Chronic kidney disease of unknown etiology in Nicaragua: investigating the role of environmental and occupational exposures

Background: In Central America, an epidemic of chronic kidney disease (CKD) primarily affects younger, male agricultural workers. Hypothesized causal agents include heat stress, agrichemicals, and heavy metals, among others, but the etiology remains unknown. Our aims were to assess job-specific changes in kidney function and injury during the sugarcane harvest season, characterize hydration practices and metals exposure, and determine whether these agents are associated with kidney function and injury. The overall goal was to address this public health emergency to inform intervention and prevention strategies. Methods: We recruited 284 sugarcane workers, representing seven job tasks, and 51 miners, all from northwestern Nicaragua. We sampled sugarcane workers at two time points (before and near the end of the harvest season) and miners at one time point. As a marker of kidney function, we measured serum creatinine to estimate glomerular filtration rate (eGFR). As markers of kidney injury, we measured urinary neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), N-acetyl-D-glucosaminidase (NAG), albumin, and creatinine. We measured blood lead and urinary cadmium, uranium, and total arsenic in a subset of sugarcane workers and miners. Results: Kidney function (eGFR) declined during the harvest season in seed cutters, irrigators, and cane cutters compared to other jobs, and kidney injury biomarkers (NGAL, IL-18) increased during the harvest, most notably among cane cutters. Electrolyte solution consumption appeared protective in cane cutters, a job with high heat exposure and heavy manual exertion. Though metal biomarkers were not elevated, there was some evidence that combined exposure to multiple metals was associated with decreased kidney function and increased injury. Albuminuria was rare. Conclusions: These findings provide evidence that occupational exposures are involved in the etiology of CKD. Heat stress and volume depletion may play a role, most likely in combination with one or more other agents, possibly environmental exposure to low-level metals. Our results do not support the hypothesis that agrichemicals are causal, but future studies that quantify exposure to specific agents are needed. The limited albuminuria and presence of tubular injury markers supports a tubulointerstitial disease that could occur with repeated subclinical injury leading to clinically apparent CKD over time

The Surgical Management of Acromegaly

Acromegaly is the condition produced by one of the benign tumors of the pituitary gland. These tumors produce a variety of disorders affecting many parts of the body, producing side effects related to abnormal hormone function. The dramatic appearance of the acromegalic giant has attracted attention over the ages. This chapter summarizes the history of the recognition and ultimate diagnosis of acromegaly. The biological and physiological elements are described. The methods of diagnosis and management are elaborated. Although the focus of the chapter is on the surgical approach for treatment, alternative strategies are also discussed, along with the outcomes of management for patients and the restoration of quality of life as a primary goal

Universal Citation and the American Association of Law Libraries: A White Paper

This white paper is a collaborative endeavor of many individuals, including members of the American Association of Law Libraries and its Digital Access to Legal Information Committee (DALIC), formerly the Electronic Legal Information Access & Citation (ELIAC) Committee. First, Justice Yvonne Kauger introduces the topic by identifying the groundbreaking steps taken by the Oklahoma Supreme Court. Law librarians Carol Billings and Kathy Carlson next provide a detailed and comprehensive history of citation reform and the American Association of Law Libraries’ leadership and involvement in the issue. They also summarize the citation reform steps taken in selected jurisdictions. Finally, John Cannan, current DALIC member, provides a look to the future, identifying reasons to advance needed citation reform now

A Search for 6^{6}Li in Stars with Planets

Using very high-resolution (R$\sim$ 125,000) and high quality (S/N $\geq$ 350) spectra, we have searched for $^{6}$Li in stars hosting extra-solar planets. From detailed profile-fitting of the Li {\sc i} resonance line at 6707.7 \AA, we find no significant amount of $^{6}$Li relative to the $^{7}$Li for any of 8 planet bearing stars ($^{6}$Li/$^{7}$Li $\leq$ 0.0 - 0.03) with a strong Li {\sc i} lines. In particular, we do not confirm the presence of $^{6}$Li with $^{6}$Li/$^{7}$Li = 0.13 reported by Israelian et al.(2001) for HD 82943, a star with two known planets. Several of the 8 stars plus HD 219542 A, the planet-less primary of a binary, have been identified in the literature as possible recipients of accreted terrestrial material. For all of the planet-hosting stars and an additional 5 planet-less stars, we find no $^{6}$Li.Comment: Accepted for MNRAS, 18 pages (12 figures included

Blogging in the physics classroom: A research-based approach to shaping students' attitudes towards physics

Even though there has been a tremendous amount of research done in how to help students learn physics, students are still coming away missing a crucial piece of the puzzle: why bother with physics? Students learn fundamental laws and how to calculate, but come out of a general physics course without a deep understanding of how physics has transformed the world around them. In other words, they get the "how" but not the "why". Studies have shown that students leave introductory physics courses almost universally with decreased expectations and with a more negative attitude. This paper will detail an experiment to address this problem: a course weblog or "blog" which discusses real-world applications of physics and engages students in discussion and thinking outside of class. Specifically, students' attitudes towards the value of physics and its applicability to the real-world were probed using a 26-question Likert scale survey over the course of four semesters in an introductory physics course at a comprehensive Jesuit university. We found that students who did not participate in the blog study generally exhibited a deterioration in attitude towards physics as seen previously. However, students who read, commented, and were involved with the blog maintained their initially positive attitudes towards physics. Student response to the blog was overwhelmingly positive, with students claiming that the blog made the things we studied in the classroom come alive for them and seem much more relevant.Comment: 20 pages, 6 figure

