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Feliciano C,Robnett B,Komaie G
Department of Sociology, University of California, Irvine, CA 92697-5100, USA. felician@uci.edu
Gendered racial exclusion among White internet daters.
Soc Sci Res. 2009 Mar;38(1):39-54
Acceptance by the dominant group reveals the current standing of racial groups in the U.S. hierarchy, as well as the possibility for assimilation. However, few researchers have addressed the gendered nature of racial preferences by whites. We examine whites' exclusion of blacks, Latinos, Asians, Middle Easterners, East Indians and Native Americans as possible dates, using a sample of profiles collected from an internet dating website. We find that white men are more willing than white women to date non-whites in general, yet, with the exception of their top two preferences for dates, whites and Latinos, the racial hierarchies of males and females differ. Among daters with stated racial preferences, white men are more likely to exclude blacks as possible dates, while white women are more likely to exclude Asians. We argue that exclusion relates to racialized images of masculinity and femininity, and shapes dating and marriage outcomes, and thus minority groups' possibilities for full social incorporation.
PMID: 19569291

Burke MK,Rose MR
Department of Ecology and Evolutionary Biology, University of California, Irvine, CA 92617-2525, USA. burkem@uci.edu
Experimental evolution with Drosophila.
Am J Physiol Regul Integr Comp Physiol. 2009 Jun;296(6):R1847-54
Experimental evolution is a powerful approach that can be used for the study of adaptation. Evolutionary biologists often use Drosophila as a model organism in experiments that test theories about the evolution of traits related to fitness. Such evolution experiments can take three forms: direct selection for a trait of interest; surveys of traits of interest in populations selected for other traits; and reverse selection. We review some of the Drosophila experiments that have provided insight into both the evolution of particular physiological traits and the correlations between physiological and life history traits, focusing on stress resistance. The most common artifacts that can obscure the results from evolution experiments are discussed. We also include a treatment of genomic technologies that are now available for the Drosophila model. The primary goal of this review is to introduce the kind of experimental evolution strategies and technologies that evolutionary physiologists might use in the future.
PMID: 19339679

Suding KN,Hobbs RJ
Ecology and Evolutionary Biology, 321 Steinhaus Hall, University of California, Irvine, Irvine, CA 92697-2525, USA. ksuding@uci.edu
Threshold models in restoration and conservation: a developing framework.
Trends Ecol Evol. 2009 May;24(5):271-9
The recognition that a system can appear resilient to changes in the environment, only to reach a critical threshold of rapid and unexpected change, is spurring work to apply threshold models in conservation and restoration. Here we address the relevance of threshold models to habitat management. Work to date indicates these concepts are highly applicable: human impacts can widen the range of habitats where threshold dynamics occur and shift communities into new states that are difficult to reverse. However, in many applied settings, threshold concepts are being adopted without evaluation of evidence and uncertainty. We suggest a framework for incorporating threshold models that reflects an emphasis on applicability to decision making and management on relatively short timescales and in human-impacted systems.
PMID: 19269057

Vilberg KL,Rugg MD
Department of Neurobiology and Behavior, Center for the Neurobiology of Learning and Memory, University of California at Irvine, Irvine, CA 92697-3800, USA. kvilberg@uci.edu
Functional significance of retrieval-related activity in lateral parietal cortex: Evidence from fMRI and ERPs.
Hum Brain Mapp. 2009 May;30(5):1490-501
The present study addressed the question whether neural activity in left lateral parietal cortex is modulated by amount of information recollected. In two experiments (one using fMRI and the other ERPs), subjects first studied pairs of pictures presented for either 1 or 6 s. They then performed a standard "Remember/Know" recognition memory test in which the old items comprised one of the pictures from each studied pair. In both experiments, a surprise posttest indicated that subjects recollected more details about the study presentation of the items presented for the longer duration. In the fMRI experiment, recollection- and familiarity-based recognition elicited activity in distinct cortical networks. Additionally, recollection-related activity in left inferior parietal cortex was of greater magnitude for test items presented for 6 s than for 1 s. In the ERP study the "left-parietal old/new effect"-a putative correlate of successful recollection-was likewise modulated by amount of information retrieved. Together, these findings provide further support for dual-process models of recognition memory and add weight to the proposal that retrieval-related activity in left inferior parietal cortex reflects processes supporting the online representation of retrieved episodic information.
PMID: 18649352

