Mol-CycleGAN - a generative model for molecular optimization

Designing a molecule with desired properties is one of the biggest challenges in drug development, as it requires optimization of chemical compound structures with respect to many complex properties. To augment the compound design process we introduce Mol-CycleGAN - a CycleGAN-based model that generates optimized compounds with high structural similarity to the original ones. Namely, given a molecule our model generates a structurally similar one with an optimized value of the considered property. We evaluate the performance of the model on selected optimization objectives related to structural properties (presence of halogen groups, number of aromatic rings) and to a physicochemical property (penalized logP). In the task of optimization of penalized logP of drug-like molecules our model significantly outperforms previous results

Impacts of natural and human drivers on the multi-decadal morphological evolution of tidally-influenced deltas

The world's deltas are at risk of being drowned due to rising relative sea levels as a result of climate change, decreasing supplies of fluvial sediment, and human responses to these changes. This paper analyses how delta morphology evolves over multi-decadal timescales under environmental change using a process-based model. Model simulations over 10^2 years are used to explore the influence of three key classes of environmental change, both individually and in combination: (i) varying combinations of fluvial water and sediment discharges; (ii) varying rates of relative sea-level rise; and (iii) selected human interventions within the delta, comprising polder-dykes and cross-dams. The results indicate that tidal asymmetry and rate of sediment supply together affect residual flows and delta morphodynamics (indicated by sub-aerial delta area, rates of progradation and aggradation). When individual drivers of change act in combination, delta building processes such as the distribution of sediment flux, aggradation, and progradation are disrupted by the presence of isolated polder-dykes or cross-dams. This suggests that such interventions, unless undertaken at a very large scale, can lead to unsustainable delta building processes. Our findings can inform management choices in real-world tidally-influenced deltas, while the methodology can provide insights into other dynamic morphological systems

Management of massive splenomegaly.

A case demonstrating diagnostic and therapeutic rational for surgical management of massive splenomegaly

Mol-CycleGAN : a generative model for molecular optimization

During the drug design process, one must develop a molecule, which structure satisfies a number of physicochemical properties. To improve this process, we introduce Mol-CycleGAN – a CycleGAN-based model that generates compounds optimized for a selected property, while aiming to retain the already optimized ones. In the task of constrained optimization of penalized logP of drug-like molecules our model significantly outperforms previous results

Crack-Like Processes Governing the Onset of Frictional Slip

We perform real-time measurements of the net contact area between two blocks of like material at the onset of frictional slip. We show that the process of interface detachment, which immediately precedes the inception of frictional sliding, is governed by three different types of detachment fronts. These crack-like detachment fronts differ by both their propagation velocities and by the amount of net contact surface reduction caused by their passage. The most rapid fronts propagate at intersonic velocities but generate a negligible reduction in contact area across the interface. Sub-Rayleigh fronts are crack-like modes which propagate at velocities up to the Rayleigh wave speed, VR, and give rise to an approximate 10% reduction in net contact area. The most efficient contact area reduction (~20%) is precipitated by the passage of slow detachment fronts. These fronts propagate at anomalously slow velocities, which are over an order of magnitude lower than VR yet orders of magnitude higher than other characteristic velocity scales such as either slip or loading velocities. Slow fronts are generated, in conjunction with intersonic fronts, by the sudden arrest of sub-Rayleigh fronts. No overall sliding of the interface occurs until either of the slower two fronts traverses the entire interface, and motion at the leading edge of the interface is initiated. Slip at the trailing edge of the interface accompanies the motion of both the slow and sub-Rayleigh fronts. We might expect these modes to be important in both fault nucleation and earthquake dynamics.Comment: 19 page, 5 figures, to appear in International Journal of Fractur

Pathology Informatics Essentials for Residents: A Flexible Informatics Curriculum Linked to Accreditation Council for Graduate Medical Education Milestones (a secondary publication)*