Meta-analysis of cognitive behaviour therapy and selective serotonin reuptake inhibitors for the treatment of hypochondriasis: Implications for trial design

Background: Classification of hypochondriasis as an obsessive-compulsive and related disorder in the International Classification of Diseases 11th Revision (ICD-11) has generated new heuristics for treatment of this common, chronic and disabling disorder. Standard treatment involves cognitive behaviour therapy (CBT) or selective serotonin reuptake inhibitors (SSRIs), but no meta-analysis has so far considered hypochondriasis as a structured diagnosis or assessed the role of medication. A clearer understanding of the relative effectiveness of these interventions and identification of clinically relevant factors moderating the treatment response is needed for clinical guideline development. Methods: The current systematic review and meta-analysis of interventions for hypochondriasis was preregistered on PROSPERO (CRD42020185768) and follows PRISMA guidelines. We searched MEDLINE, PsycINFO, and Cochrane Library databases until July 2021 for randomized controlled trials (RCTs) of interventions for patients diagnosed with hypochondriasis (or historical diagnostic equivalents). We assessed aspects of study quality using: the CONSORT Checklist for evaluation of RCTs, the Cochrane Risk of Bias 2 tool, researcher allegiance and treatment fidelity. The primary outcome was improvement in hypochondriasis symptoms, comparing intervention and control groups at trial endpoint. Moderator variables were assessed using subgroup and meta-regression analyses. Results: Searches identified 13 randomised controlled trials (RCTs) (N = 1405); 12 included CBT (N = 1212) and three included SSRI (N = 193) arms as the experimental intervention. Random effects meta-analysis yielded a moderate-to-large effect size for CBT versus all controls (g = −0.70 [95% CI -0.99 to −0.41], k = 18, I2 = 81.1%). Funnel plot asymmetry indicated possible publication bias and two potentially missing trials, reducing the effect size (g = −0.60 [95% CI -0.88 to −0.32]). Subgroup analysis showed that choice of control significantly moderated effect size, with those in CBT vs. wait-list (g = −1.32 [95% CI -1.75 to −0.90], k = 7, I2 = 0%) being double those of CBT vs. psychological or pharmacological placebo controls (g = −0.58 [95% CI -0.95 to −0.22], k = 7, I2 = 82%). Analysis of studies directly comparing CBT and SSRIs found a numerical, but not statistical advantage for SSRIs (g = 0.21 [95% CI -0.46 to 0.87], k = 2, I2 = 58.34%) and a modest effect size emerged for SSRIs vs. pill placebo (g = −0.29 [95% CI -0.57 to −0.01], k = 3, I2 = 0%). Most studies (11/13) were rated as high on potential researcher allegiance bias in favour of CBT. Meta-regressions revealed that effect sizes were larger in younger participants, and smaller in better quality and more recent RCTs and those with greater CBT fidelity. Conclusion: CBT and SSRIs are effective in the acute treatment of hypochondriasis, with some indication that intervention at a younger age produces better outcomes for CBT. In the case of CBT, effect sizes appear to have been significantly inflated by the use of wait list controls, and researcher allegiance bias. We recommend that a definitive, adequately controlled trial, designed with respect to the methodological issues raised in this meta-analysis, is needed to determine the magnitude effects for CBT and SSRIs with confidence and the long-term effect of treatments, to inform mental health service provision for this overlooked patient group

Accurate, precise modeling of cell proliferation kinetics from time-lapse imaging and automated image analysis of agar yeast culture arrays

BACKGROUND: Genome-wide mutant strain collections have increased demand for high throughput cellular phenotyping (HTCP). For example, investigators use HTCP to investigate interactions between gene deletion mutations and additional chemical or genetic perturbations by assessing differences in cell proliferation among the collection of 5000 S. cerevisiae gene deletion strains. Such studies have thus far been predominantly qualitative, using agar cell arrays to subjectively score growth differences. Quantitative systems level analysis of gene interactions would be enabled by more precise HTCP methods, such as kinetic analysis of cell proliferation in liquid culture by optical density. However, requirements for processing liquid cultures make them relatively cumbersome and low throughput compared to agar. To improve HTCP performance and advance capabilities for quantifying interactions, YeastXtract software was developed for automated analysis of cell array images. RESULTS: YeastXtract software was developed for kinetic growth curve analysis of spotted agar cultures. The accuracy and precision for image analysis of agar culture arrays was comparable to OD measurements of liquid cultures. Using YeastXtract, image intensity vs. biomass of spot cultures was linearly correlated over two orders of magnitude. Thus cell proliferation could be measured over about seven generations, including four to five generations of relatively constant exponential phase growth. Spot area normalization reduced the variation in measurements of total growth efficiency. A growth model, based on the logistic function, increased precision and accuracy of maximum specific rate measurements, compared to empirical methods. The logistic function model was also more robust against data sparseness, meaning that less data was required to obtain accurate, precise, quantitative growth phenotypes. CONCLUSION: Microbial cultures spotted onto agar media are widely used for genotype-phenotype analysis, however quantitative HTCP methods capable of measuring kinetic growth rates have not been available previously. YeastXtract provides objective, automated, quantitative, image analysis of agar cell culture arrays. Fitting the resulting data to a logistic equation-based growth model yields robust, accurate growth rate information. These methods allow the incorporation of imaging and automated image analysis of cell arrays, grown on solid agar media, into HTCP-driven experimental approaches, such as global, quantitative analysis of gene interaction networks