ALLN-177, oral enzyme therapy for hyperoxaluria

PURPOSE: To evaluate the potential of ALLN-177, an orally administered, oxalate-specific enzyme therapy to reduce urine oxalate (UOx) excretion in patients with secondary hyperoxaluria. METHODS: Sixteen male and female subjects with both hyperoxaluria and a kidney stone history were enrolled in an open-label study. Subjects continued their usual diets and therapies. During a 3-day baseline period, two 24-h (24-h) urines were collected, followed by a 4-day treatment period with ALLN-177 (7,500 units/meal, 3 × day) when three 24-h urines were collected. The primary endpoint was the change in mean 24-h UOx from baseline. Safety assessments and 24-h dietary recalls were performed throughout. RESULTS: The study enrolled 5 subjects with enteric hyperoxaluria and 11 with idiopathic hyperoxaluria. ALLN-177 was well tolerated. Overall mean (SD) UOx decreased from 77.7 (55.9) at baseline to 63.7 (40.1) mg/24 h while on ALLN-177 therapy, with the mean reduction of 14 mg/24 h, (95% CI - 23.71, - 4.13). The calcium oxalate-relative urinary supersaturation ratio in the overall population decreased from a mean of 11.3 (5.7) to 8.8 (3.8) (- 2.8; 95% CI - 4.9, - 0.79). This difference was driven by oxalate reduction alone, but not any other urinary parameters. Mean daily dietary oxalate, calcium, and fluid intake recorded by frequent diet recall did not differ by study periods. CONCLUSION: ALLN-177 reduced 24-h UOx excretion, and was well tolerated. The results of this pilot study provided justification for further investigation of ALLN-177 in patients with secondary hyperoxaluria

Criminal Justice and Suicide Outcomes with Indiana's Risk-Based Gun Seizure Law

This article examines the application and effectiveness of a 2006 Indiana law designed to prevent gun violence by authorizing police officers to separate firearms from persons who present imminent or future risk of injury to self or others, or display a propensity for violent or emotionally unstable conduct. A court hearing is held to determine ongoing risk in these cases; a judge decides whether to return the seized firearms or retain them for up to five years. The study examines the frequency of criminal arrest as well as suicide outcomes for 395 gun-removal actions in Indiana. Fourteen individuals (3.5%) died from suicide, seven (1.8%) using a firearm. The study population's annualized suicide rate was about 31 times higher than that of the general adult population in Indiana, demonstrating that the law is being applied to a population genuinely at high risk. By extrapolating information on the case fatality rate for different methods of suicide, we calculated that one life was saved for every 10 gun-removal actions, similar to results of a previous study in Connecticut. Perspectives from key stakeholders are also presented along with implications for gun policy reform and implementation

Flight Operations Analysis Tool

Flight Operations Analysis Tool (FLOAT) is a computer program that partly automates the process of assessing the benefits of planning spacecraft missions to incorporate various combinations of launch vehicles and payloads. Designed primarily for use by an experienced systems engineer, FLOAT makes it possible to perform a preliminary analysis of trade-offs and costs of a proposed mission in days, whereas previously, such an analysis typically lasted months. FLOAT surveys a variety of prior missions by querying data from authoritative NASA sources pertaining to 20 to 30 mission and interface parameters that define space missions. FLOAT provides automated, flexible means for comparing the parameters to determine compatibility or the lack thereof among payloads, spacecraft, and launch vehicles, and for displaying the results of such comparisons. Sparseness, typical of the data available for analysis, does not confound this software. FLOAT effects an iterative process that identifies modifications of parameters that could render compatible an otherwise incompatible mission set

Non-work-related services at the workplace : an exploratory study

In an era of diminishing public funds, the profession of social work is looking more and more toward the private sector as an arena for social work practice. Social work has had a long-standing interest in the impact of work and the workplace on the individual. This study was developed in response to the lack of documentation of non-work-related services in Oregon\u27s businesses and industries. The research team set out to discover what non-work-related services are available to employees at or through the workplace in the TriCounty area (Multnomah, Clackamas, and Washington Counties) of Oregon. This study was exploratory, similar to one done by Hans Spiegel and colleagues in 1974, through Hunter College in New York City

The inflammatory response in transgastric surgery: gastric content leak leads to localized inflammatory response and higher adhesive disease

Risk of gastric spillage during transgastric surgery is a potential complication of NOTES procedures. The aim of this study was to determine risk outcomes from gastric spillage in a rat survival model by measuring local and systemic inflammatory markers, adhesive disease, and morbidity. We performed a minilaparotomy with needle aspiration of 2 ml of gastric contents mixed with 2 ml of sterile saline (study group, SG) or 4 ml of sterile saline (control group, CG) injected into the peritoneal cavity of 60 male rats. Inflammatory markers (TNFα, IL-6, and IL-10) were analyzed at 1, 3, 6, and 24 h postoperatively by obtaining plasma levels and peritoneal washings. At necropsy, the peritoneal cavity was examined grossly for adhesions. Adhesions were seen more frequently in the SG versus the CG (100% vs. 33.3%, p < 0.014). There was a significant difference in the peritoneal TNFα levels in the SG compared with the CG, which peaked 1 h after surgery (p < 0.02). Both peritoneal IL-6 and IL-10 levels were higher in the SG versus the CG, which peaked 3 h after surgery (p < 0.005 and p < 0.001, respectively). All peritoneal inflammatory markers returned to undetectable levels at 24 h for both groups. Plasma cytokines were undetectable at all time intervals. The inflammatory response was found to be a localized and not systemic event, with plasma cytokine levels remaining normal while peritoneal washings revealed a brisk, short-lived localized inflammatory response. There was a significantly higher rate of adhesive disease in the SG compared with the CG; this, however did not translate into a difference in apparent clinical outcome. We conclude that gastric leakage in this NOTES rodent model induces a localized inflammatory response, followed by mild to moderate adhesive disease. This may be important in human NOTES

Fish oil supplementation and urinary oxalate excretion in normal subjects on a low-oxalate diet.

© 2014 Elsevier Inc. All rights reserved. Objective To determine if fish oil supplementation reduces endogenous oxalate synthesis in healthy subjects. Materials and Methods Fifteen healthy non-stone-forming adults participated in this study. Subjects first abstained from using vitamins, medications, or foods enriched in omega-3 fatty acids for 30 days. Next, they collected two 24-hour urine specimens while consuming a self-selected diet. Subjects consumed an extremely low-oxalate and normal-calcium diet for 5 days and collected 24-hour urine specimens on the last 3 days of this diet. Next, the subjects took 2 fish oil capsules containing 650-mg eicosapentaenoic acid and 450-mg docosahexaenoic acid twice daily for 30 days. They consumed a self-selected diet on days 1-25 and the controlled diet on days 26-30. Twenty-four-hour urine samples were collected on days 28-30. Excretion levels of urinary analytes including oxalate and glycolate were analyzed. Results Although there was a significant reduction in urinary oxalate, magnesium, and potassium excretions and an increase in uric acid excretion during the controlled dietary phases compared with the self-selected diet, there were no significant differences in their excretion during controlled diet phases with and without fish oil supplementation. Conclusion These results suggest that fish oil supplementation does not reduce endogenous oxalate synthesis or urinary oxalate excretion in normal adults during periods of extremely low oxalate intake. However, these results do not challenge the previously described reduction in urinary oxalate excretion demonstrated in normal subjects consuming a moderate amount of oxalate in conjunction with fish oil