Applying machine learning in the investigation of the link between the high-velocity streams of charged solar particles and precipitation-induced floods.

This study explores a possible link between solar activity and floods caused by precipitation. For this purpose, discrete blocks of data for 89 separate flood events in Europe in the period 2009-2018 were used. Solar activity parameters with a time lag of 0-11 days were used as input data of the model, while precipitation data in the 12 days preceding the flood were used as output data. The level of randomness of the input and output time series was determined by correlation analysis, while the potential causal relationship was established by applying machine learning classification predictive modeling. A total of 25 distinct machine-learning algorithms and four model ensembles were applied. It was shown that in 81% of cases, the designed model could explain the occurrence or absence of precipitation-induced floods 9 days in advance. Differential proton flux in the 0.068-0.115 MeV and integral proton flux > 2.5 MeV were found to be the most important factors for forecasting precipitation-induced floods. The study confirmed that machine learning is a valuable technique for establishing nonlinear relationships between solar activity parameters and the onset of floods induced by precipitation.

Seven days ex vivo perfusion of whole ewe ovaries with follicular maturation and oocyte retrieval: towards the development of an alternative fertility preservation method.

Fertility preservation methods for prepubertal women about to undergo gonadotoxic chemo and/or radiation therapy are limited. Therefore, the aim of this study was to investigate the feasibility to develop an alternative fertility preservation method based on an ex vivo perfusion platform for whole ewe ovaries. Thirteen ewe ovaries were divided into two groups (group 1 and 2) that were perfused in a bioreactor for up to 7days. Group 1 (n =3) were stimulated with human menopausal gonadotropin (hMG) administered in single daily dose, while group 2 (n =10) were stimulated continuously for 24h. The perfused ovaries in group 1 showed no significant differences in follicular density, sub-follicular morphology and oocyte quality after ischaemia and after ex vivo perfusion compared with non-perfused control ovaries. The perfused ovaries in group 2 showed a significant decrease in the follicular reserve and oocyte quality compared with the control group. In total, 16 GV-MI oocytes were retrieved from both groups. This study describes for the first time the ex vivo maintenance of viable follicles of ewe ovaries with oocyte integrity and the retrieval of oocytes after ex vivo hormonal perfusion with two different protocols for up to 7days.

Generic approach in a gradient elution HPLC method development that enables troubleshooting free method transfer.

Nowadays, method development is strongly focused on reducing time needed for method development and execution. This subject specially concerns gradient elution methods regarding the usual need for troubleshooting assistance with uncertain outcome during the method transfer from one laboratory to another. One of the main reasons for this situation is the dwell volume difference between HPLC systems. Therefore, the aim of this study was to propose a novel method development methodology that would integrate the dwell volumes differences in the optimization process. The proposed approach could be quite useful in industry that has insight in HPLC instruments planned to be used during the method life cycle. It was tested on the model mixture consisting of dabigatran etexilate mesylate and its nine impurities by use of experimental design methodology. Three different (U)HPLC instruments with high dwell volume differences were selected to challenge the methodology. Plan of experiments was defined with Plackett-Burman design for screening phase and D-optimal design for optimization phase. Initial and final amount of organic modifier, time of the gradient elution and pH value of the aqueous phase were selected as variables significant for the gradient programme profile and included in the optimization stage along with dwell volume values. The separation criteria s between critical peak pairs was selected as output for method optimization while indirect modelling together with Monte Carlo simulations enabled selection of optimal and robust chromatographic conditions. They included 24% (v/v) of initial amount of acetonitrile, 54% (v/v) of the final amount of acetonitrile, 15 min of gradient elution run time and pH value equal to 4.9. The proposed method was successfully validated, met all validation criteria and thus proved its utility.

Integrating in silico with in vivo approach to investigate phthalate and bisphenol A mixture-linked asthma development: Positive probiotic intervention.

The aim of this study was to explore the mechanisms of bis(2- ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP) and bisphenol A (BPA) mixture-induced asthma development and test probiotic as a potential positive intervention. Comparative Toxicogenomics Database (CTD) and ToppGene Suite were used as the main tools for in silico analysis. In vivo 28-day experiment was conducted on rats - seven groups (n = 6): (1) Control: corn oil, (2) P: probiotic (8.78 * 108 CFU/kg/day); (3) DEHP: 50 mg/kg b.w./day, (4) DBP: 50 mg/kg b.w./day, (5) BPA: 25 mg/kg b.w./day; (6) MIX: DEHP + DBP + BPA; (7) MIX + P. Lungs, thymus and kidneys were extracted and prepared for redox status and essential metals analysis. By conducting additional in vitro experiment, probiotic phthalate and BPA binding ability was explored. There were 24 DEHP, DBP and BPA asthma-related genes, indicating the three most probable mechanisms - apoptosis, inflammation and oxidative stress. In vivo experiment confirmed that significant changes in redox status/essential metal parameters were either prominent, or only present in the MIX group, indicating possible additive effects. In vitro experiment confirmed the ability of the multy-strain probiotic to bind DEHP/DBP/BPA mixture, while probiotic administration ameliorated mixture-induced changes in rat tissue.

