Xenotransplantation of cryopreserved human ovarian tissue--a systematic review of MII oocyte maturation and discussion of it as a realistic option for restoring fertility after cancer treatment.

OBJECTIVE To systematically review the reporting of MII (MII) oocyte development after xenotransplantation of human ovarian tissue. DESIGN Systematic review in accordance with the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). SETTING Not applicable. PATIENT(S) Not applicable. INTERVENTION(S) Formation of MII oocytes after xenotransplantation of human ovarian tissue. MAIN OUTCOME MEASURE(S) Any outcome reported in Pubmed. RESULT(S) Six publications were identified that report on formation of MII oocytes after xenotransplantation of human ovarian tissue. CONCLUSION(S) Xenografting of human ovarian tissue has proved to be a useful model for examining ovarian function and follicle development in vivo. With human follicles that have matured through xenografting, the possibility of cancer transmission and relapse can also be eliminated, because cancer cells are not able to penetrate the zona pellucida. The reported studies have demonstrated that xenografted ovarian tissue from a range of species, including humans, can produce antral follicles that contain mature (MII) oocytes, and it has been shown that mice oocytes have the potential to give rise to live young. Although some ethical questions remain unresolved, xenotransplantation may be a promising method for restoring fertility. This review furthermore describes the value of xenotransplantation as a tool in reproductive biology and discusses the ethical and potential safety issues regarding ovarian tissue xenotransplantation as a means of recovering fertility.

Laparoscopic Cerclage as a Treatment Option for Cervical Insufficiency

Background: The traditional surgical treatment for cervical insufficiency is vaginal placement of a cervical cerclage. However, in a small number of cases a vaginal approach is not possible. A transabdominal approach can become an option for these patients. Laparoscopic cervical cerclage is associated with good pregnancy outcomes but comes at the cost of a higher risk of serious surgical complications. The aim of the present study was to evaluate intraoperative and long-term pregnancy outcomes after laparoscopic cervical cerclage, performed either as an interval procedure or during early pregnancy, using a new device with a blunt grasper and a flexible tip. Methods: All women who underwent laparoscopic cervical cerclage for cervical insufficiency in our institution using the Goldfinger® device (Ethicon Endo Surgery, Somerville, NJ, USA) between January 2008 and March 2014 were included in the study. Data were collected from the patients' medical records and included complications during and after the above-described procedure. Results: Eighteen women were included in the study. Of these, six were pregnant at the time of laparoscopic cervical cerclage. Mean duration of surgery was 55 ± 10 minutes. No serious intraoperative or postoperative complications occurred. All patients were discharged at 2.6 ± 0.9 days after surgery. One pregnancy ended in a miscarriage at 12 weeks of gestation. All other pregnancies ended at term (> 37 weeks of gestation) with good perinatal and maternal outcomes. Summary: Performing a laparoscopic cervical cerclage using a blunt grasper device with a flexible tip does not increase intraoperative complications, particularly in early pregnancy. We believe that use of this device, which is characterized by increased maneuverability, could be an important option to avoid intraoperative complications if surgical access is limited due to the anatomical situation. However, because of the small sample size, further studies are needed to confirm our findings.

Retention in care during the first 3 years of antiretroviral therapy for women in Malawi's option B+ programme: an observational cohort study

