bluuebunny/crossref_metadata_2025 huggingface dataset:
Temporal compliance trends in a cluster randomization with crossover trial of out-of-hospital cardiac arrest
Authors: Schmicker Robert H , Leroux Brian G , Sears Gena K , Stiell Ian , Morrison Laurie J , Aufderheide Tom P , Fowler Ray , Lowe Rusty , Morrow Stanley , Plumlee Ed , Cheskes Sheldon ,   for the Resuscitation Outcomes Consortium (ROC) Investigators
Published: March 2012

Background Low compliance to randomized nondrug interventions can affect treatment estimates of clinical trials. Cluster-randomized crossover may be appropriate for increasing compliance in the out-of-hospital cardiac arrest setting.

Purpose The purpose was to determine whether the elapsed time from start of a nonblinded treatment period to episode enrollment date in a cluster-randomized crossover trial is associated with compliance to either a period of brief cardiopulmonary resuscitation (CPR) with electrocardiogram (ECG) rhythm analysis or a period of longer CPR with a delayed ECG rhythm analysis in patients with out-of-hospital cardiac arrest.

Methods The Resuscitation Outcomes Consortium PRIMED Analyze Late (AL) versus Analyze Early (AE) trial was a cluster-randomized crossover trial at 10 North American regional sites. Clusters were created based on local service preference with treatment periods varying from 3 to 12 months depending on the expected enrollment rate of each randomizing unit. Episodes on the AL arm had a target of 180 s from CPR start to shock assessment and were deemed compliant if total time was between 150 and 210 s. Episodes on the AE arm had a target of <30 s from CPR start to shock assessment and were deemed compliant if total time was <60 s. We used logistic regression to examine the association between compliance (yes/no) and the elapsed number of days from the start of the treatment period to the episode in the framework of generalized estimating equations, controlling for randomized treatment (Late, reference = Early) and treatment period length (reference = 3, 4–5, 6, 7–11, and 12 months).

Results We had 8769 episodes in our analysis population. Overall compliance to the randomized arm was 63.5%. After adjusting for treatment arm and treatment period length, the odds of compliance for episodes occurring >300 days from treatment period start were 33% lower (odds ratio (OR): 0.67; 95% confidence interval (CI): 0.52, 0.86) than for those <60 days from treatment period start. There was no significant difference in compliance between episodes before and immediately after a cluster crossed over to the opposite arm (OR: 0.81; 95% CI: 0.57, 1.16).

Limitations A major challenge was the lack of synchronicity between training cycles and agency crossover dates.

Conclusion We found a significant decrease in compliance to the AL versus AE cardiac arrest intervention as the elapsed time from start of treatment period increased. We did not find a difference in compliance immediately before and after a crossover. While these results suggest that future cluster with crossover trials in the out-of-hospital setting be designed with short treatment periods and frequent crossovers, provider logistical concerns must also be considered.
Intersection of mechanisms of type 2A VWD through defects in VWF multimerization, secretion, ADAMTS-13 susceptibility, and regulated storage
Authors: Jacobi Paula M. , Gill Joan Cox , Flood Veronica H. , Jakab David A. , Friedman Kenneth D. , Haberichter Sandra L.
Published: March 2012

Type 2A VWD is characterized by the absence of large VWF multimers and decreased platelet-binding function. Historically, type 2A variants are subdivided into group 1, which have impaired assembly and secretion of VWF multimers, or group 2, which have normal secretion of VWF multimers and increased ADAMTS13 proteolysis. Type 2A VWD patients recruited through the T. S. Zimmerman Program for the Molecular and Clinical Biology of VWD study were characterized phenotypically and potential mutations identified in the VWF D2, D3, A1, and A2 domains. We examined type 2A variants and their interaction with WT-VWF through expression studies. We assessed secretion/intracellular retention, multimerization, regulated storage, and ADAMTS13 proteolysis. Whereas some variants fit into the traditional group 1 or 2 categories, others did not fall clearly into either category. We determined that loss of Weibel-Palade body formation is associated with markedly reduced secretion. Mutations involving cysteines were likely to cause abnormalities in multimer structure but not necessarily secretion. When coexpressed with wild-type VWF, type 2A variants negatively affected one or more mechanisms important for normal VWF processing. Type 2A VWD appears to result from a complex intersection of mechanisms that include: (1) intracellular retention or degradation of VWF, (2) defective multimerization, (3) loss of regulated storage, and (4) increased proteolysis by ADAMTS13.
Pathologic shear triggers shedding of vascular receptors: a novel mechanism for down-regulation of platelet glycoprotein VI in stenosed coronary vessels
Authors: Al-Tamimi Mohammad , Tan Chee Wee , Qiao Jianlin , Pennings Gabrielle J. , Javadzadegan Ashkan , Yong Andy S. C. , Arthur Jane F. , Davis Amanda K. , Jing Jing , Mu Fi-Tjen , Hamilton Justin R. , Jackson Shaun P. , Ludwig Andreas , Berndt Michael C. , Ward Christopher M. , Kritharides Leonard , Andrews Robert K. , Gardiner Elizabeth E.
Published: March 2012

