bluuebunny/crossref_metadata_2025 huggingface dataset:
Ergosterol from the soilborne fungus Ganoderma boninense
Authors: Toh Choon R. L. , Sariah M. , Siti Mariam M.N.
Published: December 2011

Ergosterol is the main component of the fungal membrane and is not found in plants or other microbial cells. Therefore, it can be a useful biomarker for the quantification of fungal biomass. We are now reporting the first isolation and characterisation of ergosterol from the mycelium of G. boninense. The ergosterol structure was detected by Thin Liquid Chromatography (TLC) and Ultra Performance Liquid Chromatography (UPLC) and confirmed with Gas Chromatography coupled with Mass Spectrometry (GCMS) and Nuclear Magnetic Resonance (NMR) analysis. (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Entropy analysis of tri‐axial leg acceleration signal waveforms for measurement of decrease of physiological variability in human gait
Authors: Tochigi Yuki , Segal Neil A. , Vaseenon Tanawat , Brown Thomas D.
Published: December 2011

Disease‐related and senescent decrease of physiological variability in biological time‐series outputs (e.g., heart rate) has drawn increasing attention as a potential new type of biomarker. In this paradigm, measurement of variability in periodic motion may enable quantitative evaluation of functional limitation in people with musculoskeletal disorders. A novel technique to measure variability of leg motion patterns during level walking was used to study 52 adults with symptomatic knee osteoarthritis (OA), and 57 asymptomatic control subjects over a wide range of age (20–79 years). The hypothesis was that cycle‐to‐cycle variability in leg motion patterns, indexed by tri‐axial acceleration signal entropy, would be lower in those with greater age or with knee symptoms. Leg motions were assessed using portable inertial monitors attached bilaterally just above each ankle. The tri‐axial acceleration data were analyzed using a nonlinear variability measurement tool designated as Sample Entropy (SampEn). SampEn data for asymptomatic subjects exhibited a significant negative correlation (r = −0.287, p = 0.0306) with greater age. OA subjects had significantly lower SampEn values (p = 0.0002) than did age‐matched asymptomatic subjects who walked at equivalent velocity. This approach holds promise as a basis for valid, inexpensive, and convenient objective evaluation of limitations in human gait function. © 2011 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:897–904, 2012
Postcombat outcomes among marines with preexisting mental diagnoses
Authors: Crain Jenny A. , Larson Gerald E. , Highfill‐McRoy Robyn M. , Schmied Emily A.
Published: December 2011

Preexisting mental disorders are not always considered in mental health studies with military populations, even though prior diagnoses may be a risk factor for additional psychiatric harm stemming from combat exposure, as well as postdeployment behavioral problems. The objectives of this study were to investigate postcombat psychiatric and career outcomes among Marines with preexisting mental disorder diagnoses who deployed to combat in Iraq, Afghanistan, or Kuwait from 2002 to 2008. Marines with a preexisting diagnosis were 3.6 times (p < .001) more likely to have at least 1 postdeployment mental health disorder within 6 months postdeployment compared with Marines with no prior psychiatric diagnoses. Marines with a preexisting diagnosis were also 1.8 (p < .001) times more likely to receive a new‐onset psychiatric diagnosis within 6 months postdeployment, indicating that postdeployment mental health concerns in this cohort extend beyond continuation of earlier disorders. Additionally, demotions and separation were significantly associated with having any preexisting mental health diagnoses (yielding odds ratios of 2.34 and 2.00, p < .001, respectively. Based on the current findings, it may be advisable to mandate a full medical and psychiatric record review during deployment health screening as part of new initiatives to address whether combat exposure has worsened preexisting conditions or compounded them with new‐onset concerns.
Narrative quality and disturbance pre‐ and post‐emotion‐focused therapy for child abuse trauma
Authors: Mundorf Elisabeth S. , Paivio Sandra C.
Published: December 2011

This study predicted that the quality of trauma narratives written before and following emotion‐focused therapy for child abuse trauma would be positively associated with psychological disturbance before and following therapy. Narratives for 37 clients were coded for emotion words, temporal orientation, incoherence, and depth of experiencing. At pretreatment, negative emotion words and experiencing were correlated with abuse resolution, r(35) = −.36, and r(35) = −.34, respectively. At posttreatment, narrative incoherence was correlated with trauma symptoms, r(35) = .33, whereas present–future orientation and experiencing were correlated with abuse resolution, r(35) = −.37, and r(35) = −.31, respectively. Pretreatment incoherence was associated with posttreatment trauma symptoms, r(35) = .42, and pretreatment depth of experiencing was associated with posttreatment abuse resolution, r(35) = −.37. Results support narrative quality as an index of trauma disturbance.
Territory occupancy by common loons in response to disturbance, habitat, and intraspecific relationships
Authors: Hammond Christopher A. M. , Mitchell Michael S. , Bissell Gael N.
Published: December 2011

