Constructing medium sized efficient functional programs in Clean

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A comparison of the beta-geometric model with landmarking for dynamic prediction of time to pregnancy

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Treatment-independent live birth after in-vitro fertilisation : a retrospective cohort study of 2,133 women

Acknowledgements We acknowledge the data management support of the Grampian Data Safe Haven (DaSH) and the associated financial support of NHS Research Scotland, through NHS Grampian investment in the Grampian DaSH. For more information, visit the DaSH website http://www.abdn.ac.uk/iahs/facilities/grampian-data-safe-haven.php. We would like to thank all the staff at Aberdeen Fertility Clinic for their help with database queries and case note searching. Funding This work was funded by a Chief Scientist Office Postdoctoral Training Fellowship in Health Services Research and Health of the Public Research (Ref PDF/12/06). The views expressed here are those of the authors and not necessarily those of the Chief Scientist Office. The funder did not have any role in the study design, in the collection, analysis, and interpretation of data, in the writing of the report nor in the decision to submit the paper for publication.Peer reviewedPostprin

Design space exploration of a poultry fillet processing system using discrete-event simulation

Developments in the poultry processing industry, such as how livestock is raised and how consumers buy meat, make it increasingly difficult to design poultry processing systems that meet evolving standards. More and more iterations of (re)design are required to optimize the product flow in these systems. This paper presents a method for design space exploration of production systems using discrete-event simulation. This method automates most steps of design space exploration: iterating on the design, model construction, performing simulation experiments, and interpreting the simulation results. This greatly reduces the time and effort required to iterate through different designs. A case study is presented which shows that this method can be effective for design space exploration of poultry processing systems.Comment: FOODOPS 202

Correctness of an STM Haskell implementation

A concurrent implementation of software transactional memory in Concurrent Haskell using a call-by-need functional language with processes and futures is given. The description of the small-step operational semantics is precise and explicit, and employs an early abort of conflicting transactions. A proof of correctness of the implementation is given for a contextual semantics with may- and should-convergence. This implies that our implementation is a correct evaluator for an abstract specification equipped with a big-step semantics

External validation of a dynamic prediction model for repeated predictions of natural conception over time

This work was supported by a Chief Scientist Office postdoctoral training fellowship in health services research and health of the public research (ref PDF/12/06). There are no conflicts of interest.Peer reviewedPostprin

IVF for unexplained subfertility : whom should we treat?

Acknowledgements The authors would like to thank Tenovus Scotland and the Amsterdam Reproduction & Development Research Group for funding this project. We acknowledge the data management support of the Grampian Data Safe Haven (DaSH) and the associated financial support of NHS Research Scotland, through NHS Grampian investment in the Grampian DaSH. For more information, visit the DaSH website http://www.abdn.ac.uk/iahs/facilities/grampian-data-safe-haven.php. Funding Tenovus Scotland [grant G17.04], travel was supported by the Amsterdam Reproduction & Development Research Group [grant V.000296 to RvE].Peer reviewedPostprin

Numerical Investigation of Pyrolysis Gas Blowing Pattern and Thermal Response using Orthotropic Charring Ablative Material

An orthotropic material model is implemented in a three-dimensional material response code, and numerically studied for charring ablative material. Model comparison is performed using an iso-Q sample geometry. The comparison is presented using pyrolysis gas streamlines and time series of temperature at selected virtual thermocouples. Results show that orthotropic permeability affects both pyrolysis gas flow and thermal response, but orthotropic thermal conductivity essentially changes the thermal performance of the material. The effect of orthotropic properties may have practical use such that the material performance can be manipulated by altering the angle of orthotropic orientation

Cost-effectiveness of medically assisted reproduction or expectant management for unexplained subfertility:when to start treatment?

