Prioritization of molecular targets for antimalarial drug discovery

There is a shift in antimalarial drug discovery from phenotypic screening toward target-based approaches, as more potential drug targets are being validated i

Initiation of Psychotropic Medication after Partner Bereavement: A Matched Cohort Study

Background Recent changes to diagnostic criteria for depression in DSM-5 remove the bereavement exclusion, allowing earlier diagnosis following bereavement. Evaluation of the potential effect of this change requires an understanding of existing psychotropic medication prescribing by non-specialists after bereavement. Aims To describe initiation of psychotropic medication in the first year after partner bereavement. Methods In a UK primary care database, we identified 21,122 individuals aged 60 and over with partner bereavement and no psychotropic drug use in the previous year. Prescribing (anxiolytic/hypnotic, antidepressant, antipsychotic) after bereavement was compared to age, sex and practice matched controls. Results The risks of receiving a new psychotropic prescription within two and twelve months of bereavement were 9.5% (95% CI 9.1 to 9.9%) and 17.9% (17.3 to 18.4%) respectively; an excess risk of initiation in the first year of 12.4% compared to non-bereaved controls. Anxiolytic/hypnotic and antidepressant initiation rates were highest in the first two months. In this period, the hazard ratio for initiation of anxiolytics/hypnotics was 16.7 (95% CI 14.7 to 18.9) and for antidepressants was 5.6 (4.7 to 6.7) compared to non-bereaved controls. 13.3% of those started on anxiolytics/hypnotics within two months continued to receive this drug class at one year. The marked variation in background family practice prescribing of anxiolytics/hypnotics was the strongest determinant of their initiation in the first two months after bereavement. Conclusion Almost one in five older people received a new psychotropic drug prescription in the year after bereavement. The early increase and trend in antidepressant use after bereavement suggests some clinicians did not adhere to the bereavement exclusion, with implications for its recent removal in DSM-5. Family practice variation in use of anxiolytics/hypnotics suggests uncertainty over their role in bereavement with the potential for inappropriate long term use

The False Economy of Seeking to Eliminate Delayed Transfers of Care: Some Lessons from Queueing Theory

This is the final version. Available on open access from Springer via the DOI in this recordBackground It is a stated ambition of many healthcare systems to eliminate delayed transfers of care (DTOCs) between acute and step-down community services. Objective This study aims to demonstrate how, counter to intuition, pursual of such a policy is likely to be uneconomical, as it would require large amounts of community capacity to accommodate even the rarest of demand peaks, leaving much capacity unused for much of the time. Methods Some standard results from queueing theory—a mathematical discipline for considering the dynamics of queues and queueing systems—are used to provide a model of patient flow from the acute to community setting. While queueing models have a track record of application in healthcare, they have not before been used to address this question. Results Results show that ‘eliminating’ DTOCs is a false economy: the additional community costs required are greater than the possible acute cost saving. While a substantial proportion of DTOCs can be attributed to inefficient use of resources, the remainder can be considered economically essential to ensuring cost-efficient service operation. For England’s National Health Service (NHS), our modelling estimates annual cost savings of £117m if DTOCs are reduced to the 12% of current levels that can be regarded as economically essential. Conclusion This study discourages the use of ‘zero DTOC’ targets and instead supports an assessment based on the specific characteristics of the healthcare system considered.Health Data Research U