Structure and distribution of animal territories are driven by a variety of environmental and demographic factors. A peninsular population of common loons (Gavia immer) nests on lakes in northwestern Montana, but does not occupy all apparently suitable breeding territories, suggesting unexplained limitations on population growth. To evaluate territorial dynamics of breeding loons in Montana, we created and tested occupancy models that evaluated the hypothesized effects of disturbance, habitat, and intraspecific relationships on territory occupancy by common loons in Montana from 2003 to 2007. Model‐averaged results indicated that the abundance of feeding lakes within 10 km (i.e., forage quality) and the number of territorial pairs within 10 km (i.e., density of loons) were equally supported and related to probabilities of occupancy. We found substantial support that the population was in a state of equilibrium, with the numbers of occupied territories stable in time, but not space. We also found that density of territorial pairs was related to the likelihood that an existing territory would be abandoned, but did not influence the establishment of new territories, suggesting the presence of territorial pairs could be a stronger indicator of territory quality to loons than physical lake characteristics. Our index of human disturbance was not well‐supported compared to other factors. Our results suggest management for stable or growing loon populations could be achieved using long‐term monitoring and protection of occupied territorial lakes and nearby feeding lakes, because these factors most influenced the probability of occupancy of surrounding lakes. © 2011 The Wildlife Society.
Is a Mandatory Intensive Care Unit Stay Needed After Liver Transplantation? Feasibility of Fast-Tracking to the Surgical Ward After Liver Transplantation
Authors: Taner Burcin C. , Willingham Darrin L. , Bulatao Ilynn G. , Shine Timothy S. , Peiris Prith , Torp Klaus D. , Canabal Juan , Nguyen Justin H. , Kramer David J.
Published: December 2011

The continuation of hemodynamic, respiratory, and metabolic support for a variable period after liver transplantation (LT) in the intensive care unit (ICU) is considered routine by many transplant programs. However, some LT recipients may be liberated from mechanical ventilation shortly after the discontinuation of anesthesia. These patients might be appropriately discharged from the postanesthesia care unit (PACU) to the surgical ward and bypass the ICU entirely. In 2002, our program started a fast-tracking program: select LT recipients are transferred from the operating room to the PACU for recovery and tracheal extubation with a subsequent transfer to the ward, and the ICU stay is completely eliminated. Between January 1, 2003 and December 31, 2007, 1045 patients underwent LT at our transplant program; 175 patients were excluded from the study. Five hundred twenty-three of the remaining 870 patients (60.10%) were fast-tracked to the surgical ward, and 347 (39.90%) were admitted to the ICU after LT. The failure rate after fast-tracking to the surgical ward was 1.90%. The groups were significantly different with respect to the recipient age, the raw Model for End-Stage Liver Disease (MELD) score at the time of LT, the recipient body mass index (BMI), the retransplantation status, the operative time, the warm ischemia time, and the intraoperative transfusion requirements. A multivariate logistic regression analysis revealed that the raw MELD score at the time of LT, the operative time, the intraoperative transfusion requirements, the recipient age, the recipient BMI, and the absence of hepatocellular cancer/cholangiocarcinoma were significant predictors of ICU admission. In conclusion, we are reporting the largest single-center experience demonstrating the feasibility of bypassing an ICU stay after LT.
Liver Transpl 18:361–369, 2012.
© 2012 AASLD.
Repeated transplantation of hepatocytes prevents fulminant hepatitis in a rat model of Wilson's disease
Authors: Sauer Vanessa , Siaj Ramsi , Stöppeler Sandra , Bahde Ralf , Spiegel Hans-Ullrich , Köhler Gabriele , Zibert Andree , Schmidt Hartmut H.-J.
Published: December 2011

The outcome of consecutive hepatocyte transplants was explored in a rat model of Wilson's disease before the onset of fulminant hepatitis without preconditioning regimens. Rats received a high-copper diet in order to induce a rapid induction of liver failure. Sham-operated rats (15/15) developed jaundice and fulminant hepatitis, and they died within 4 weeks of first transplantation. Despite the continuation of a high dietary copper challenge, long-term survival was observed for a notable proportion of the transplanted animals (7/18). All survivors displayed normalized levels of hepatitis-associated serum markers and ceruloplasmin oxidase activity by posttransplant days 50 and 98, respectively. The liver copper concentrations, the liver histology, and the expression of marker genes were significantly restored within 4 months of transplantation in comparison with the control group. The high expression of a copper transporter gene (ATPase Cu++ transporting beta polypeptide) in the livers of the survivors indicated a high rate of repopulation by donor hepatocytes. Our data suggest that repeated cell transplantation can overcome the limitations of a single therapy session in rats with severe hepatic disease by functionally restoring the host liver without preconditioning. Liver Transpl 18:248–259, 2012. © 2011 AASLD.
Diagnostic and Therapeutic Challenges in Pediatric Primary Sclerosing Cholangitis
Authors: Shneider Benjamin L.
Published: December 2011

Sclerosing cholangitis, an uncommon disorder in children, is progressive and is, therefore, an important indication for pediatric liver transplantation. This review summarizes current challenges in the diagnosis and treatment of this rare form of pediatric liver disease.
Liver Transpl 18:277–281, 2012.
© 2011 AASLD.
Meeting Report of the 2011 Joint International Congress of the International Liver Transplantation Society, the European Liver and Intestine Transplant Association, and the Liver Intensive Care Group of Europe
Authors: Levitsky Josh , Guckelberger Olaf
Published: December 2011

