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Mutations at the arg-6 locus in Neurospora crassa are divided into two complementation groups (A and B) and a third noncomplementing group. There are many suppressible nonsense mutations among mutants in complementation group B and one in the noncomplementing group; no nonsense mutations exist among mutants in complementation group A (Davis, R. H., and Weiss, R. L. (1983) Mol. Gen. Genet. 192, 46-50). We show here that the mutants are defective in either or both of two enzymes of arginine biosynthesis, acetylglutamate kinase and/or acetylglutamyl-phosphate reductase. Mutants in complementation group A lack acetylglutamate kinase, those in complementation group B lack acetylglutamyl-phosphate reductase, and those in the noncomplementing group lack both activities. Mutants in group B also have reduced levels of acetylglutamate kinase. The enzymes from purified mitochondria are readily separable by gel filtration and by Blue A dye affinity chromatography. Acetylglutamate kinase appears to be an octamer with a molecular weight of 400,000, whereas acetylglutamyl-phosphate reductase appears to be a dimer with a molecular weight of 93,000. This suggests that the two activities reside on distinct polypeptides. These results are best accommodated by the following model: the arg-6 locus encodes a single mRNA which is translated into a single polypeptide; the latter is then cleaved post-translationally to yield two physically separable enzymes.

N-Acetylglutamate synthase, an early enzyme of the arginine pathway, provides acetylglutamate for ornithine synthesis in the so-called "acetylglutamate cycle." Because acetylglutamate is regenerated as ornithine is formed, the enzyme has only a catalytic or anaplerotic role in the pathway, maintaining "bound" acetyl groups during growth. We have detected this enzyme in crude extracts of Neurospora crassa and have localized it to the mitochondria along with other ornithine biosynthetic enzymes. The enzyme is bound to the mitochondrial membrane. The enzyme has a pH optimum of 9.0 and Km values for glutamate and CoASAc of 6.3 and 1.6 mM, respectively. It is feedback-inhibited by L-arginine (I0.5 = 0.16 mM), and its specific activity is augmented 2-3-fold by arginine starvation of the mycelium. Mutants of the newly recognized arg-14 locus lack activity for the enzyme. Because these mutants are complete auxotrophs, we conclude that N-acetylglutamate synthase is an indispensible enzyme of arginine biosynthesis in N. crassa. This work completes the assignment of enzymes of the arginine pathway of N. crassa to corresponding genetic loci. The membrane localization of the enzyme suggests a novel mechanism by which feedback inhibition might occur across a semipermeable membrane.

The response of Neurospora to changes in the availibility of exogenous arginine was investigated. Upon addition of arginine to the growth medium, catabolism is initiated within minutes. This occurs prior to expansion of the arginine pool or augmentation of catabolic enzyme levels. (Basal levels are approximately 25% of those found during growth in arginine-supplemented medium.) Catabolism of arginine is independent of protein synthesis, indicating that the catabolic enzymes are active but that arginine is not available for catabolism unless present in the medium. Upon exhaustion of the supply of exogenous arginine, catabolism ceases abruptly, despite an expanded arginine pool and induced levels of the catabolic enzymes. The arginine pool supports protein synthesis until the cells regain their normal capacity for endogenous arginine synthesis. These observations, combined with the known small level of induction of arginine catabolic enzymes, non-repressibility of most biosynthetic enzymes, and vesicular localization of the bulk of the arginine pool, suggest that compartmentation plays a significant role in controlling arginine metabolism in Neurospora.

The intracellular locations of enzymes and metabolites were determined for ornithine metabolism in Neurospora. Pulse label experiments were used to measure the rates of intracellular translocations and the sizes of compartmented pools of metabolites in the mitochondrial, cytosolic and vesicular compartments. The results indicate that rapid equilibration occurs between these pools during growth in minimal medium, although the vast majority of the ornithine is confined to the vesicular compartment. Arginine, the biosynthetic end-product of ornithine metabolism, regulates ornithine utilization through a combination of feedback inhibition, repression, and control of intracellular translocations. The last phenomenon plays a decisive role indicating that the regulation of intercompartmental translocations may be a common mechanism in rapid adaptation responses in eukaryotic cells.

The arg-6 locus of Neurospora crassa encodes two enzymes of arginine synthesis, acetylglutamate kinase and acetylglutamyl phosphate reductase. Mutants lacking one or the other enzyme fall into two different complementation groups; a large non-complementing group lacks both enzymes. We wished to survey over 50 alleles for suppressibility by a nonsense suppressor. We compared two methods of assessing suppressibility. One, based on trans-action of a nonsense suppressor, was simple, but not efficient in detecting all suppressible alleles. The other, based on crosses involving a marker linked to the locus surveyed was very efficient in methodology and is suited to all cases, such as the arg-6 locus, in which allelic crosses are sterile. The data indicate that the arg-6 locus encodes a bifunctional protein. © 1983 Springer-Verlag.

