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Clarkson disease, or monoclonal gammopathy-associated idiopathic systemic capillary leak syndrome (ISCLS), is a rare, relapsing-remitting disorder featuring the abrupt extravasation of fluids and proteins into peripheral tissues, which in turn leads to hypotensive shock, severe hemoconcentration, and hypoalbuminemia. The specific leakage factor(s) and pathways in ISCLS are unknown, and there is no effective treatment for acute flares. Here, we characterize an autonomous vascular endothelial defect in ISCLS that was recapitulated in patient-derived endothelial cells (ECs) in culture and in a mouse model of disease. ISCLS-derived ECs were functionally hyperresponsive to permeability- inducing factors like VEGF and histamine, in part due to increased endothelial nitric oxide synthase (eNOS) activity. eNOS blockade by administration of W(y)-nitro-L-arginine methyl ester (L-NAME) ameliorated vascular leakage in an SJL/J mouse model of ISCLS induced by histamine or VEGF challenge. eNOS mislocalization and decreased protein phosphatase 2A (PP2A) expression may contribute to eNOS hyperactivation in ISCLS-derived ECs. Our findings provide mechanistic insights into microvascular barrier dysfunction in ISCLS and highlight a potential therapeutic approach., Introduction The initial presentation of Clarkson disease, or monoclonal gammopathy- associated idiopathic systemic capillary leak syndrome (ISCLS), is frequently complicated by multiple organ dysfunction syndrome (MODS), rhabdomyolysis, and intravascular thrombosis [...]

In my comments, I address two issues that are important but not central to the paper under review here. First, I present a reading of the postphenomenological concept of multistability by going back to Merleau-Ponty's notion of the primacy of perception. I conclude that assertions affirming the multistability of technologies should not be seen as merely empirical. Second, I address the adequacy of using the language of 'empirical' and 'transcendental' as a means to categorize exclusionary approaches in philosophy of technology., Author(s): Kirk M. Besmer [sup.1] Author Affiliations: (1) grid.256410.4, 0000 0001 0668 7980, Philosophy Department, Gonzaga University, , 502 E. Boone Ave, 99258, Spokane, WA, USA In the paper under [...]

Systemic capillary leak syndrome (SCLS), also known as Clarkson disease, is a rare disease of unknown etiology that most commonly develops in adults 50-70 years of age (1). Since SCLS [...]

Myocardin (MYOCD) is the founding member of a class of transcriptional coactivators that bind the serum-response factor to activate gene expression programs critical in smooth muscle (SM) and cardiac muscle development. Insights into the molecular functions of MYOCD have been obtained from cell culture studies, and to date, knowledge about in vivo roles of MYOCD comes exclusively from experimental animals. Here, we defined an often lethal congenital human disease associated with inheritance of pathogenic MYOCD variants. This disease manifested as a massively dilated urinary bladder, or megabladder, with disrupted SM in its wall. We provided evidence that monoallelic loss-of-function variants in MYOCD caused congenital megabladder in males only, whereas biallelic variants were associated with disease in both sexes, with a phenotype additionally involving the cardiovascular system. These results were supported by cosegregation of MYOCD variants with the phenotype in 4 unrelated families by in vitro transactivation studies in which pathogenic variants resulted in abrogated SM gene expression and by the finding of megabladder in 2 distinct mouse models with reduced Myocd activity. In conclusion, we have demonstrated that variants in MYOCD result in human disease, and the collective findings highlight a vital role for MYOCD in mammalian organogenesis., Introduction Urinary tract and kidney malformations often result in termination of pregnancy after being detected on ultrasound screening, and these anomalies are also a major cause of renal failure in [...]