The International Liver Transplantation Society held its yearly meeting as a joint conference with the European Liver and Intestine Transplant Association and the Liver Intensive Care Group of Europe at the Valencia Congress Center (Valencia, Spain) from June 22 to 25, 2011. Nearly 1500 registrants attended the meeting, which opened with a premeeting conference entitled “Global Challenges and Controversies in Liver Transplantation.” This was followed by numerous oral and poster abstract sessions and topic sessions focused on medical, surgical, and intensive care aspects of liver transplantation (LT). This report summarizes key symposia and oral abstracts delivered at the meeting and is conveniently divided into subsections relevant to LT. It is not meant to be a critical or comprehensive evaluation of all the meeting presentations and is merely intended to highlight presentations and associated published literature dealing with key topics.
Liver Transpl 18:282–289, 2012.
© 2011 AASLD.
Retrospective Review of the Incidence of Cytomegalovirus Infection and Disease After Liver Transplantation in Pediatric Patients: Comparison of Prophylactic Oral Ganciclovir and Oral Valganciclovir
Authors: Bedel Ashley N. , Hemmelgarn Trina S. , Kohli Rohit
Published: December 2011

Cytomegalovirus (CMV) is the most common viral infection after solid organ transplantation (SOT). Safe and effective prophylactic regimens that decrease its incidence after SOT are essential for long-term graft survival. Although valganciclovir is not Food and Drug Administration–approved for CMV prophylaxis in liver transplant recipients, postmarketing studies have shown valganciclovir to be as effective as ganciclovir in high-risk adult patients undergoing SOT. Currently, data are lacking for pediatric liver transplantation. The purpose of this study was to compare the efficacy and safety of valganciclovir and ganciclovir for CMV infection prophylaxis in pediatric liver transplant recipients. This was a retrospective study of 56 pediatric liver transplant recipients who were prescribed either oral ganciclovir (n = 37) or valganciclovir (n = 19). Patients were followed until 200 days after transplantation or death. The primary outcome measure compared the rates of early-onset CMV infection and CMV disease in the 2 medication groups. Secondary outcome measures identified patient-specific factors that contributed to CMV acquisition and the incidence of late-onset CMV infection or disease. The rates of adverse drug effects and discontinuation were also evaluated. Early-onset CMV disease was documented in 0% of valganciclovir patients and in 5.4% of ganciclovir patients (P = 0.54). There were no statistically significant differences in the secondary outcomes. An increased incidence of late-onset CMV disease was seen in the valganciclovir group versus the ganciclovir group (22.2% versus 8.1%, P = 0.23). No differences in adverse events were reported. In conclusion, no statistically significant differences were found in the incidence of CMV infection or disease between patients receiving oral valganciclovir and patients receiving oral ganciclovir.
Liver Transpl 18:347–354, 2012.
© 2012 AASLD.
Exercise capacity and muscle strength in patients with cirrhosis
Authors: Jones Jacqueline C. , Coombes Jeff S. , Macdonald Graeme A.
Published: December 2011

Exercise capacity and muscle strength are predictors of outcome in a number of clinical populations. Advanced liver disease is a catabolic state, and patients often have muscle wasting. However, the relationships between exercise capacity, strength, and outcomes for patients undergoing liver transplantation are poorly understood. Thirteen studies have examined the association between these parameters in patients with cirrhosis, and they have found a significant reduction in the exercise capacity and muscle strength of patients with cirrhosis versus healthy controls. These impairments appear to be independent of the etiology of cirrhosis, but the data are equivocal with respect to their association with disease severity. Two studies reported a significant and independent association between pretransplant exercise capacity and posttransplant survival. Another 2 studies found that exercise training was well tolerated in patients with cirrhosis and resulted in improvements in exercise capacity (both studies) and muscle mass (1 study). These data are provocative and suggest that measuring and improving the exercise capacity and muscle strength of patients with cirrhosis who are awaiting liver transplantation could potentially improve outcomes. Liver Transpl 18:146–151, 2012. © 2011 AASLD.
Development and Validation of a Questionnaire Evaluating the Impact of Hepatitis B Immune Globulin Prophylaxis on the Quality of Life of Liver Transplant Recipients
Authors: Franciosi Monica , Caccamo Lucio , De Simone Paolo , Pinna Antonio Daniele , Di Costanzo Giovanni Giuseppe , Volpes Riccardo , Scuderi Vincenzo , Strignano Paolo , Boccagni Patrizia , Burra Patrizia , Nicolucci Antonio
Published: December 2011

To date, there is still a lack of instruments for specifically assessing the impact of anti–hepatitis B virus prophylaxis after liver transplantation (LT) on health-related quality of life (HRQOL) and treatment satisfaction. Focusing on the use of hepatitis B immune globulin (HBIG), we developed and validated the Immunoglobulin Therapy After Liver Transplantation Questionnaire (ITaLi-Q), which includes 41 items and covers 5 domains (side effects, positive and negative feelings, impact on the flexibility of daily activities, support, and satisfaction). The questionnaire was tested by 177 consecutive LT patients [71.8% were male, 38.4% were more than 60 years old, 58.8% were on intramuscular (IM) HBIG, and 41.2% were on intravenous (IV) HBIG]. A factor analysis confirmed the hypothesized structure, and a multitrait, multi-item analysis showed favorable psychometric characteristics for ITaLi-Q: item-scale correlations > 0.40 for all items but 1, high scaling success rates (>90% for all scales but 1), excellent internal consistency (Cronbach's α ≥ 0.8 for all scales), and good reproducibility (test-retest coefficient > 0.70 for all scales but 2). ITaLi-Q was able to discriminate between subgroups of patients according to their clinical and sociodemographic characteristics. In comparison with patients on IV HBIG, patients on IM HBIG reported significantly better HRQOL scores on the Flexibility (81.5 ± 21.4 versus 73.1 ± 24.2, P = 0.01) and Negative Feelings scales (90.1 ± 17.3 versus 85.4 ± 20.7, P = 0.04), but they reported worse HRQOL scores on the Side Effects scale (81.8 ± 22.8 versus 95.6 ± 7.4, P < 0.001). No differences were found between the route of HBIG administration and the Satisfaction, Positive Feelings, Impact, and Support scales. In conclusion, ITaLi-Q showed adequate psychometric characteristics and revealed that the route of HBIG administration has a significant impact on specific HRQOL domains beyond a patient's satisfaction.
Liver Transpl 18:332–339, 2012.
© 2012 AASLD.
New Index for Assessing the Chronotropic Response in Patients With End-Stage Liver Disease Who Are Undergoing Dobutamine Stress Echocardiography
Authors: Rudzinski Wojciech , Waller Alfonso H. , Prasad Amit , Sood Sunita , Gerula Christine , Samanta Arun , Koneru Baburao , Klapholz Marc
Published: December 2011