Subducted, detached, and torn slabs beneath the Greater Caucasus

© 2014 Published by Elsevier Ltd. The Greater Caucasus Mountains contain the highest peaks in Europe and define, for over 850. km along strike, the leading edge of the second-largest active collisional orogen on Earth. However, the mechanisms by which this range is being constructed remain disputed. Using a new database of earthquake records from local networks in Georgia, Russia, and Azerbaijan, together with previously published hypocenter locations, we show that the central and eastern Greater Caucasus Mountains are underlain by a northeast-dipping zone of mantle seismicity that we interpret as a subducted slab. Beneath the central Greater Caucasus (east of 45°E), the zone of seismicity extends to a depth of at least 158. km with a dip of ~40°NE and a slab length of ~130-280. km. In contrast, beneath the western GC (west of 45°E) there is a pronounced lack of events below ~50. km, which we infer to reflect slab breakoff and detachment. We also observe a gap in intermediate-depth seismicity (45-75. km) at the western end of the subducted slab beneath the central Greater Caucasus, which we interpret as an eastward-propagating tear. This tear coincides with a region of minimum horizontal convergence rates between the Lesser and Greater Caucasus, as expected in a region of active slab breakoff. Active subduction beneath the eastern Greater Caucasus presents a potentially larger seismic hazard than previously recognized and may explain historical records of large magnitude (M 8) seismicity in this region

From Boatyard to Museum: 3D laser scanning and digital modelling of the Qatar Museums watercraft collection, Doha, Qatar

This is the final version of the article. Available from Wiley via the DOI in this record.This article presents the results of a project to 3D laser scan and digitally model 14 watercraft from the Qatar Museums collection, comprising a range of regional vessels: most had not been surveyed previously. The project used the resulting point clouds generated 2D naval lines and orthographic records of the vessels in their current condition, and photorealistic 3D digital models for gallery display. This case study provides illustrative examples of the intermediate stages and final outputs. It assesses the pros and cons of 3D laser scanning as a survey technology for nautical scholars in terms of the time, cost, and skillset, as well as logistical considerations. It also compares the accuracy of traditional hand survey methods.We wish to thank QM for enabling and funding this research (Grant number SL-05894)

The Role of Individual Variables, Organizational Variables and Moral Intensity Dimensions in Libyan Management Accountants’ Ethical Decision Making

This study investigates the association of a broad set of variables with the ethical decision making of management accountants in Libya. Adopting a cross-sectional methodology, a questionnaire including four different ethical scenarios was used to gather data from 229 participants. For each scenario, ethical decision making was examined in terms of the recognition, judgment and intention stages of Rest’s model. A significant relationship was found between ethical recognition and ethical judgment and also between ethical judgment and ethical intention, but ethical recognition did not significantly predict ethical intention—thus providing support for Rest’s model. Organizational variables, age and educational level yielded few significant results. The lack of significance for codes of ethics might reflect their relative lack of development in Libya, in which case Libyan companies should pay attention to their content and how they are supported, especially in the light of the under-development of the accounting profession in Libya. Few significant results were also found for gender, but where they were found, males showed more ethical characteristics than females. This unusual result reinforces the dangers of gender stereotyping in business. Personal moral philosophy and moral intensity dimensions were generally found to be significant predictors of the three stages of ethical decision making studied. One implication of this is to give more attention to ethics in accounting education, making the connections between accounting practice and (in Libya) Islam. Overall, this study not only adds to the available empirical evidence on factors affecting ethical decision making, notably examining three stages of Rest’s model, but also offers rare insights into the ethical views of practising management accountants and provides a benchmark for future studies of ethical decision making in Muslim majority countries and other parts of the developing world

Interdisciplinary Design Studio: Programming Document Visioning for a Robotic Demonstration, Research, and Engagement Dairy