Background Obstructive uropathy (OU) is a common cause of end-stage renal disease (ESRD) in children. Children who escape the newborn period with mild-to-moderate chronic kidney disease (CKD) continue to be at increased risk. The predictive ability of clinically available markers throughout childhood is poorly defined. Methods Patients with OU were identified in the Chronic Kidney Disease in Children Study. The primary outcome of interest was renal replacement therapy (RRT) (cases). Controls were age matched and defined as patients within the OU cohort who did not require RRT during study follow-up. Results In total, 27 cases and 41 age-matched controls were identified. Median age at baseline and age at outcome measurement were 10 vs. 16 years, respectively. First available glomerular filtration rate (GFR) (36.9 vs. 53.5 mL/min per 1.73 m.sup.2), urine protein/creatinine (Cr) (0.40 vs. 0.22 mg/mg) and microalbumin/Cr (0.58 vs. 0.03 mg/mg), and serum CO.sub.2 (20 vs. 22 mmol/L) and hemoglobin (12.4 vs. 13.2 g/dL) differed significantly between cases and controls, respectively. GFR declined 3.07 mL/min per 1.73 m.sup.2/year faster in cases compared to that in controls (p < 0.0001). Urine protein/Cr and microalbumin/Cr increased by 0.16 and 0.11 per year more in cases compared to those in controls, respectively (p [less than or equal to] 0.001 for both). Serum phosphate increased by 0.11 mg/dL and serum albumin and hemoglobin decreased by 0.04 (g/dL) and 0.14 (g/dL) per year more for cases compared to those for controls, respectively (p < 0.05 for all). Conclusions Age-specific baseline and longitudinal measures of readily available clinical measures predict progression to ESRD in children with mild-to-moderate CKD from OU., Author(s): Daryl J. McLeod [sup.1] [sup.2] , Christina B. Ching [sup.1] [sup.3] , Yuri V. Sebastião [sup.2] , Jason H. Greenberg [sup.4] , Susan L. Furth [sup.5] , Kirk M. [...]

The clinical and financial impact of chronic kidney disease (CKD) is significant, while its progression and prognosis is variable and often poor. Studies using the megabladder (mgb.sup.-/-) model of CKD show that renal urothelium plays a key role in modulating early injury responses following the development of congenital obstruction. The aim of this review is to examine the role that urothelium has in normal urinary tract development and pathogenesis. We discuss normal morphology of renal urothelium and then examine the role that uroplakins (Upks) play in its development. Histologic, biochemical, and molecular characterization of Upk1b.sup.RFP/RFP mice indicated Upk1b expression is essential for normal urinary tract development, apical plaque/asymmetric membrane unit (AUM) formation, and differentiation and functional integrity of the renal urothelium. Our studies provide the first evidence that Upk1b is directly associated with the development of congenital anomalies of the urinary tract (CAKUT), spontaneous age-dependent hydronephrosis, and dysplastic urothelia. These observations demonstrate the importance of proper urothelial differentiation in normal development and pathogenesis of the urinary tract and provide a unique working model to test the hypothesis that the complex etiology associated with CKD is dependent upon predetermined genetic susceptibilities that establish pathogenic thresholds for disease initiation and progression., Author(s): Ashley R. Carpenter [sup.1] [sup.2] , Kirk M. McHugh [sup.2] [sup.3] Author Affiliations: (1) 0000 0001 2285 7943grid.261331.4Biomedical Sciences Graduate Program, The Ohio State University, Columbus, OH, USA (2) [...]

We report the discovery of a new monomeric peptide that reduces body weight and diabetic complications in rodent models of obesity by acting as an agonist at three key metabolically-related peptide hormone receptors: glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and glucagon receptors. This triple agonist demonstrates supraphysiological potency and equally aligned constituent activities at each receptor, all without cross-reactivity at other related receptors. Such balanced unimolecular triple agonism proved superior to any existing dual coagonists and best-in-class monoagonists to reduce body weight, enhance glycemic control and reverse hepatic steatosis in relevant rodent models. Various loss-of-function models, including genetic knockout, pharmacological blockade and selective chemical knockout, confirmed contributions of each constituent activity in vivo. We demonstrate that these individual constituent activities harmonize to govern the overall metabolic efficacy, which predominantly results from synergistic glucagon action to increase energy expenditure, GLP-1 action to reduce caloric intake and improve glucose control, and GIP action to potentiate the incretin effect and buffer against the diabetogenic effect of inherent glucagon activity. These preclinical studies suggest that, so far, this unimolecular, polypharmaceutical strategy has potential to be the most effective pharmacological approach to reversing obesity and related metabolic disorders., Obesity and its comorbidities, including type 2 diabetes, represent a global health threat and a rapidly increasing burden to economic prosperity (1). Therapeutic intervention is urgently required because lifestyle modification [...]

