Infertility Patients' Motivation for, Experiences of, Cross-Border Reproductive Services (CBRS): An Asynchronous Online Investigation

The desire for, and provision of, cross border reproductive services (CBRS) (i.e. gamete donation and surrogacy) is a growing international phenomenon. CBRS describes the travel by infertile patients from one country or jurisdiction where access to treatment is limited or unavailable to another country or jurisdiction to seek infertility treatment. There are numerous reasons for CBRS and it is an under- researched and undertheorised area of health research. The aim of this thesis was to explore patients’ motivations for and experiences of CBRS. This study provided themes on the decision making process of CBRS patients and contextualised them within a partial trans-Theoretical Model. Data regarding CBRS were collected from 26 international participants by means of asynchronous email in-depth semi-structured interviews via two international infertility networks. SPSS was used to analyse the quantitative data whereas NVivo 10 software aided the systematic thematic coding method within an Interpretative Grounded Theory. Participants’ motivations for and experiences of CBRS are complex. Seven stages of patients’ infertility journeys emerged: 1. Pre-contemplation: participants had no awareness of their own infertility; 2. Contemplation: participants became aware of their infertility and treatment at home and / or CBRS; 3. Preparation: participants researched CBRS using internet/infertility networks; 4. Action: participants took specific steps to initiate CBRS; 5: Maintenance: participants’ expectations and experiences were important to whether or not they would continue with CBRS; 6: Exit: some participants successfully built their family. Others’ overall experience was negative, their expectations were not met and they decided to quit treatment; 7: Re-engagement: some participants re-engaged with infertility treatment; some participants re-considered their decision regarding infertility treatment either at home or CBRS. A partial Trans-Theoretical Model could explain some of the decision-making process in seeking CBRS. Future research is needed to explore the implications of CBRS for patients, donors, offspring and healthcare systems

Family building using embryo adoption: relationships and contact arrangements between provider and recipient families — a mixed-methods study

STUDY QUESTION What contact arrangements are established between providers and recipients of embryos using Snowflakes® Embryo Adoption Program? SUMMARY ANSWER Contact arrangements varied considerably and were generally positively described, although some challenges were acknowledged. WHAT IS KNOWN ALREADY Reproductive technologies create new and diverse family forms, and the ways in which families created by embryo adoption are negotiated in practice have not been extensively investigated. STUDY DESIGN, SIZE, DURATION This exploratory, mixed-methods study had two phases: (i) an online survey (open May-September 2013) and (ii) qualitative semi-structured interviews by email (conducted between 2014 and 2015), exploring participants’ experiences of contact with their embryo provider or recipient. PARTICIPANTS/MATERIALS, SETTING, METHODS Phase I included 17 providers (14 women and 3 men) and 28 recipients (27 women and 1 man). Phase II included 8 providers (5 women and 3 men) and 12 recipients (10 women and 2 men). All participants, except one, were located in the US. MAIN RESULTS AND THE ROLE OF CHANCE This study illustrates how embryo adoption in the US, as a form of conditional donation, can operate and how the participants define and negotiate these emerging relationships. All families were open with their children about how they were conceived and early contact between recipients and providers (frequently before birth) was valued. On the whole, participants were happy with the amount and type of contact they had, and where the current contact did not involve the children, it was seen as a way of keeping the channels open for future contact when the children were older. Participants often portrayed the opportunities for contact as being in the best interests of the child. LIMITATIONS, REASONS FOR CAUTION The study participants are a particular group who had chosen to either receive or give their embryos via a conditional embryo adoption agency in the US and had established contact. Therefore, this is not a representative sample of those who provide or receive embryos for family building. WIDER IMPLICATIONS OF THE FINDINGS This embryo adoption model clearly fulfils a need; some people want to use a conditional embryo donation programme such as Snowflakes®. Some form of ‘ongoing support mechanism’ such as counselling could be useful for those negotiating the complex sets of new kinship patterns and balancing these relationships with their children's welfare. STUDY FUNDING/COMPETING INTEREST(S) The authors have no conflict of interest to declare. Snowflakes is a commercial adoption agency and the authors have no relation to the organization, other than requesting that they participate in this research project. TRIAL REGISTRATION NUMBER N/A