Context: Recognition of the importance of informatics to the practice of pathology has surged. Training residents in pathology informatics has been a daunting task for most residency programs in the United States because faculty often lacks experience and training resources. Nevertheless, developing resident competence in informatics is essential for the future of pathology as a specialty. Objective: To develop and deliver a pathology informatics curriculum and instructional framework that guides pathology residency programs in training residents in critical pathology informatics knowledge and skills, and meets Accreditation Council for Graduate Medical Education Informatics Milestones. Design: The College of American Pathologists, Association of Pathology Chairs, and Association for Pathology Informatics formed a partnership and expert work group to identify critical pathology informatics training outcomes and to create a highly adaptable curriculum and instructional approach, supported by a multiyear change management strategy. Results: Pathology Informatics Essentials for Residents (PIER) is a rigorous approach for educating all pathology residents in important pathology informatics knowledge and skills. PIER includes an instructional resource guide and toolkit for incorporating informatics training into residency programs that vary in needs, size, settings, and resources. PIER is available at http:// www.apcprods.org/PIER (accessed April 6, 2016). Conclusions: PIER is an important contribution to informatics training in pathology residency programs. PIER introduces pathology trainees to broadly useful informatics concepts and tools that are relevant to practice. PIER provides residency program directors with a means to implement a standardized informatics training curriculum, to adapt the approach to local program needs, and to evaluate resident performance and progress over time

Improving inpatient postnatal services: midwives views and perspectives of engagement in a quality improvement initiative

Background: despite major policy initiatives in the United Kingdom to enhance women's experiences of maternity care, improving in-patient postnatal care remains a low priority, although it is an aspect of care consistently rated as poor by women. As part of a systems and process approach to improving care at one maternity unit in the South of England, the views and perspectives of midwives responsible for implementing change were sought. Methods: a Continuous Quality Improvement (CQI) approach was adopted to support a systems and process change to in-patient care and care on transfer home in a large district general hospital with around 6000 births a year. The CQI approach included an initial assessment to identify where revisions to routine systems and processes were required, developing, implementing and evaluating revisions to the content and documentation of care in hospital and on transfer home, and training workshops for midwives and other maternity staff responsible for implementing changes. To assess midwifery views of the quality improvement process and their engagement with this, questionnaires were sent to those who had participated at the outset. Results: questionnaires were received from 68 (46%) of the estimated 149 midwives eligible to complete the questionnaire. All midwives were aware of the revisions introduced, and two-thirds felt these were more appropriate to meet the women's physical and emotional health, information and support needs. Some midwives considered that the introduction of new maternal postnatal records increased their workload, mainly as a consequence of colleagues not completing documentation as required. Conclusions: this was the first UK study to undertake a review of in-patient postnatal services. Involvement of midwives at the outset was essential to the success of the initiative. Midwives play a lead role in the planning and organisation of in-patient postnatal care and it was important to obtain their feedback on whether revisions were pragmatic and achieved anticipated improvements in care quality. Their initial involvement ensured priority areas for change were identified and implemented. Their subsequent feedback highlighted further important areas to address as part of CQI to ensure best quality care continues to be implemented. Our findings could support other maternity service organisations to optimise in-patient postnatal services

Simultaneous chronic rupture of quadriceps tendon and contra-lateral patellar tendon in a patient affected by tertiary hyperparatiroidism

Spontaneous ruptures of the extensor mechanism of the knee are very rare. They tend to increase considerably in patients with metabolic diseases such as chronic renal failure, hyperparathyroidism, diabetes, gout, and systemic lupus erythematosus. The reported case regards a 48-year-old man with chronic, spontaneous and simultaneous quadriceps, and contra-lateral patellar tendon rupture. The patient suffered from chronic renal failure and for the past year from tertiary hyperparathyroidism. Ruptured tendons were repaired and both knee were evaluated monthly for the next 12 months. Good functional recovery was achieved on both knees without relapse. This case emphasizes the importance of long-term high parathyroid hormone level in the etiology of tendons ruptures