The inability to achieve 85% of the maximum predicted heart rate (MPHR) on dobutamine stress echocardiography (DSE) is defined as chronotropic incompetence and is a predictor of major cardiac events after orthotopic liver transplantation (OLT). The majority of patients with end-stage liver disease (ESLD) receive beta-blockers for the prevention of variceal bleeding. In these patients, it is impossible to determine whether chronotropic incompetence is secondary to cirrhosis-related autonomic dysfunction or is merely a beta-blocker effect. We evaluated the usefulness of the maximum achieved heart rate (MAHR) and the heart rate reserve (HRR) in the detection of chronotropic incompetence in ESLD patients on beta-blocker therapy before DSE. We also evaluated the usefulness of a new index, the modified heart rate reserve (MHRR), in diagnosing chronotropic incompetence and predicting major cardiovascular adverse events after OLT. The study population consisted of 284 ESLD patients. The mean values of MAHR (expressed as a percentage of 85% of MPHR) and HRR were significantly lower for patients on beta-blockers versus patients off beta-blockers [97.1% versus 101.6% (t = 5.01, P < 0.001) and 71.7% versus 77.3% (t = 4.03, P < 0.001), respectively], whereas the values of MHRR were similar in patients on beta-blockers and patients off beta-blockers [102.3% versus 102.1% (t = 0.04, P = 0.97)]. A regression analysis showed a significant association of MAHR (P < 0.001) and HRR (P < 0.001) with beta-blockers, whereas MHRR was not associated with beta-blocker treatment (P = 0.92). MAHR and HRR were found to have no value for diagnosing chronotropic incompetence in ESLD patients. MHRR was not affected by beta-blocker therapy. Patients who developed heart failure (HF) and myocardial infarction (MI) after OLT had significantly lower MHRR values according to pretransplant DSE. MHRR was significantly associated with the subsequent development of HF (P = 0.01) and MI (P = 0.01) after OLT. MHRR may be useful for the determination of the target heart rate for stress testing, the diagnosis of chronotropic incompetence, and the prediction of adverse cardiac events after OLT.
Liver Transpl 18:355–360, 2012.
© 2012 AASLD.
Molecular Bottlebrushes with Polypeptide Backbone Prepared via Ring‐Opening Polymerization of NCA and ATRP
Authors: Liu Yu , Chen Ping , Li Zhibo
Published: December 2011

A new type of molecular bottlebrush with poly‐L‐lysine (PLL) as backbone was synthesized via ROP followed by ATRP. A Nϵ‐bromoisobutyryl functionalized Nα‐CBZ‐L‐lysine was firstly synthesized and converted in polymerizable α‐amino acid N‐carboxyanhydride (NCA), which was then polymerized using Ni(0) transition metal complex to give well‐defined bromo‐functionalized homopolypeptide (PBrLL), from which we prepared two types of polypeptide bottlebrushes with polystyrene and poly(oligoethylene glycol methacrylate) as side‐chains. PBrLL macroinitiator was demonstrated to have high initiation efficiency for ATRP, which allowed good control over side‐chain length. CD and FTIR characterization revealed that both PBrLL macroinitiator and PLL backbone of bottlebrushes adopted α‐helical conformation in appropriate solvents.
High‐resolution sodium imaging of human brain at 7 T
Authors: Qian Yongxian , Zhao Tiejun , Zheng Hai , Weimer Jonathan , Boada Fernando E.
Published: December 2011

The feasibility of high‐resolution sodium magnetic resonance imaging on human brain at 7 T was demonstrated in this study. A three‐dimensional anisotropic resolution data acquisition was used to address the challenge of low signal‐to‐noise ratio associated with high resolution. Ultrashort echo‐time sequence was used for the anisotropic data acquisition. Phantoms and healthy human brains were studied on a whole‐body 7‐T magnetic resonance imaging scanner. Sodium images were obtained at two high nominal in‐plane resolutions (1.72 and 0.86 mm) at a slice thickness of 4 mm. Signal‐to‐noise ratio in the brain image (cerebrospinal fluid) was measured as 14.4 and 6.8 at the two high resolutions, respectively. The actual in‐plane resolution was measured as 2.9 and 1.6 mm, 69–86% larger than their nominal values. The quantification of sodium concentration on the phantom and brain images enabled better accuracy at the high nominal resolutions than at the low nominal resolution of 3.44 mm (measured resolution 5.5 mm) due to the improvement of in‐plane resolution. Magn Reson Med, 2012. © 2011 Wiley Periodicals, Inc.
RF pulse optimization for Bloch‐Siegert B mapping
Authors: Khalighi Mohammad Mehdi , Rutt Brian K. , Kerr Adam B.
Published: December 2011