Background Studies of Malawi's option B+ programme for HIV-positive pregnant and breastfeeding women have reported high loss to follow-up during pregnancy and at the start of antiretroviral therapy (ART), but few data exist about retention during breastfeeding and after weaning. We examined loss to follow-up and retention in care in patients in the option B+ programme during their first 3 years on ART. Methods We analysed two data sources: aggregated facility-level data about patients in option B+ who started ART between Oct 1, 2011, and June 30, 2012, at 546 health facilities; and patient-level data from 20 large facilities with electronic medical record system for HIV-positive women who started ART between Sept 1, 2011, and Dec 31, 2013, under option B+ or because they had WHO clinical stages 3 or 4 disease or had CD4 counts of less than 350 cells per μL. We used facility-level data to calculate representative estimates of retention and loss to follow-up. We used patient-level data to study temporal trends in retention, timing of loss to follow-up, and predictors of no follow-up and loss to follow-up. We defined patients who were more than 60 days late for their first follow-up visit as having no follow-up and patients who were more than 60 days late for a subsequent visit as being lost to follow-up. We calculated proportions and cumulative probabilities of patients who had died, stopped ART, had no follow-up, were lost to follow-up, or were retained alive on ART for 36 months. We calculated odds ratios and hazard ratios to examine predictors of no follow-up and loss to follow-up. Findings Analysis of facility-level data about patients in option B+ who had not transferred to a different facility showed retention in care to be 76·8% (20 475 of 26 658 patients) after 12 months, 70·8% (18 306 of 25 849 patients) after 24 months, and 69·7% (17 787 of 25 535 patients) after 36 months. Patient-level data included 29 145 patients. 14 630 (50·2%) began treatment under option B+. Patients in option B+ had a higher risk of having no follow-up and, for the first 2 years of ART, higher risk of loss to follow-up than did patients who started ART because they had CD4 counts less than 350 cells per μL or WHO clinical stage 3 or 4 disease. Risk of loss to follow-up during the third year was low and similar for patients retained for 2 years. Retention rates did not change as the option B+ programme matured. Interpretation Our data suggest that pregnant and breastfeeding women who start ART immediately after they are diagnosed with HIV can be retained on ART through the option B+ programme, even after many have stopped breastfeeding. Interventions might be needed to improve retention in the first year on ART in option B+. Funding Bill & Melinda Gates Foundation, Partnerships for Enhanced Engagement in Research Health, and National Institute of Allergy and Infectious Diseases.

Comparative cost-effectiveness of Option B+ for prevention of mother-to-child transmission of HIV in Malawi.

OBJECTIVE To estimate the cost-effectiveness of prevention of mother-to-child transmission (MTCT) of HIV with lifelong antiretroviral therapy (ART) for pregnant and breastfeeding women ('Option B+') compared with ART during pregnancy or breastfeeding only unless clinically indicated ('Option B'). DESIGN Mathematical modelling study of first and second pregnancy, informed by data from the Malawi Option B+ programme. METHODS Individual-based simulation model. We simulated cohorts of 10 000 women and their infants during two subsequent pregnancies, including the breastfeeding period, with either Option B+ or B. We parameterized the model with data from the literature and by analysing programmatic data. We compared total costs of antenatal and postnatal care, and lifetime costs and disability-adjusted life-years of the infected infants between Option B+ and Option B. RESULTS During the first pregnancy, 15% of the infants born to HIV-infected mothers acquired the infection. With Option B+, 39% of the women were on ART at the beginning of the second pregnancy, compared with 18% with Option B. For second pregnancies, the rates MTCT were 11.3% with Option B+ and 12.3% with Option B. The incremental cost-effectiveness ratio comparing the two options ranged between about US$ 500 and US$ 1300 per DALY averted. CONCLUSION Option B+ prevents more vertical transmissions of HIV than Option B, mainly because more women are already on ART at the beginning of the next pregnancy. Option B+ is a cost-effective strategy for PMTCT if the total future costs and lost lifetime of the infected infants are taken into account.

Retention in care of HIV-infected pregnant and lactating women starting art under Option B+ in rural Mozambique.

OBJECTIVE In 2013, Mozambique adopted Option B+, universal lifelong antiretroviral therapy (ART) for all pregnant and lactating women, as national strategy for prevention of mother-to-child transmission of HIV. We analyzed retention in care of pregnant and lactating women starting Option B+ in rural northern Mozambique. METHODS We compared ART outcomes in pregnant ("B+pregnant"), lactating ("B+lactating") and non-pregnant-non-lactating women of childbearing age starting ART after clinical and/or immunological criteria ("own health") between July 2013 and June 2014. Lost to follow-up was defined as no contact >180 days after the last visit. Multivariable competing risk models were adjusted for type of facility (type 1 vs. peripheral type 2 health center), age, WHO stage and time from HIV diagnosis to ART. RESULTS Over 333 person-years of follow-up (of 243 "B+pregnant", 65″B+lactating" and 317 "own health" women), 3.7% of women died and 48.5% were lost to follow-up. "B+pregnant" and "B+lactating" women were more likely to be lost in the first year (57% vs. 56.9% vs. 31.6%; p<0.001) and to have no follow-up after the first visit (42.4% vs. 29.2% vs. 16.4%; p<0.001) than "own health" women. In adjusted analyses, risk of being lost to follow-up was higher in "B+pregnant" (adjusted subhazard ratio [asHR]: 2.77; 95% CI: 2.18-3.50; p<0.001) and "B+lactating" (asHR: 1.94; 95% CI: 1.37-2.74; p<0.001). Type 2 health center was the only additional significant risk factor for loss to follow-up. CONCLUSIONS Retaining pregnant and lactating women in option B+ ART was poor; losses to follow-up were mainly early. The success of Option B+ for prevention of mother-to-child transmission of HIV in rural settings with weak health systems will depend on specific improvements in counseling and retention measures, especially at the beginning of treatment. This article is protected by copyright. All rights reserved.