Congenital obstructive nephropathy remains one of the leading causes of chronic renal failure in children. The direct link between obstructed urine flow and abnormal renal development and subsequent dysfunction represents a central paradigm of urogenital pathogenesis that has far-reaching clinical implications. Even so, a number of diagnostic, prognostic, and therapeutic quandaries still exist in the management of congenital obstructive nephropathy. Studies in our laboratory have characterized a unique mutant mouse line that develops in utero megabladder, variable hydronephrosis, and progressive renal failure. Megabladder mice represent a valuable functional model for the study of congenital obstructive nephropathy. Recent studies have begun to shed light on the genetic etiology of [mgb.sup.(-/-)] mice as well as the molecular pathways controlling disease progression in these animals. Keywords Congenital obstructive nephropathy * Kidney pathogenesis * Animal models of disease * Long-range enhancer, Introduction One key component in studying the complex processes involved in the pathogenesis of human disease is the use of animal models. Whether experimental, surgical or genetic, animal models provide [...]

The scaffold protein p62 (sequestosome 1; SQSTM1) is an emerging key molecular link among the metabolic, immune, and proliferative processes of the cell. Here, we report that adipocyte-specific, but not [...]

Congenital obstructive nephropathy is the leading cause of chronic renal disease in children. As a result, it represents a tremendous societal burden in terms of morbidity and mortality, as well as in health care expenses of caring for children with chronic kidney disease and end-stage renal disease. The various diagnostic, prognostic, and therapeutic challenges associated with congenital obstructive nephropathy highlight the importance of developing effective experimental models for studying this disease process. In this review, we define the clinical entity that is congenital obstructive nephropathy, outline the current standards of diagnosis and care, and discuss the utilization of current experimental models designed to help clarify some of the clinical conundrums associated with this important disease. Keywords Kidney * Bladder * Congenital obstructive nephropathy * Chronic kidney disease * Genetics * Animal models, Introduction Congenital obstructive nephropathy (CON) is a complex disease process involving pathologic changes in kidney development and function that occur as a result of impaired antegrade urine flow beginning in [...]

Objective: Restaurant employees often have high rates of heavy drinking and problems with alcohol. This study evaluates reductions in drinking and associated problems at work, in connection with a new program for prevention and early intervention. The program, called Team Resilience, is designed for young restaurant workers. Method: A cluster-randomized trial design was used, with 28 stores from a national casual-dining restaurant chain and 235 of their employees (54% male, 46% female). Fourteen stores received the Team Resilience training workshop, consisting of three 2-hour sessions held on 3 consecutive days. Sessions included group discussion, role-play and practice activities, and a learning game. Results: Workers in trained stores reported significantly greater decreases in recurring heavy drinking (i.e., having five or more drinks on the same occasion, on 5 or more days in the past month) and work-related problems with alcohol than workers in control stores. In the intervention group, the odds of recurring heavy drinking declined by about one half and the number of work-related problem areas declined by one third following training. In addition, drinking behaviors and problems were tied to age and were most common among employees in their middle 20s. Conclusions: Findings support Team Resilience as an effective intervention for reducing drinking and associated problems among young restaurant workers, a population with substantial needs. (J. Stud. Alcohol Drugs, 72, 117-124, 2011), MISUSE OF ALCOHOL IS A CHALLENGE among restaurant workers in the United States. Such workers have reported heavy drinking rates substantially above the national average across industries (Moore et al., [...]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.jsat.2008.12.002 Byline: Kirk M. Broome, Danica K. Knight, Jennifer R. Edwards, Patrick M. Flynn Keywords: Counseling staff; Burnout; Job satisfaction; Leadership; Hierarchical linear models Abstract: Counselors are a critical component of substance abuse treatment programming, but their working experiences are not yet well understood. As treatment improvement efforts focus increasingly on these individuals, their perceptions of program leadership, emotional burnout, and job satisfaction and related attitudes take on greater significance. This study explores counselor views and the impact of organizational context using data from a nationwide set of 94 outpatient drug-free treatment programs in a hierarchical linear model analysis. Results show counselors hold generally positive opinions of program director leadership and job satisfaction and have low levels of burnout, but they also have important variations in their ratings. Higher counselor caseloads were related to poorer ratings, and leadership behaviors predicted both satisfaction and burnout. These findings add further evidence that treatment providers should also address the workplace environment for staff as part of quality improvement efforts. Author Affiliation: Institute of Behavioral Research, Texas Christian University, Fort Worth, TX 76129, USA Article History: Received 24 July 2008; Revised 7 December 2008; Accepted 18 December 2008