Milne RL,Benítez J,Nevanlinna H,Heikkinen T,Aittomäki K,Blomqvist C,Arias JI,Zamora MP,Burwinkel B,Bartram CR,Meindl A,Schmutzler RK,Cox A,Brock I,Elliott G,Reed MW,Southey MC,Smith L,Spurdle AB,Hopper JL,Couch FJ,Olson JE,Wang X,Frederi
Affiliations of authors: Genetic and Molecular Epidemiology Group (RLM) and Human Genetics Group (JBe), Spanish National Cancer Research Centre [CNIO], Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras [CIBERER], Madrid, Spain (JBe); Department of Obstetrics and Gynecology (HN, TH), Department of Clinical Genetics (KA), and Department of Oncology (CB), Helsinki University Central Hospital, Helsinki, Finland; Servicio de Cirugía General y Especialidades, Hospital Monte Naranco, Oviedo, Spain (JIA); Servicio de Oncología Médica, Hospital Universitario La Paz, Madrid, Spain (MPZ); Department of Obstetrics and Gynecology (BB) and Institute of Human Genetics (CRB), University of Heidelberg, Heidelberg, Germany; Molecular Epidemiology Group (BB) and Division of Cancer Epidemiology (JC-C), German Cancer Research Center [DKFZ]), Heidelberg, Germany; Department of Gynaecology and Obstetrics, Technical University of Munich, Munich, Germany (AMe); Department of Gynaecology and Obstetrics, Clinical Center University of Cologne, Köln, Germany (RKS); Institute for Cancer Studies (AC, IB, GE) and Academic Unit of Surgical Oncology (MWRR), Sheffield University Medical School, Sheffield, UK; Centre for Molecular, Environmental, Genetic and Analytic Epidemiology (JLH, DRE) and Department of Pathology (MCS, LS), University of Melbourne, Victoria, Australia; Department of Laboratory Medicine and Pathology (FJC, XW) and Department of Health Sciences Research (JEO, ZF), Mayo Clinic, Rochester, MN; Department of Obstetrics and Gynaecology (TD, PS, PHi, NVB, MBe) and Department of Radiation Oncology (MBr, NVB), Hannover Medical School, Hannover, Germany; Department of Human Genetics (PD), Department of Pathology (PD), Department of Clinical Genetics (CJvA), and Department of Surgery (RAEMT), Leiden University Medical Centre, Leiden, the Netherlands; Department of Medical Oncology, Rotterdam Family Cancer Clinic, Erasmus MC-Daniel den Hoed Cancer Center, Rotterdam, the Netherlands (CS); Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden (PHa, KC); Human Genetics Laboratory, Genome Institute of Singapore, Singapore (JLi, YL); Department of Oncology (SA, AMD, MM, PDPP), Department of Public Health and Primary Care (PDPP), University of Cambridge, Cambridge, UK; Division of Genetics and Population Health (GC-T, JBee, ABS), Queensland Institute of Medical Research (AOCS), Brisbane, Australia; Peter MacCallum Cancer Center, Melbourne, Australia (kConFab, AOCS); N.N. Alexandrov Research Institute of Oncology and Medical Radiology, Minsk, Belarus (NVB, NNA, IVZ); Department of Epidemiology, University of California Irvine, Irvine, CA (HA-C, AZ); Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany (HB, CJ); University of Tübingen, Tübingen, Germany (HB, CJ); Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany (Y-DK); Institute of Pathology, University of Bonn, Bonn, Germany (SHa); University Breast Center (PAF, RS, MWB) and Institute of Human Genetics (ABE), University Hospital Erlangen, Erlangen, Germany; Department of Gynecology and Obstetrics, David Geffen School of Medicine, Division of Hematology and Oncology, University of California at Los Angeles, Los Angeles, CA (PAF); Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia (GGG, GS, LB); Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, London, UK (OF, NJ); Cancer Research UK Epidemiology and Genetics Group, London School of Hygiene and Tropical Medicine, London, UK (OF, IdSS, JP); Section of Cancer Genetics (CT, SHi, AR, NR), Institute of Cancer Research (JP), Sutton, Surrey, UK; Department of Clinical Biochemistry and Department of Breast Surgery, Herlev University Hospital, University of Copenhagen, Denmark (BGN, SEB, HF); Seoul National University College of Medicine, Seoul, Korea (DK, K-YY, D-YN); Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Kuopio (AMa, V-MK); Department of Oncology and Department of Pathology, University Hospital of Kuopio and Biocenter Kuopio, Kuopio, Finland (VK); Department of Oncology, Vaasa Central Hospital, Vaasa, Finland (VK); Division of Cancer Epidemiology and Genetics (MG-C, SC) and Hormonal and Reproductive Epidemiology Branch (LAB), National Cancer Institute, Rockville, MD; Department of Cancer Epidemiology and Prevention, M. Sklodowska-Curie Memorial Cancer Center & Institute of Oncology, Warsaw, Poland (JLis); Department of Gynecology and Obstetrics, Ulm Medical School, Ulm, Germany (SW-G); Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan (C-YS, H-CW); Department of Surgery, Tri-Service General Hospital, Taipei, Taiwan (J-CY); Department of Surgery, Changhua Christian Hospital, Changhua, Taiwan (S-TC); Institute of Biochemistry and Genetics, Ufa Scientific Center of Russian Academy of Sciences, Ufa, Russia (MBe, EK); Department of Medical Genetics, Yakut Research Center of Russian Academy of Medical Sciences, Yakutsk, Russia (TN); Cancer Research UK Genetic Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK (MKH, JM, RP, DFE).
Risk of Estrogen Receptor-Positive and -Negative Breast Cancer and Single-Nucleotide Polymorphism 2q35-rs13387042.
J Natl Cancer Inst. 2009 Jun 30;:
Background A recent genome-wide association study identified single-nucleotide polymorphism (SNP) 2q35-rs13387042 as a marker of susceptibility to estrogen receptor (ER)-positive breast cancer. We attempted to confirm this association using the Breast Cancer Association Consortium. Methods 2q35-rs13387042 SNP was genotyped for 31 510 women with invasive breast cancer, 1101 women with ductal carcinoma in situ, and 35 969 female control subjects from 25 studies. Odds ratios (ORs) were estimated by logistic regression, adjusted for study. Heterogeneity in odds ratios by each of age, ethnicity, and study was assessed by fitting interaction terms. Heterogeneity by each of invasiveness, family history, bilaterality, and hormone receptor status was assessed by subclassifying case patients and applying polytomous logistic regression. All statistical tests were two-sided. Results We found strong evidence of association between rs13387042 and breast cancer in white women of European origin (per-allele OR = 1.12, 95% confidence interval [CI] = 1.09 to 1.15; P(trend) = 1.0 x 10(-19)). The odds ratio was lower than that previously reported (P = .02) and did not vary by age or ethnicity (all P >/= .2). However, it was higher when the analysis was restricted to case patients who were selected for a strong family history (P = .02). An association was observed for both ER-positive (OR = 1.14, 95% CI = 1.10 to 1.17; P = 10(-15)) and ER-negative disease (OR = 1.10, 95% CI = 1.04 to 1.15; P = .0003) and both progesterone receptor (PR)-positive (OR = 1.15, 95% CI = 1.11 to 1.19; P = 5 x 10(-14)) and PR-negative disease (OR = 1.10, 95% CI = 1.06 to 1.15; P = .00002). Conclusion The rs13387042 is associated with both ER-positive and ER-negative breast cancer in European women.
PMID: 19567422