The Bloch–Siegert (B–S) method of B mapping has been shown to be fast and accurate, yet has high SAR and moderately long TE. These limitations can lengthen scan times and incur signal loss due to B0 inhomogeneity, particularly at high field. The B–S method relies on applying a band‐limited off‐resonant B–S radiofrequency pulse to induce a B‐dependent frequency‐shift for resonant spins. A method for optimizing the B–S radiofrequency pulse is presented here, which maximizes B–S B measurement sensitivity for a given SAR and T2. A 4‐ms optimized pulse is shown to have 35% less SAR compared with the conventional 6‐ms Fermi pulse while still improving B map angle‐to‐noise ratio by 22%. The optimized pulse performance is validated both in phantom and in vivo brain imaging at 7 T. Magn Reson Med, 2012. © 2011 Wiley Periodicals, Inc.
PAX7+ satellite cells in young and older adults following resistance exercise
Authors: Walker Dillon K. , Fry Christopher S. , Drummond MICAH J. , Dickinson Jared M. , Timmerman Kyle L. , Gundermann David M. , Jennings Kristofer , Volpi Elena , Rasmussen Blake B.
Published: December 2011

Introduction:

Resistance exercise (RE) stimulates a muscle protein anabolic response partially through enhanced satellite cell (SC) activity, however, age‐ and gender‐related changes in SC content over a 24‐h time course are not known.

Methods:

Ten young (27 ± 2 years) men and women and 11 older (70 ± 2 years) men and women performed an acute bout of RE. Myofiber and SC characteristics were determined from muscle biopsies of the vastus lateralis using immunohistochemistry. Immunoblotting was used to determine phosphorylation of cyclin‐dependent kinase‐2 and protein expression of p27Kip1 and cyclin D1.

Results:

Pax7+ SC were significantly increased in young men 24 h following RE. Percent SC were significantly increased in older women at 6 and 24 h following RE. Aging decreased myonuclear domain and increased protein expression of p27Kip1.

Conclusions:

An acute bout of RE increases SC content in young men at 24 h and older women at 6 and 24 h. Muscle Nerve 46: 51–59, 2012
Geographical distribution of A seropositive myasthenia gravis population
Authors: Heldal Anne Taraldsen , Eide Geir Egil , Gilhus Nils Erik , Romi Fredrik
Published: December 2011

Introduction:

To assess age‐ and sex‐specific myasthenia gravis (MG) occurrence and incidence in the different geographical regions in Norway and thereby to identify factors that may contribute to the development of MG.

Methods:

Multiple Poisson regression analysis was used to assess variation in incidence dependent on year, gender and onset age in five geographically defined health regions.

Results:

The study population comprised 419 individuals with first time seropositive tests from 1995 to 2007. Annual MG incidence ranged from < 1 to 14 per million, with an average of 7.04 per million for all five health regions combined.

Conclusions:

This is the first nation‐wide epidemiological study of seropositive MG that elucidates the geographical differences within a country. The incidence of seropositive MG did not vary significantly between the regions. Mid‐Norway tended to have a higher incidence, and North tended to have a lower incidence. Muscle Nerve 45: 815–819, 2012
Inter‐organ proteomic analysis reveals insights into the molecular mechanisms underlying the anti‐diabetic effects of cis‐9, trans‐11‐conjugated linoleic acid in ob/ob mice
Authors: Rungapamestry Vanessa , McMonagle Jolene , Reynolds Clare , Rucklidge Garry , Reid Martin , Duncan Gary , Ross Karen , Horgan Graham , Toomey Sinead , Moloney Aidan P. , de Roos Baukje , Roche Helen M.
Published: December 2011

cis‐9, trans‐11‐Conjugated linoleic acid (c9 t11 CLA) exerts anti‐diabetic effects by improving systemic insulin sensitivity and inflammation. Levels of CLA in beef can be increased by feeding cattle on pasture. This study aimed to explore the efficacy of a CLA‐rich diet (0.6% w/w c9 t11 CLA), presented as beef enriched with CLA or beef supplemented with synthetic CLA (c9 t11 CLA), for 28 days on molecular biomarkers of the metabolic syndrome, and adipose, hepatic, and skeletal muscle proteome in male ob/ob mice. Despite equal weight gain, CLA‐fed mice had lower plasma glucose, insulin, non‐esterified fatty acid, triacylglycerol and interleukin‐6, and higher adiponectin concentrations than controls. c9 t11 CLA induced differential regulation of redox status across all tissues, and decreased hepatic and muscle endoplasmic reticulum stress. CLA also modulated mechanistic links between the actin cytoskeleton, insulin signalling, glucose transport and inflammation in the adipose tissue. In the liver and muscle, c9 t11 CLA improved metabolic flexibility through co‐ordination between carbohydrate and energy metabolism. c9 t11 CLA may ameliorate systemic insulin sensitivity in obesity‐induced diabetes by altering cellular stress and redox status, and modulating nutrient handling in key insulin‐sensitive tissues through complex biochemical interplay among representative proteomic signatures.
1H NMR study of the hetero‐association of unsaturated alcohols with pyridine
Authors: Lomas John S.
Published: December 2011

