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Alchemical free energy campaigns can be planned using graph theory by building networks that contain nodes representing molecules that are connected by possible transformations as edges. We introduce Konnektor, an open-source Python package, for systematically planning, modifying, and analyzing free energy calculation networks. Konnektor is designed to aid in the drug discovery process by enabling users to easily setup free energy campaigns using complex graph manipulation methods. The package contains functions for network operations including concatenation of networks, deletion of transformations, and clustering of molecules along with a framework for combining these tools with existing network generation algorithms to enable the development of more complex methods for network generation. A comparison of the various network layout features offered is carried out using toy data sets. Additionally, Konnektor contains visualization and analysis tools, making the investigation of network features much simpler. Besides the content of the package, the paper also offers application examples, demonstrating how Konnektor can be used and how the different networks perform from a graph theory perspective. Konnektor is freely available via GitHub at https://github.com/OpenFreeEnergy/konnektor under the permissive MIT License.

This paper presents a comprehensive overview of the National Sleep Research Resource (NSRR), a National Heart Lung and Blood Institute-supported repository developed to share data from clinical studies focused on the evaluation of sleep disorders. The NSRR addresses challenges presented by the heterogeneity of sleep-related data, leveraging innovative strategies to optimize the quality and accessibility of available datasets. It provides authorized users with secure centralized access to a large quantity of sleep-related data including polysomnography, actigraphy, demographics, patient-reported outcomes, and other data. In developing the NSRR, we have implemented data processing protocols that ensure de-identification and compliance with FAIR (Findable, Accessible, Interoperable, Reusable) principles. Heterogeneity stemming from intrinsic variation in the collection, annotation, definition, and interpretation of data has proven to be one of the primary obstacles to efficient sharing of datasets. Approaches employed by the NSRR to address this heterogeneity include (1) development of standardized sleep terminologies utilizing a compositional coding scheme, (2) specification of comprehensive metadata, (3) harmonization of commonly used variables, and (3) computational tools developed to standardize signal processing. We have also leveraged external resources to engineer a domain-specific approach to data harmonization. We describe the scope of data within the NSRR, its role in promoting sleep and circadian research through data sharing, and harmonization of large datasets and analytical tools. Finally, we identify opportunities for approaches for the field of sleep medicine to further support data standardization and sharing., (© The Author(s) 2024. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

A novel crystallographic fragment screening data set was generated and used in the SAMPL7 challenge for protein-ligands. The SAMPL challenges prospectively assess the predictive power of methods involved in computer-aided drug design. Application of various methods to fragment molecules are now widely used in the search for new drugs. However, there is little in the way of systematic validation specifically for fragment-based approaches. We have performed a large crystallographic high-throughput fragment screen against the therapeutically relevant second bromodomain of the Pleckstrin-homology domain interacting protein (PHIP2) that revealed 52 different fragments bound across 4 distinct sites, 47 of which were bound to the pharmacologically relevant acetylated lysine (Kac) binding site. These data were used to assess computational screening, binding pose prediction and follow-up enumeration. All submissions performed randomly for screening. Pose prediction success rates (defined as less than 2 Å root mean squared deviation against heavy atom crystal positions) ranged between 0 and 25% and only a very few follow-up compounds were deemed viable candidates from a medicinal-chemistry perspective based on a common molecular descriptors analysis. The tight deadlines imposed during the challenge led to a small number of submissions suggesting that the accuracy of rapidly responsive workflows remains limited. In addition, the application of these methods to reproduce crystallographic fragment data still appears to be very challenging. The results show that there is room for improvement in the development of computational tools particularly when applied to fragment-based drug design., (© 2022. The Author(s).)

Per- and polyfluoroalkyl substances (PFAS) are increasingly of interest to drinking water utilities due to state regulations, the release of federal and state health advisories, and public concern. Pilot-scale data were fitted for 16 PFAS species and five commercial-activated carbons using an open-source pore and surface diffusion model that includes an automated parameter-fitting tool. The estimated model parameters are presented, and an uncertainty analysis was evaluated considering the expected temporal variability of influent concentrations. Expected treatment performance differed between two seasons in the pilot phase for the same carbon, which was not captured by modeled uncertainty. However, modeling results can support a utility's decision to choose activated carbon, and make design and operational decisions that can address changing water production rates and treatment goals. For the utility that undertook this pilot study and their desired treatment goals, granular activated carbon (GAC) was found to be an effective treatment technology for PFAS removal.

The recent advances in relative protein-ligand binding free energy calculations have shown the value of alchemical methods in drug discovery. Accurately assessing absolute binding free energies, although highly desired, remains a challenging endeavour, mostly limited to small model cases. Here, we demonstrate accurate first principles based absolute binding free energy estimates for 128 pharmaceutically relevant targets. We use a novel rigorous method to generate protein-ligand ensembles for the ligand in its decoupled state. Not only do the calculations deliver accurate protein-ligand binding affinity estimates, but they also provide detailed physical insight into the structural determinants of binding. We identify subtle rotamer rearrangements between apo and holo states of a protein that are crucial for binding. When compared to relative binding free energy calculations, obtaining absolute binding free energies is considerably more challenging in large part due to the need to explicitly account for the protein in its apo state. In this work we present several approaches to obtain apo state ensembles for accurate absolute Δ G calculations, thus outlining protocols for prospective application of the methods for drug discovery., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Recently developed endovascular techniques to create percutaneous arteriovenous fistulas are an alternative to surgical arteriovenous fistula creation, although there is currently a lack of high-level evidence regarding their creation, maturation, utilization, and long-term function. Recognizing this, the Society of Interventional Radiology Foundation sponsored a Research Consensus Panel and Summit for the prioritization of a research agenda to identify and address the gaps in current knowledge., (Copyright © 2021 SIR. Published by Elsevier Inc. All rights reserved.)