Wang TH,Kruggel F,Rugg MD
Center for the Neurobiology of Learning and Memory, and Department of Neurobiology and Behavior, University of California, Irvine, Irvine, CA 92697-3800, United States. tracy.wang@uci.edu
Effects of advanced aging on the neural correlates of successful recognition memory.
Neuropsychologia. 2009 Apr;47(5):1352-61
Functional neuroimaging studies have reported that the neural correlates of retrieval success (old>new effects) are larger and more widespread in older than in young adults. In the present study we investigated whether this pattern of age-related 'over-recruitment' continues into advanced age. Using functional magnetic resonance imaging (fMRI), retrieval-related activity from two groups (N=18 per group) of older adults aged 84-96 years ('old-old') and 64-77 years ('young-old') was contrasted. Subjects studied a series of pictures, half of which were presented once, and half twice. At test, subjects indicated whether each presented picture was old or new. Recognition performance of the old-old subjects for twice-studied items was equivalent to that of the young-old subjects for once-studied items. Old>new effects common to the two groups were identified in several cortical regions, including medial and lateral parietal and prefrontal cortex. There were no regions where these effects were of greater magnitude in the old-old group, and thus no evidence of over-recruitment in this group relative to the young-old individuals. In one region of medial parietal cortex, effects were greater (and only significant) in the young-old group. The failure to find evidence of over-recruitment in the old-old subjects relative to the young-old group, despite their markedly poorer cognitive performance, suggests that age-related over-recruitment effects plateau in advanced age. The findings for the medial parietal cortex underscore the sensitivity of this cortical region to increasing age.
PMID: 19428399

Pyles JA,Grossman ED
Center for Cognitive Neuroscience & Department of Cognitive Sciences, University of California, Irvine, California 92697-5100, United States. jpyles@uci.edu
Neural adaptation for novel objects during dynamic articulation.
Neuropsychologia. 2009 Apr;47(5):1261-8
Human observers readily identify objects with moving parts, and recognize their underlying structure even when the component parts undergo complex movement. This suggests the existence of neural representations that are invariant to motion and state of articulation, which together allow our visual system to maintain 'object constancy'. Ventral temporal cortex has previously been implicated in object perception and in coding object identity, but it is unclear where this is achieved when objects undergo motion-driven shape changes. In the present study, we use fMRI adaptation to probe the neural response properties when subjects view dynamic novel objects. Our results reveal neural selectivity for novel objects in the LOC region of the occipito-temporal lobe, even when those objects are viewed as moving and articulating. We also identify a bilateral area of posterior fusiform outside of the LOC with neural populations invariant to changes in the articulatory state of an object, a critical feature of object constancy. These results demonstrate the functional importance of ventral temporal cortex in the perception of moving objects, and the existence of neural populations coding for object constancy across movement and articulation.
PMID: 19428389

Wilson SE,O'Riordan W,Hopkins A,Friedland HD,Barriere SL,Kitt MM,
Department of Surgery, University of California, Irvine School of Medicine, Orange, CA, USA. wilsonse@uci.edu
Telavancin versus vancomycin for the treatment of complicated skin and skin-structure infections associated with surgical procedures.
Am J Surg. 2009 Jun;197(6):791-6
BACKGROUND: We compared telavancin with vancomycin for the treatment of complicated skin and skin-structure infections (cSSSI) caused by Gram-positive bacteria. METHODS: This was a retrospective analysis of clinical and microbiologic efficacy assessed at test-of-cure (7 to 14 days after completing therapy) in 194 patients from 2 randomized, double-blind clinical trials comparing telavancin (10 mg/kg intravenous [IV] every 24 hours; n = 101) with vancomycin (1 g IV every 12 hours; n = 93) for the treatment of cSSSI. RESULTS: Baseline characteristics were similar for both treatment groups. Clinical cure and microbiologic eradication rates demonstrated consistent trends favoring telavancin over vancomycin; however, the differences were not statistically significant. The incidence of adverse events was mostly similar between groups. CONCLUSIONS: The efficacy of telavancin was at least equivalent to that of vancomycin for the treatment of cSSSI. These data suggest that telavancin may be a useful alternative for treatment of cSSSI caused by S. aureus, particularly MRSA.
PMID: 19095213