Stable isotope analysis of diet switching by fishes often is hampered by slow turnover rates of the tissues analyzed (usually muscle or fins). We examined epidermal mucus as a potentially faster turnover 'tissue' that might provide a more rapid assessment of diet switching. In a controlled hatchery experiment, we switched the diet of juvenile steelhead (sea-run rainbow trout, Oncorhynchus mykiss) from a plant-based feed with low [delta][sup.13]C and [delta][sup.15]N to a fish-meal-based diet with higher delta values. We found mucus to provide a significantly more rapid response to diet switching (half-life = 36 days for [delta][sup.15]N, 30 days for [delta][sup.13]C) than muscle tissue (half-life = 94 days for [delta][sup.15]N, 136 days for [delta][sup.13]C), even for growing juvenile fish. Mucus may provide a rapid turnover 'tissue' for analysis of diet (or habitat) switching by fish. It has the additional advantage that it may be sampled nonlethally in some fishes, thereby avoiding problems in studying threatened or endangered species. This is the first report of the use of fish mucus in stable isotope analyses of fish tissues. Les analyses de changements de regime alimentaire chez les poissons au moyen des isotopes stables sont souvent entravees par les faibles taux de remplacement des tissus analyses (generalement les muscles ou les branchies). Nous evaluons l'utilisation du mucus epidermique comme [much less than] tissu [much greater than] a taux de renouvellement potentiellement plus eleve qui pourrait fournir une appreciation plus hative des changements de regime. Dans une experience en conditions controlees de pisciculture, nous avons modifie l'alimentation de jeunes truites arc-en-ciel anadromes (Oncorhynchus mykiss) d'un regime a base de plantes a [delta][sup.13]C et [delta][sup.15]N bas, a un regime a base de farine de poisson avec des valeurs plus elevees des deltas. Le mucus reagit significativement plus rapidement au changement de regime (demi-vie = 36 jours pour [delta][sup.15]N et 30 jours pour [delta][sup.13]C) que le muscle (demi-vie = 94 jours pour [delta][sup.15]N et 136 jours pour [delta][sup.13]C), meme chez les jeunes poissons en croissance. Le mucus peut donc constituer un [much less than] tissu [much greater than] a taux de renouvellement rapide pour l'analyse des changements de regime (ou d'habitat) chez les poissons. Il presente, de plus, l'avantage de pouvoir etre echantillonne chez certains poissons sans devoir sacrifier l'animal, ce qui evite quelques-uns des problemes associes a l'etude des especes menaces ou en voie de disparition. C'est la premiere fois que le mucus de poisson est utilise pour l'analyse des isotopes stables dans les tissus de poisson. [Traduit par la Redaction], Introduction The analysis of stable isotope ratios in fish can be a powerful tool for studying fish ecology, including, for example, movement of fish from one habitat (and diet) to [...]

Tipranavir (TPV), a protease inhibitor, has box warnings for intracranial hemorrhage (ICH) and hepatotoxicity (including hepatic failure and death). A box warning is a labeling statement about serious adverse events leading to significant injury and/or death. A box warning is the most serious warning placed in the labeling of a prescription medication. As a result of the respective morbidity and mortality associated with ICH and hepatic failure, the Food and Drug Administration's (FDA's) Adverse Event Reporting System (AERS) was searched for reports of these adverse events in HIV-infected patients receiving a tipranavir/ritonavir (TPV/r)-based regimen. This search comprised part of the FDA's safety analysis for traditional approval. From July 2006 to March 2007, 10 cases of ICH were identified in AERS. From June 2005 to March 2007, 12 cases of liver-associated deaths were identified. One patient experienced liver failure and fatal ICH. Most patients with these events had additional risk factors. Among patients with liver-associated deaths, 3 had HIV-RNA less than 400 copies per milliliter at the time of hepatic failure. Among 10 patients who discontinued TPV/r when hepatic failure developed, median number of days post-TPV/r to death was 23 (range, 2-69 days). Review of AERS did not identify new safety concerns regarding ICH. Among most patients with liver-associated deaths, death appears to occur soon after hepatic failure develops. If considering TPV/r, careful assessment of risk/benefit is suggested for patients at risk for ICH and hepatic failure.