It is currently estimated that clinical laboratory services are, overall, approximately 3.0% of total health care expenditures.Clinical laboratory expenditures have and will continue to be one of many targets for attempting to reduce the growth in health are expenditures.The article examines the current and alternative methodolgies for Medicare payments as well as any impact on the clinical laboratory. [ABSTRACT FROM AUTHOR]

A high jugular bulb is often discovered as an incidental finding that is asymptomatic. Conductive hearing loss in association with this anomaly may occur, but has been reported infrequently in the literature. We report five cases of high jugular bulb and associated conductive hearing loss. Mechanisms to explain the conductive hearing loss include contact of the jugular bulb with the tympanic membrane, interference with the ossicular chain, and obstruction of the round window niche. The operative findings, radiographic and audiometric data that support these mechanisms of conductive hearing loss are presented. [ABSTRACT FROM AUTHOR]

More nurses without critical care experience are being hired by intensive care units. Eleven newly hired nurses participated in a phased program designed to improve the efficiency of intensive care unit orientation. A pre-post implementation design demonstrated that although there was a 14% reduction in orientation time, there were no statistically significant changes in new hire or preceptor satisfaction nor in first-year registered nurse turnover rates. Expansion of the program is needed to demonstrate its impact., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

The COVID-19 pandemic impacted every aspect of the personal and professional lives of healthcare providers. Nursing professional development practitioners are challenged with ongoing classroom education, new hire onboarding, and just-in-time education for staff. This article is intended to present the unique challenges that the COVID-19 pandemic placed on nursing professional development practitioners in a large academic medical center and how opportunities presented to revise old education practices., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Context.—: The diagnostic workup of lymphoma continues to evolve rapidly as experience and discovery led to the addition of new clinicopathologic entities and techniques to differentiate them. The optimal clinically effective, efficient, and cost-effective approach to diagnosis that is safe for patients can be elusive, in both community-based and academic practice. Studies suggest that there is variation in practice in both settings., Objective.—: To develop an evidence-based guideline for the preanalytic phase of testing, focusing on specimen requirements for the diagnostic evaluation of lymphoma., Design.—: The American Society for Clinical Pathology, the College of American Pathologists, and the American Society of Hematology convened a panel of experts in the laboratory workup of lymphoma to develop evidence-based recommendations. The panel conducted a systematic review of literature to address key questions. Using the Grading of Recommendations Assessment, Development, and Evaluation approach, recommendations were derived based on the available evidence, strength of that evidence, and key judgements as defined in the Grading of Recommendations Assessment, Development, and Evaluation Evidence to Decision framework., Results.—: Thirteen guideline statements were established to optimize specimen selection, ancillary diagnostic testing, and appropriate follow-up for safe and accurate diagnosis of indolent and aggressive lymphoma., Conclusions.—: Primary diagnosis and classification of lymphoma can be achieved with a variety of specimens. Application of the recommendations can guide decisions on specimen suitability, diagnostic capabilities, and correct use of ancillary testing. Disease prevalence in patient populations, availability of ancillary testing, and diagnostic goals should be incorporated into algorithms tailored to each practice environment., Competing Interests: Authors' disclosures of potential conflicts of interest and author contributions are found in the Appendix at the end of this article., (© 2021 College of American Pathologists.)

Objectives: The diagnostic workup of lymphoma continues to evolve rapidly as experience and discovery lead to the addition of new clinicopathologic entities and techniques to differentiate them. The optimal clinically effective, efficient, and cost-effective approach to diagnosis that is safe for patients can be elusive, in both community-based and academic practice. Studies suggest that there is variation in practice in both settings., The Aim of This Review Is to: develop an evidence-based guideline for the preanalytic phase of testing, focusing on specimen requirements for the diagnostic evaluation of lymphoma., Methods: The American Society for Clinical Pathology, the College of American Pathologists, and the American Society of Hematology convened a panel of experts in the laboratory workup of lymphoma to develop evidence-based recommendations. The panel conducted a systematic review of the literature to address key questions. Using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach, recommendations were derived based on the available evidence, the strength of that evidence, and key judgments as defined in the GRADE Evidence to Decision framework., Results: Thirteen guideline statements were established to optimize specimen selection, ancillary diagnostic testing, and appropriate follow-up for safe and accurate diagnosis of indolent and aggressive lymphoma., Conclusions: Primary diagnosis and classification of lymphoma can be achieved with a variety of specimens. Application of the recommendations can guide decisions about specimen suitability, diagnostic capabilities, and correct utilization of ancillary testing. Disease prevalence in patient populations, availability of ancillary testing, and diagnostic goals should be incorporated into algorithms tailored to each practice environment., (© American Society for Clinical Pathology, 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: To determine whether different laboratory developed test (LDT) risk stratification proposals would assign differing levels of risk to selected LDTs as a measure of the validity of those proposals, and whether there would be differing interrater agreement rates as a measure of the reliability of those proposals., Methods: A total of 4 reviewers applied 6 proposals for risk stratification of 4 LDTs. Interrater agreement was calculated as a measure of the reliability of the proposals. Also, a consensus risk categorization and concordance rate for each LDT was developed as a measure of the validity of the proposals., Results: Interrater agreement rates (reliability) ranged from 38% to 100%, and concordance rates (validity) ranged from 20% to 100%., Conclusions: A spectrum of reliability and validity was observed depending on the policy used and the LDT categorized. Before implementation or legislation of risk-stratification methods, large evaluations of reliability and validity should be conducted on any proposed method., (© American Society for Clinical Pathology 2018. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