Introduction: Bovine injuries are a common and significant cause of trauma, often requiring admission and operative treatment. We review all bovine-related injuries over 5 years, both emergency and general practitioner (GP) referrals at an adult major trauma center in England., Methods: Retrospective evaluation was undertaken using the keywords through radiology referrals and hospital admissions speciality databases. By searching patient notes, demographics were collected as well as the mechanism and the situation of injury; trauma scores were calculated using: injury severity score (ISS) and probability of survival (Ps19). The results were divided into emergency patients and GP referrals., Results: Sixty-seven patients were identified retrospectively over 5 years, 44 emergency patients (including 23 major traumas), and 23 GP referrals. Combined (emergency and GP) mean age 52 years old; 67% male; and mean ISS 11. Most common combined mechanism of injury, kicked ( n = 23). In emergency patients, trampling injuries were the most common. Eighty-six percent of the trampled patients were major traumas and associated with increased ISS (mean 13). Indirect injuries mainly involved farm gates (92%). Seventy-three percent of bull-related injuries were major traumas and had increased ISS scores (mean 17). Orthopaedics was the most common admitting speciality followed by cardiothoracic and neurosurgery. In emergency patients, fractures were the most common primary injury ( n = 20), upper limb followed by spine. In GP, soft-tissue injuries were the most common primary injury. Seventy percent of the emergency referrals required admission and 50% operations. Fracture fixation was the most common operative procedure. Only, one GP referral required an operation. There were significant delays in GP patients presenting. Two patients had a Ps19 score <90. There were two mortalities., Conclusion: Cattle-related injuries are a significant cause of severe morbidity and mortality. They are under-reported. Patterns of injury are similar to high-velocity road traffic collisions and bull-related injuries or trampling in particular, should alert the clinician to more significant trauma. Farm gates are a frequent cause of trauma associated with cattle. GP referrals with ongoing symptoms for more than 2 weeks seeking medical advice should alert the clinician to a more serious diagnosis., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Journal of Emergencies, Trauma, and Shock.)

Background: Testosterone therapy is indicated for the treatment of hypogonadism. Evidence-based guidelines recommend testosterone treatment only for men with symptoms and signs of testosterone deficiency and consistently low serum testosterone concentrations; luteinizing hormone (LH) and follicle-stimulating hormone (FSH) measurements and discussion of risks and benefits of testosterone prior to therapy. However, the US Department of Veterans Affairs (VA) Office of the Inspector General (OIG) report found that health care providers were adhering poorly to guideline recommendations for the diagnosis and treatment of men with hypogonadism., Methods: A prior authorization drug request (PADR) testosterone order template was implemented at VA Puget Sound Health Care System. A retrospective chart review was conducted in veterans who were prescribed testosterone and had no previous prescription in the prior year. Eligible veterans were evaluated 6 months before (pretemplate) and after (posttemplate) implementation of the template, and 3 months after removal of alternative testosterone ordering pathways (posttemplate/no alternative ordering pathways) that were discovered after PADR template implementation. We assessed the proportion of eligible veterans with documented symptoms of testosterone deficiency; appropriate diagnosis and evaluation of hypogonadism with ≥ 2 low serum testosterone and LH and FSH levels; and discussion of risks and benefits of testosterone treatment., Results: In the pretemplate period, only 20 of 80 eligible veterans (25%) had a completed PADR for testosterone. In the posttemplate period, 18 of 45 (44%) eligible veterans had a completed PADR but only 7 (17%) had the testosterone order template completed. In the posttemplate/no alternative ordering pathways period, 13 (68%) and 11 (58%) of 19 eligible veterans had a completed PADR and testosterone order template, respectively. In all 3 periods, documentation of clinical symptoms and a discussion of risks and benefits were similar. In contrast, the proportion of veterans who had ≥ 2 low testosterone levels with LH and FSH levels measured in the posttemplate and posttemplate/no alternative ordering pathways periods were higher (41% and 37%, respectively) vs the pretemplate period (23%). Veterans with documented clinical symptoms, discussion of risks and benefits, and ≥ 2 low testosterone with gonadotropin measurements were 100%, 57%, and 71%, respectively, in the posttemplate/no alternative ordering pathways period., Conclusions: Implementation of a PADR order template may be a promising approach to improve the diagnosis of hypogonadism and appropriate testosterone therapy in accordance with established evidence-based clinical practice guidelines, particularly in veterans who are receiving new prescriptions., Competing Interests: Author disclosures The authors report no actual or potential conflicts of interest with regard to this article., (Copyright © 2021 Frontline Medical Communications Inc., Parsippany, NJ, USA.)

Introduction and Objectives: Patients with obstructive pyelonephritis (OPN) require urgent decompression through retrograde ureteral stent (RUS) or percutaneous nephrostomy (PCN). In 2016, the urology and interventional radiology (IR) departments at our institution established a protocol for patients with OPN with sepsis. The primary objectives were to assess this protocol's impact on improving time to decompression and whether more expedient decompression decreased length of stay (LOS). Secondarily, we assessed the impact of the protocol and clinical factors on receipt of PCN over RUS. Materials and Methods: One hundred forty-seven patients at our institution who underwent PCN from 2012 to 2017 or stent from 2014 to 2017 for stone-related OPN meeting sepsis criteria were retrospectively reviewed. Univariate descriptive statistics compared patient characteristics and outcomes between RUS and PCN pre- and postprotocol implementation. Multivariable logistic regression assessed predictors of decompression with PCN ( vs RUS) and of prolonged LOS (pLOS; >5 days). Results: Utilization of PCN increased after implementation of the protocol from 4 to 14 PCN/year with a decrease in the median time from urologic consultation to PCN from 9.2 to 4.3 hours ( p  = 0.001) with overall median time to decompression decreasing from 5.4 to 4.5 hours ( p  = 0.017). Predictors of undergoing PCN ( vs RUS) included increasing comorbidity and ≥1 cm obstructing stone. On multivariable analysis controlling for comorbidity, leukocytosis, and septic shock, increasing hours to decompression increased odds of pLOS (1.08, 95% confidence interval 1.02-1.15, p  = 0.014). Conclusions: After implementing our OPN with sepsis protocol, time to decompression decreased with dramatic improvement in time to PCN. Quicker decompression was independently associated with reduced odds of prolonged hospital stay. A well-designed protocol engages both urology and IR in the management of these acutely ill patients and improves outcomes.