A prospective study of women and girls undergoing fertility preservation due to oncologic and non-oncologic indications in Sweden-Trends in patients' choices and benefit of the chosen methods after long-term follow up.

INTRODUCTION: In Scandinavian countries, programs for fertility preservation are offered free of charge at tertiary-care university hospitals to all patients facing treatments with risk of subsequent sterility. In this prospective study we aimed to investigate trends in female patients' choices after counseling and fertility preservation outcomes during follow up in relation to benign vs malignant indications. MATERIAL AND METHODS: Data on 1254 females including 1076 adults and 178 girls who received fertility preservation counseling for either oncologic (n = 852) or benign indications (n = 402) at Karolinska University Hospital, Stockholm, between 1 October 1998 and 1 December 2018 were analyzed. As appropriate, t tests and chi-square tests were used to compare groups. Logistic regression was used to compare outcomes among groups depending on indications. RESULTS: Adult women generally elected to undergo oocyte retrieval after controlled ovarian stimulation for cryopreservation of embryos or oocytes (n = 538, 73%), whereas a minor proportion opted for cryopreservation of ovarian tissue retrieved through laparoscopy (n = 221, 27%). More than half of the women with a partner chose either not to fertilize their oocytes aiming at cryopreservation of oocytes or to share obtained oocytes attempting both cryopreservation of oocytes and cryopreservation of embryos. All pre-pubertal (n = 48) and 73% of post-pubertal girls (n = 66) elected cryopreservation of ovarian tissue. In recent years, an increasing number of teenagers have opted for controlled ovarian stimulation aiming at cryopreservation of oocytes, either before (n = 24, 17%) or after completion of cancer treatment (n = 15, 10%). During follow up, 27% of the women returned for a new reproductive counseling, additional fertility preservation or to attempt pregnancy. Utilization rates among individuals who were alive and of childbearing age by December 2018 indicated 29%, 8% and 5% for embryos, oocytes and ovarian tissue with live birth rates of 54%, 46% and 7%, respectively. Women with benign indications were significantly younger than women with previous malignant indications at the time of attempting pregnancy. Although the pregnancy rates were similar among both groups, the live birth rate was significantly higher in women with benign vs previous malignant indications (47% vs 21%, P = .002). CONCLUSIONS: Trends in fertility preservation choices have changed over time. Women with previous malignancy had lower live birth rates than women with benign fertility preservation indications.

Simulation for Training and Assessment in Hysteroscopy: A Systematic Review.

Hysteroscopy simulation complements conventional training on patients, yet evidence-based recommendations about its implementation and use are lacking. This systematic review analyzes and critically discusses hysteroscopy simulation literature published over the last 30 years. Systematic searches on PubMed, Embase, PsychINFO, ERIC, and the Cochrane Library produced 27 original articles published through 2017. Strategies based on different simulation models (e.g., animal organs, vegetables, synthetic uteri, virtual reality) were evaluated by users and appeared to facilitate learning. Observational studies have suggested a large impact on the knowledge and technical skills of novices for a wide range of hysteroscopic procedures, including for diagnosis, resection, and sterilization. Pretest/posttest studies show large improvements in performance time (6 studies; pooled effect size, 1.45; 95% confidence interval, 1.06-1.85) and overall performance scores (4 studies; pooled effect size, 3.19; 95% confidence interval, 1.45-4.94). Additionally, performance assessment on simulated models distinguishes novices from experts. Caution should be exercised because the available evidence largely originates from heterogeneous studies with weak designs, conducted in experimental settings with nonclinical participants (i.e., medical students). Moreover, neither clinical outcomes nor the clinical value of simulation-based assessment has been addressed. Hysteroscopy simulation may be supported ethically and pedagogically, but its role should be evaluated in pragmatic contexts, with robust interventional studies and broader competence-defining outcomes that include nontechnical skills.

Livebirth after uterus transplantation.

