Concentrated urine, low urine flow, and postoperative elevation of plasma creatinine: A retrospective analysis of pooled data.

Elevations of plasma creatinine are common after major surgery, but their pathophysiology is poorly understood. To identify possible contributing mechanisms, we pooled data from eight prospective studies performed in four different countries to study circumstances during which elevation of plasma creatinine occurs. We included 642 patients undergoing mixed major surgeries, mostly open gastrointestinal. Plasma and urinary creatinine and a composite index for renal fluid conservation (Fluid Retention Index, FRI) were measured just before surgery and on the first postoperative morning. Urine flow was measured during the surgery. The results show that patients with a postoperative increase in plasma creatinine by >25% had a high urinary creatinine concentration (11.0±5.9 vs. 8.3±5.6 mmol/L; P 25% also showed higher creatinine and a higher FRI value on the first postoperative morning (P 50% of baseline were associated with slightly lower mean arterial pressure (73 ± 10 vs. 80 ± 12 mmHg; P< 0.005). We conclude that elevation of plasma creatinine in the perioperative period was associated with low urine flow and greater blood loss during surgery and with concentrated urine both before and after the surgery. Renal water conservation-related mechanisms seem to contribute to the development of increased plasma creatinine after surgery

Giant right coronary artery aneurysm presenting with non-ST elevation myocardial infarction and severe mitral regurgitation: a case report

<p>Abstract</p> <p>Introduction</p> <p>Coronary artery aneurysms are seen in 1.5-5% of patients presenting for coronary angiography, but giant aneurysms, defined as being greater than 2 cm in diameter, are rare. Given the paucity of cases and limited experience in diagnosis and management of the disease, each case is a learning tool in itself.</p> <p>Case presentation</p> <p>We report the rare case of a 78-year-old Caucasian man who presented to a peripheral emergency department with chest pain and was subsequently found to have a giant right coronary artery aneurysm. Following initial investigation and treatment he was referred to our hospital for definitive management.</p> <p>Conclusion</p> <p>The case described illustrates one of the varied presentations and subsequent management of an ill-defined and heterogeneous disease process. Given the limited experience with giant aneurysms in the coronary circulation, this case provides valuable insight into the clinical presentation of the disease and gives an example of the management of the most recent such case at our hospital.</p

Search algorithms as a framework for the optimization of drug combinations

Combination therapies are often needed for effective clinical outcomes in the management of complex diseases, but presently they are generally based on empirical clinical experience. Here we suggest a novel application of search algorithms, originally developed for digital communication, modified to optimize combinations of therapeutic interventions. In biological experiments measuring the restoration of the decline with age in heart function and exercise capacity in Drosophila melanogaster, we found that search algorithms correctly identified optimal combinations of four drugs with only one third of the tests performed in a fully factorial search. In experiments identifying combinations of three doses of up to six drugs for selective killing of human cancer cells, search algorithms resulted in a highly significant enrichment of selective combinations compared with random searches. In simulations using a network model of cell death, we found that the search algorithms identified the optimal combinations of 6-9 interventions in 80-90% of tests, compared with 15-30% for an equivalent random search. These findings suggest that modified search algorithms from information theory have the potential to enhance the discovery of novel therapeutic drug combinations. This report also helps to frame a biomedical problem that will benefit from an interdisciplinary effort and suggests a general strategy for its solution.Comment: 36 pages, 10 figures, revised versio

Can the Universe Create Itself?

The question of first-cause has troubled philosophers and cosmologists alike. Now that it is apparent that our universe began in a Big Bang explosion, the question of what happened before the Big Bang arises. Inflation seems like a very promising answer, but as Borde and Vilenkin have shown, the inflationary state preceding the Big Bang must have had a beginning also. Ultimately, the difficult question seems to be how to make something out of nothing. This paper explores the idea that this is the wrong question --- that that is not how the Universe got here. Instead, we explore the idea of whether there is anything in the laws of physics that would prevent the Universe from creating itself. Because spacetimes can be curved and multiply connected, general relativity allows for the possibility of closed timelike curves (CTCs). Thus, tracing backwards in time through the original inflationary state we may eventually encounter a region of CTCs giving no first-cause. This region of CTCs, may well be over by now (being bounded toward the future by a Cauchy horizon). We illustrate that such models --- with CTCs --- are not necessarily inconsistent by demonstrating self-consistent vacuums for Misner space and a multiply connected de Sitter space in which the renormalized energy-momentum tensor does not diverge as one approaches the Cauchy horizon and solves Einstein's equations. We show such a Universe can be classically stable and self-consistent if and only if the potentials are retarded, giving a natural explanation of the arrow of time. Some specific scenarios (out of many possible ones) for this type of model are described. For example: an inflationary universe gives rise to baby universes, one of which turns out to be itself. Interestingly, the laws of physics may allow the Universe to be its own mother.Comment: 48 pages, 8 figure