Supermileage Chassis Dynamometer

This report describes the final design and analysis of a hydraulic chassis dynamometer as a testing tool for California Polytechnic State University, San Luis Obispo Supermileage Vehicle Team (CPSMV). Literature review was conducted to understand the various types of chassis dynamometers on the market as of the year 2011. After rigorous research, it was determined that a hydraulic system was the best system for a chassis dynamometer in terms of functionality, performance, and cost. Critical study of hydraulics, dynamometers, and data acquisition systems (DAQ) was followed by a complete design of a hydraulic system. The chassis dynamometer proposed in this report tests a vehicle under a load provided by a hydraulic pump. A proportional valve imparts a load on the vehicle by restricting flow and creating a pressure differential. A fluid conditioning loop comprising a strainer is incorporated into the return line to maintain proper fluid cleanliness. This project combined different principles of mechanical, manufacturing, control, and electric and computer engineering to provide a testing tool to aid in the tuning of CPSMV’s current and future vehicles

A validation study of a smartphone application for functional mobility assessment of the elderly

AbstractBackgroundTo minimize the reaction time and position judgment error using stopwatch-timed measures, we developed a smartphone application to measure performance in the five-time sit-to-stand (FTSTS) and timed up-and-go (TUG) tests.ObjectiveThis study aimed to validate this smartphone application by comparing its measurement with a laboratory-based reference condition.MethodsThirty-two healthy elderly people were asked to perform the FTSTS and TUG tests in a randomized sequence. During the tests, their performance was concurrently measured by the smartphone application and a force sensor installed in the backrest of a chair. The intraclass correlation coefficient [ICC(2,1)] and Bland–Altman analysis were used to calculate the measurement consistency and agreement, respectively, between these two methods.ResultsThe smartphone application demonstrated excellent measurement consistency with the lab-based reference condition for the FTSTS test [ICC(2,1) = 0.988] and TUG test [ICC(2,1) = 0.946]. We observed a positive bias of 0.27 seconds (95% limits of agreement, −1.22 to 1.76 seconds) for the FTSTS test and 0.48 seconds (95% limits of agreement, −1.66 to 2.63 seconds) for the TUG test.ConclusionWe cross-validated the newly developed smartphone application with the laboratory-based reference condition during the examination of FTSTS and TUG test performance in healthy elderly

Discovering Novel Small Molecule Compound for Prevention of Monoclonal Antibody Self-Association

Designing an antibody with the desired affinity to the antigen is challenging, often achieved by lengthening the hydrophobic CDRs, which can lead to aggregation and cause major hindrance to the development of successful biopharmaceutical products. Aggregation can cause immunogenicity, viscosity and stability issues affecting both the safety and quality of the product. As the hydrophobic residues on the CDR are required for direct binding to antigens, it is not always possible to substitute these residues for aggregation-reduction purposes. Therefore, discovery of specific excipients to prevent aggregation is highly desirable for formulation development. Here, we used a combination of in silico screening methods to identify aggregation-prone regions on an aggregation-prone therapeutic antibody. The most aggregation-prone region on the antibody was selected to conduct virtual screening of compounds that can bind to such regions and act as an aggregation breaker. The most promising excipient candidate was further studied alongside plain buffer formulations and formulations with trehalose using coarse-grained molecular dynamics (CGMD) simulations with MARTINI force field. Mean interaction value between two antibody molecules in each formulation was calculated based on 1024 replicates of 512 ns of such CGMD simulations. Corresponding formulations with an excipient:antibody ratio of 1:5 were compared experimentally by measuring the diffusion interaction parameter kD and accelerated stability studies. Although the compound with the highest affinity score did not show any additional protective effects compared with trehalose, this study proved using a combination of in silico tools can aid excipient design and formulation development

A validation study of a smartphone application for functional mobility assessment of the elderly