BACKGROUND: Uterus transplantation is the first available treatment for absolute uterine infertility, which is caused by absence of the uterus or the presence of a non-functional uterus. Eleven human uterus transplantation attempts have been done worldwide but no livebirth has yet been reported. METHODS: In 2013, a 35-year-old woman with congenital absence of the uterus (Rokitansky syndrome) underwent transplantation of the uterus in Sahlgrenska University Hospital, Gothenburg, Sweden. The uterus was donated from a living, 61-year-old, two-parous woman. In-vitro fertilisation treatment of the recipient and her partner had been done before transplantation, from which 11 embryos were cryopreserved. FINDINGS: The recipient and the donor had essentially uneventful postoperative recoveries. The recipient's first menstruation occurred 43 days after transplantation and she continued to menstruate at regular intervals of between 26 and 36 days (median 32 days). 1 year after transplantation, the recipient underwent her first single embryo transfer, which resulted in pregnancy. She was then given triple immunosuppression (tacrolimus, azathioprine, and corticosteroids), which was continued throughout pregnancy. She had three episodes of mild rejection, one of which occurred during pregnancy. These episodes were all reversed by corticosteroid treatment. Fetal growth parameters and blood flows of the uterine arteries and umbilical cord were normal throughout pregnancy. The patient was admitted with pre-eclampsia at 31 full weeks and 5 days, and 16 h later a caesarean section was done because of abnormal cardiotocography. A male baby with a normal birthweight for gestational age (1775 g) and with APGAR scores 9, 9, 10 was born. INTERPRETATION: We describe the first livebirth after uterus transplantation. This report is a proof-of-concept for uterus transplantation as a treatment for uterine factor infertility. Furthermore, the results show the feasibility of live uterus donation, even from a postmenopausal donor. FUNDING: Jane and Dan Olsson Foundation for Science.

Viability and function of the cryopreserved whole rat ovary: comparison between slow-freezing and vitrification.

OBJECTIVE: To investigate four different protocols for cryopreservation of the whole rat ovary with intact vasculature to evaluate whether differences exist in post-thawing viability of the ovary after either vitrification or slow freezing. DESIGN: Experimental study. SETTING: Obstetrics and gynecology department. ANIMAL(S): Immature Sprague-Dawley female rats. INTERVENTION(S): Ovaries were isolated with the vascular tree intact up to the bifurcation of the abdominal aorta and were subsequently cannulated. The ovaries were flushed with increasing concentrations of the cryoprotectant dimethyl sulfoxide (DMSO) to either 1.5 or 7 M. The ovaries underwent cryopreservation by vitrification or passive slow freezing. MAIN OUTCOME MEASURE(S): After thawing, the ovaries were subjected to neutral red viability staining to assess the density of viable small follicles and for long-term (48 hours) incubation evaluation of steroid secretion, histology, and apoptosis assay. RESULT(S): The follicular viability was decreased in both vitrification groups and in the slow-freezing group with the high concentration of DMSO, as compared with fresh controls. Estradiol levels in the incubation medium followed the same pattern. Light microscopy revealed well-preserved morphology in all groups after 48 hours' incubation. Apoptosis was increased in both vitrified and cryopreserved ovaries. CONCLUSION(S): We have developed a new method that can be used in basic studies to improve cryopreservation protocols. Our initial findings suggest that a moderate concentration of the cryoprotectant DMSO is superior to a high DMSO concentration for both vitrification and slow freezing.

The human postmenopausal ovary as a tool for evaluation of cryopreservation protocols towards whole ovary cryopreservation.

PURPOSE: Cryopreservation of a complete ovary may be a future method for fertility preservation in cancer patients. Difficulties exist in cryopreservation of the relatively large ovarian tissue mass. This study evaluates whether a human postmenopausal ovary can be used, as a complement to animal models, in studies of this research field. METHODS: Postmenopausal human ovaries (n = 10) were isolated and flushed through ovarian arteries with either the cryoprotectant dimethylsulphoxide or Ringer-Acetate, followed by slow freezing. After thawing, production of androgens during in vitro perfusion and morphology (light/electron microscopy) were assessed. RESULTS: The dimethylsulphoxide-cryopreserved ovaries showed larger secretion of androgens during perfusion than Ringer Acetate-cryopreserved ovaries. Light microscopy showed well preserved morphology in both groups. Electron microscopy revealed normal appearance of stroma and vessels in the dimethylsulphoxide group. CONCLUSIONS: The study demonstrates the potential to use the postmenopausal human ovary for further studies aiming at optimizing cryopreservation protocols, with special reference to ovarian vascularity and stroma.

Whole sheep ovary cryopreservation: evaluation of a slow freezing protocol with dimethylsulphoxide.

PURPOSE: To evaluate a slow freezing method for whole ovary cryopreservation by evaluating effects of added cryoprotectant. METHODS: Sheep ovaries were isolated during surgery, flushed with either Ringer-Acetate or dimethylsulphoxide and cryopreserved by slow freezing. After rapid thawing, viability was assessed by ovarian in vitro perfusion, cell culture, histology and fluorescent live-dead assay. RESULTS: Production of cyclic AMP and progesterone was slightly higher in the dimethylsulphoxide group. Cultured ovarian cells from dimethylsulphoxide-preserved ovaries secreted larger amounts of progesterone than cells from Ringer-Acetate preserved. Light microscopy of ovarian biopsies obtained after perfusion, revealed well-preserved tissue in the dimethysulphoxide group but not in the Ringer-Acetate group. The density of small follicles and ovarian cell viability were higher in dimethysulphoxide ovaries compared to Ringer-Acetate ovaries. CONCLUSIONS: Equilibrium with its protective effect can be achieved by slow freezing protocol, with an additional protective effect by the presence of dimethylsulphoxide.