Measures of satisfaction have become increasingly popular as indications of psychotherapy outcome both in research and in practice. Several studies have explored the relationship between satisfaction and symptomatic change, with mixed results. The present study examines the relationship among satisfaction, symptomatic improvement, perceived change, and end-point functioning from multiple perspectives. Sixty-six clients from 2 Midwestern community mental health centers. 48 of their spouses and significant others, and their therapists participated in the study. Results indicated that satisfaction was not significantly related to symptomatic change, Satisfaction and perceived change were significantly related from all 3 perspectives. Satisfaction was also significantly related to end-point functioning from the client and significant other perspectives. The unique contribution of satisfaction data to a comprehensive outcome evaluation strategy is discussed. Researchers, administrators, and practitioners are encouraged to use satisfaction measures with a greater awareness of both their strengths and their limitations as outcome indicators. Keywords: psychotherapy, satisfaction, symptomatic improvement, end-point functioning

Byline: Jennifer L. DiGiacinto, PharmD (Office of Clinical Pharmacology, Division IV, US Food and Drug Administration, Silver Spring, Maryland); Kirk M. Chan-Tack, MD (Office of New Drugs, Division of Anti-Viral [...]

To purchase or authenticate to the full-text of this article, please visit this link: http://dx.doi.org/10.1111/j.1468-5906.2007.00363.x Byline: JOSEPH J. SHIELDS (1), KIRK M. BROOME (2), PETER J. DELANY (3), BENNETT W. FLETCHER (4), PATRICK M. FLYNN (5) Abstract: The relationship between personal religiousness and substance abuse treatment outcomes has emerged as an important issue in the public health arena. Using the 'moral community' perspective, a conceptual framework developed by Stark, Kent, and Doyle (1982) to analyze the contextual effects of religion, we explore the degree to which religion influences two drug treatment outcome measures-critical retention and commitment to treatment. The data are derived from the Drug Abuse Treatment Outcome Studies (DATOS), a national study of 10,010 clients enrolled in 70 drug treatment programs. Three research questions were addressed: (1) What is the relationship between an individual's level of religiosity and retention in treatment and commitment to treatment? (2) How does the ecological context of treatment programs shape the individual-level relationships? (3) To what extent are program practices and characteristics directly linked to outcome level? The findings are supportive of the literature that shows a weak to moderate relationship between religiosity and treatment outcomes. However, the findings did not show strong support for the 'moral community' hypothesis. Although there was a wide variation in the size of the individual-level religiosity-treatment correlations, the variation could not be conclusively attributed to the overall religious emphasis of the programs. The findings suggest that further research is needed in order to understand fully the role of religion in substance abuse treatment. Author Affiliation: (1)Joseph J. Shields, Ph.D. is Associate Professor of Social Work at the National Catholic School of Social Service, the Catholic University of America. (2)Kirk M. Broome, Ph.D. is Research Scientist at the Institute of Behavioral Research, Texas Christian University. E-mail:k.broome@tcu.edu (3)Peter J. Delany, Ph.D. is Program Director for Health Services Research at the National Institutes on Alcohol Abuse and Alcoholism, National Institutes of Health. E-mail:delanyp@mail.nih.gov (4)Bennett W. Fletcher is Senior Research Psychologist at the National Institute for Drug Abuse, National Institutes of Health. E-mail:Bfletche@mail.nih.gov (5)Patrick M. Flynn, Ph.D. is Professor of Psychology and Deputy Director of the Institute of Behavioral Research at Texas Christian University. E-mail:p.flynn@tcu.edu Article note: Correspondence should be addressed to Joseph J. Shields, Social Work, National Catholic School of Social Service, the Catholic University of America, Washington, DC 20064. E-mail: Shields@cua.edu

Because work environment is central to understanding job performance, drug counselor perceptions of their programs and their skills were examined in relation to their attitudes about innovations training and its utilization. Latent profile analysis of measures on organizational climate and staff attributes for 1047 counselors from 345 programs defined three categories of counselors--labeled as isolated, integrated, and exceptional. All had generally positive views of their professional skills, although the isolated group scored lower on scales representing professional growth and influence on peers. They were less positive about the 'climate' of programs in which they worked and were higher on stress. Program resources predicted the counselor groups, with the isolated having more limited resources. Counselor categorizations also differed in terms of workshop training experiences, with the isolated group of counselors reporting significantly less exposure, satisfaction, and program-wide use of workshop training. Keywords: Workshop training; Readiness for change; Working environment; Counselor typology; Latent profile analysis