For patients who desire transgender care, providers must use appropriate language, know the basics of cross-sex hormone therapy, and understand the risks and adverse effects of treatment options., Competing Interests: Author disclosures The authors report no actual or potential conflicts of interest with regard to this article.

Objectives/hypothesis: To assess balloon dilation of the Eustachian tube with Eustachian tube balloon catheter in conjunction with medical management as treatment for Eustachian tube dilatory dysfunction., Study Design: In this prospective, multicenter, randomized, controlled trial, we assigned, in a 2:1 ratio, patients age 22 years and older with Eustachian tube dilatory dysfunction refractory to medical therapy to undergo balloon dilation of the Eustachian tube with balloon catheter in conjunction with medical management or medical management alone., Methods: The primary endpoint was normalization of tympanogram at 6 weeks. Additional endpoints were normalization of Eustachian Tube Dysfunction Questionaire-7 symptom scores, positive Valsalva maneuver, mucosal inflammation, and safety., Results: Primary efficacy results demonstrated superiority of balloon dilation of the Eustachian tube with balloon catheter + medical management compared to medical management alone. Tympanogram normalization at 6-week follow-up was observed in 51.8% (72/139) of investigational patients versus 13.9% (10/72) of controls (P < .0001). Tympanogram normalization in the treatment group was 62.2% after 24 weeks. Normalization of Eustachian Tube Dysfunction Questionaire-7 Symptom scores at 6-week follow-up was observed in 56.2% (77/137) of investigational patients versus 8.5% (6/71) controls (P < .001). The investigational group also demonstrated substantial improvement in both mucosal inflammation and Valsalva maneuver at 6-week follow-up compared to controls. No device- or procedure-related serious adverse events were reported for those who underwent balloon dilation of the Eustachian tube., Conclusions: This study demonstrated superiority of balloon dilation of the Eustachian tube with balloon catheter + medical management compared to medical management alone to treat Eustachian tube dilatory dysfunction in adults., Level of Evidence: 1b. Laryngoscope, 128:1200-1206, 2018., (© 2017 The American Laryngological, Rhinological and Otological Society, Inc.)