The Impact of the IRS Retirement Option Relative Value

This study evaluates the effects of the new Government regulations in regards to the relative value notification of retirement plan options. It looks at how these new regulations will affect retirement plan option utilization and how retirement plan providers will change options in order to minimize risk.

Exploring the use of pharmaceutical patient assistance programs as an option to improve access to and affordability of prescription drugs

Background. Pharmaceutical-sponsored patient assistance programs (PAPs) are charity programs that provide free or reduced-priced medications to eligible patients. PAPs have the potential to improve prescription drug accessibility for patients but currently there is limited information about their use and effectiveness. ^ Objectives and methods. This dissertation described the use of PAPs in the U.S. through the conduct of two studies: (1) a systematic review of primary studies of PAPs from commercially-published and “grey” literature sources; and (2) a retrospective, cross-sectional study of cancer patients' use of PAPs at a tertiary care cancer outpatient center. ^ Results. (1) The systematic review identified 33 studies: 15 evaluated the impact of PAP enrollment assistance programs on patient healthcare outcomes; 7 assessed institutional costs of providing enrollment assistance; 7 surveyed stakeholders; 4 examined other aspects. Standardized mean differences calculated for disease indicator outcomes (most of which were single group, pre-posttest designs) showed significant decreases in glycemic and lipid control, and inconsistent results for blood pressure. Grey literature abstracts reported insufficient statistics for calculations. Study heterogeneity made weighted summary estimates inappropriate. Economic analyses indicated positive financial benefits to institutions providing enrollment assistance (cost) compared to the wholesale value of the medications provided (benefit); analyses did not value health outcomes. Mean quality of reporting scores were higher for observational studies in commercially-published articles versus full text, grey literature reports. (2) The cross-sectional study found that PAP outpatients were significantly more likely to be uninsured, indigent, and < 65 years old than non-PAP patients. Nearly all non-PAP and PAP prescriptions were for non-cancer conditions, either for co-morbidities (e.g., hypertension) or the management of treatment side effects (e.g., pain). Oral chemotherapies from PAPs were significantly more likely to be for breast versus other cancers, and be a newer, targeted versus traditional chemotherapy.^ Conclusions. In outpatient settings, PAP enrollment assistance plus additional medication services (e.g., counseling, reminders, and free samples) is associated with improved disease indicators for patients. Healthcare institutions, including cancer centers, can offset financial losses from uncompensated drug costs and recoup costs invested in enrollment assistance programs by procuring free PAP medications. Cancer patients who are indigent and uninsured may be able to access more outpatient medications for their supportive care needs through PAPs, than for cancer treatment options like oral chemotherapies. Because of the selective availability of drugs through PAPs, there may be more options for newer, oral, targeted chemotherapies for the treatment breast cancer versus other for other cancers.^

Valuation of a new entrant in an oligopolistic market, including its option to abandon: A real-life case

The purpose of this paper is to increase current empirical evidence on the relevance of real options for explaining firm investment decisions in oligopolistic markets. We study an actual investment case in the Spanish mobile telephony industry, the entrant in the market of a new operator, Yoigo. We analyze the option to abandon in order to show the relevance of the possibility of selling the company in an oligopolistic market where competitors are not allowed free entrance. The NPV (net present value) of the new entrant is calculated as a starting point. Then, based on the general approach proposed by Copeland and Antikarov (2001), a binomial tree is used to model managerial flexibility in discrete time periods, and value the option to abandon. The strike price of the option is calculated based on incremental EBITDA margins due to selling customers or merging with a competitor.