A key goal of drug abuse treatment providers is getting their clients to engage and participate in therapeutic activities as a first step toward deriving longer-term benefits. Much research had focused on personal characteristics that relate to client engagement; program characteristics have received less attention. This study explored client and program differences in engagement ratings using data from a nationwide set of 94 outpatient drug-free treatment programs in a hierarchical linear model analysis. The results show that elements of program context, including structural features (e.g., smaller size and Joint Commission on the Accreditation of Healthcare Organizations/Commission on Accreditation of Rehabilitation Facilities accreditation) and staff's perceptions of personal efficacy, organizational climate, and communal workplace practices, relate to better overall client engagement. These findings add further evidence that treatment providers should also address the workplace environment for staff as part of quality improvement efforts. Keywords: Client engagement; Organizational factors; Program structure; Work environment; Outpatient drug-free treatment

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.addbeh.2006.11.021 Byline: George W. Joe, Patrick M. Flynn, Kirk M. Broome, D. Dwayne Simpson Keywords: Drug use expectations; Follow-up outcomes; Latent class analyses; Longitudinal assessments; Methadone drug use Abstract: Expectations about future behavior have been shown to have a positive relationship with subsequent behavior. For patients in drug treatment, recovery should manifest changes in drug use and in cognitive perceptions of being able to refrain from use. The present study identified latent patterns of the longitudinal relationship between drug use expectation and illegal drug use during treatment. Latent variable mixture modeling identified three patterns of change over successive 3-month intervals during treatment: Improvers (48%), Decliners (33%), and Continuing Users (19%). The sample consisted of 497 patients in community-based outpatient methadone treatment. The utility of the latent patterns was shown through their relationship to treatment engagement, where Continuing Users had lower counseling rapport and time in treatment. These latent patterns also differed on drug use measures at follow-up. Additional analyses of expectations with measures of opioid use, cocaine use, or criminality yielded similar latent patterns. Expectations about future drug use were found to be a useful measure of cognitive change corresponding to drug use change. Its potential as a brief treatment management tool is noted. Author Affiliation: Institute of Behavioral Research, Texas Christian University, TCU Box 298740, Fort Worth, TX 76129, United States Article Note: (footnote) [star] More information (including data collection instruments that can be downloaded without charge) is available on the Internet at www.ibr.tcu.edu, and electronic mail can be sent to ibr@tcu.edu.

Immune reconstitution inflammatory syndrome (IRIS) encompasses a variety of conditions that occur among HIV-infected patients in a temporal relationship with increases in CD4 cell count as a result of highly active antiretroviral therapy (HAART). Most conditions associated with IRIS are infectious. Malignancies, such as Kaposi's sarcoma, have also been reported. We report a case of sinusitis with presumptive inflammatory pseudotumor as a manifestation of IRIS that occurred 20 weeks after the initiation of HAART.

The combination of atazanavir (ATV) plus lopinavir/ritonavir (LPV/r) has been used in practice. However, clinical data supporting its use are limited. The objective of this study was to evaluate the efficacy and tolerability of regimens with ATV + LPV/r in protease inhibitor (PI)-susceptible and PI-resistant patients. A retrospective review of 2703 charts was performed to identify all patients who received ATV + LPV/r. From June 2003 to January 2005, 33 patients received ATV + LPV/r with nucleoside reverse trancriptase inhibitors (NRTIs) for 3 months or more. Virologic success (HIV-RNA < 400 copies per milliliter) was achieved in 30 patients (91%) in a median of 10 weeks (range, 2-68). Nineteen of the 23 patients (83%) who had ultrasensitive viral load (VL) assays were nondetectable. Among patients with 6 or more protease resistance (PR) mutations (PI-resistant), 11 of 14 (79%) achieved virologic success. Eleven of those received phenotypic testing (10 Virtual Phenotype, VircoLab, Baltimore, MD). Despite predicted phenotypic resistance to ATV (6 patients) and LPV/r (7 patients), virologic success was achieved in 4 of 6 (67%) and 4 of 7 (57%), respectively. The 3 PI-resistant patients who were virologic failures had extensive prior LPV/r use, 8-11 PR mutations, and predicted phenotypic resistance to LPV/r, but 2 of 3 had CD4 increases with ATV + LPV/r. Overall, 28 patients (85%) continue to tolerate ATV + LPV/r for a median of 32 weeks follow-up (range, 12-76). Combination ATV + LPV/r with NRTIs appears safe, tolerable, and efficacious in PI-resistant patients ([greater than or equal to] 6 PR mutations) and predicted phenotypic resistance to ATV and LPV/r. Further studies of ATV + LPV/r in HIV-treatment are warranted.