Importance: Suboptimal outcomes of endoscopic sinus surgery (ESS) are often associated with restenosis and inflammation of frontal sinus ostia. Steroid-releasing sinus implants have been shown to maintain sinus patency by minimizing inflammation and scar tissue formation. An hourglass-shaped, bioabsorbable, steroid-releasing implant was developed to provide mechanical support and optimize drug delivery to paranasal sinus ostia., Objective: To assess the safety and efficacy of the hourglass-shaped, bioabsorbable, steroid-releasing sinus implant in improving postoperative outcomes when placed in the frontal sinus ostia (FSO) following ESS in patients with chronic rhinosinusitis (CRS)., Design, Setting, and Participants: In a prospective, multicenter, randomized clinical trial using an intrapatient control design (ESS followed by implant placement within 1 FSO vs ESS alone on the contralateral side) 80 adult patients, with a mean (SD) age of 49.5 (13.4) years and consisting of 53 (66%) men and 27 (34%) women, were enrolled and underwent bilateral frontal sinusotomies with 1 frontal sinus randomized to receive a steroid-releasing implant. The study was carried out in 12 US centers between July 2015 and March 2016., Interventions: A bioabsorbable steroid-releasing implant with hourglass shape containing 370 µg of mometasone furoate. All patients received standardized postoperative care., Main Outcomes and Measures: The need for postoperative interventions, medical and surgical, in the FSO at day 30, as determined based on review of video endoscopic findings by an independent blinded surgeon. Also, endoscopic grading by the independent reviewer and clinical investigators at day 30 and day 90 and computed tomographic scan at day 90., Results: The mean (SD) age of patients was 49.5 (13.4) years, 53 (66%) were men. Implants were successfully placed in all 80 randomized treatment sinuses. At day 30, steroid-releasing implants significantly reduced the need for postoperative interventions to 11.5% compared with 32.8% by surgery alone (mean difference, -21.3%; 95% CI, -35.1% to -7.6%), as assessed by the independent reviewer. Real-time endoscopic assessment by clinical investigators at day 30 demonstrated significant reduction in need for postoperative intervention (mean difference, -17.3%; 95% CI, -27.9% to -6.7%), significant reduction in inflammation score (mean difference, -12.3 mm; 95% CI, -18.3 to -6.4 mm), and significant reduction in rate of frontal restenosis or occlusion (mean difference, -22.7%; 95% CI, -33.5% to -11.9%) on treated compared with control sides. The results favoring the treatment sides were sustained through day 90: reduced need for postoperative interventions (mean difference, -11.7%; 95% CI, -21.0% to -2.4%) and reduction in restenosis and/or occlusion of the frontal ostium (mean difference, -17.4%; 95% CI, -28.6% to -6.1%). No implant-related adverse events were observed., Conclusions and Relevance: The hourglass-shaped steroid-releasing sinus implant was safe and more effective in maintaining FSO patency and improving surgical outcomes compared with surgery alone in the setting where no other immediate postoperative corticosteroids were administered., Trial Registration: ClinicalTrials.gov identifier: NCT02266810.

Background: Twenty-five years ago, the Food and Drug Administration (FDA) asserted in a draft document that "home brew" tests-now commonly referred to as laboratory-developed tests (LDTs)-are subject to the same regulatory oversight as other in vitro diagnostics (IVDs) 4 . In 2010, the FDA began work on developing a proposed framework for future LDT oversight. Released in 2014, the draft guidance sparked an intense debate over potential LDT regulation. While the proposed guidance has not been implemented, many questions regarding LDT oversight remain unresolved., Content: This review provides an overview of federal statutes and regulations related to IVDs and clinical laboratory operations, with a focus on those potentially applicable to LDTs and proposed regulatory efforts. Sources reviewed include the Code of Federal Regulations, the Federal Register, congressional hearings, guidance and policy documents, position statements, published literature, and websites., Summary: Federal statutes regarding IVDs were passed without substantive evidence of congressional consideration toward the concept of LDTs. The FDA has clear oversight authority over IVD reagents introduced into interstate commerce. A 16-year delay in publicly asserting FDA authority over LDTs, the pursuit of a draft guidance approach toward oversight, and establishment of regulations under the Clinical Laboratory Improvement Amendments of 1988 (CLIA'88) applicable to LDTs contributed to community uncertainty toward LDT oversight. Future regulatory and/or legislative efforts may be required to resolve this uncertainty., (© 2017 American Association for Clinical Chemistry.)

With the changing landscape of medicine in general, and pathology in particular, a greater emphasis is being placed on laboratory management as a means of controlling spiraling medical costs and improving health-care efficiency. To meet this challenge, pathology residency programs have begun to incorporate formal laboratory management training into their curricula, using institutional curricula and/or online laboratory management courses offered by professional organizations. At the University of Utah, and its affiliated national reference laboratory, ARUP Laboratories, Inc, interested residents are able to supplement the departmental lecture-based and online laboratory management curriculum by participating in assistant medical directorship programs in one of several pathology subspecialty disciplines. The goals of many of the assistant medical directorship positions include the development of laboratory management skills and competencies. A survey of current and recent assistant medical directorship participants revealed that the assistant medical directorship program serves as an excellent means of improving laboratory management skills, as well as improving performance as a fellow and practicing pathologist., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: To determine the optimal workflow combination of flow cytometry (FC) and immunohistochemistry tests for efficient and cost-effective evaluation of plasma cell (PC) neoplasms (PCNs) in bone marrow (BM) specimens., Methods: Various workflow combinations of immunohistochemistry and FC for 4,031 BM specimens worked up for PCNs were compared. Turnaround time (TAT), immunohistochemistry usage, technical charges, and addendum/amendment rates were compared between periods to determine the optimal workflow combination., Results: Five distinct workflow periods were identified, with varying combinations of full or limited FC panels for assessing PC clonality and CD138/κ/λ immunohistochemistry for PC quantification. Replacement of full FC with limited FC was associated with significant reductions in TAT and number of immunostains performed per case. Elimination of immunohistochemistry on cases determined to be polyclonal by FC also resulted in significant reductions in immunohistochemistry usage and significant cost savings., Conclusions: Assessment of PC clonality using a limited FC panel followed by reflex CD138 immunohistochemistry on cases that are monoclonal by FC provides an optimal and cost-effective workflow for evaluating PCNs in BM samples., (Copyright© by the American Society for Clinical Pathology.)