Numerical methods for option pricing.

This thesis aims to introduce some fundamental concepts underlying option valuation theory including implementation of computational tools. In many cases analytical solution for option pricing does not exist, thus the following numerical methods are used: binomial trees, Monte Carlo simulations and finite difference methods. First, an algorithm based on Hull and Wilmott is written for every method. Then these algorithms are improved in different ways. For the binomial tree both speed and memory usage is significantly improved by using only one vector instead of a whole price storing matrix. Computational time in Monte Carlo simulations is reduced by implementing a parallel algorithm (in C) which is capable of improving speed by a factor which equals the number of processors used. Furthermore, MatLab code for Monte Carlo was made faster by vectorizing simulation process. Finally, obtained option values are compared to those obtained with popular finite difference methods, and it is discussed which of the algorithms is more appropriate for which purpose.

Assessment of irrigators’ preferences for different water supply risk management tools: option contract and insurance.

Irrigators face the risk of not having enough water to meet their crops’ demand. There are different mechanisms to cope with this risk, including water markets (option contracts) or insurance. A farmer will purchase them when the expected utility change derived from the tool is positive. This paper presents a theoretical assessment of the farmer’s expected utility under two different option contracts, a drought insurance and a combination of an option contract and the insurance. We analyze the conditions that determine farmer’s reference for one instrument or the other and perform a numerical application that is relevant for a Spanish region.

Water option contracts for reducing water supply risks: an application to the Tagus-Segura Transfer