The 1H NMR titration method is used to investigate the association of some unsaturated alcohols with pyridine in benzene. The association constant for allyl alcohol (2‐propen‐1‐ol) is slightly higher than for alkanols, but putting one methylene group between the OH and vinyl group completely eliminates this enhancement. In alkynols both the OH and ≡CH protons associate with pyridine. Here, the effects of chain‐lengthening on the association constant are irregular. Values for alkynols and some alcohols with hetero‐atom substituents are lower than expected on the basis of a Taft polar constant (σ*) correlation of alkanol association constants and of a correlation with the pKa’s of the corresponding carboxylic acids. It is suggested that stabilization of the ground state by OH/π interactions is responsible for these low association constants. Small increases in the NMR shifts of the OH protons in the 3‐carbon and 4‐carbon alkenols and alkynols can also be attributed to OH/π interactions, but the 5‐carbon analogues have shifts as low as alkanols. Copyright © 2011 John Wiley & Sons, Ltd.
Manipulating morphology and orientation in thermally responsive block copolymer thin films
Authors: Kelly Jennifer Y. , Albert Julie N. L. , Howarter John A. , Stafford Christopher M. , Epps Thomas H. , Fasolka Michael J.
Published: December 2011

We demonstrate the use of combined thermal annealing and solvent vapor annealing (SVA) to tune the morphology of thermally responsive block copolymer (BCP) thin films. The BCP, poly(styrene‐b‐tert‐butyl acrylate) (PS‐b‐PtBA), undergoes a chemical deprotection to poly(styrene‐b‐acrylic anhydride) (PS‐b‐PAH) above a temperature threshold, giving rise to a structural and morphological transition. Our experiments systematically examine different thermal annealing and SVA protocols with two solvents (tetrahydrofuran and acetone) and map the resulting morphologies. Assessments of these processing protocols were accelerated using temperature gradients. Our results demonstrate that the final nanoscale morphologies after SVA are determined by the changes in the relative solvent/polymer interactions and surface tensions of the polymer blocks that accompany deprotection. Because of these driving forces, certain processing combinations led to irreversible morphological states, whereas others present opportunities for further manipulation. Accordingly, our study reveals that the morphology of this thermally sensitive BCP can be altered through judicious choice of annealing protocol. The protocols that combine equal numbers of SVA and thermal annealing (TA) steps are not necessarily equivalent, and the order of the SVA relative to TA is a deciding factor in the final morphology. © 2011 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys, 2011
Determination of the dipole moments of RNAse SA wild type and a basic mutant
Authors: Chari Ravi , Singh Shubhadra N. , Yadav Sandeep , Brems David N. , Kalonia Devendra S.
Published: December 2011

In this study, we report the effects of acidic to basic residue point mutations (5K) on the dipole moment of RNAse SA at different pHs. Dipole moments were determined by measuring solution capacitance of the wild type (WT) and the 5K mutant with an impedance analyzer. The dipole moments were then (1) compared with theoretically calculated dipole moments, (2) analyzed to determine the effect of the point mutations, and (3) analyzed for their contribution to overall protein–protein interactions (PPI) in solution as quantitated by experimentally derived second virial coefficients. We determined that experimental and calculated dipoles were in reasonable agreement. Differences are likely due to local motions of residue side chains, which are not accounted for by the calculated dipole. We observed that the proteins' dipole moments increase as the pH is shifted further from their isoelectric points and that the wild‐type dipole moments were greater than those of the 5K. This is likely due to an increase in the proportion of one charge (either negative or positive) relative to the other. A greater charge disparity corresponded to a larger dipole moment. Finally, the larger dipole moments of the WT resulted in greater attractive overall PPI for that protein as compared to the 5K. Proteins 2011; © 2011 Wiley Periodicals, Inc.
The Kondo effect in reduced graphene oxide films
Authors: McIntosh Ross , Bhattacharyya Somnath
Published: December 2011

The influence of spin in reduced graphene oxide (RGO) is demonstrated through a temperature dependent metal–insulator transition in resistance (at ∼30 K) as well as high field magneto‐resistance (MR) measurements. RGO samples, prepared using an unconventional organic acid reduction method, showed a quadratic temperature dependence of resistance at low temperatures, which changed to a logarithmic dependence at higher temperatures. Analysis of these features in RGO, combined with negative MR which scales with a Kondo characteristic temperature, establishes the interaction between conduction electrons propagating through intact graphene nano‐islands and localized magnetic moments found in disordered regions. (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Why a Bayesian approach to safety analysis in pharmacovigilance is important
Authors: Prieto‐Merino David , Quartey George , Wang Jixian , Kim Joseph
Published: December 2011

Large databases of routinely collected data are a valuable source of information for detecting potential associations between drugs and adverse events (AE). A pharmacovigilance system starts with a scan of these databases for potential signals of drug–AE associations that will subsequently be examined by experts to aid in regulatory decision‐making. The signal generation process faces some key challenges: (1) an enormous volume of drug–AE combinations need to be tested (i.e. the problem of multiple testing); (2) the results are not in a format that allows the incorporation of accumulated experience and knowledge for future signal generation; and (3) the signal generation process ignores information captured from other processes in the pharmacovigilance system and does not allow feedback. Bayesian methods have been developed for signal generation in pharmacovigilance, although the full potential of these methods has not been realised. For instance, Bayesian hierarchical models will allow the incorporation of established medical and epidemiological knowledge into the priors for each drug–AE combination. Moreover, the outputs from this analysis can be incorporated into decision‐making tools to help in signal validation and posterior actions to be taken by the regulators and companies. We discuss in this paper the apparent advantage of the Bayesian methods used in safety signal generation and the similarities and differences between the two widely used Bayesian methods. We will also propose the use of Bayesian hierarchical models to address the three key challenges and discuss the reasons why Bayesian methodology still have not been fully utilised in pharmacovigilance activities. Copyright © 2011 John Wiley & Sons, Ltd.
An assessment of the statistical methods used to analyse toxicology studies
Authors: Jarvis Philip , Saul Jim , Aylott Mike , Bate Simon , Geys Helena , Sherington John
Published: December 2011