Traditionally, iodine has been delivered as a solution, tablet or resin to disinfect water. In this study we evaluated the "I 2 vapor infusion" (I 2 VP) technology which passes an airstream through a matrix containing elemental iodine (I 2 ) to produce I 2 vapor as an innovative method of iodine delivery for water disinfection. Pressured air was provided either by a compressor or hand pump. Testing was performed with water inoculated with either Gram-negative ( Escherichia , Salmonella ) or Gram-positive ( Enterococcus ) bacteria or with pre-formed Acinetobacter or Staphylococcus biofilms. Bacterial colony forming units were used to assess efficacy of the device. In distilled water all bacteria and biofilms were eliminated after brief exposures (<90 s). Culturable bacteria were also eliminated from pond and municipal sewer water, but the technology was mostly ineffective against dairy lagoon water with high turbidity and organic particulate. Longer duration infusion and higher air volumes used to overcome interference from organic matter were also associated with higher concentrations of residual iodine. We conclude that I 2 vapor infusion has the potential to be useful for emergency water treatment and potentially for reducing microbiological contamination of some waste streams.

A key component of quality improvement (QI) is developing leaders who can implement QI projects collaboratively. A yearlong interprofessional, workplace-based, continuing professional development program devoted to QI trained 2 cohorts of teams (dyads or triads) to lead QI projects in their areas of work using Plan-Do-Study-Act methodology. Teams represented different specialties in both inpatient and outpatient settings. They spent 4 to 6 hours/week on seminars, online modules, bimonthly meetings with a QI coach, and QI project work. Evaluations conducted after each session included pre-post program QI self-efficacy and project milestones. Post-program participants reported higher levels of QI self-efficacy (mean = 3.47; SD = 0.39) compared with pre program (mean = 2.02, SD = 0.51; P = .03, Cohen's d = 3.19). Impact on clinical units was demonstrated, but varied. The coach was identified as a key factor for success. An interprofessional, workplace-based, continuing professional development program focused on QI increased QI knowledge and skills and translated to improvements in the clinical setting.

Emission inventories are the foundation for cost-effective air quality management activities. In 2005, a report by the public/private partnership North American Research Strategy for Tropospheric Ozone (NARSTO) evaluated the strengths and weaknesses of North American emissions inventories and made recommendations for improving their effectiveness. This paper reviews the recommendation areas and briefly discusses what has been addressed, what remains unchanged, and new questions that have arisen. The findings reveal that all emissions inventory improvement areas identified by the 2005 NARSTO publication have been explored and implemented to some degree. The U.S. National Emissions Inventory has become more detailed and has incorporated new research into previously under-characterized sources such as fine particles and biomass burning. Additionally, it is now easier to access the emissions inventory and the documentation of the inventory via the internet. However, many emissions-related research needs exist, on topics such as emission estimation methods, speciation, scalable emission factor development, incorporation of new emission measurement techniques, estimation of uncertainty, top-down verification, and analysis of uncharacterized sources. A common theme throughout this retrospective summary is the need for increased coordination among stakeholders. Researchers and inventory developers must work together to ensure that planned emissions research and new findings can be used to update the emissions inventory. To continue to address emissions inventory challenges, industry, the scientific community, and government agencies need to continue to leverage resources and collaborate as often as possible. As evidenced by the progress noted, continued investment in and coordination of emissions inventory activities will provide dividends to air quality management programs across the country, continent, and world. Implications : In 2005, a report by the public/private partnership North American Research Strategy for Tropospheric Ozone (NARSTO) evaluated the strengths and weaknesses of North American air pollution emissions inventories. This paper reviews the eight recommendation areas and briefly discusses what has been addressed, what remains unchanged, and new questions that have arisen. Although progress has been made, many opportunities exist for the scientific agencies, industry, and government agencies to leverage resources and collaborate to continue improving emissions inventories.

Purpose: To report the effect of partial splenic embolization (PSE) on hematological indices and the procedure's safety in pre- and post-liver transplant (LT) patients., Materials and Methods: A single-center retrospective study evaluating all patients who underwent PSE over a 16-year period was performed. Inclusion criteria were splenomegaly confirmed by imaging and at least one of the following cytopenias: hemoglobin ≤10 g/dL, WBC count ≤1500 μL -1 , or platelet count ≤100,000 μL -1 . 38 of 102 patients (37%) met criteria (24 pre- and 14 post-LT) for a total of 40 PSEs., Results: No effect was seen on median hemoglobin beyond 2 weeks post-PSE. There was a significant and sustained increase in median WBC counts (from 3400 μL -1 to 5400 μL -1 at 2 years) and platelet count (from 65,000 μL -1 to 117,000 μL -1 at 3.5 years). In 6 out of 40 PSEs (15%) a major complication occurred which included pleural effusion, ascites, spontaneous bacterial peritonitis, pneumonia, and inferior vena cava thrombus. Similar efficacy was observed in pre- and post-LT cohorts, with a trend toward higher complication rate in pre-LT patients., Conclusions: PSE is efficacious in increasing WBC count out to 2 years and platelet count out to 3.5 years in patients with hypersplenism. Efficacy and safety appeared independent of pre- or post-LT status. The intervention is associated with major complications and special care should be taken when selecting patients for PSE., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: The gold standard for diagnosing sleep disorders is polysomnography, which generates extensive data about biophysical changes occurring during sleep. We developed the National Sleep Research Resource (NSRR), a comprehensive system for sharing sleep data. The NSRR embodies elements of a data commons aimed at accelerating research to address critical questions about the impact of sleep disorders on important health outcomes., Approach: We used a metadata-guided approach, with a set of common sleep-specific terms enforcing uniform semantic interpretation of data elements across three main components: (1) annotated datasets; (2) user interfaces for accessing data; and (3) computational tools for the analysis of polysomnography recordings. We incorporated the process for managing dataset-specific data use agreements, evidence of Institutional Review Board review, and the corresponding access control in the NSRR web portal. The metadata-guided approach facilitates structural and semantic interoperability, ultimately leading to enhanced data reusability and scientific rigor., Results: The authors curated and deposited retrospective data from 10 large, NIH-funded sleep cohort studies, including several from the Trans-Omics for Precision Medicine (TOPMed) program, into the NSRR. The NSRR currently contains data on 26 808 subjects and 31 166 signal files in European Data Format. Launched in April 2014, over 3000 registered users have downloaded over 130 terabytes of data., Conclusions: The NSRR offers a use case and an example for creating a full-fledged data commons. It provides a single point of access to analysis-ready physiological signals from polysomnography obtained from multiple sources, and a wide variety of clinical data to facilitate sleep research.