Context: Competency gaps in leadership and laboratory management skills continue to exist between what training programs deliver and what recent graduates and future employers expect. A number of recent surveys substantiate this. Interest in delivering content in these areas is challenged by time constraints, the presence of knowledgeable faculty role models, and the necessary importance placed on diagnostic skills development, which overshadows any priority trainees have toward developing these skills., Objective: To describe the problem, the near-future horizon, the current solutions, and the recommendations for improving resident training in laboratory management., Data Sources: The demands of new health care delivery models and the value being placed on these skills by the Pathology Milestones and Next Accreditation System initiative of the Accreditation Council for Graduate Medical Education for training programs emphasizes their importance. This initiative includes 6 milestone competencies in laboratory management. Organizations like the American Society for Clinical Pathology, the American Pathology Foundation, the College of American Pathologists, and the Association of Pathology Chairs Program Directors Section recognize these competencies and are working to create new tools for training programs to deploy., Conclusions: It is our recommendation that (1) every training program develop a formal educational strategy for management training, (2) greater opportunity and visibility be afforded for peer-reviewed publications on management topics in mainstream pathology literature, and (3) pathology milestones-oriented tools be developed to assist program directors and their trainees in developing this necessary knowledge and skills.

"High complexity" clinical laboratories are approved under the Clinical Laboratory Improvement Amendments to develop, validate, and offer a laboratory-developed test (LDT) for clinical use. The Food and Drug Administration considers LDTs to be medical devices under their regulatory jurisdiction, and that at least certain LDTs should be subject to greater regulatory scrutiny. This review describes the current regulatory framework for LDTs and suggests ways in which to appropriately enhance this framework.

Through the combined efforts of the American Pathology Foundation (APF), the American Society for Clinical Pathology (ASCP), and the Program Directors Section (PRODS) of the Association of Pathology Chairs (APC), a needs assessment was performed via a survey on the PRODS listserv, workshops at the APC/PRODS annual meetings in 2009 and 2010, and a Work Group of representatives of APF, ASCP, and PRODS. Residency program needs and resource constraints common to training pathology residents in practice and laboratory management were identified. In addition, a consensus curriculum for management training was created to serve as a resource for residency training program directors and others. The curriculum was converted into a "wiki" design tool for use by program directors, residents, and faculty.

Background: Calcific aortic stenosis (CAS) is the most common acquired valvular disorder in industrialized countries. This study investigates the correlation of different known biomarkers for CAS as a first step towards the development of a panel of biomarkers that can be used in prognostic staging., Methods: Venous blood samples were obtained from both patients with CAS scheduled for surgery and healthy individuals. Plasma levels of fetuin-A, NT-proBNP, BNP, homocysteine and osteopontin were measured by enzyme-linked immunosorbent assay (ELISA). CAS was measured by echocardiography and was defined as an aortic valve area of less than 2.0 cm(2). Non-paired t-tests were used for comparison., Results: CAS was present in 33 subjects (mean age 75.9 y) and absent in 11 subjects (mean age 55.36 y). Individuals with CAS exhibited higher plasma levels of NT-proBNP (1.33 versus 0.73 pmol/mL, P < 0.05), BNP fragment (1.47 versus 0.34 ng/mL P < 0.05), and osteopontin (60.79 versus 25.42 ng/mL P < 0.05) compared with controls. Fetuin-A levels were lower in individuals with CAS than in healthy controls (0.25 versus 0.34g/L, P < 0.05). Asymmetric dimethylarginine (ADMA) were lower (1.08 versus 1.1 micromol/L, P > 0.05) while homocysteine levels (20.34 +/- 2.14 versus 19.23 +/- 4.19 P > 0.05) were higher in the CAS patients., Conclusion: This study demonstrates a direct correlation of NT-pro-BNP, BNP, and osteopontin and the presence of CAS, while fetuin A showed an inverse correlation. Plasma ADMA and homocysteine levels were comparable in the CAS patients and healthy individuals. This is the first study in which several biomarkers previously studied independently in patients with CAS have been investigated simultaneously in the same study population., (Copyright 2010 Elsevier Inc. All rights reserved.)