Kosins AM,McConnell MP,Mendoza C,Shepard B,Scholz T,Evans GR,Keirstead HS
Department of Tissue Engineering and Regenerative Medicine, Reeve-Irvine Research Center, Aesthetic and Plastic Surgery Institute, University of California, Irvine, Calif 92868, USA. akosins@uci.edu
A novel model to measure the regenerative potential of the peripheral nervous system after experimental immunological demyelination.
Plast Reconstr Surg. 2009 Jun;123(6):1688-96
BACKGROUND: Immunological demyelination is a proposed strategy to improve nerve regeneration in the peripheral nervous system. To investigate the remyelinating potential of Schwann cells in vivo in the peripheral nervous system, the authors have reproduced and expanded upon a novel model of immunological demyelination in the adult rat sciatic nerve. The authors demonstrate (1) the peripheral nervous system's quantitative, regenerative response to immunological demyelination and (2) whether Schwann cells within a region of demyelination are induced to divide in the presence of demyelinated axons. METHODS: The sciatic nerves of female Sprague-Dawley rats were exposed and injected with demyelinating agent bilaterally. At 3 days (n = 3), 7 days (n = 3), and 14 days (n = 3), the animals were euthanized for histological evaluation. A second group of animals (n = 3) was similarly injected with demyelinating agent and then exposed to bromodeoxyuridine between 48 and 72 hours after the onset of demyelination. These animals were euthanized soon after the last injection of bromodeoxyuridine. The tissue was analyzed for Schwann cells (labeled with antibodies to S100) and bromodeoxyuridine assay. RESULTS: A single epineural injection of complement proteins plus antibodies to galactocerebroside resulted in demyelination followed by Schwann cell remyelination. At 3 days after injection, peripheral nerve demyelination and Schwann cell proliferation were evident. Maximum demyelination was seen at 7 days; however, Schwann cell proliferation and remyelination peaked at 14 days after injection. CONCLUSIONS: These studies demonstrate an immunological model of demyelination and remyelination in the peripheral nervous system and quantitatively measure regenerative potential. This model will be used to isolate nerve segments and to measure their regenerative potential when given demyelinating agent after acute contusion and transection injuries.
PMID: 19483567

Hawkins JS,Casey BM,Lo JY,Moss K,McIntire DD,Leveno KJ
Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, Texas, USA. jshawkin@uci.edu
Weekly compared with daily blood glucose monitoring in women with diet-treated gestational diabetes.
Obstet Gynecol. 2009 Jun;113(6):1307-12
OBJECTIVE: To estimate whether daily blood glucose self-monitoring reduces macrosomia when compared with weekly office testing in women with gestational diabetes. METHODS: Between January 1991 and December 1997, standard treatment at our hospital for women with diet-treated gestational diabetes included routine office monitoring of fasting blood glucose. Beginning in January 1998, blood glucose self-monitoring (four times daily) became the standard management. Women with diet-treated gestational diabetes who underwent routine office-based monitoring of fasting glucose values were compared with similar women who used blood glucose self-monitoring. The outcomes of interest were birthweight at or above 4,000 g and large for gestational age (LGA) in relation to the method of blood glucose self-monitoring. RESULTS: A total of 315 women used daily blood glucose self-monitoring, and they were compared with 675 women with weekly office-based glucose testing. Women with daily blood glucose self-monitoring had fewer macrosomic (29.5% compared with 21.9%, P=.013) and LGA neonates (34.4% compared with 23.1%, P < or = .001) and gained significantly less weight (median 0.56, interquartile range 0.22-1.08 lb per week compared with 0.74, interquartile range 0.33-1.17 lb per week, P=.009). CONCLUSION: Daily blood glucose self-monitoring, compared with weekly office-based testing, is associated with a reduction in the incidence of macrosomia. LEVEL OF EVIDENCE: II.
PMID: 19461427

Odgers CL,Mulvey EP,Skeem JL,Gardner W,Lidz CW,Schubert C
Department of Psychology and Social Behavior, University of California-Irvine, Irvine, CA 92697-7085, USA. codgers@uci.edu
Capturing the ebb and flow of psychiatric symptoms with dynamical systems models.
Am J Psychiatry. 2009 May;166(5):575-82
OBJECTIVE: Psychiatric symptoms play a crucial role in psychology and psychiatry. However, little is known about how dimensions of symptoms--other than symptom level--relate to psychiatric outcomes. Until recently, methods for measuring dynamic aspects of symptoms have not been available to clinicians or researchers. The authors sought to test whether systematic patterns of change in psychiatric symptoms can be recovered across weekly assessments of individuals at high risk for violence. A secondary objective was to explore whether dynamic features of symptoms (specifically, oscillation speed and dysregulation) are concurrently associated with violence, an important indicator of functional impairment for these individuals. METHOD: Participants (N=132) were drawn from a sample of patients evaluated at the emergency room of an urban psychiatric hospital. Patients actuarially classified as being at high risk for violence were eligible for participation in the study. Participants and collateral informants were interviewed weekly for 26 weeks following an acute psychiatric evaluation. Psychiatric symptoms were assessed using the Brief Symptom Inventory. Measures of symptom fluctuation and regulation were derived using dynamical systems models. Involvement in violence was assessed using self, informant, and official reports. RESULTS: Individuals' symptom dynamics were recovered by a linear oscillator model that described how quickly symptoms oscillated and whether symptoms were amplifying or moving back toward equilibrium across time. Patterns of rapid symptom fluctuation and symptom amplification were concurrently associated with violence. CONCLUSIONS: Psychiatric researchers and clinicians have long been interested in adopting more dynamic approaches to understanding symptom change. This study is the first to demonstrate that systematic fluctuations in symptom patterns may be captured by dynamic models. Moreover, the concurrent association between symptom dynamics and violence suggests avenues for future research to test how features of symptom fluctuation could affect behavior.
PMID: 19369320