How cyclooxygenase-2 (COX-2) and its proinflammatory metabolite prostaglandin E2 (PGE2) enhance colon cancer progression remains poorly understood. We show that PGE2 stimulates colon cancer cell growth through its heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptor, EP2, by a signaling route that involves the activation of phosphoinositide 3-kinase and the protein kinase Akt by free G protein βγ subunits and the direct association of the G protein [α.sub.s] subunit with the regulator of G protein signaling (RGS) domain of axin. This leads to the inactivation and release of glycogen synthase kinase 3β from its complex with axin, thereby relieving the inhibitory phosphorylation of β-catenin and activating its signaling pathway. These findings may provide a molecular framework for the future evaluation of chemopreventive strategies for colorectal cancer., Colorectal cancer represents the third leading cause of cancer-related deaths in both men and women in the United States (1). The development of colon cancer results from the sequential accumulation [...]

Development of improved genetic traits in maize (Zea mays L.) requires robust measures to prevent pollen-mediated gene flow (PMGF) and assure isolation of new traits, whether these traits are the result of conventional breeding or of modern genetic techniques. Studies were conducted in California and Washington to evaluate the relationship of distance and temporal separation for isolation from PMGF. Kernel color was used to detect outcrossing from source plots of 0.4 to 1.2 ha in size to receptor plots planted at distances up to 750 m and planting intervals of up to 3 wk from the pollen source. Outcrossing from source to receptor plots was observable to 0.0002% (1 kernel in ≅ 500 000 kernels). Increasing temporal separation reduced the distance required to achieve genetic isolation. Outcrossing was, THE MAIZE PLANT is one of mankind's most productive technological innovations, multiplying the weight of a single seed from 500 to 1000 times in each growing cycle, while producing that [...]

Author(s): Per H. Mygind [1, 8]; Rikke L. Fischer [2, 8]; Kirk M. Schnorr [1, 8]; Mogens T. Hansen [1]; Carsten P. Sönksen [1]; Svend Ludvigsen [3]; Dorotea Raventós [1]; [...]

The processing of constitutive poly(A) sites is examined in detail along with the fundamental mechanisms responsible for the regulation of alternative ploy(A) site selection. The recognition of three distinct sequence elements by CFI(sub m), CPSF, and CstF suggests that vertebrate ploy(A) site definition is mechanistically more similar to that of yeast and plants than anticipated.

Advanced power systems for electromagnetic propulsion depend on capacitor banks as the first stage of pulsed power. Significant electrical energy is required to support a number of anticipated launch applications. In support of successful integration of these technologies, TPL has developed an improved dielectric material for high energy density capacitors. Recent developments have led to a novel dielectric film that can be fabricated and incorporated into innovative, high-voltage designs using conventional manufacturing processes. Full-scale (100 kJ) capacitors incorporating TPL's established film technology is projected to provide an energy density between 3.5 and 4.0 J/[cm.sup.3]. Index Terms--Capacitors, dielectrics, polymer/paper, siloxane.

This study examined patient and program factors that influenced the receipt of scheduled supportive services in the Drug Abuse Treatment Outcome Studies (DATOS). Patients (N = 2,932) in 21 long-term residential (LTR) programs, 27 outpatient methadone treatment (OMT), and 25 outpatient drug-free programs were interviewed at admission and at 3 months during treatment. A hierarchical regression analysis was used to examine the relationship between patient-level and program-level factors associated with receiving supportive services in seven categories (medical, psychological, family, legal, educational, vocational, and financial). LTR patients received more services on average than outpatients (especially OMT), but patients overall received few services in the first 3 months of treatment. The patient-level likelihood of receiving services was related to being female and to having higher problem severity at intake. At the program level, outpatient clientele with higher problem severity received more services if they entered a program whose other enrolled patients were less troubled on average. Keywords. Treatment service utilization; Supportive services; Patient and program factors

Patient attributions for their own long-term recovery were obtained in a 5-year followup of 432 admissions to 18 outpatient methadone treatment programs. Subjects were classified into two groups--recovering and non-recovering--strictly defined and based on both biological and self-report measures of no opioid or cocaine use, less than daily use of alcohol, and no arrests or illegal activity during the year prior to interview. The 28% who were in recovery at Year 5 reported that they had relied primarily upon personal motivation, treatment experiences, religion/spirituality, family, and their job/career. Particular value was placed on the support from family and close friends, indicating the importance of stronger efforts to develop social networks for support of drug-free functioning, especially among patients who lack these resources of need them strengthened. More information is available on the Internet at www.ibr.tcu.edu. Keywords: Recovery; Opioids; Addiction; Methadone treatment; Treatment outcomes

