Robust Optimization in Simulation: Taguchi and Response Surface Methodology

Optimization of simulated systems is tackled by many methods, but most methods assume known environments. This article, however, develops a 'robust' methodology for uncertain environments. This methodology uses Taguchi's view of the uncertain world, but replaces his statistical techniques by Response Surface Methodology (RSM). George Box originated RSM, and Douglas Montgomery recently extended RSM to robust optimization of real (non-simulated) systems. We combine Taguchi's view with RSM for simulated systems, and apply the resulting methodology to classic Economic Order Quantity (EOQ) inventory models. Our results demonstrate that in general robust optimization requires order quantities that differ from the classic EOQ.Pareto frontier;bootstrap;Latin hypercube sampling

Robust Optimization in Simulation:Taguchi and Krige Combined

Optimization of simulated systems is the goal of many methods, but most methods as- sume known environments. We, however, develop a `robust' methodology that accounts for uncertain environments. Our methodology uses Taguchi's view of the uncertain world, but replaces his statistical techniques by Kriging. We illustrate the resulting methodology through classic Economic Order Quantity (EOQ) inventory models. Our results suggest that robust optimization requires order quantities that dier from the classic EOQ. We also compare our latest results with our previous results that do not use Kriging but Response Surface Methodology (RSM).

Ultrasonic assessment of cesarean section scar to vesicovaginal fold distance: an instrument to estimate pre-labor uterine rupture risk

Background: The number of Cesarean sections (CS) is growing worldwide, intensifying the risk of complications in subsequent pregnancies and leading to increased maternal and fetal morbidity and mortality. In particular, the literature shows a higher risk of uterine rupture (UR) in subsequent pregnancy with trial of labor after cesarean section (TOLAC) Furthermore, there are few data about pre-labor UR in scarred uteri. Objective: Since the key factor for management is timing, the aim of this study was to evaluate the accuracy of prenatal ultrasound (US) of scars in the early determining of pre-labor UR risk in women with a previous CS during their subsequent pregnancy Methods: From April 2014 to November 2018 a retrospective analysis was performed in order to evaluate the scar to vesicovaginal fold (VVF) distance in three patients with pre-labor UR and in 60 cases of the control group. Results: The periconceptional CS scar-VVF distance in the three UR cases resulted significantly increased compared to the controls (23.7 ± 3.5 mm vs 2.3 ± 2.7 mm, p < 005); moreover, a time interval of less than 18 months and a previous pre-labor preterm CS were found as known risk factors. Conclusion: In this study, a higher uterine incision due to placenta previa or isthmic myoma seems to be correlated with a major risk of UR. Therefore, periconceptional US examination of CS-VVF distance, (which represents the level of the previous CS), seems to be a useful predictive factor of pre-labor UR in subsequent pregnancies

Primary Vaginal Carcinoma Arising on Cystocele Mimicking Vulvar Cancer

Background: Primary vaginal carcinoma is a rare gynaecological tumour representing 1%–3% of all gynaecologic cancers. Several studies report increased vaginal cancer risk associated with genital prolapse following the occurrence of inflammatory lesions or decubitus ulcers. Case: We report the rare case of an 82-year-old woman with primary squamous cell carcinoma arising from vaginal wall prolapse. Vaginal carcinoma was suspected during gynaecological examination for vulvar bleeding. A wide local excision was performed and pathologic examination revealed a primary squamous cell carcinoma of the vagina. Conclusion: Persistent genital prolapse may be at risk for vaginal carcinoma, and cytological and a colposcopic assessments are essential to identify patients who require diagnostic biopsy

“Intestinal-Type” Vulvar Adenocarcinoma: A Review of the MITO Rare Tumors Group

Intestinal-type adenocarcinoma (VAIt) represents a sporadic variant of vulvar carcinoma. It appears frequently localized to epithelial glands in the vulvar region, and it probably derives from cloacal remnants persisting in the adult. We performed a systematic review of the limited cases reported in the literature, with the intent to assess the specific peculiarities of this rare neoplasia and to state consistent management recommendations. The principal histological VAIt characteristic is that it resembles mucinous colonic carcinomas. Therefore, immunohistochemical workup, with different tumor markers including CK20, CDX2, and CK7 staining, is needed. To confirm vulvar origin, a thorough diagnostic, and radiological examination is required to rule out other primary malignancies. The gold standard of treatment for VAIt is surgery, with local excision with tumor-free margins. Lymph node staging is an option advised if the tumor size is >2 cm or if lymph node metastases are suspected on imaging. On the other hand, the role of neoadjuvant therapy is still in doubt, but a good response to adjuvant chemotherapy treatments has been described in both advanced and recurrent diseases. Sometimes, VAIt behavior can be unpredictable, with relapses even after many years, so more experiences and longer follow-up periods are needed to elucidate the best therapeutic management and its long-term prognosis