The 2022 COLLABORATE Design Studio brought together students from various disciplines to address a complex, real-world project which required collaborative input from different perspectives. The studio worked to advance the co-creation of knowledge between external stakeholders, students, and instructors. The course was co-taught by faculty from different disciplines, and areas of expertise. During the semester, Nate Bicak and Steven Hardy worked with students from Architecture and Interior Design in collaboration with students in Dr. Tami Brown-Brandl’s students in Biological Systems Engineering and Animal Science to explore the values, spatial qualities, and area requirements of a Robotic Demonstration, Research, and Engagement Dairy. Students organized a series of meetings and participatory activities to gather information from a range of project stakeholders including: Heather Akin (Agricultural Leadership, Education & Communication), Kris Bousquet (NE Dairy Association), Paul Kononoff (Animal Science), Eric Markvicka (Mechanical and Material Engineering), Julia McQuillan (Sociology), Santosh Pitla (BioSystems and Agricultural Engineering), Ling Ling Sun (NE Public Media), and Rosanna Villa Rojas (Food Science & Technology). The information gathered helped to frame the overall problem - both quantitative and qualitative - to be addressed during the design visioning stage (not included in this document). Student contributors included: Sarah Alduaylij, Noor Al-Maamari, Devyn Beekman, Kelsey Belgum, Lauren Chubb, Nicholas Forte, Mitchell Hill, Joshua Holstein, Dylan Lambe, Phuong Le, Mia LeRiger, Elizabeth Loftus, Josh Lorenzen , Megan Lovci, Alex Martino, Zade Miller, Hannah Morgan , Annabelle Nichols , Collin Shearman, Rebecca Sowl, Nalin Theplikhith, Angela Vu, Shaylee Wagner, Ethan Watermeier, Trever Zelenk

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead.

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology

Identifying bereaved subjects at risk of complicated grief: Predictive value of questionnaire items in a cohort study

<p>Abstract</p> <p>Background</p> <p>Bereavement is a condition which most people experience several times during their lives. A small but noteworthy proportion of bereaved individuals experience a syndrome of prolonged psychological distress in relation to bereavement. The aim of the study was to develop a clinical tool to identify bereaved individuals who had a prognosis of complicated grief and to propose a model for a screening tool to identify those at risk of complicated grief applicable among bereaved patients in general practice and palliative care.</p> <p>Methods</p> <p>We examined the responses of 276 newly bereaved individuals to a variety of standardised and ad hoc questionnaire items eight weeks post loss. Inventory of Complicated Grief (ICG-R) was used as a gold standard of distress at six months after bereavement. Receiver operating characteristic (ROC) curves analysis was performed for all scales and items regarding ICG-R score. Sensitivity, specificity and area under curve (AUC) were calculated for scales and items with the most promising ROC curve analyses.</p> <p>Results</p> <p>Beck's Depression Inventory (BDI) was the scale with the highest AUC (0.83) and adding a single item question ('Even while my relative was dying, I felt a sense of purpose in my life') gave a sensitivity of 80% and specificity of 75%. The positive/negative predictive values for this combination of questions were 70% and 85%, respectively. With this screening tool bereaved people could be categorized into three groups where group 1 had 7%, group 2 had 23% and group 3 had 64% propensity of suffering from complicated grief six months post loss.</p> <p>Conclusions</p> <p>This study shows that the BDI in combination with a single item question eight weeks post loss may be used for clinical screening for risk of developing complicated grief after six months. The feasibility and clinical implications of the screening tool has to be tested in a clinical setting.</p

The Senility of Group Solidarity and Contemporary Multiculturalism: a Word of Warning from a Medieval Arabic Thinker

This paper discusses the thought of the medieval Maghrebin thinker Ibn Khaldun through the prism of the philosophy and sociology of law and politics. I will first try to illustrate how, even if Ibn Khaldun wrote in the fourteenth century, he anticipated many core concepts that are characteristic of modern Western sociological and philosophical thought. The argument is thus made that his thought can, and indeed must, be rescued from the wide neglect that, outside the specialized field of Khaldunian studies, it has so far suffered in our treatment and teaching of the history of politico\u2010legal sociological thought. I will then claim that the scheme he devised to explain the rise and fall of civilizations can also, with due care, be used to frame and understand the political and cultural landscape in which the West and the Islamic world are presently engaged in a difficult dialogue. The discussion is in this sense offered in the hope of making a contribution to the current politico\u2010legal philosophical and sociological debate on multiculturalism, and on the limits of its scope