Background: Sleep-disordered breathing (SDB) is common in pregnancy, but there are limited data on predictors., Objectives: The objective of this study was to develop predictive models of sleep-disordered breathing during pregnancy., Study Design: Nulliparous women completed validated questionnaires to assess for symptoms related to snoring, fatigue, excessive daytime sleepiness, insomnia, and restless leg syndrome. The questionnaires included questions regarding the timing of sleep and sleep duration, work schedules (eg, shift work, night work), sleep positions, and previously diagnosed sleep disorders. Frequent snoring was defined as self-reported snoring ≥3 days per week. Participants underwent in-home portable sleep studies for sleep-disordered breathing assessment in early (6-15 weeks gestation) and mid pregnancy (22-31 weeks gestation). Sleep-disordered breathing was characterized by an apnea hypopnea index that included all apneas, plus hypopneas with ≥3% oxygen desaturation. For primary analyses, an apnea hypopnea index ≥5 events per hour was used to define sleep-disordered breathing. Odds ratios and 95% confidence intervals were calculated for predictor variables. Predictive ability of the logistic models was estimated with area under the receiver-operating-characteristic curves, along with sensitivities, specificities, and positive and negative predictive values and likelihood ratios., Results: Among 3705 women who were enrolled, data were available for 3264 and 2512 women in early and mid pregnancy, respectively. The corresponding prevalence of sleep-disordered breathing was 3.6% and 8.3%, respectively. At each time point in gestation, frequent snoring, chronic hypertension, greater maternal age, body mass index, neck circumference, and systolic blood pressure were associated most strongly with an increased risk of sleep-disordered breathing. Logistic regression models that included current age, body mass index, and frequent snoring predicted sleep-disordered breathing in early pregnancy, sleep-disordered breathing in mid pregnancy, and new onset sleep-disordered breathing in mid pregnancy with 10-fold cross-validated area under the receiver-operating-characteristic curves of 0.870, 0.838, and 0.809. We provide a supplement with expanded tables, integrated predictiveness, classification curves, and an predicted probability calculator., Conclusion: Among nulliparous pregnant women, logistic regression models with just 3 variables (ie, age, body mass index, and frequent snoring) achieved good prediction of prevalent and incident sleep-disordered breathing. These results can help with screening for sleep-disordered breathing in the clinical setting and for future clinical treatment trials., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To estimate whether sleep-disordered breathing during pregnancy is a risk factor for the development of hypertensive disorders of pregnancy and gestational diabetes mellitus (GDM)., Methods: In this prospective cohort study, nulliparous women underwent in-home sleep-disordered breathing assessments in early (6-15 weeks of gestation) and midpregnancy (22-31 weeks of gestation). Participants and health care providers were blinded to the sleep test results. An apnea-hypopnea index of 5 or greater was used to define sleep-disordered breathing. Exposure-response relationships were examined, grouping participants into four apnea-hypopnea index groups: 0, greater than 0 to less than 5, 5 to less than 15, and 15 or greater. The study was powered to test the primary hypothesis that sleep-disordered breathing occurring in pregnancy is associated with an increased incidence of preeclampsia. Secondary outcomes were rates of hypertensive disorders of pregnancy, defined as preeclampsia and antepartum gestational hypertension, and GDM. Crude and adjusted odds ratios and 95% confidence intervals (CIs) were calculated from univariate and multivariate logistic regression models., Results: Three thousand seven hundred five women were enrolled. Apnea-hypopnea index data were available for 3,132 (84.5%) and 2,474 (66.8%) women in early and midpregnancy, respectively. The corresponding prevalence of sleep-disordered breathing was 3.6% and 8.3%. The prevalence of preeclampsia was 6.0%, hypertensive disorders of pregnancy 13.1%, and GDM 4.1%. In early and midpregnancy the adjusted odds ratios for preeclampsia when sleep-disordered breathing was present were 1.94 (95% CI 1.07-3.51) and 1.95 (95% CI 1.18-3.23), respectively; hypertensive disorders of pregnancy 1.46 (95% CI 0.91-2.32) and 1.73 (95% CI 1.19-2.52); and GDM 3.47 (95% CI 1.95-6.19) and 2.79 (95% CI 1.63-4.77). Increasing exposure-response relationships were observed between apnea-hypopnea index and both hypertensive disorders and GDM., Conclusion: There is an independent association between sleep-disordered breathing and preeclampsia, hypertensive disorders of pregnancy, and GDM.

Abstract: Professional sleep societies have identified a need for strategic research in multiple areas that may benefit from access to and aggregation of large, multidimensional datasets. Technological advances provide opportunities to extract and analyze physiological signals and other biomedical information from datasets of unprecedented size, heterogeneity, and complexity. The National Institutes of Health has implemented a Big Data to Knowledge (BD2K) initiative that aims to develop and disseminate state of the art big data access tools and analytical methods. The National Sleep Research Resource (NSRR) is a new National Heart, Lung, and Blood Institute resource designed to provide big data resources to the sleep research community. The NSRR is a web-based data portal that aggregates, harmonizes, and organizes sleep and clinical data from thousands of individuals studied as part of cohort studies or clinical trials and provides the user a suite of tools to facilitate data exploration and data visualization. Each deidentified study record minimally includes the summary results of an overnight sleep study; annotation files with scored events; the raw physiological signals from the sleep record; and available clinical and physiological data. NSRR is designed to be interoperable with other public data resources such as the Biologic Specimen and Data Repository Information Coordinating Center Demographics (BioLINCC) data and analyzed with methods provided by the Research Resource for Complex Physiological Signals (PhysioNet). This article reviews the key objectives, challenges and operational solutions to addressing big data opportunities for sleep research in the context of the national sleep research agenda. It provides information to facilitate further interactions of the user community with NSRR, a community resource., (© 2016 Associated Professional Sleep Societies, LLC.)