Guenther GG,Edinger AL
Department of Developmental and Cell Biology, University of California-Irvine, Irvine, CA 92697-2300, USA.
A new take on ceramide: starving cells by cutting off the nutrient supply.
Cell Cycle. 2009 Apr 15;8(8):1122-6
Ceramide generation is increased by a broad array of signals. In general, ceramide limits cell survival and proliferation and promotes differentiation and senescence. Despite its role in the pathogenesis of multiple human diseases, ceramide's mechanism of action remains poorly defined. Understanding how this sphingolipid modulates cell physiology is therefore an important goal. Building on prior observations that ceramide induces autophagy, we demonstrate that ceramide kills cells by inducing severe bioenergetic stress secondary to nutrient transporter downregulation. In support of this model, maintaining nutrient access blocks ceramide-induced autophagy and cell death. This bioenergetic mechanism of action may explain the increased sensitivity of cancer cells to ceramide. Starvation induces quiescence in normal cells. Tumor cells, in contrast, carry oncogenic mutations that block the switch to catabolism and prevent a reduction in metabolic demand leading to a bioenergetic crisis when nutrients become scarce. We propose that the non-lethal effects of ceramide might also stem from ceramide-induced starvation. While severe nutrient stress kills cells, mild nutrient limitation slows proliferation and may contribute to the induction of senescence. In sum, our new model for ceramide action suggests that regulated nutrient transporter expression may play a previously unappreciated role in cancer and other diseases where ceramide metabolism is altered.
PMID: 19282666

Nguyen NT,Hinojosa MW,Smith BR,Gray J,Varela E
Department of Surgery, University of California, Irvine Medical Center, 333 City Blvd. West, Suite 850, Orange, CA 92868, USA. ninhn@uci.edu
Improvement of restrictive and obstructive pulmonary mechanics following laparoscopic bariatric surgery.
Surg Endosc. 2009 Apr;23(4):808-12
BACKGROUND: Morbidly obese patients often have impaired respiratory mechanics leading to restrictive and obstructive lung diseases. Weight loss after bariatric surgery has been shown to improve or resolve many obesity-related comorbidities. However, few studies have examined long-term changes in pulmonary mechanics after bariatric surgery. We hypothesize that pulmonary function improves after surgically induced weight loss. METHODS: We examined the pulmonary function of 104 morbidly obese patients who underwent laparoscopic gastric bypass or gastric banding. Pulmonary studies, including forced expiratory volume in 1 s (FEV(1)), forced vital capacity (FVC), peak expiratory flow (PEF), and forced expiratory volume at midexpiratory phase (FEV(25-75%)) were measured preoperatively and at 3-month intervals. All results are expressed as a percentage of the baseline values. RESULTS: There were 80 females and 24 males with a mean age of 41 years. The mean body mass index was 48 kg/m(2). The mean percentage of excess body weight loss at 12 months was 54%. At 12 months postoperatively, restrictive pulmonary mechanics significantly improved as demonstrated by an increase in the FEV(1) to 112% of baseline value, increase in the FVC to 109% of baseline value, increase in the PEF to 115% of baseline value, and increase in the FEV(25-75%) to 130% of baseline value. Additionally, the percentage of patients with obstructive lung pattern (FEV(1)/FVC ratio less than 0.8) decreased from 9.6% preoperatively to 1.9% postoperatively (p=0.03). CONCLUSIONS: Weight loss after laparoscopic gastric bypass significantly improves restrictive and obstructive respiratory mechanics. The improvements were observed as early as 3 months postoperatively.
PMID: 18806943

Silman E,Langdorf MI,Rudkin S,Lotfipour S
Department of Emergency Medicine, University of California Irvine School of Medicine.
Images in Emergency Medicine: Pediatric Spinal Cord Injury without Radiographic Abnormality.
West J Emerg Med. 2008 May;9(2):124
PMID: 19561722

Milenkovi? T,Filippis I,Lappe M,Przulj N
Department of Computer Science, University of California Irvine, Irvine, CA, USA.
Optimized null model for protein structure networks.
PLoS One. 2009;4(6):e5967
Much attention has recently been given to the statistical significance of topological features observed in biological networks. Here, we consider residue interaction graphs (RIGs) as network representations of protein structures with residues as nodes and inter-residue interactions as edges. Degree-preserving randomized models have been widely used for this purpose in biomolecular networks. However, such a single summary statistic of a network may not be detailed enough to capture the complex topological characteristics of protein structures and their network counterparts. Here, we investigate a variety of topological properties of RIGs to find a well fitting network null model for them. The RIGs are derived from a structurally diverse protein data set at various distance cut-offs and for different groups of interacting atoms. We compare the network structure of RIGs to several random graph models. We show that 3-dimensional geometric random graphs, that model spatial relationships between objects, provide the best fit to RIGs. We investigate the relationship between the strength of the fit and various protein structural features. We show that the fit depends on protein size, structural class, and thermostability, but not on quaternary structure. We apply our model to the identification of significantly over-represented structural building blocks, i.e., network motifs, in protein structure networks. As expected, choosing geometric graphs as a null model results in the most specific identification of motifs. Our geometric random graph model may facilitate further graph-based studies of protein conformation space and have important implications for protein structure comparison and prediction. The choice of a well-fitting null model is crucial for finding structural motifs that play an important role in protein folding, stability and function. To our knowledge, this is the first study that addresses the challenge of finding an optimized null model for RIGs, by comparing various RIG definitions against a series of network models.
PMID: 19557139