The Statisticians in the Pharmaceutical Industry Toxicology Special Interest Group has collated and compared statistical analysis methods for a number of toxicology study types including general toxicology, genetic toxicology, safety pharmacology and carcinogenicity. In this paper, we present the study design, experimental units and analysis methods. Copyright © 2011 John Wiley & Sons, Ltd.
Middle atmosphere predictability in a numerical weather prediction model: revisiting the inverse error cascade
Authors: Ngan K. , Eperon G. E.
Published: December 2011

The spectral predictability of the Met Office's Unified Model is examined using identical‐twin experiments and the relative kinetic energy. In the troposphere, previous NWP results are recovered, namely the emergence of distinct regimes and the maximisation of the growth rate on synoptic scales at early times; in the middle atmosphere, the predictability decay is slower. This difference is attributed to the increase in the amplitude of gravity waves. The influence of small‐scale motions is highlighted: improving their numerical representation by decreasing the timestep enhances predictability. Copyright © 2011 British Crown copyright, the MetOffice. Published by John Wiley & Sons Ltd.
A hierarchical rank test for crossover trials with censored data
Authors: Brittain Erica , Follmann Dean
Published: December 2011

We propose an approach to analyze survival time in a crossover clinical trial by performing a primary ranking on whether events occur and a secondary ranking on event times. This hierarchical ranking method is meant to reflect the idea that the goal of therapy is to prevent a clinical event and, failing that, to delay the occurrence of the event, hopefully for a substantial amount of time. We compare our approach with other methods including one method proposed by Feingold and Gillespie, a recommended procedure. The power is similar in many settings, but the hierarchical ranking can have substantially greater power under certain censoring patterns and also under a cure model, or models where treatment induces a substantial delay in some fraction of patients. We additionally feel that the hierarchical ranking method should be more clinically relevant in many settings. The method can also be applied to continuous outcomes censored by a limit of detection, such as HIV viremia. Copyright © 2011 John Wiley & Sons, Ltd.
Estimating the agreement and diagnostic accuracy of two diagnostic tests when one test is conducted on only a subsample of specimens
Authors: Katki Hormuzd A. , Li Yan , Edelstein David W. , Castle Philip E.
Published: December 2011

We focus on the efficient usage of specimen repositories for the evaluation of new diagnostic tests and for comparing new tests with existing tests. Typically, all pre‐existing diagnostic tests will already have been conducted on all specimens. However, we propose retesting only a judicious subsample of the specimens by the new diagnostic test. Subsampling minimizes study costs and specimen consumption, yet estimates of agreement or diagnostic accuracy potentially retain adequate statistical efficiency. We introduce methods to estimate agreement statistics and conduct symmetry tests when the second test is conducted on only a subsample and no gold standard exists. The methods treat the subsample as a stratified two‐phase sample and use inverse‐probability weighting. Strata can be any information available on all specimens and can be used to oversample the most informative specimens. The verification bias framework applies if the test conducted on only the subsample is a gold standard. We also present inverse‐probability‐weighting‐based estimators of diagnostic accuracy that take advantage of stratification. We present three examples demonstrating that adequate statistical efficiency can be achieved under subsampling while greatly reducing the number of specimens requiring retesting. Naively using standard estimators that ignore subsampling can lead to drastically misleading estimates. Through simulation, we assess the finite‐sample properties of our estimators and consider other possible sampling designs for our examples that could have further improved statistical efficiency. To help promote subsampling designs, ourRpackageCompareTestscomputes all of our agreement and diagnostic accuracy statistics. Copyright © 2011 John Wiley & Sons, Ltd.
Intermittent observation of time‐dependent explanatory variables: a multistate modelling approach
Authors: Tom Brian D.M. , Farewell Vernon T.
Published: December 2011

Motivated by investigations of factors related to various patient‐reported outcome measures in psoriatic arthritis patients, after controlling for the effect of disease activity on these outcomes, we outline an approach for dealing with a rapidly fluctuating explanatory variable in a multistate model. On the basis of a representation of this variable as an ordinal classification, we suggest the use of an expanded multistate model. We examine the bias in estimating effects associated with other variables via simulation for different modelling choices. We present an analysis of a motivating data set on physical functional disability in psoriatic arthritis patients. Copyright © 2011 John Wiley & Sons, Ltd.
Improper analysis of trials randomised using stratified blocks or minimisation
Authors: Kahan Brennan C. , Morris Tim P.
Published: December 2011

Many clinical trials restrict randomisation using stratified blocks or minimisation to balance prognostic factors across treatment groups. It is widely acknowledged in the statistical literature that the subsequent analysis should reflect the design of the study, and any stratification or minimisation variables should be adjusted for in the analysis. However, a review of recent general medical literature showed only 14 of 41 eligible studies reported adjusting their primary analysis for stratification or minimisation variables. We show that balancing treatment groups using stratification leads to correlation between the treatment groups. If this correlation is ignored and an unadjusted analysis is performed, standard errors for the treatment effect will be biased upwards, resulting in 95% confidence intervals that are too wide, type I error rates that are too low and a reduction in power. Conversely, an adjusted analysis will give valid inference. We explore the extent of this issue using simulation for continuous, binary and time‐to‐event outcomes where treatment is allocated using stratified block randomisation or minimisation. Copyright © 2011 John Wiley & Sons, Ltd.
Output characteristics model for an a‐Si ISFET pH sensor
Authors: Hashim Yasir , Sidek Othman
Published: December 2011