Objectives: Obstructive respiratory events often terminate with an associated respiratory-related leg movement (RRLM). Such leg movements are not scored as periodic leg movements (periodic limb movements during sleep, PLMS), although the criteria for distinguishing RRLM from PLMS differ between the American Academy of Sleep Medicine (AASM) and the World Association of Sleep Medicine (WASM)/ International Restless Legs Syndrome Study Group (IRLSSG) scoring manuals. Such LMs may be clinically significant in patients with obstructive sleep apnea (OSA). The prevalence and correlation of RRLM in men with OSA were examined., Methods: A case-control sample of 575 men was selected from all men with an apnea-hypopnea index (AHI, ≥3% desaturation criteria) ≥ 10 and good data from piezoelectric leg movement sensors at the first in-home sleep study in the MrOS cohort (mean age = 76.8 years). Sleep studies were rescored for RRLMs using five different RRLM definitions varying in both latency of leg movement onset from respiratory event termination and duration of the leg movement. The quartile of RRLM% (the number of RRLM/the number of hypopneas + apneas) was derived., Results: The nonparametric densities of RRLM% were most influenced by alterations in the latency rather than the duration of the LM. The most liberal RRLM definition (latency 0-5 s, duration 0.5-10 s) led to a median RRLM% of 23.4 (interquartile range 12.41, 37.12) in this sample. The average AHI and arousal index increased as the quartile of RRLM% increased, as well as the prevalence of chronic obstructive pulmonary disease (COPD). The prevalence of those with a history of hypertension decreased as RRLM% increased. The non-Caucasian race was associated with lower RRLM%., Conclusion: Within an elderly sample with moderate to severe OSA, piezoelectric-defined RRLM% is associated with a number of sleep-related and demographic factors. Further study of the optimal definition, predictors, and consequences of RRLM is warranted., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Benign prostatic hyperplasia (BPH) is one of the most common conditions affecting middle-aged men. This condition can be microscopic, macroscopic, symptomatic, or asymptomatic. Up to 15% to 25% of men aged 50-65 years have lower urinary tract symptoms (LUTS) consisting of nocturia, urgency, frequency, a sensation of not completely emptying the bladder, stop-start urination, straining to urinate, a need to urinate soon after voiding, and weak urinary stream. These symptoms usually are associated with benign enlargement of the prostate gland that is of sufficient severity to interfere with a man's quality of life. Although LUTS is often associated with BPH, LUTS can also be due to various unrelated syndromes such as heart failure, urinary tract infections, and diabetes. Most men will have benign hyperplasia of the prostate gland and this benign growth compresses the urethra resulting in LUTS. This article will discuss the evaluation, pharmacological management, minimally invasive treatment, and surgical therapy of this common condition affecting millions of American men.

Although heart disease and cancer are the number one and two causes of death in the United States, respectively, obesity is gaining speed as a contributing cause to both of those conditions, along with diabetes, arthritis, dyslipidemia, coronary heart disease, gallbladder disease, and certain malignancies. Nearly one-third of the adults in the United States is overweight with a body mass index (BMI) greater than 25 kg/m(2), and another third of the adult population is obese, with a BMI greater than 30 kg/m(2). This article reviews the root causes of obesity, the societal implications, and the implications of obesity on various urologic diseases.

Tobacco use remains the single largest preventable cause of disease and premature death in the United States, and smoking is a leading cause of cancer and death from cancer. There is also evidence that smoking is associated with several urologic diseases. Urologists have a unique opportunity to help our patients lead healthy lifestyles, which includes ending their dependence on nicotine and tobacco. This article points out the various urologic conditions associated with smoking and tobacco use with the intention of providing physicians and patients with knowledge and education regarding this connection.

Tremendous gains and novel methods are often developed when people are challenged to do something new or difficult. This process is enhanced when people compete against each other-this can be seen in sport as well as in science and technology (e.g. the space race). The SAMPL challenges, like the CASP challenges, aim to challenge modellers and software developers to develop new ways of looking at molecular interactions so the community as a whole can progress in the accurate prediction of these interactions. In order for this challenge to occur, data must be supplied so the prospective test can be done. We have supplied unpublished data related to a drug discovery program run several years ago on HIV integrase for the SAMPL4 challenge. This paper describes the methods used to obtain these data and the chemistry involved.

Lysine specific demethylase 1 (LSD1), the first identified histone demethylase, plays an important role in epigenetic regulation of gene activation and repression. The up-regulated LSD1's expression has been reported in several malignant tumors. In the current study, we designed and synthesized five series of 1,2,3-triazole-dithiocarbamate hybrids and screened their inhibitory activity toward LSD1. We found that some of these compounds, especially compound 26, exhibited the most specific and robust inhibition of LSD1. Interestingly, compound 26 also showed potent and selective cytotoxicity against LSD1 overexpressing gastric cancer cell lines MGC-803 and HGC-27, as well as marked inhibition of cell migration and invasion, compared to 2-PCPA. Furthermore, compound 26 effectively reduced the tumor growth bared by human gastric cancer cells in vivo with no signs of adverse side effects. These findings suggested that compound 26 deserves further investigation as a lead compound in the treatment of LSD1 overexpressing gastric cancer.

Emissions factors are important for estimating and characterizing emissions from sources of air pollution. There is no quantitative indication of uncertainty for these emission factors, most factors do not have an adequate data set to compute uncertainty, and it is very difficult to locate the data for those that do. The objectives are to compare the current emission factors of Electric Generating Unit NOx sources with currently available continuous emission monitoring data, develop quantitative uncertainty indicators for the Environmental Protection Agency (EPA) data quality rated emission factors, and determine the possible ranges of uncertainty associated with EPA's data quality rating of emission factors. EPA's data letter rating represents a general indication of the robustness of the emission factor and is assigned based on the estimated reliability of the tests used to develop the factor and on the quantity and representativeness of the data. Different sources and pollutants that have the same robustness in the measured emission factor and in the representativeness of the measured values are assumed to have a similar quantifiable uncertainty. For the purposes of comparison, we assume that the emission factor estimates from source categories with the same letter rating have enough robustness and consistency that we can quantify the uncertainty of these common emission factors based on the qualitative indication of data quality which is known for almost all factors. The results showed that EPA's current emission factor values for NOx emissions from combustion sources were found to be reasonably representative for some sources; however AP-42 values should be updated for over half of the sources to reflect current data. The quantified uncertainty ranges were found to be 25-62% for A rated emission factors, 45-75% for B rated emission factors, 60-82% for C rated emission factors, and 69-86% for D rated emission factors, and 82-92% for E rated emission factors.

