Antagonistic Regulation of Circadian Output and Synaptic Development by JETLAG and the DYSCHRONIC-SLOWPOKE Complex

Circadian output genes act downstream of the clock to promote rhythmic changes in behavior and physiology, yet their molecular and cellular functions are not well understood. Here we characterize an interaction between regulators of circadian entrainment, output, and synaptic development in Drosophila that influences clock-driven anticipatory increases in morning and evening activity. We previously showed the JETLAG (JET) E3 ubiquitin ligase resets the clock upon light exposure, whereas the PDZ protein DYSCHRONIC (DYSC) regulates circadian locomotor output and synaptic development. Surprisingly, we find that JET and DYSC antagonistically regulate synaptic development at the larval neuromuscular junction, and reduced JET activity rescues arrhythmicity of dysc mutants. Consistent with our prior finding that DYSC regulates SLOWPOKE (SLO) potassium channel expression, jet mutations also rescue circadian and synaptic phenotypes in slo mutants. Collectively, our data suggest that JET, DYSC, and SLO promote circadian output in part by regulating synaptic morphology

How Useful Are Early Economic Models?; Comment on “Problems and Promises of Health Technologies: The Role of Early Health Economic Modelling”

Early economic modelling has long been recommended to aid research and development (R&D) decisions in medical innovation, although they are less frequently published and critically appraised. A review of 30 innovations by Grutters et al provides an opportunity to evaluate how early models are used in practice. The evidence of early models can be used to inform two types of decision: to continue development (“stop or go”) or to alter future R&D activities. I argue that early models have limited use in stop or go decisions, as less resource and data undermine the reliability of the models’ indicative estimates of cost-effectiveness. Whilst they are far more useful for informing future R&D directions, the best techniques available from statistical decision science, such as value of information analysis, are not regularly used. It is highly recommended that early models adopt these methods to best deal with uncertainty, quantify the potential value of further research, identify areas of study with the greatest potential benefit and generate recommendations on study design and sample size

Water resource problems of energy projects in the Colorado River Basin

The successful development of western coal and oil shale deposits is dependent, to a significant degree, on the availability of adequate water supplies. EQL is involved in a study of the aggregate effects of various energy activities in the upper Colorado River Basin on downstream water quantity and quality. These activities will tend to reduce the available water in the river, and could increase its salinity, which is already so high as to interfere with downstream domestic and agricultural use

Assessment of alternative strategies for sludge disposal into deep ocean basins off Southern California

The general framework of engineering alternatives for regional ocean sludge disposal is well described in a report by Raksit, and will not be repeated here. The various ocean disposal alternatives are less costly than all land-disposal and incineration/pyrolysis systems studied. Even though ocean sludge disposal is currently contrary to both state and federal regulations, it is hoped that this study will advance our scientific and engineering knowledge of the behavior and effects of sludge discharge in deep water, in case the regulatory policy is reexamined in the future. With this report we hope we have demonstrated the potential and difficulties of some new modeling techniques for predicting the effects of sludge discharge in the ocean. In the future. we believe it will be possible to formulate policy of ocean sludge discharges with much better case-by-case predictions of impacts for comparison with other alternatives (such as land disposal). not only for the Los Angeles/Orange County areas, but for all coastal urban areas

Explaining Latent Factor Models for Recommendation with Influence Functions

Latent factor models (LFMs) such as matrix factorization achieve the state-of-the-art performance among various Collaborative Filtering (CF) approaches for recommendation. Despite the high recommendation accuracy of LFMs, a critical issue to be resolved is the lack of explainability. Extensive efforts have been made in the literature to incorporate explainability into LFMs. However, they either rely on auxiliary information which may not be available in practice, or fail to provide easy-to-understand explanations. In this paper, we propose a fast influence analysis method named FIA, which successfully enforces explicit neighbor-style explanations to LFMs with the technique of influence functions stemmed from robust statistics. We first describe how to employ influence functions to LFMs to deliver neighbor-style explanations. Then we develop a novel influence computation algorithm for matrix factorization with high efficiency. We further extend it to the more general neural collaborative filtering and introduce an approximation algorithm to accelerate influence analysis over neural network models. Experimental results on real datasets demonstrate the correctness, efficiency and usefulness of our proposed method