STUDY QUESTION Over a time period of 3 years, which order of expectant management (EM), IUI with ovarian stimulation (IUI-OS) and IVF is the most cost-effective for couples with unexplained subfertility with the female age below 38 years? SUMMARY ANSWER If a live birth is considered worth Euro32 000 or less, 2 years of EM followed by IVF was the most cost-effective, whereas above Euro32 000 this was 1 year of EM, 1 year of IUI-OS and then 1 year of IVF. WHAT IS KNOWN ALREADY IUI-OS and IVF are commonly used fertility treatments for unexplained subfertility although many couples can conceive naturally, as no identifiable barrier to conception could be found by definition. Few countries have guidelines on when to proceed with medically assisted reproduction (MAR), mostly based on the expected probability of live birth after treatment, but there is a lack of evidence to support the strategies proposed by these guidelines. The increased uptake of IUI-OS and IVF over the past decades and costs related to reimbursement of these treatments are pressing concerns to health service providers. For MAR to remain affordable, sustainable and a responsible use of public funds, guidance is needed on the cost-effectiveness of treatment strategies for unexplained subfertility, including EM. STUDY DESIGN, SIZE, DURATION We developed a decision analytic Markov model that follows couples with unexplained subfertility of which the woman is under 38 years of age for a time period of 3 years from completion of the fertility workup onwards. We divided the time axis of 3 years into three separate periods, each comprising 1 year. The model was based on contemporary evidence, most notably the dynamic prediction model for natural conception, which was combined with MAR treatment effects from a network meta-analysis on randomized controlled trials. We changed the order of options for managing unexplained subfertility for the 1 year periods to yield five different treatment policies in total: IVF-EM-EM (immediate IVF), EM-IVF-EM (delayed IVF), EM-EM-IVF (postponed IVF), IUIOS-IVF-EM (immediate IUI-OS) and EM-IUIOS-IVF (delayed IUI-OS). PARTICIPANTS/MATERIALS, SETTING, METHODS The main outcomes per policy over the 3-year period were the probability of live birth, the average treatment and delivery costs, the probability of multiple pregnancy, the incremental cost-effectiveness ratio (ICER) and finally, which policy yields the highest net benefit in which costs for a policy were deducted from the health effects, i.e. live births gained. We chose the Dutch societal perspective, but the model can be easily modified for other locations or other perspectives. The probability of live birth after EM was taken from the dynamic prediction model for natural conception and updated for Years 2 and 3. The relative effects of IUI-OS and IVF in terms of odds ratios, taken from the network meta-analysis, were applied to the probability of live birth after EM. We applied standard discounting procedures for economic analyses for Years 2 and 3. The uncertainty around effectiveness, costs and other parameters was assessed by probabilistic sensitivity analysis in which we drew values from distributions and repeated this procedure 20 000 times. In addition, we changed model assumptions to assess their influence on our results. MAIN RESULTS AND THE ROLE OF CHANCE From IVF-EM-EM to EM-IUIOS-IVF, the probability of live birth varied from approximately 54-64% and the average costs from approximately Euro4000 to Euro9000. The policies IVF-EM-EM and EM-IVF-EM were dominated by EM-EM-IVF as the latter yielded a higher cumulative probability of live birth at a lower cost. The policy IUIOS-IVF-EM was dominated by EM-IUIOS-IVF as the latter yielded a higher cumulative probability of live birth at a lower cost. After removal of policies that were dominated, the ICER for EM-IUIOS-IVF was approximately Euro31 000 compared to EM-EM-IVF. The range of ICER values between the lowest 25% and highest 75% of simulation replications was broad. The net benefit curve showed that when we assume a live birth to be worth approximately Euro20 000 or less, the policy EM-EM-IVF had the highest probability to achieve the highest net benefit. Between Euro20 000 and Euro50 000 monetary value per live birth, it was uncertain whether EM-EM-IVF was better than EM-IUIOS-IVF, with the turning point of Euro32 000. When we assume a monetary value per live birth over Euro50 000, the policy with the highest probability to achieve the highest net benefit was EM-IUIOS-IVF. Results for subgroups with different baseline prognoses showed the same policies dominated and the same two policies that were the most likely to achieve the highest net benefit but at different threshold values for the assumed monetary value per live birth. LIMITATIONS, REASONS FOR CAUTION Our model focused on population level and was thus based on average costs for the average number of cycles conducted. We also based the model on a number of key assumptions. We changed model assumptions to assess the influence of these assumptions on our results. The change in relative effectiveness of IVF over time was found to be highly influential on results and their interpretation. WIDER IMPLICATIONS OF THE FINDINGS EM-EM-IVF and EM-IUIOS-IVF followed by IVF were the most cost-effective policies. The choice depends on the monetary value assigned to a live birth. The results of our study can be used in discussions between clinicians, couples and policy makers to decide on a sustainable treatment protocol based on the probability of live birth, the costs and the limitations of MAR treatment. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by the ZonMw Doelmatigheidsonderzoek (80-85200-98-91072). The funder had no role in the design, conduct or reporting of this work. B.W.M. is supported by a NHMRC Practitioner Fellowship (GNT1082548). B.W.M. reports consultancy for ObsEva, Merck KGaA and Guerbet and travel and research support from ObsEva, Merck and Guerbet. TRIAL REGISTRATION NUMBER N/A

Both androgen receptor and glucocorticoid receptor are able to induce prostate-specific antigen expression, but differ in their growth-stimulating properties of LNCaP cells

Androgen receptor-positive LNCaP cells were stably transfected with a rat glucocorticoid receptor (GR) expression plasmid. Ligand-binding studies in the generated cell lines revealed high-affinity binding of the cognate ligands to their receptors. Transfection experiments with the newly derived cell lines showed that, like androgen receptor, GR can induce activity of a prostate-specific antigen promoter fragment linked to the luciferase gene. Similarly, dexamethasone can stimulate expression of endogenous prostate-specific antigen messenger RNA. Cell proliferation could be induced by R1881. In contrast, dexamethasone treatment of the GR-positive sublines had no stimulatory effect on cell growth. Using the differential display technique, a so far unknown complementary DNA fragment, designated 21.1, specifically induced by androgens and not by glucocorticoids, has been identified. In conclusion, the newly generated cell lines, together with the parental LNCaP cell line, form an attractive system with which to study the mechanism of specificity of steroid hormone regulation of gene expression