The genomic landscape of 8-oxodG reveals enrichment at specific inherently fragile promoters

8-Oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) is the most common marker of oxidative stress and its accumulation within the genome has been associated with major human health issues such as cancer, aging, cardiovascular and neurodegenerative diseases. The characterization of the different genomic sites where 8-oxodG accumulates and the mechanisms underlying its formation are still poorly understood. Using OxiDIP-seq, we recently derived the genome-wide distribution of 8-oxodG in human non-tumorigenic epithelial breast cells (MCF10A). Here, we identify a subset of human promoters that accumulate 8-oxodG under steady-state condition. 8-oxodG nucleotides co-localize with double strand breaks (DSBs) at bidirectional and CG skewed promoters and their density correlate with RNA Polymerase II co-occupancy and transcription. Furthermore, by performing OxiDIP-seq in quiescent (G0) cells, we found a strong reduction of oxidatively-generated damage in the majority of 8-oxodG-positive promoters in the absence of DNA replication. Overall, our results suggest that the accumulation of 8-oxodG at gene promoters occurs through DNA replication-dependent or -independent mechanisms, with a possible contribution to the formation of cancer-associated translocation events

Germinal ovarian tumors in reproductive age women: Fertility-sparing and outcome

MOGCTs (malignant ovarian germ cell tumors) are rare tumors that mainly affect patients of reproductive age. The aim of this study was to evaluate the fertility and survival outcomes in young women with MOCGTs treated with fertility-sparing surgery (FSS).From 2000 to 2018, data from 28 patients of reproductive age with a diagnosis of MOGCT at the University of Bari were collected. Most received FSS, and in patients treated conservatively, the reproductive outcome and survival were investigated. Data of patient demographics, clinical presentation, oncology marker dosage, staging, type of surgery, histological examination, survival, and reproductive outcome were collected from hospital and office charts. All informed consent was obtained from all patients. The median age was 24 (range: 9-45 years). The majority of the patients had stage IIIC. Twenty-four woman received FSS consisting of unilateral ovariectomy and omentectomy, whereas only 4 women, based on their stage (IIIC), received a radical surgery (hysterectomy with bilateral adnexectomy, lymphadenectomy, and omentectomy). Our study shows that FSS in MOGCTs can produce good results both on reproductive outcomes and on survival. Indeed, in our group, there was only 1 case of exitus as result of recurrence. Furthermore, patients after FSS maintained normal ovarian function and 5 of 5 women who tried to get pregnant succeeded spontaneously. The median follow-up was 90 months (range 3-159).Conservative surgery for MOGCTs should be considered for women of reproductive age who wish to preserve fertility

Reproductive outcomes and fertility preservation strategies in women with malignant ovarian germ cell tumors after fertility sparing surgery

Malignant ovarian germ cell tumors are rare tumors that mainly affect patients of reproductive age. The aim of this study was to investigate the reproductive outcomes and fertility preservation strategies in malignant ovarian germ cell tumors after fertility-sparing surgery. Data in literature support that fertility-sparing surgery is associated with an excellent oncological outcome not only in early stages malignant ovarian germ cell tumors but also in advanced stages. Moreover, the possibility of performing conservative treatment should be considered even in case of relapse or advanced disease, given the high chemosensitivity. Indeed, available data have shown that menstrual function is maintained after platinum-based regimens in over 85–95% of patients with malignant ovarian germ cell tumors and rate of premature menopause reported in literature ranges between 3% and 7.4%, while premature ovarian failure rates are between 3.4% and 5%. Moreover, reproductive outcomes are about 80% with no increase in the risk of teratogenicity compared to general population. Therefore, conservative surgery for malignant ovarian germ cell tumors currently may represent a therapeutic option in patients who wish to preserve fertility but must be available for extended follow-up and after subscribing to informed consent