Motoyama S,Sarai M,Harigaya H,Anno H,Inoue K,Hara T,Naruse H,Ishii J,Hishida H,Wong ND,Virmani R,Kondo T,Ozaki Y,Narula J
Department of Cardiology, Fujita Health University School of Medicine, Toyoake, Japan; Division of Cardiology, University of California Irvine School of Medicine, Irvine, California.
Computed tomographic angiography characteristics of atherosclerotic plaques subsequently resulting in acute coronary syndrome.
J Am Coll Cardiol. 2009 Jun 30;54(1):49-57
OBJECTIVES: In a computed tomographic (CT) angiography study, we identified the characteristics of atherosclerotic lesions that were associated with subsequent development of acute coronary syndrome (ACS). BACKGROUND: The CT characteristics of culprit lesions in ACS include positive vessel remodeling (PR) and low-attenuation plaques (LAP). These 2 features have been observed in the lesions that have already resulted in ACS, but their prospective relation to ACS has not been previously described. METHODS: In 1,059 patients who underwent CT angiography, atherosclerotic lesions were analyzed for the presence of 2 features: PR and LAP. The remodeling index, and plaque and LAP areas and volumes were calculated. The plaque characteristics of lesions resulting in ACS during the follow-up of 27 +/- 10 months were evaluated. RESULTS: Of the 45 patients showing plaques with both PR and LAP (2-feature positive plaques), ACS developed in 10 (22.2%), compared with 1 (3.7%) of the 27 patients with plaques displaying either feature (1-feature positive plaques). In only 4 (0.5%) of the 820 patients with neither PR nor LAP (2-feature negative plaques) did ACS develop. None of the 167 patients with normal angiograms had acute coronary events (p < 0.001). ACS was independently predicted by PR and/or LAP (hazard ratio: 22.8, 95% confidence interval: 6.9 to 75.2, p < 0.001). Among 2- or 1-feature positive segments, those resulting in ACS demonstrated significantly larger remodeling index (126.7 +/- 3.9% vs. 113.4 +/- 1.6%, p = 0.003), plaque volume (134.9 +/- 14.1 mm(3) vs. 57.8 +/- 5.7 mm(3), p < 0.001), LAP volume (20.4 +/- 3.4 mm(3) vs. 1.1 +/- 1.4 mm(3), p < 0.001), and percent LAP/total plaque area (21.4 +/- 3.7 mm(2) vs. 7.7 +/- 1.5 mm(2), p = 0.001) compared with segments not resulting in ACS. CONCLUSIONS: The patients demonstrating positively remodeled coronary segments with low-attenuation plaques on CT angiography were at a higher risk of ACS developing over time when compared with patients having lesions without these characteristics.
PMID: 19555840

Herscu G,Wilson SE
Department of Surgery, University of California, Irvine Medical Center, Orange, CA 92868, USA. gherscu@uci.edu
Prosthetic infection: lessons from treatment of the infected vascular graft.
Surg Clin North Am. 2009 Apr;89(2):391-401, viii
Surgical prosthetics provide unquestioned benefit to patients in maintenance of life and limb. However, complications associated with prosthetic devices continue to represent a significant source of morbidity and mortality. Even as the surgeon becomes more adept at management of infections, the bacterial characteristics change in favor of increased virulence and greater resistance to antimicrobials. Excision or retention of the prosthesis depends on the time of presentation, the microbial isolates recovered, and the extent of surrounding tissue destruction. Recent work shows improving results with in situ replacement.
PMID: 19281890

Charvet CJ,Striedter GF
Department of Neurobiology & Behavior and Center for the Neurobiology of Learning & Memory, University of California, Irvine, California 92697, USA. ccharvet@uci.edu
Developmental origins of mosaic brain evolution: Morphometric analysis of the developing zebra finch brain.
J Comp Neurol. 2009 May 10;514(2):203-13
In adult zebra finches (Taeniopygia guttata), the telencephalon occupies 64% of the entire brain. This fraction is similar to what is seen in parrots, but many other birds possess a significantly smaller telencephalon. The aim of the present study was to determine the developmental time course and cellular basis of telencephalic enlargement in zebra finches, and then to compare these findings with what is known about telencephalic enlargement in other birds. To this end we estimated the volumes of all major brain regions from serial sections in embryonic and post-hatching zebra finches. We also labeled proliferating cells with antibodies against proliferating cell nuclear antigen and phosphorylated histone H3. An important finding to emerge from this work is that the telencephalon of zebra finches at hatching contains a thick proliferative subventricular zone (SVZ) that extends from the subpallium into the dorsal pallium. The data also show that the onset and offset of telencephalic neurogenesis are both delayed in zebra finches relative to quail (Galliformes). This delay in neurogenesis, in conjunction with the expanded SVZ, probably accounts for most of the telencephalic enlargement in passerines such as the zebra finch. In addition, passerines enlarged their telencephalon by decreasing the proportional size of their midbrain tectum. Because the presumptive tectum is proportionally smaller in zebra finches than quail before neurogenesis begins, this difference in tectum size cannot be due to evolutionary alterations in neurogenesis timing. Collectively these findings indicate that several different developmental mechanisms underlie the evolution of a large telencephalon in passerines.
PMID: 19266567

Kasof J
Department of Psychology and Social Behavior, School of Social Ecology, University of California, Irvine, California 92697-7085, USA. jkasof@uci.edu
Cultural variation in seasonal depression: cross-national differences in winter versus summer patterns of seasonal affective disorder.
J Affect Disord. 2009 May;115(1-2):79-86
BACKGROUND: Research suggests that two dimensions of national culture, individualism-collectivism and power distance, predict affective responses to the seasonally varying levels of ambient sunlight that may underlie regular cycles of mood and behavior in Seasonal Affective Disorder (SAD). Specifically, negative affect is predicted by the diminished sunlight of fall-winter in countries higher in individualism and lower in power distance, and by the increased sunlight of spring-summer in countries lower in individualism and higher in power distance. This study tests whether individualism correlates positively, and power distance negatively, with the frequency of winter-SAD relative to that of summer-SAD. METHOD: A search for studies reporting frequencies of both winter-SAD and summer-SAD identified 55 samples encompassing 18 countries and 38,408 participants, including 1931 with SAD. RESULTS: The frequency of winter-SAD, relative to that of summer-SAD, correlated positively with individualism (r=.67, p=.001) and negatively with power distance (r=-.72, p=.0001). Countries in which winter-SAD was more common than summer-SAD were significantly more individualistic and less power-distant than countries in which summer-SAD was more common than winter-SAD. Results survived various tests of threats to validity. LIMITATIONS: The study is limited by the quantity, quality, diversity, and representativeness of the research under review and by its correlational design. CONCLUSIONS: Individualism and power distance are strongly related to the relative prevalence of winter-SAD and summer-SAD. Culture may play an important but previously overlooked role in the etiology of SAD.
PMID: 18849078