A mathematical model for the calculation of the output characteristics of amorphous silicon hydrogenated (a‐Si:H) ion‐sensitive field‐effect transistors (ISFET) is developed, which depends on the integration of the conductivity channel versus gate voltage curve at fixed drain voltage. Single curve integration was changed to integration with many simple lines to obtain the ID − VD characteristics using computer programming. The results of this model were tested with those of experiments. © 2011 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.
Introducing WIREs Developmental Biology
Authors: Gerhart John C. , Martin Gail R. , Wieschaus Eric F.
Published: December 2011

WIREs Dev Biol 2012, 1:1–2. doi: 10.1002/wdev.13

For further resources related to this article, please visit the WIREs website.
Reoptimization of the minimum spanning tree
Authors: Paschos Stratos A. , Paschos Vangelis Th.
Published: December 2011

We implement a fast reoptimization algorithm for MIN SPANNING TREE under vertex insertions, initially proposed and analyzed in the work of Boria and Paschos [Boria N, Paschos VTh. Fast reoptimization for the minimum spanning tree problem. J Discrete Algor 2010, 8:296–310] and study its experimental approximation behavior in randomly generated graphs. The reoptimization setting can briefly be formulated as follows: given an instance of the problem for which we already know some optimal solution, and given some ‘small’ perturbations on this instance, is it possible to compute a new (optimal or at least near‐optimal) solution for the modified instance without computation from scratch? We focus in this article on the most popular modification: vertex‐insertion. WIREs Comput Stat 2012, 4:211–217. doi: 10.1002/wics.204

This article is categorized under:

Algorithms and Computational Methods > Dynamic Programming
Interactions of nanomaterials with the immune system
Authors: Hussain Salik , Vanoirbeek Jeroen A. J. , Hoet Peter H. M.
Published: December 2011

Evaluation of the immunomodulatory potentials of nanomaterials is essential for developing safe and consumer‐friendly nanotechnology. Various nanomaterials interact with the immune system, in a beneficial or deleterious way, but mechanistic details about such interactions are scarce. A lack of agreed‐upon guidelines for evaluating the immunotoxicity of nanoparticles (NPs) adds to the complexity of the issue. Various review articles have summarized the immune system interactions of biodegradable NPs (with pharmaceutical uses), but such information is largely lacking for nonbiodegradable NPs. Here we give an overview of interactions of nonbiodegradable, persistent NPs with the immune system. Particular emphases include key factors that shape such interactions, cell‐specific responses, allergy and immune‐sensitive respiratory disorders. WIREs Nanomed Nanobiotechnol 2012, 4:169–183. doi: 10.1002/wnan.166

This article is categorized under:

Nanotechnology Approaches to Biology > Nanoscale Systems in Biology

Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials
Ionothermal Synthesis of a NaCl‐type Topological Network Based on Trinuclear Cobalt(II) Clusters as Nodes
Authors: Liang Yan‐Fang , Zhang Ya‐Ru , Han Zheng‐Bo
Published: December 2011

A new metal‐organic network [Co3(tbip)3(H2O)4]·2H2O (1) (H2tbip = 5‐tert‐butyl‐isophthalic acid) was synthesized through the ionothermal reaction of H2tbip, cobalt nitrate, and [bmim]Br ionic liquid ([bmim]Br = 1‐butyl‐3‐methylimidazolium bromide). It exhibits a three‐dimensional (3D) framework with NaCl topology based on trinuclear cobalt(II) clusters as nodes. The magnetic studies show that there exist antiferromagnetic interactions between the CoII ions.
Physicochemical Properties and Adhesion Performance of Canola Protein Modified with Sodium Bisulfite
Authors: Li Ningbo , Qi Guangyan , Sun Xiuzhi Susan , Stamm Michael J. , Wang Donghai
Published: December 2011

The objective of this research was to study the adhesion properties of sodium bisulfite (NaHSO3)‐modified canola protein. Protein was extracted from canola meal through alkali solubilization and acid precipitation methods, then modified with different concentrations of NaHSO3 (0–15 g/L) during the isolation process. As NaHSO3 concentration increased, canola protein purities decreased. Amino acid profiles showed that the hydrophobic amino acids in canola protein constituted only 27% of total protein, indicating that canola protein is mostly hydrophilic. The reducing effects of NaHSO3 were exerted on canola protein through the breaking of disulfide bonds in both its cruciferin and napin components, as reflected by the protein electrophoresis profile, DSC data, and morphological images. The wet protein isolates were used as adhesives. The greatest wet shear strength of canola protein adhesive without modification was 3.97 MPa with 100% wood cohesive failure (WCF), observed at a curing temperature of 190 °C. NaHSO3 had slight weakening effects on the adhesion performance of canola protein. Canola protein modified with 3 g/L NaHSO3 exhibited wet shear strength similar to the control at 190 °C and higher strength at 150 and 170 °C. The NaHSO3 modification significantly improved handling and flowability of canola protein adhesives.