Understanding the role of the built environment on physical activity behavior among older adults is an important public health goal, but evaluating these relationships remains complicated due to the difficulty of measuring specific attributes of the environment. As a result, there is conflicting evidence regarding the association between perceived and objectively measured walkability and physical activity among urban-dwelling older adults. This suggests that both actual environmental features and perceptions of these attributes influence walking behavior. The purpose of this pilot project is to create an Objective Walkability Index (OWI) by census block using a Geographic Information System (GIS) and supplement the results with resident perceptions thus more accurately characterizing the context of walkability. Computerized Neighborhood Environment Tracking (ComNET) was used to systematically assess environmental risks impacting activity patterns of older adults in two New York City neighborhoods. In addition, the Senior Center Evaluation of the Neighborhood Environment (SCENE) survey was administered to older adults attending two senior centers located within the target neighborhoods. The results indicate that there is substantial variation in OWI score both between and within the neighborhoods suggesting that residence in some communities may increase the risk of inactivity among older adults. Also, low walkability census blocks were clustered within each neighborhood providing an opportunity for targeted investigation into localized threats to walkability. A lack of consensus regarding the association between the built environment and physical activity among older adults is a consequence of the problems inherent in measuring these determinants. Further empirical evidence evaluating the complex relationships between the built environment and physical activity is an essential step towards creating active communities.

Objective: Assess two-year postoperative clinical outcomes for patients receiving balloon catheter sinusotomy., Methods: Patients who had sinus ostia dilated with balloon catheters were prospectively evaluated two years after surgery by Sinonasal Outcome Test (SNOT-20) and computed tomographic (CT) scan., Results: Sixty-five patients (195 ballooned sinuses) were followed for two years after surgery, including 34 "balloon-only" patients and 31 "hybrid" patients. SNOT-20 symptom scores were significantly improved from baseline (0.87 vs 2.17 baseline, P < 0.001) and stable compared to six months and one year; this was the case for both balloon-only (1.09 vs 2.09, P < 0.001) and hybrid (0.64 vs 2.26, P < 0.001) patients. Lund-MacKay CT scores were significantly improved from baseline (2.69 vs 9.66, P < 0.001) and stable compared to one year, confirmed for both balloon-only (1.75 vs 5.67, P < 0.015) and hybrid (3.25 vs 12.05, P < 0.001) subsets of patients. A total of 85% of patients reported improvement of their sinus symptoms, with 15% same and 0% worsened. Revision treatment was required in seven of 195 sinuses (3.6%) in six of 65 patients (9.2%)., Conclusion: Patients who receive balloon catheter sinusotomy in endoscopic sinus surgery have significant improvement in symptoms two years after surgery. Radiographic evidence also confirms resolution of disease after two years. This demonstrates durability of clinical results previously reported at 24 weeks and one year after surgery.

Objectives: This study assesses the safety and effectiveness of balloon catheters used as instruments in sinus surgery in a "real-world" multicenter registry of 1,036 patients across 27 US otolaryngology practices., Methods: Data were collected by standardized chart review with centralized database administration for all consecutive functional endoscopic sinus surgeries that included the use of balloon catheters across the 18-month time period from December 2005 to May 2007., Results: Balloon catheters were used in 3,276 peripheral (maxillary, frontal, and sphenoid) sinuses, for an average of 3.2 sinuses per patient. There were no major adverse events related to the use of balloon catheter instruments. The revision rate was 1.3% of sinuses treated with a balloon catheter after an average follow-up of 40.2 weeks. Sinus symptoms were improved in 95.2%, unchanged in 3.8%, and worse in 1.0% of patients. Postoperative sinus infections were significantly less frequent and less severe compared to infections before surgery. The results were consistent across all patient categories, including balloon-only patients and revision patients., Conclusions: Use of balloon catheters as instruments in sinus surgery appears to be relatively safe and effective and to improve the patient's quality of life. The results are consistent and generalizable across a wide range of sinusitis patients and physician practices. The complication rates, revision rates, and patient symptom improvement rates all compare favorably with previously reported results of functional endoscopic sinus surgery.

Objective: The aim of this study was to determine the extent of radiation exposure to the patient and the surgeon in balloon catheter dilation., Methods: Dosimeters were used to record radiation exposure to both patients and surgeons. The mean radiation dose per sinus treated and per patient treated was calculated for each dosimeter location., Results: The mean patient dose (108 sinuses treated in 34 patients), was 0.32 mSv per sinus and 1.02 mSv per patient over the eye and 1.33 mSv per sinus and 4.22 mSv per patient over the temple. The average total fluoroscopy time was 3.6 minutes per patient. The average number of sinuses treated was 3.2. The mean surgeon dose at the chest (254 sinuses in 89 patients) was 0.025 mSv per sinus and 0.072 mSv per patient. The mean surgeon dose at the hand (182 sinuses in 68 patients) was 0.009 mSv per sinus and 0.023 mSv per patient., Conclusions: The use of fluoroscopy in balloon catheter dilation exposes both the patient and surgeon to very low doses of radiation.