“A Massive Long Way”: Interconnecting Histories, a “Special Child,” ADHD, and Everyday Family Life

Focusing on one family from a study of dual-earner middle-class families carried out in Los Angeles, California, this article draws on interview and video-recorded data of everyday interactions to explore illness and healing as embedded in the microcultural context of the Morris family. For this family, an important aspect of what is at stake for them in their daily lives is best understood by focusing on 9-year-old Mark, who has been diagnosed with attention-deficit/hyperactivity disorder (ADHD). In this article, we grapple with the complexity of conveying some sense of how Mark’s condition is experienced and relationally enacted in everyday contexts. Through illuminating connections between lives as lived and lives as told, we explore the narrative structuring of healing in relation to Mark’s local moral world with the family at its center. We examine how his parents understand the moral consequences of the child’s past for his present and future, and work to encourage others to give due weight to his troubled beginnings before this child joined the Morris family. At the same time, we see how the Morris parents act to structure Mark’s moral experience and orient to a desired future in which Mark’s “success” includes an appreciation of how he is accountable to others for his actions. Through our analyses, we also seek to contribute to discussions on what is at stake in everyday life contexts for children with ADHD and their families, through illuminating aspects of the cultural, moral and relational terrain that U.S. families navigate in contending with a child’s diagnosis of ADHD. Further, given that ADHD is often construed as a “disorder of volition,” we seek to advance anthropological theorizing about the will in situations where volitional control over behavior is seen to be disordered

The UCSC cancer genomics browser: update 2011

The UCSC Cancer Genomics Browser (https://genome-cancer.ucsc.edu) comprises a suite of web-based tools to integrate, visualize and analyze cancer genomics and clinical data. The browser displays whole-genome views of genome-wide experimental measurements for multiple samples alongside their associated clinical information. Multiple data sets can be viewed simultaneously as coordinated ‘heatmap tracks’ to compare across studies or different data modalities. Users can order, filter, aggregate, classify and display data interactively based on any given feature set including clinical features, annotated biological pathways and user-contributed collections of genes. Integrated standard statistical tools provide dynamic quantitative analysis within all available data sets. The browser hosts a growing body of publicly available cancer genomics data from a variety of cancer types, including data generated from the Cancer Genome Atlas project. Multiple consortiums use the browser on confidential prepublication data enabled by private installations. Many new features have been added, including the hgMicroscope tumor image viewer, hgSignature for real-time genomic signature evaluation on any browser track, and ‘PARADIGM’ pathway tracks to display integrative pathway activities. The browser is integrated with the UCSC Genome Browser; thus inheriting and integrating the Genome Browser’s rich set of human biology and genetics data that enhances the interpretability of the cancer genomics data

Y1 and Y5 Receptors Are Both Required for the Regulation of Food Intake and Energy Homeostasis in Mice

Neuropeptide Y (NPY) acting in the hypothalamus is one of the most powerful orexigenic agents known. Of the five known Y receptors, hypothalamic Y1 and Y5 have been most strongly implicated in mediating hyperphagic effects. However, knockout of individual Y1 or Y5 receptors induces late-onset obesity – and Y5 receptor knockout also induces hyperphagia, possibly due to redundancy in functions of these genes. Here we show that food intake in mice requires the combined actions of both Y1 and Y5 receptors. Germline Y1Y5 ablation in Y1Y5−/− mice results in hypophagia, an effect that is at least partially mediated by the hypothalamus, since mice with adult-onset Y1Y5 receptor dual ablation targeted to the paraventricular nucleus (PVN) of the hypothalamus (Y1Y5Hyp/Hyp) also exhibit reduced spontaneous or fasting-induced food intake when fed a high fat diet. Interestingly, despite hypophagia, mice with germline or hypothalamus-specific Y1Y5 deficiency exhibited increased body weight and/or increased adiposity, possibly due to compensatory responses to gene deletion, such as the decreased energy expenditure observed in male Y1Y5−/− animals relative to wildtype values. While Y1 and Y5 receptors expressed in other hypothalamic areas besides the PVN – such as the dorsomedial nucleus and the ventromedial hypothalamus – cannot be excluded from having a role in the regulation of food intake, these studies demonstrate the pivotal, combined role of both Y1 and Y5 receptors in the mediation of food intake