El agua es un recurso cada vez más escaso y valioso. Por ello, los recursos hídricos disponibles deben asignarse de una forma eficiente entre los diferentes usos. El cambio climático aumentará la frecuencia y severidad de los eventos extremos, y podría incrementar la demanda de agua de los cultivos. El empleo de mecanismos flexibles de asignación de agua puede ser imprescindible para hacer frente a este aumento en la variabilidad del balance hídrico y para asegurar que los riesgos de suministro, y no solo los recursos, son compartidos de manera eficiente entre los usuarios. Los mercados de agua permiten la reasignación de los recursos hídricos, favoreciendo su transferencia desde los usos de menor a los de mayor valor. Diferentes tipos de mercados de agua se han establecido en diferentes partes del mundo, ayudando a los participantes a afrontar los problemas de escasez de agua en esas zonas. En España, los intercambios de agua están permitidos desde 1999, aunque la participación de los usuarios en el mercado ha sido limitada. Hay varios aspectos de los mercados de agua en España que deben mejorarse. Esta tesis, además de proponer una serie de cambios en el marco regulatorio, propone la introducción de contratos de opción de agua como una posible mejora. La principal ventaja de este tipo de contratos es la estabilidad legal e institucional que éstos proporcionan tanto a compradores como vendedores. Para apoyar esta propuesta, se han llevado a cabo diferentes análisis que muestran el potencial de los contratos de opción como herramienta de reducción del riesgo asociado a una oferta de agua inestable. La Cuenca del Segura (Sureste de España), la Cuenca del Tajo y el Acueducto Tajo- Segura han sido seleccionados como casos de estudio. Tres análisis distintos aplicados a dicha región se presentan en esta tesis: a) una evaluación de los contratos de opción como mecanismo para reducir los riesgos de disponibilidad de agua sufridos por los regantes en la Cuenca del Segura; b) un marco teórico para analizar las preferencias de los regantes por diferentes mecanismos de gestión del riesgo de disponibilidad de agua, su disposición a pagar por ellos y los precios aproximados de estos instrumentos (seguro de sequía y contratos de opción de agua); y c) una evaluación del papel de los contratos de opción en las decisiones de aprovisionamiento de agua de una comunidad de regantes ante una oferta de agua incierta. Los resultados muestran el potencial de reducción del riesgo de los contratos de opción para regantes en España, pero pueden ser extrapolados a otros sectores o regiones. Las principales conclusiones de esta tesis son: a) la agricultura será uno de los sectores más afectados por el cambio climático. Si los precios del agua aumentan, la rentabilidad de los cultivos puede caer hasta niveles negativos, lo que podría dar lugar al abandono de cultivos de regadío en algunas zonas de España. Las políticas de cambio climático y de agua deben estar estrechamente coordinadas para asegurar un uso de agua eficiente y la rentabilidad de la agricultura; b) aunque los mercados de agua han ayudado a algunos usuarios a afrontar problemas de disponibilidad del recurso en momentos de escasez, hay varios aspectos que deben mejorarse; c) es necesario desarrollar mercados de agua más flexibles y estables para garantizar una asignación eficiente de los recursos entre los usuarios de agua; d) los resultados muestran los beneficios derivados del establecimiento de un contrato de opción entre usuarios de agua del Tajo y del Segura para reducir el riesgo de disponibilidad de agua en la cuenca receptora; e) la disposición a pagar de los regantes por un contrato de opción de agua o un seguro de sequía hidrológica, que representa el valor que tienen estos mecanismos para aquellos usuarios de agua que se enfrentan a riesgos relacionados con la disponibilidad del recurso, es consistente con los resultados obtenidos en estudios previos y superior al precio de mercado de estos instrumentos, lo que favorece la viabilidad de estos mecanismos de gestión del riesgo ; y f) los contratos de opción podrían ayudar a optimizar las decisiones de aprovisionamiento de agua bajo incertidumbre, proporcionando más estabilidad y flexibilidad que los mercados temporales de agua. ABSTRACT Water is becoming increasingly scarce and valuable. Thus, existing water resources need to be efficiently allocated among users. Climate change is expected to increase the frequency and severity of extreme events, and it may also increase irrigated crops' water demand. The implementation of flexible allocation mechanisms could be essential to cope with this increased variability of the water balance and ensure that supply risks, and not only water resources, are also efficiently shared and managed. Water markets allow for the reallocation of water resources from low to high value uses. Different water trading mechanisms have been created in different parts of the world and have helped users to alleviate water scarcity problems in those areas. In Spain, water trading is allowed since 1999, although market activity has been limited. There are several issues in the Spanish water market that should be improved. This thesis, besides proposing several changes in the legislative framework, proposes the introduction of water option contracts as a potential improvement. The main advantage for both buyer and seller derived from an option contract is the institutional and legal stability it provides. To support this proposal, different analyses have been carried out that show the potential of option contracts as a risk reduction tool to manage water supply instability. The Segura Basin (Southeast Spain), the Tagus Basin and the Tagus-Segura inter-basin Transfer have been selected as the case study. Three different analyses applied to this region are presented in this thesis: a) an evaluation of option contracts as a mechanisms to reduce water supply availability risks in the Segura Basin; b) a theoretical framework for analyzing farmer’s preferences for different water supply risk management tools and farmers’ willingness to pay for them, together with the assessment of the prices of these mechanisms (drought insurance and water option contracts); and c) an evaluation of the role of option contracts in water procurement decisions under uncertainty. Results show the risk-reduction potential of option contracts for the agricultural sector in Spain, but these results can be extrapolated to other sectors or regions. The main conclusions of the thesis are: a) agriculture would be one of the most affected sectors by climate change. With higher water tariffs, crop’s profitability can drop to negative levels, which may result in the abandoning of the crop in many areas. Climate change and water policies must be closely coordinated to ensure efficient water use and crops’ profitability; b) although Spanish water markets have alleviated water availability problems for some users during water scarcity periods, there are several issues that should be improved; c) more flexible and stable water market mechanisms are needed to allocate water resources and water supply risks among competing users; d) results show the benefits derived from the establishment of an inter-basin option contract between water users in the Tagus and the Segura basins for reducing water supply availability risks in the recipient area; e) irrigators’ willingness to pay for option contracts or drought insurance, that represent the value that this kind of trading mechanisms has for water users facing water supply reliability problems, are consistent with results obtained in previous works and higher than the prices of this risk management tools, which shows the feasibility of these mechanisms; and f) option contracts would help to optimize water procurement decisions under uncertainty, providing more flexibility and stability than the spot market.