The present study reports on the potential effectiveness of motivational interviewing (MI) in changing the way batterers think about their violent behavior. Thirty-three domestic violence offenders who were court-mandated to treatment were randomly assigned to MI or a control condition before attending their first mandated treatment group. Consistent with predictions, the MI group demonstrated generally more improvement on stages of change subscales than the control group. Further, the MI group demonstrated a significantly greater decrease in the extent to which they blamed their violence on external factors. Current data indicate that MI has the potential to increase batterers' motivation to change, although validation trials with larger sample sizes and more refined measures are required.

Compensation for pathologist and clinical laboratory services generally depends upon standardized procedural coding systems, the coverage determinations of individual insurance companies, fee schedules that assign reimbursement rates for those services, and contractual compensation arrangements. Procedural coding relies primarily on the American Medical Association's Current Procedural Terminology (CPT) nomenclature. Disease conditions, signs, and symptoms are coded using the International Classification of Diseases, Ninth Revision, Clinical Modification. The single largest health insurance "company" in the United States is the Center for Medicare and Medicaid Services (CMS), and most private insurance companies look to CMS as a model for health services compensation. CMS uses a Physician Fee Schedule and a separate Clinical Laboratory Fee Schedule, whose designs and annual updates differ.

Several current forces have set anticipated future changes in health care in motion, or, at least, have set the stage for change. End-consumer demand increasingly drives the market; as a result, entire businesses are transforming or emerging anew to meet these demands. In general, consumers demand high quality at reasonable cost, to be delivered as fast as possible with minimal inconvenience. The health care consumer takes this expectation further, to include the desire for all helpful information regarding one's health to be made readily available for him/her to make the best decision and minimize morbidity, mortality, misdiagnosis, and inconvenience. This article addresses the impact upon the laboratory by considering four key interrelated dynamics that affect these trends: market, medicine, technology, and information systems.

Successful and ethical management of a clinical laboratory requires vigilant focus on proper business conduct. A comprehensive risk management program must encompass government standards as provided for financial and marketing practices, including fraud and abuse, antitrust, antikickback, privacy, and security. The program also must incorporate the appropriate reaction to medical malpractice litigation along with considerations of expert testimony.

Objective: The aim of this study was to further evaluate the safety and effectiveness of balloon catheter devices to dilate obstructed sinus ostia/perform sinusotomy., Methods: Through a prospective, multicenter evaluation, safety was assessed by rate of adverse events, patency was determined by endoscopic examination, and sinus symptoms were determined by the Sino-Nasal Outcome Test (SNOT 20)., Results: At the conclusion of the 24-week analysis, endoscopy determined that the sinusotomy was patent in 80.5% (247 of 307) sinuses and nonpatent in 1.6% (5 of 307), and could not determine ostial patency status in 17.9% (55 of 307). Of the ostia visualized on endoscopy, 98% were patent (247 of 252), while 2% (5 of 252) were considered nonpatent. SNOT 20 scores showed consistent symptomatic improvement over baseline. Revision treatment was required in 3 sinuses (3 of 307 sinuses, 0.98%) in 3 patients (3 of 109 patients, 2.75%)., Conclusion: Balloon catheter technology appears safe and effective in relieving ostial obstruction. Patients were pleased and indicated that they experienced symptomatic improvement.

The business of medicine requires more than just the knowledge and skills necessary to provide quality patient care. A growing number of opportunities are available for physicians to learn how to better manage the business side of their practices. Today's clinical laboratories, particularly those in health care organizations under pressure to efficiently use limited resources, benefit from having management and leadership specifically trained for these roles.

A consortium of investigators is engaged in a functional genomics project centered on the filamentous fungus Neurospora, with an eye to opening up the functional genomic analysis of all the filamentous fungi. The overall goal of the four interdependent projects in this effort is to accomplish functional genomics, annotation, and expression analyses of Neurospora crassa, a filamentous fungus that is an established model for the assemblage of over 250,000 species of non yeast fungi. Building from the completely sequenced 43-Mb Neurospora genome, Project 1 is pursuing the systematic disruption of genes through targeted gene replacements, phenotypic analysis of mutant strains, and their distribution to the scientific community at large. Project 2, through a primary focus in Annotation and Bioinformatics, has developed a platform for electronically capturing community feedback and data about the existing annotation, while building and maintaining a database to capture and display information about phenotypes. Oligonucleotide-based microarrays created in Project 3 are being used to collect baseline expression data for the nearly 11,000 distinguishable transcripts in Neurospora under various conditions of growth and development, and eventually to begin to analyze the global effects of loss of novel genes in strains created by Project 1. cDNA libraries generated in Project 4 document the overall complexity of expressed sequences in Neurospora, including alternative splicing alternative promoters and antisense transcripts. In addition, these studies have driven the assembly of an SNP map presently populated by nearly 300 markers that will greatly accelerate the positional cloning of genes.

