To assess whether electrical impedance spectroscopy (EIS) as an adjunctive technology enhances the performance of colposcopy. DESIGN: Prospective cohort study. SETTING: University Hospital colposcopy clinic. PARTICIPANTS: Colposcopy with EIS for 647 women and conventional colposcopy for 962 women. INTERVENTIONS: Comparison of the performance of colposcopy by referral cervical cytology in two cohorts, with and without EIS as an adjunctive technology. OUTCOME MEASURES: Prevalence of cervical intraepithelial neoplasia grade 2 or worse (CIN2+), diagnostic testing accuracy to detect CIN2+ with and without EIS and their relative differences between cohorts. RESULTS: The prevalence of CIN2+ varied between the cohorts according to referral cytology: 17.0% after abnormal squamous cells of unknown significance referral cytology in EIS cohort and 9.1% in the reference cohort, 16.5% and 18.9% after low-grade squamous intraepithelial lesion (LSIL), 44.3% and 58.2% after atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (HSIL) (atypical squamous cells that cannot exclude HSIL), and 81.9% and 77.0% after HSIL cytology, respectively. Sensitivity to detect CIN2+ was higher in the EIS cohort, varying from 1.79 (95% CI 1.30 to 2.45) after LSIL referral cytology to 1.16 (95% CI 1.09 to 1.23) after HSIL referral cytology, with correspondingly lower specificity after any referral cytology. CONCLUSIONS: Colposcopy with EIS had overall higher sensitivity but lower specificity to detect CIN2+ than conventional colposcopy. CIN2+ prevalence rates were, however, not consistently higher in the EIS cohort, suggesting innate differences between the cohorts or truly lower detection rates of CIN2+ for EIS, highlighting the need for randomised controlled trials on the effectiveness of EIS.

Is the colposcopically directed punch biopsy a reliable diagnostic test in women with minor cytological lesions?

OBJECTIVE: The study aimed to determine the accuracy of the colposcopy-directed punch biopsy (punch) to detect or exclude high-grade cervical intraepithelial neoplasia (CIN 2 or 3) in women with atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesion (LSIL) cytological result and minor colposcopic findings. MATERIALS AND METHODS: In a diagnostic test accuracy study, women with ASCUS or LSIL cytological result and minor colposcopic changes had a single colposcopy-targeted punch biopsy was performed immediately followed by a loop electrocautery excision procedure (LEEP) biopsy. The trial was powered to detect a level of κ for a dichotomous outcome of 0.4 (i.e., fair-to-moderate agreement), with a two-sided significance level of 5% and a power of 90%. Accuracy parameters were computed using a cutoff for positive punch biopsy result of CIN 1+ and CIN 2+ for an outcome of CIN 2+ and CIN 3+ assessed in the LEEP specimen. RESULTS: Sixty-eight punch biopsy/LEEP-paired samples were analyzed. Of the 8 CIN 3 lesions, 6 and 4 were detected at cutoff CIN 1+ and CIN 2+, respectively (sensitivity, 50% and 75%). The corresponding specificities were 65% (39/60) and 97% (58/60). The punch biopsies identified only 14 (67%) or 6 (20%) of the 21 CIN 2+ lesions at cutoff CIN 1+ or CIN 2+, respectively. Of the punch biopsies, 31 (45.6%) accurately detected the severity of cervical abnormality. CONCLUSIONS: A single colposcopically directed punch biopsy appears to be insufficient to exclude underlying CIN 2 or 3.

HPV vaccination and cervical screening: the knowledge and attitudes of mothers of adolescent girls.

OBJECTIVE: Mothers play a significant role in decision making about human papillomavirus (HPV) vaccination for their daughters and about cervical screening attendance for themselves. This study had three objectives, to explore: (1) mothers' knowledge and attitudes about HPV and HPV vaccination, (2) their knowledge and attitudes about cervical cancer and screening, and (3) whether their daughter's HPV vaccination invitation was an opportunity to nudge mothers to attend screening. DESIGN: 138 women from North Staffordshire completed a cross-sectional survey and 15 took part in follow-up focus groups. RESULTS: Despite high self-reported engagement with both the cervical screening and HPV vaccination programmes, relatively low levels of knowledge and some uncertainty were evident. There was mixed opinion about the potential of using the vaccination invite as an opportunity to nudge mothers to attend cervical screening. CONCLUSION: Even amongst women who do engage positively with the programmes, knowledge is not as complete and certain as it could be. Further research is needed with women who are less likely to accept the vaccination for their daughters. Women need to be better informed, which may go some way to reversing the decline in screening and maintaining high levels of vaccination.

FAU regulates carboplatin resistance in ovarian cancer.

The development of chemotherapy resistance by cancer cells is complex, using different mechanisms and pathways. The gene FAU (Finkel-Biskis-Reilly murine sarcoma virus (FBR-MuSV)-associated ubiquitously expressed gene) was identified through functional expression cloning and previous data have shown that overexpression enhances apoptosis in several cell types. We demonstrate that the expression of FAU was reduced in the A2780cis (cisplatin resistant subclone of A2780) cell line compared with the A2780 ovarian cancer cell line, and was directly related to the cell line's sensitivity to carboplatin. Downregulation of FAU in the A2780 cell line by transfection with two predesigned short-interfering RNAs (siRNAs) to FAU resulted in a significant increase in resistance to carboplatin-induced cell death. Downregulation resulted in increased cell viability and reduced apoptosis after 72 hr of drug treatment compared with the negative controls (Kruskal-Wallis P = 0.0002). Transfection of the A2780cis cell line with the pcDNA3 plasmid containing FAU was associated with increased sensitivity to carboplatin-induced apoptosis, with decreased cell viability and increased apoptosis (Mann Whitney P < 0.0001). The expression of FAU was examined by quantitative real-time reverse transcriptase polymerase chain reaction in normal and malignant ovarian tissue. A significant reduction in the expression of FAU was seen in the malignant compared with normal ovarian samples (Kruskal-Wallis P = 0.0261). These data support a role for FAU in the regulation of platinum-resistance in ovarian cancer. Further research is needed into the apoptotic pathway containing FAU to investigate the potential for targeted therapies to increase or restore the platinum sensitivity of ovarian cancer.

Improving early detection of ovarian cancer.

Ovarian cancer is the fifth most common cancer in women, accounting for more than 6700 new cases diagnosed each year in the U.K. The incidence has increased over the past 20-25 years, particularly in the 65 and over age group. The outcome for women with ovarian cancer is generally poor, with an overall five-year survival rate of less than 35%. Most women are diagnosed with advanced stage disease. Earlier diagnosis could improve survival outcome. Although 93% of women experience symptoms before diagnosis, a GP with an average sized practice may only see one case of ovarian cancer every five years. Evidence has shown that combining a number of symptoms that occur on a persistent or frequent basis (particularly more than 12 times per month) can have a sensitivity of up to 85% and a positive predictive value of the order of 0.2%. NICE recommends that serum CA125 should be the initial test followed by pelvic and abdominal ultrasound if the serum CA125 is abnormal. These tests should be requested by GPs prior to definitive referral. If both tests are abnormal, then these women should be referred on the two-week urgent referral pathway to the local specialist unit. When ultrasound, CA125 and clinical status suggest ovarian cancer, a CT scan of the pelvis and abdomen should be performed to establish the extent of disease.