Ruf IK,Houmani JL,Sample JT
Department of Molecular Biology and Biochemistry, University of California Irvine, Irvine, CA, USA. iruf@uci.edu
Epstein-Barr virus independent dysregulation of UBP43 expression alters interferon-stimulated gene expression in Burkitt lymphoma.
PLoS One. 2009;4(6):e6023
Epstein-Barr virus (EBV) persists as a life-long latent infection within memory B cells, but how EBV may circumvent the innate immune response within this virus reservoir is unclear. Recent studies suggest that the latency-associated non-coding RNAs of EBV may actually induce type I (antiviral) interferon production, raising the question of how EBV counters the negative consequences this is likely to have on viral persistence. We addressed this by examining the type I interferon response in Burkitt lymphoma (BL) cell lines, the only in vitro model of the restricted program of EBV latency-gene expression in persistently infected B cells in vivo. Importantly, we observed no effect of EBV on interferon alpha-induced signaling or evidence of type I interferon production, suggesting that EBV in this latent state is silent to the cell's innate antiviral surveillance. We did uncover, however, a defect in the negative feedback control of interferon signaling in a subpopulation of BL lines as was revealed by prolonged interferon-stimulated gene transcription consistent with sustained tyrosine phosphorylation on STAT1 and STAT2. This was due to inadequate induction of expression of the ubiquitin-specific protease UBP43, which removes the ubiquitin-like ISG15 polypeptide conjugated to proteins (ISGylation) in response to type I interferons. Results here are consistent with previous findings in genetically engineered Ubp43(-/-) murine cells that UBP43 down-regulates interferon signaling, independent of its ISG15 isopeptidase activity, by precluding the protein kinase JAK1 from the interferon receptor. This natural deficiency in UBP43 expression may therefore provide a useful model to further probe the biological roles of UBP43 and ISGylation.
PMID: 19551150

Zell JA,Ignatius Ou SH
Survival prognostication in non-small cell lung cancer.
J Thorac Oncol. 2009 Jul;4(7):785-6
PMID: 19550241

Chernyavsky AI,Arredondo J,Qian J,Galitovskiy V,Grando SA
University of California Irvine, United States.
Coupling of ionic events to protein kinase signaling cascades upon activation of alpha7 nicotinic receptor: Cooperative regulation of alpha2-integrin expression and Rho-kinase activity.
J Biol Chem. 2009 Jun 23;:
Defining the signaling mechanisms and effector proteins mediating phenotypic and mechanical plasticity of keratinocytes (KCs) during wound epithelialization is one of the major goals in epithelial cell biology. The acetylcholine (ACh)-gated ion channels, or nicotinic ACh receptors (nAChRs), mediate the nicotinergic signaling that controls crawling locomotion of KCs. To elucidate relative contributions of the ionic and protein kinase-mediated events elicited due to activation of a7 nAChRs, we quantitated expression of a2-integrin gene at the mRNA and protein levels and also measured Rho-kinase activity in KCs stimulated with the a7 agonist AR-R17779 while blocking the Na+ or Ca2+ entry and/or inhibiting signaling kinases. The results demonstrated the existence of the two-component signaling systems coupling the ionic events and protein kinase signaling cascades downstream of a7 nAChR to simultaneous upregulation of a2-integrin expression and activation of Rho-kinase (ROK). The Raf/MEK1/ERK1/2 cascade upregulating a2-integrin was activated due to both Ca2+-dependent recruitment of Ca2+/calmodulin-dependent protein-kinase II (CaMKII) and protein kinase C and Ca2+-independent activation of Ras. Likewise, the PI3K-mediated activation of ROK was elicited due to both Ca2+ entry-dependent involvement of CaMKII and Ca2+-independent activation of Jak2. Thus, although the initial signals emanating from activated a7 nAChR are different in nature the pathways intersect at common effector molecules providing for a common endpoint effect. This novel paradigm of nAChR mediated coordination of the ionic and metabolic signaling events can allow an auto/paracrine ACh to simultaneously alter gene expression and induce reciprocal changes in the cytoskeleton and contractile system of KCs required to compete a particular step of wound epithelialization.
PMID: 19549780