The low rate of homologous recombination exhibited by wild-type strains of filamentous fungi has hindered development of high-throughput gene knockout procedures for this group of organisms. In this study, we describe a method for rapidly creating knockout mutants in which we make use of yeast recombinational cloning, Neurospora mutant strains deficient in nonhomologous end-joining DNA repair, custom-written software tools, and robotics. To illustrate our approach, we have created strains bearing deletions of 103 Neurospora genes encoding transcription factors. Characterization of strains during growth and both asexual and sexual development revealed phenotypes for 43% of the deletion mutants, with more than half of these strains possessing multiple defects. Overall, the methodology, which achieves high-throughput gene disruption at an efficiency >90% in this filamentous fungus, promises to be applicable to other eukaryotic organisms that have a low frequency of homologous recombination.

Context: Laboratory data are essential to the medical care of fetuses, infants, children, and adolescents. However, the performance and interpretation of laboratory tests on specimens from these patients, which may constitute a significant component of the workload in general hospitals and integrated health care systems as well as specialized perinatal or pediatric centers, present unique challenges to the clinical pathologist and the laboratory. Therefore, pathology residents should receive training in pediatric laboratory medicine., Objective: Children's Health Improvement through Laboratory Diagnostics, a group of pathologists and laboratory scientists with interest and expertise in pediatric laboratory medicine, convened a task force to develop a list of curriculum topics, key resources, and training experiences in pediatric laboratory medicine for trainees in anatomic and clinical pathology or straight clinical pathology residency programs and in pediatric pathology fellowship programs., Data Sources: Based on the experiences of 11 training programs, we have compiled a comprehensive list of pediatric topics in the areas of clinical chemistry, endocrinology, hematology, urinalysis, coagulation medicine, transfusion medicine, immunology, microbiology and virology, biochemical genetics, cytogenetics and molecular diagnostics, point of care testing, and laboratory management. This report also includes recommendations for training experiences and a list of key texts and other resources in pediatric laboratory medicine., Conclusions: Clinical pathologists should be trained to meet the laboratory medicine needs of pediatric patients and to assist the clinicians caring for these patients with the selection and interpretation of laboratory studies. This review helps program directors tailor their curricula to more effectively provide this training.

N. crassa has two forms of arginase. The physiological role of multiple arginases is not understood. The two forms were shown to be differentially expressed from a single locus (aga) and both proteins are localized to the cytoplasm. The 36-kDa protein was expressed in minimal and arginine supplemented medium, whereas the 41-kDa form was detected only in the presence of arginine. In this study we examined developmental expression of the two arginase transcripts and proteins in conidia and during conidial germination. Two novel observations are revealed, storage of both arginase proteins in conidia and temporal expression of aga transcripts during early germination. To better understand the role of arginase in conidia and the nature of the temporal expression, we examined the effects of related metabolites, arginine, ornithine, proline, glutamate and glutamine on protein storage and temporal expression. These metabolites were used as supplements or sole nitrogen sources. Storage of arginase protein was detected in all conidial samples examined except when glutamate was used as the nitrogen source. The aga temporal RNA expression early in germination was abolished when arginine related metabolites were used as nitrogen sources. The exception to this result is observed with glutamate where temporal expression was seen when glutamate was the sole nitrogen source and abolished with glutamate supplementation. The temporal expression result supports a unique role for arginase in glutamate accumulation early in germination whereas the protein storage result supports the existence of a novel pathway utilizing arginase for glutamate synthesis in asexual spore development.

Polyethyleneimine (PEI)-coated slides were used for attachment of unknown extremophiles and their cultures grown at high temperature and low pH. Selective adhesion of cells in natural samples and cultural isolates was compared to polylysine (PL) and several other coatings. PEI is superior to PL for adhesion of extremophiles.

Clinical laboratories use reference laboratories for laboratory services that they, themselves, routinely are unable to provide, often for economic and/or competency-related reasons. Decisions on reference laboratory providers usually are based upon reputation, quality of service, depth of test menu, other value-added services, testing frequency and turnaround time, price, client services support, information technology support, and logistics. The referring laboratory also is faced with the challenge of how to manage physician ordering patterns and their requests for esoteric testing. This is particularly important and problematic in cases of questionable medical necessity, high cost, or both. This article attempts to address this dilemma and how best to manage the utilization of expensive esoteric tests, particularly in the face of little or no reimbursement for these services by payers and health plans.