Brief but comprehensive instruments measuring patient motivation, psychosocial functioning, treatment process, social network support, and services received are needed for monitoring drug abuse treatment delivery and patient progress. Combining this information across patients within a program also provides useful indicators about institutional composition and functioning. Consequently, the same assessment tools can be used to identify areas where treatment protocols need to be changed, and to monitor improvements following such changes. The Texas Christian University (TCU) Client Evaluation of Self and Treatment (CEST) (1) is a 144-item self-rating instrument that includes 16 scales measuring patient functioning and treatment perceptions. Psychometric properties (including reliability and construct validity) of the scales are examined in this article, based on patient samples drawn from 87 programs that participated in a series of staff training workshops. Acceptable reliabilities (.70 or above) were generally reported, and construct validity was also demonstrated (although the confirmatory factor analyses suggested some item pools could represent more than one factor). Prediction analyses were conducted using selected scales from each measurement domain to illustrate their sensitivity to treatment program contexts. Keywords: Psychosocial functioning; Organizational assessment; Patient monitoring; Program monitoring; Reliability; Validity

This article provides an evaluation of the Ohio Scales, a psychometric tool used to forecast treatment outcomes for children and teenagers receiving mental health services. The authors conclude that initial studies demonstrate that the Ohio Scales is a valid and effective tool, however, they suggest more studies be conducted.

Self-efficacy has been shown to be related to outcomes from interventions for alcohol and tobacco abuse but relatively little attention has been focused on it in evaluations of treatment for illicit drug abuse. Almost no research has examined offenders involved with drugs. The current study, therefore, adapted the Alcohol Abstinence Self-efficacy Scale of DiClemente, Carbonari, Montgomery, and Hughes and administered it to 250 probationers mandated to 6 months of residential treatment. With some modifications, confirmatory factory models replicated four previously reported dimensions, e.g., Negative Affect, Social/Positive, Physical and Other Concerns, Cravings and Urges. Findings also indicated high construct validity for the Alcohol Abstinence Self-efficacy Scale as adapted here. Studies are needed to examine the use of self-efficacy as a prospective measure of treatment progress and to explore its association with outcomes from corrections-based treatment.

A study of clients in long-term residential drug treatment facilities examined the combined impact of internal and external factors on engagement and retention. Results indicate little significant interaction effect between treatment readiness and legal pressure.

This study examined the relationship between perceptions of parent-child relations in the family of origin and antisocial tendency in a sample of drug-addicted adults. Data included retrospective accounts of childhood family factors, adolescent antisocial tendency, and self-reported hostility and risk-taking prior to treatment entry. A developmental model was tested that included adolescent antisocial tendency as a mediator of the relationship between childhood parenting factors and adulthood antisocial tendency. The effects of parental support and conflict were found to operate primarily through adolescent measures. Specifically, lower levels of parental support and higher levels of conflict with parents predicted greater adolescent antisocial tendency, which in turn predicted more hostility and risk-taking in adulthood. Thus, parental support appears to serve as a buffer against deviant behavior and drug use., INTRODUCTION Drug-dependent adults enter treatment with a variety of psychosocial problems that can interfere with treatment efforts. In addition to low self-esteem and depression, many drug-dependent clients report a history [...]

Research was conducted to analyze rat tracheal smooth muscle actin and myosin expression in cultured airway smooth muscle cells. Results indicate through protein and mRNA analyses that airway SMC in culture continue to express several of the SM-specific contractile proteins seen in vivo. Findings also demonstrate that the level of expression of markers is different just like in vascular cells, depending on growth state.

N. S. Jacobson and P. Truax's (1991) method for evaluating the clinical significance of client change has gained some prominence in psychotherapy outcome research. However, little has been done to investigate the validity of this methodology. This study addresses this limitation by comparing (a) the perceived level of change (as subjectively reported from 3 distinct perspectives) across outcome groupings based on Jacobson and Truax's reliable change index (RCI) and (b) subjective reports of therapeutic alliance and satisfaction across outcome groupings. The results of these comparisons indicate that the RCI is effective in identifying those who make reliable improvement in therapy but is less effective in differentiating between no-changers and deteriorators. In addition, the relationship between treatment outcome and satisfaction with service is questioned.