Glioblastoma, the most malignant form of brain cancer, is responsible for 23% of primary brain tumors and has extremely poor outcome. Confounding the clinical management of glioblastomas is the extreme local invasiveness of these cancer cells. The mechanisms that govern invasion are poorly understood. To gain insight into glioblastoma invasion, we conducted experiments on the patterns of growth and dispersion of U87 glioblastoma tumor spheroids in a three-dimensional collagen gel. We studied two different cell lines, one with a mutation to the EGFR (U87DeltaEGFR) that is associated with increased malignancy, and one with an endogenous (wild-type) receptor (U87WT). We developed a continuum mathematical model of the dispersion behaviors with the aim of identifying and characterizing discrete cellular mechanisms underlying invasive cell motility. The mathematical model quantitatively reproduces the experimental data, and indicates that the U87WT invasive cells have a stronger directional motility bias away from the spheroid center as well as a faster rate of cell shedding compared to the U87DeltaEGFR cells. The model suggests that differences in tumor cell dispersion may be due to differences in the chemical factors produced by cells, differences in how the two cell lines remodel the gel, or different cell-cell adhesion characteristics.

Liver biopsy is a common study performed after hepatic transplantation. Most centers routinely perform a biopsy 1 week after surgery to evaluate for the possibility of acute rejection. Subsequent biopsies are based on clinical symptoms and routine hepatic function laboratory testing. We report the clinical presentation and treatment of a biliary-venous fistula resulting in sepsis and bilhemia (elevated serum bilirubin levels caused by a biliary-venous fistula) in a 2(1/2)-year-old patient 4 months after partial left lateral segment living related liver transplantation. This case is unusual in that the fistula is the reversal of the more common venous-biliary fistula. The fistula developed after a percutaneous liver biopsy was performed.

Purpose: We determine the effect of long-term suppression of dihydrotestosterone with finasteride, a specific type II 5alpha-reductase inhibitor, on bone mineral density., Materials and Methods: As part of a large (3,040 cases) 4-year, double-blind, placebo controlled trial designed to assess the long-term effects of finasteride in men with benign prostatic hyperplasia, 157 men 46 to 76 years old who were randomized to receive either 5 mg. finasteride or placebo underwent dual energy x-ray absorptiometry of the lumbar spine at baseline and at years 2, 3 and 4., Results: Of 117 patients who had a baseline measurement and at least 1 additional measurement during the study baseline mean plus or minus standard deviation bone mineral density values were 1.12 +/- 0.17 gm./cm.2 in the finasteride group (63) and 1.10 +/- 0.17 gm./cm.2 in the placebo group (54). After 4 years bone mineral density was not different between treatment groups (finasteride 1.14 +/- 0.17 gm./cm.2 and placebo 1.13 +/- 0.18 gm./cm.2). Similar results were obtained for the 33 finasteride and 25 placebo treated patients who completed the study with year 4 bone mineral density measurements., Conclusions: These data demonstrate that long-term inhibition of type II 5alpha-reductase with finasteride does not adversely affect bone mineral density.

Objectives: To compare the efficacy and safety of finasteride 5 mg in older (65 years old or older) versus younger (45 to younger than 65 years old) men with benign prostatic hyperplasia (BPH)., Methods: The Proscar Long-Term Efficacy and Safety Study (PLESS) was a 4-year, randomized, double-blind, placebo-controlled trial assessing the efficacy and safety of finasteride 5 mg in 3040 men 45 to 78 years old with symptomatic BPH, enlarged prostates, and no evidence of prostate cancer. The endpoints included urinary symptoms, prostate volume, occurrence of acute urinary retention and/or BPH-related surgery, and safety., Results: In both age cohorts, finasteride treatment led to a 51% reduction (P <0.001) in the relative risk for acute urinary retention and/or BPH-related surgery, a significant (P <0.001) and durable improvement in symptom score, and a significant (P <0.001) and sustained reduction in prostate volume. Within each age cohort, no significant differences were found between the placebo and finasteride-treated patients in the incidence of cardiovascular adverse events. Significant differences were evident between the placebo and finasteride groups in the incidence of the typical, known, drug-related adverse events, but no specific differences were associated with age. No drug interactions of clinical importance were observed in the finasteride-treated patients., Conclusions: The present analysis from PLESS demonstrates that in both older (65 years old or older) and younger men with symptomatic BPH and enlarged prostates, finasteride is highly effective in improving symptoms and reducing prostate volume in many men and in reducing the risk of acute urinary retention and BPH-related surgery. In addition, the safety profile of finasteride in both older and younger men is similar and no drug interactions of clinical importance were observed.

Objective: To compare the efficacy and safety of controlled-release oxybutynin with conventional, immediate-release oxybutynin and determine rates of dry mouth., Methods: Patients (n = 226) who were known to be responsive to anticholinergic therapy and who had seven or more urge incontinence episodes per week were randomized to receive controlled-release oxybutynin or immediate-release oxybutynin. After an initial placebo run-in period, dosing in each began at 5 mg per day and increased weekly by 5 mg per day to a maximum of 20 mg per day or when a balance between improvement of incontinence symptoms and tolerability of side effects was achieved. Rates of urge incontinence and dry mouth were compared. Post hoc Kaplan-Meier survival analysis was used to describe elimination of incontinence episodes by dose and to analyze dry mouth risk by dose., Results: Reductions in urge urinary incontinence episodes from baseline to the end of treatment were 18.6 to 2.9 per week (83% mean decrease) and 19.8 to 4.4 per week (76% mean decrease) in the controlled- and immediate-release oxybutynin groups (P =.36), respectively. At equal doses, comparable proportions of patients in both groups reported the absence of urge incontinence (P =.85). The incidence of dry mouth increased with dose in both groups, but there was no difference in dry mouth rates between the groups: 47.7% and 59.1% for the controlled- and immediate-release oxybutynin (P =.09), respectively. However, Kaplan-Meier analysis to examine first report of dry mouth at a given dose revealed that a significantly lower proportion of patients taking controlled-release oxybutynin had moderate to severe dry mouth (P =.007) or any dry mouth (P =.003) compared with those taking immediate-release oxybutynin., Conclusion: At the same daily dose, controlled- and immediate-release oxybutynin demonstrated comparable efficacy in reduction of urge incontinence episodes. The incidence of dry mouth was dose dependent but equal in both groups; first report of moderate to severe dry mouth was significantly lower in the controlled-release group.