A Fantasy in Sci-Fi's Clothing: Interstellar and the Liberation of Magic from Genre

In his film Interstellar (2014) Christopher Nolan depicts an outer space filled with black holes, gravitational phenomenon, ghosts, and tesseracts. As the protagonist ventures into space to find a new habitable planet, he encounters incredible scientific challenges, moral dilemmas, and religious questions. Religion and morality are established themes in space films and in science fiction, and the film was largely acknowledged for its attempts to grapple with larger ontological and religious questions. However, the film is often overlooked for its magical elements. Interstellar is largely a fantasy film but is also incredibly rich in science fictional tropes and themes. In this essay, I will argue that Interstellar can be reduced to neither a fantasy film nor a science fiction one, and that the complex relationship between science and magic are explored in a unique and artistically valuable way.Ope

Effect of Airflow Exposure on the Tear Meniscus

Purpose. To compare the effect of airflow exposure on the tear meniscus and blink frequency in normal and evaporative dry eye subjects. Methods. In 9 normal subjects and 9 short tear breakup time (SBUT) dry eye subjects, lower tear meniscus height (TMH) and area (TMA) and blink frequency were measured with anterior segment optical coherence tomography (OCT) before and after 5 minutes of airflow exposure (1.5 ± 0.5 m/s). Results. In SBUT dry eyes, both TMH and TMA decreased significantly (P = 0.027, P = 0.027) with a significant increase of blink frequency after airflow exposure, while significant increase in TMA was found in normal eyes. Conclusion. Measurement of the tear meniscus with anterior segment OCT seems to be useful as a noninvasive and objective method for evaluating the effect of airflow on tear film

Estimating Social Variation in the Health Effects of Changes in Health Care Expenditure

Background. A common aim of health expenditure is to reduce unfair inequalities in health. Although previous research has attempted to estimate the total health effects of changes in health expenditure, little is known about how changes affect different groups in the population. Methods. We propose a general framework for disaggregating the total health effects of changes in health expenditure by social groups. This can be performed indirectly when the estimate of the total health effect has first been disaggregated by a secondary factor (e.g., disease area) that can be linked to social characteristics. This is illustrated with an application to the English National Health Service. Evidence on the health effects of expenditure across 23 disease areas is combined with data on the distribution of disease-specific hospital utilization by age, sex, and area-level deprivation. Results. We find that the health effects from NHS expenditure changes are produced largely through disease areas in which individuals from more deprived areas account for a large share of health care utilization, namely, respiratory and neurologic disease and mental health. We estimate that 26% of the total health effect from a change in expenditure would accrue to the fifth of the population living in the most deprived areas, compared with 14% to the fifth living in the least deprived areas. Conclusions. Our approach can be useful for evaluating the health inequality impacts of changing health budgets or funding alternative health programs. However, it requires robust estimates of how health expenditure affects health outcomes. Our example analysis also relied on strong assumptions about the relationship between health care utilization and health effects across population groups

Optimal management of acute kidney injury in critically ill patients with invasive fungal infections being treated with liposomal amphotericin B.

Critically ill patients are at risk of developing both acute kidney injury (AKI) and invasive fungal infections (IFIs). Prompt and efficient treatment of the IFI is essential for the survival of the patient. This article examines three distinct clinical situations where liposomal amphotericin B, a broad-spectrum antifungal agent, was successfully used in the setting of AKI. The first was Aspergillus infection in a 63-year-old man with bleeding oesophageal varices related to advanced liver disease. The second was gastrointestinal mucormycosis in a 74-year-old man who developed a small bowel obstruction following an autologous stem cell transplant for mantle cell lymphoma. The third was a Fusarium infection in a 32-year-old woman on immunosuppression for a bilateral lung transplant for cystic fibrosis. In all three cases, liposomal amphotericin B was required for urgent management of the patient's IFI. We discuss the rationale for treatment with a potentially nephrotoxic agent in this setting