Berger WE,Kerwin E,Bernstein DI,Pedinoff A,Bensch G,Karafilidis J
Allergy and Asthma Associates of Southern California, Mission Viejo, California, USA. wberger@uci.edu
Efficacy and safety evaluation of ciclesonide in subjects with mild-to-moderate asthma not currently using inhaled corticosteroids.
Allergy Asthma Proc. 30(3):304-14
Inhaled corticosteroids (ICSs) are a first-line treatment for persistent asthma. This study was designed to compare the efficacy and safety of ciclesonide (CIC) in subjects with mild-to-moderate persistent asthma not using an ICS. This was a multicenter, double-blind, parallel-group, placebo-controlled, 16-week study in subjects who were > or =12 years old, had a > or =6-month history of persistent asthma, a forced expiratory volume in 1 second (FEV(1)) of > or =60 to < or =85% predicted, and who were not using an ICS < or =30 days before study entry. Subjects were randomized to CIC, 80 microg twice daily (CIC80 b.i.d.; n = 170); CIC, 160 microg once daily in the morning (CIC160 q.d. in the A.M.; n = 173); CIC80 b.i.d. for 4 weeks followed by CIC160 q.d. for 12 weeks (CIC80 b.i.d./CIC160 q.d.; n = 171); or placebo (n = 177). Change in FEV(1) from baseline to the average of weeks 12 and 16 (primary end point) and to week 16, A.M. peak expiratory flow, rescue albuterol use, nighttime awakenings, asthma symptom scores, and safety were evaluated. FEV(1) improved from baseline to the average of weeks 12 and 16 for CIC80 b.i.d. (+0.30L; p < 0.0001), CIC160q.d. (+0.19L; p < 0.0001), CIC80 b.i.d./CIC160 q.d. (+0.19L; p < 0.0001), and placebo (+0.06L; p = 0.0251); improvement was greatest for CIC80 b.i.d. (p < 0.01). At week 16, all CIC treatments significantly improved FEV(1) and A.M. PEF from baseline (p < 0.0001) and compared with placebo (p < or = 0.015). All treatments reduced albuterol use and nighttime awakenings and improved asthma symptom scores (p < or = 0.05 versus baseline); these improvements were greater for CIC80 b.i.d. than for placebo (p < 0.01). The incidence of adverse events was similar among treatment groups (range, 53-58%). In this study, CIC80 b.i.d. improved disease control in subjects with mild-to-moderate persistent asthma not using an ICS and provided greater improvements than CIC160 q.d.
PMID: 19549432

Amin A,Spyropoulos AC,Dobesh P,Shorr A,Hussein M,Mozaffari E,Benner JS
Department of Medicine, University of California Irvine, Irvine, CA, USA, anamin@uci.edu.
Are hospitals delivering appropriate VTE prevention? The venous thromboembolism study to assess the rate of thromboprophylaxis (VTE start).
J Thromb Thrombolysis. 2009 Jun 23;:
The 7th conference of the American College of Chest Physicians (ACCP7) provides recommendations on the type, dose, and duration of thromboprophylaxis in hospitalized patients at risk of venous thromboembolism (VTE), but the extent to which hospitals follow these criteria has not been well studied. Discharge and billing records for patients admitted to any of 16 acute-care hospitals from January 2005 to December 2006 were obtained. Patients 18 years or older who had an inpatient stay >/=2 days and no apparent contraindications for thromboprophylaxis were grouped into the categories of critical care, surgery and medically ill before being assessed for additional VTE risk factors based on the diagnostic criteria outlined in ACCP7. For patients at risk, the recommended type (mechanical or pharmacologic), dose, and duration of thromboprophylaxis was identified based on the guidelines and compared to the regimen actually received, if any. Among the 258,556 hospitalized patients, 68,278 (26.4%) were determined to be at risk of VTE without apparent contraindications for thromboprophylaxis. The proportions of patients who received the appropriate type, dose, and duration of thromboprophylaxis were 10.5, 9.8, and 17.9% for critical care, medical, and surgical patients, respectively. Of those at risk, 36.8% received no thromboprophylaxis and an additional 50.2% received thromboprophylaxis deemed inappropriate for one or more reasons. The implementation of ACCP7 guidelines for type, dosage, and duration of thromboprophylaxis is low in patients at risk of VTE. There is a need for physicians and health systems to improve awareness and implementation of recommended thromboprophylaxis.
PMID: 19548071

Zell JA,Tsang WY,Taylor TH,Mehta RS,Anton-Culver H
Department of Epidemiology, Genetic Epidemiology Research Institute, School of Medicine, University of California-Irvine, Irvine, CA 92697, USA. jzell@uci.edu
Prognostic impact of human epidermal growth factor-like receptor 2 and hormone receptor status in inflammatory breast cancer (IBC): analysis of 2,014 IBC patient cases from the California Cancer Registry.
Breast Cancer Res. 2009;11(1):R9
INTRODUCTION: Inflammatory breast cancer (IBC) is an aggressive form of breast cancer associated with overexpression of Her2/Neu (human epidermal growth factor-like receptor 2 (HER2)) and poor survival. We investigated survival differences for IBC patient cases based on hormone receptor status and HER2 receptor status using data from the California Cancer Registry, as contrasted with locally advanced breast cancer (LABC), metastatic breast cancer (MBC) and non-T4 breast cancer. METHODS: A case-only analysis of 80,099 incident female breast cancer patient cases in the California Cancer Registry during 1999 to 2003 was performed, with follow-up through March 2007. Overall survival (OS) and breast cancer-specific survival (BC-SS) were analyzed using Kaplan-Meier methods and Cox proportional hazards ratios. RESULTS: A total of 2,014 IBC, 1,268 LABC, 3,059 MBC, and 73,758 non-T4 breast cancer patient cases were identified. HER2+ was associated with advanced tumor stage (P < 0.0001). IBC patient cases were more likely to be HER2+ (40%) and less likely to be hormone receptor-positive (HmR+) (59%) compared with LABC (35% and 69%, respectively), MBC (35% and 74%), and non-T4 patient cases (22% and 82%). HmR+ status was associated with improved OS and BC-SS for each breast cancer subtype after adjustment for clinically relevant factors. In multivariate analysis, HER2+ (versus HER2-) status was associated with poor BC-SS for non-T4 patient cases (hazards ratio = 1.16, 95% confidence interval 1.05 to 1.28) and had a borderline significant association with improved BC-SS for IBC (hazards ratio = 0.82, 95% confidence interval = 0.68 to 0.99). CONCLUSIONS: Despite an association with advanced tumor stage, HER2+ status is not an independent adverse prognostic factor for survival among IBC patient cases.
PMID: 19228416


 
 
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