Background: To minimize the reaction time and position judgment error using stopwatch-timed measures, we developed a smartphone application to measure performance in the five-time sit-to-stand (FTSTS) and timed up-and-go (TUG) tests. Objective: This study aimed to validate this smartphone application by comparing its measurement with a laboratory-based reference condition. Methods: Thirty-two healthy elderly people were asked to perform the FTSTS and TUG tests in a randomized sequence. During the tests, their performance was concurrently measured by the smartphone application and a force sensor installed in the backrest of a chair. The intraclass correlation coefficient [ICC(2,1)] and Blande-Altman analysis were used to calculate the measurement consistency and agreement, respectively, between these two methods. Results: The smartphone application demonstrated excellent measurement consistency with the lab-based reference condition for the FTSTS test [ICC(2,1) = 0.988] and TUG test [ICC(2,1) = 0.946]. We observed a positive bias of 0.27 seconds (95% limits of agreement, -1.22 to 1.76 seconds) for the FTSTS test and 0.48 seconds (95% limits of agreement, -1.66 to 2.63 seconds) for the TUG test. Conclusion: We cross-validated the newly developed smartphone application with the laboratory-based reference condition during the examination of FTSTS and TUG test performance in healthy elderly

The Demands of the Extra-Time Period of Soccer: A Systematic Review

Objective: Soccer match-play is typically contested over 90 min; however, in some cup and tournament scenarios, when matches are tied, they proceed to an additional 30 min, which is termed “extra-time” (ET). This systematic review sought to appraise the literature available on 120-min of soccer-specific exercise, with a view to identifying practical recommendations and future research opportunities. Methods: The review was conducted according to the PRISMA guidelines. Independent researchers performed a systematic search of PubMed, CINAHL, and PsycINFO in May 2019, with the following keywords entered in various combinations: “soccer”, “football”, “extra-time”, “extra time”, “extratime”, “120 minutes”, “120 min”, “additional 30 minutes”, and “additional 30 min”. Results: The search yielded an initial 73 articles. Following the screening process, 11 articles were accepted for analyses. Articles were subsequently organized into the following 5 categories: movement demands of ET, performance responses to ET, physiological and neuromuscular response during ET, nutritional interventions, and recovery and ET. The results highlighted that during competitive match-play, players cover 5%–12% less distance relative to match duration (i.e., meters per minute) during ET compared to the preceding 90 min. Reductions in technical performance (i.e., shot speed, number of passes and dribbles) were also observed during ET. Additionally, carbohydrate provision may attenuate and improve dribbling performance during ET. Moreover, objective and subjective measures of recovery may be further compromised following ET when compared to 90 min. Conclusion: Additional investigations are warranted to further substantiate these findings and identify interventions to improve performance during ET

Enhanced Thermal Stability and Reduced Aggregation in an Antibody Fab Fragment at Elevated Concentrations

The aggregation of protein therapeutics such as antibodies remains a major challenge in the biopharmaceutical industry. The present study aimed to characterize the impact of the protein concentration on the mechanisms and potential pathways for aggregation, using the antibody Fab fragment A33 as the model protein. Aggregation kinetics were determined for 0.05 to 100 mg/mL Fab A33, at 65 °C. A surprising trend was observed whereby increasing the concentration decreased the relative aggregation rate, ln(v) (% day-1), from 8.5 at 0.05 mg/mL to 4.4 at 100 mg/mL. The absolute aggregation rate (mol L-1 h-1) increased with the concentration following a rate order of approximately 1 up to a concentration of 25 mg/mL. Above this concentration, there was a transition to an apparently negative rate order of -1.1 up to 100 mg/mL. Several potential mechanisms were examined as possible explanations. A greater apparent conformational stability at 100 mg/mL was observed from an increase in the thermal transition midpoint (Tm) by 7-9 °C, relative to those at 1-4 mg/mL. The associated change in unfolding entropy (△Svh) also increased by 14-18% at 25-100 mg/mL, relative to those at 1-4 mg/mL, indicating reduced conformational flexibility in the native ensemble. Addition of Tween or the crowding agents Ficoll and dextran, showed that neither surface adsorption, diffusion limitations nor simple volume crowding affected the aggregation rate. Fitting of kinetic data to a wide range of mechanistic models implied a reversible two-state conformational switch mechanism from aggregation-prone monomers (N*) into non-aggregating native forms (N) at higher concentrations. kD measurements from DLS data also suggested a weak self-attraction while remaining colloidally stable, consistent with macromolecular self-crowding within weakly associated reversible oligomers. Such a model is also consistent with compaction of the native ensemble observed through changes in Tm and △Svh