Purpose: We compared the efficacy and safety of once daily controlled and immediate release oxybutynin for incontinence., Materials and Methods: This multicenter, randomized, double-blind, active control, parallel study was designed to evaluate urge urinary incontinence episodes using a 7-day diary., Results: A total of 97 women and 8 men 34 to 76 years old with urge incontinence or mixed incontinence with a clinically significant urge component were enrolled in the study. The number of weekly urge incontinence episodes decreased from 27.4 to 4.8 after controlled and from 23.4 to 3.1 after immediate release oxybutynin (p = 0.56), and total incontinence episodes decreased from 29.3 to 6 and from 26.3 to 3.8, respectively (p = 0.6). Weekly urge incontinence episodes from baseline to end of study also decreased to 84% after controlled and 88% after immediate release oxybutynin (p = 0.7). Continence was achieved in 41% of the controlled and 40% of the immediate release group (p = 0.9). Dry mouth of any severity was reported by 68 and 87% of the controlled and immediate release groups, respectively (p = 0.04), and moderate or severe dry mouth occurred in 25 and 46%, respectively (p = 0.03)., Conclusions: Participants taking a single daily does of controlled release oxybutynin had similar reductions in urge incontinence and total incontinence episodes compared to those taking oxybutynin 1 to 4 times daily. A lower incidence of dry mouth was reported for controlled release oxybutynin.

A large urban university medical center used a unique set of strategies in preparation for its triennial survey conducted by the Joint Commission on Accreditation of Healthcare Organizations. Although the medical center had experienced many Joint Commission surveys, this particular survey was the first to include associated physician offices in multiple diverse settings. To address these challenges, the hospital developed a structure and process that engaged all levels of staff and ensured a successful survey outcome.

Erectile dysfunction is a common condition affecting men over age 50. With the recent increase in public awareness about available therapies, more and more men are seeking help. Primary care physicians usually can prescribe first-line treatments without acquiring additional equipment or staff. Patients who are not satisfied with oral medication, vacuum devices, injection therapy, or intraurethral suppositories may be referred to a urologist for further treatment. Development of new medical therapies is ongoing, and within the next few years, we expect to see the introduction of more medications for treatment of erectile dysfunction. Some agents act peripherally on the penile circulation and others centrally on the portion of the brain involved in producing erections.

Traditionally, drug therapy for benign prostatic hyperplasia (BPH) has been reserved for patients with mild or moderate symptoms. The objective of this analysis was to compare responses to an alpha 1-adrenergic receptor blocker, doxazosin, in patients with severe, intermediate, and mild disease. Data were analyzed from patients with symptomatic BPH who were enrolled in two 16-week, double-masked, placebo-controlled studies of doxazosin. In study 1, 163 hypertensive patients were stratified according to baseline maximum (Qmax) and mean (Qmean) urinary flow rate as having severe, intermediate, or mild disease. In study 2, 82 normotensive patients were stratified according to their baseline American Urological Association (AUA) BPH symptom severity score and modified Boyarsky symptom bothersomeness score. Overall, doxazosin was significantly more effective than placebo in improving Qmax and Qmean in study 1 and in improving the AUA-derived and modified Boyarsky scores in study 2. There were statistically significant differences in the response to treatment, as represented by Qmax' Qmean, and modified Boyarsky score, between patients with severe, intermediate, and mild disease. There were no significant differences in the AUA-derived scores of patients in the three severity groups. These results have important clinical implications, suggesting that the majority of BPH patients are candidates for a course of drug therapy, regardless of baseline disease status.

The urinary symptoms characteristic of benign prostatic hyperplasia (BPH) can have a considerable impact on patients' quality of life. Symptom score assessment is now used in BPH, although a number of different instruments are available. Controlled clinical trials with selective alpha 1 adrenoceptor antagonists such as doxazosin, prazosin and terazosin have shown these agents to be effective in the treatment of BPH. The effects of doxazosin on the severity and bothersomeness of BPH symptoms were determined in three multicentre, double-blind, placebo-controlled clinical studies, involving a total of 609 normotensive and hypertensive patients. Doxazosin was initiated at a dosage of 0.5 or 1 mg once daily, with a final dose range of up to 12 mg once daily. The duration of active treatment was 12 to 14 weeks. Significant improvements were seen in symptom severity and bothersomeness with doxazosin compared with placebo, in both patient populations. The onset of symptomatic improvement was rapid, occurring within two weeks of treatment initiation, and efficacy was sustained throughout the treatment period. A long-term, open label extension of these studies has demonstrated sustained efficacy during 48 months of follow-up. Since symptom relief is the primary goal of therapy in BPH, and since doxazosin's effects are rapid in onset and sustained in duration, it appears that doxazosin is an effective agent for the treatment of symptomatic BPH in both normotensive and hypertensive men.

This article reports a rare case of primary signet-ring cell carcinoma of the bladder with transitional cell and adenocarcinoma variants and metachronous metastases to the penis and lungs. This combination of lesions has not previously been reported. Together, they portend widespread dissemination and an early demise as is frequently the case with signet-ring cell carcinomas arising in other organs such as the breast and gastrointestinal tract. The optimal therapeutic intervention for this myriad of neoplasms with metastasis to the penis has yet to be ascertained because of the rarity of the lesions. Early diagnosis and an aggressive surgical approach appear to offer the best chance for quality survival and possible cure.

Purpose: We evaluated the sustained efficacy and safety of doxazosin for long-term treatment (up to 48 months) of normotensive and hypertensive patients with benign prostatic hyperplasia (BPH)., Materials and Methods: A total of 272 normotensive and 178 mildly to moderately hypertensive men entered a long-term extension study of doxazosin therapy (1 to 8 and 1 to 12 mg. 1 time daily, respectively) for BPH following participation in double-blind, placebo controlled studies. The starting dose of doxazosin was 1 mg. with upward titrations at 2-week intervals to a stable, efficacious and well tolerated dose. At the time of data analysis patients had received between 1 and 48 months of stable dose doxazosin therapy (mean 668 days for normotensive and 807 for hypertensive patients). Mean daily doses were 4 and 6.4 mg. for normotensive and hypertensive men, respectively., Results: At the end point analysis doxazosin treatment resulted in significant increases above baseline in maximum and average urinary flow rates (1.9 and 1.0 ml. per second, respectively). As assessed by the patient, total, obstructive and irritative BPH symptoms also improved significantly with doxazosin treatment. In the 28 patients who completed 45 to 48 months of treatment improvement in symptom bothersomeness (13.2%) was similar to that of the overall group at the end point (14.8%). Sustained blood pressure decreases (approximately 8/11 mm. Hg systolic/diastolic blood pressure) with doxazosin were statistically and clinically significant in hypertensive patients. Blood pressure decreases in normotensive patients were not clinically significant (approximately 4/2 mm. Hg) and few withdrew from study for reasons related directly to decreased blood pressure or hypotension. Changes in heart rate were not significant. Doxazosin was well tolerated with almost 90% of adverse experiences considered mild or moderate in severity. The most common adverse events were dizziness, headache and fatigue in normotensive and hypertensive patients., Conclusions: In this study long-term doxazosin treatment was significantly effective and well tolerated for treating BPH in normotensive and hypertensive patients.

Hospital administrators are under pressure to provide a quality product at reasonable prices. As a result, all aspects of hospital structure and culture are under review, which places continuous improvement (CI) programs addressing quality and satisfaction in a more prominent role. Although the theory, data collection methods, and analysis techniques of continuous improvement have grown considerably since the days of quality assurance, clinical problems in healthcare organizations are also increasingly complex and difficult to solve. From this perspective, research has a great deal to offer our current continuous improvement efforts. This paper proposes that CI and research are similar problem-solving approaches, based on philosophies that provide direction for theorizing, collecting and analyzing data, and identifying solutions. A clinical problem elaborates on the similarities of each approach. Finally, common misconceptions are discussed.

Interstitial cystitis is fairly common in primary care practices and very common in urology practices. Still, it is probably underdiagnosed. Because symptoms can be confusing, patients are sometimes thought to have psychogenic problems or are treated repeatedly with antibiotics, despite the absence of evidence of bacterial infection. The key to correct diagnosis is awareness of the condition and its characteristics. In patients who have symptoms that resemble routine cystitis but normal results on urinalysis, interstitial cystitis should be considered as the working diagnosis. This is especially applicable in women, who are affected far wore often than men. Various therapies have been tried, but the cure, like the cause, remains unknown. Many patients respond to some form of therapy and may even have long-term remissions. However, arriving at the form of therapy that relieves symptoms in a given patient is often a trial-and-error process. A short-term trial of various methods is warranted initially. Ultimately, however, referral to a urologist may be necessary for definite diagnostic testing and additional therapy.

Purpose: Zanoterone (100 to 800 mg.) versus placebo was studied in 463 patients with benign prostatic hyperplasia., Materials and Methods: Study end points were maximum urinary flow rate, American Urological Association symptom index, prostate volume, prostate specific antigen and sex steroid concentrations after 6 months of treatment., Results: Mean increases in maximum urinary flow rate were 2 to 3-fold over placebo, although only the 200 mg. group had significant results (1.7 ml. per second, p = 0.026). There were no statistically significant differences between the zanoterone and placebo groups in symptom index or prostate volume. Estradiol and testosterone concentrations, and the incidence of breast pain and gynecomastia increased significantly with zanoterone compared with placebo. Prostate specific antigen levels decreased significantly., Conclusion: Zanoterone did not demonstrate a favorable risk-to-benefit profile for the treatment of benign prostatic hyperplasia.

Penile prostheses are a well-established form of therapy for erectile dysfunction. We report our experience with 333 cases using the Mentor Alpha I inflatable penile prosthesis. With a follow-up period of 15.4 months, there were 25 (7.5%) complications with 15 (4.5%) major complications that required reoperation. We also review the advantages and the procedures for implanting the penile prosthesis on an outpatient basis or a one-day hospital stay.

This study reports the experience with 35 men who were implanted with a GFS Mark II inflatable penile prosthesis. The advantages of using the connectorless prosthesis with a reservoir/pump are reviewed.

Fine-needle aspiration biopsy cytology is widely used to screen masses in adults. The authors present a series of 89 fine-needle aspiration biopsies performed between January 1973 and December 1988 on 86 pediatric patients with clinically significant head and neck masses. All fine-needle aspiration diagnoses were confirmed by subsequent surgical biopsy, autopsy, or clinical follow-up for a minimum of 18 months. Of 21 tumors identified, 19 were malignant. Of the 89 aspirations performed, 67 required no subsequent surgical biopsy. In 11 of these cases, metastatic or recurrent tumor was diagnosed and appropriate therapy instituted. Fifteen of the 89 aspirates revealed previously undiagnosed tumors requiring surgical intervention. One false-negative and two false-positive results were obtained. No radical treatment resulted from the false-positive diagnoses, and no patient delay in treatment occurred because of the false-negative result. The sensitivity was 94.4%, and the specificity was 97.1%. The usefulness and cost-effectiveness of fine-needle aspiration is stressed.

Using the PHYLOGEN tree-forming programs, we evaluate the published 5S rRNA sequences in certain of the files in the Berlin DataBank in an attempt to identify the connection between archaebacteria and the eukaryotic protists. These programs are based on methods of string analysis developed by Sankoff and others. Their discriminatory power is derived from their continuous realignment of sequences through repeated assessment of insertions and deletions as well as substitutions. The programs demonstrate that even these small molecules (ca. 120 bases) retain substantial records of evolutionary events that occurred over a billion years ago. The eukaryotes seem to have been derived from ancestors near the common origins of the halobacterial and Methanococcales groups. Identifying what might have been a primordial eukaryote is more difficult because several of the species considered as early derivatives from the common root are isolated species with large genetic differences from each other and from all other extant forms that have been sequenced. The ameboid, flagellated, and ciliated protists seem to have emerged nearly simultaneously from an ancient cluster, but the sarcodinid protozoa have preference as the group of most ancient origin. The euglenozoa and the ciliates are of later derivation. Our ability to tease plausible trees from such small molecules suggests that the mode of analysis rather than the size of the molecule is often a major limitation in the reconstruction of acceptable ancient phylogenics.(ABSTRACT TRUNCATED AT 250 WORDS)

The efficacy and safety of carbenicillin indanyl sodium were evaluated in 16 patients with acute or chronic bacterial prostatitis. Each patient received carbenicillin indanyl sodium (Geocillin) tablets, at a dosage of two 500 mg tablets (each tablet equivalent to 382 mg of carbenicillin) four times daily for either 14 days (acute patients) or 28 days (chronic patients). Clinical and bacteriologic success rates, based upon 4 week post therapy followup, were 93 per cent and 75 per cent respectively. There were no adverse reactions. Results with cephalexin in a concurrently treated alternative therapy group were generally unsatisfactory. Further evaluations of carbenicillin indanyl sodium in this treatment of resistant populations are clearly warranted.