Ligand-induced ectodomain shedding of glycoprotein VI (GPVI) is a metalloproteinase-dependent event. We examined whether shear force, in the absence of GPVI ligand, was sufficient to induce shedding of GPVI. Human-citrated platelet-rich plasma or washed platelets were subjected to increasing shear rates in a cone-plate viscometer, and levels of intact and cleaved GPVI were examined by Western blot and ELISA. Pathophysiologic shear rates (3000-10 000 seconds−1) induced platelet aggregation and metalloproteinase-dependent appearance of soluble GPVI ectodomain, and GPVI platelet remnant. Shedding of GPVI continued after transient exposure to shear. Blockade of αIIbβ3, GPIbα, or intracellular signaling inhibited shear-induced platelet aggregation but minimally affected shear-induced shedding of GPVI. Shear-induced GPVI shedding also occurred in platelet-rich plasma or washed platelets isolated from a von Willebrand disease type 3 patient with no detectable VWF, implying that shear-induced activation of platelet metalloproteinases can occur in the absence of GPVI and GPIbα ligands. Significantly elevated levels of sGPVI were observed in 10 patients with stable angina pectoris, with well-defined single vessel coronary artery disease and mean intracoronary shear estimates at 2935 seconds−1 (peak shear, 19 224 seconds−1). Loss of GPVI in platelets exposed to shear has potential implications for the stability of a forming thrombus at arterial shear rates.
Genomic survey, expression profile and co-expression network analysis of OsWD40 family in rice
Authors: Ouyang Yidan , Huang Xiaolong , Lu Zhanhua , Yao Jialing
Published: March 2012

Background

WD40 proteins represent a large family in eukaryotes, which have been involved in a broad spectrum of crucial functions. Systematic characterization and co-expression analysis of OsWD40 genes enable us to understand the networks of the WD40 proteins and their biological processes and gene functions in rice.

Results

In this study, we identify and analyze 200 potential OsWD40 genes in rice, describing their gene structures, genome localizations, and evolutionary relationship of each member. Expression profiles covering the whole life cycle in rice has revealed that transcripts of OsWD40 were accumulated differentially during vegetative and reproductive development and preferentially up or down-regulated in different tissues. Under phytohormone treatments, 25 OsWD40 genes were differentially expressed with treatments of one or more of the phytohormone NAA, KT, or GA3 in rice seedlings. We also used a combined analysis of expression correlation and Gene Ontology annotation to infer the biological role of the OsWD40 genes in rice. The results suggested that OsWD40 genes may perform their diverse functions by complex network, thus were predictive for understanding their biological pathways. The analysis also revealed that OsWD40 genes might interact with each other to take part in metabolic pathways, suggesting a more complex feedback network.

Conclusions

All of these analyses suggest that the functions of OsWD40 genes are diversified, which provide useful references for selecting candidate genes for further functional studies.
The mitochondrial alternative oxidase pathway protects the photosynthetic apparatus against photodamage in Rumex K-1 leaves
Authors: Zhang Li-Tao , Zhang Zi-Shan , Gao Hui-Yuan , Meng Xiang-Long , Yang Cheng , Liu Jian-Guo , Meng Qing-Wei
Published: March 2012

Background

It is known that excess reducing equivalents in the form of NADPH in chloroplasts can be transported via shuttle machineries, such as the malate-oxaloacetate (OAA) shuttle, into the mitochondria, where they are efficiently oxidised by the mitochondrial alternative oxidase (AOX) respiratory pathway. Therefore, it has been speculated that the AOX pathway may protect plants from photoinhibition, but the mechanism by which this protection occurs remains to be elucidated.

Results

The observation that the malate-OAA shuttle activity and the AOX pathway capacity increased markedly after intense light treatment in Rumex K-1 leaves indicates that excess NADPH was transported from the chloroplasts and oxidised by the AOX pathway. The inhibition of the AOX pathway by salicylhydroxamic acid (SHAM) caused the over-reduction of the photosystem I (PSI) acceptor side, as indicated by the increases in the extent of reduction of P700+. Furthermore, the photosynthetic linear electron flow was restricted, which was indicated by the decreases in the PSII electron transport rate (ETR) and the photosynthetic O2 evolution rate. The restriction of the photosynthetic linear electron flow, which generates the thylakoid ΔpH, inevitably decreased the de-epoxidation of the xanthophyll cycle (ΔPRI). Therefore, the induction of non-photochemical quenching (NPQ) was suppressed when the AOX pathway was inhibited. The effect of the inhibition of the AOX pathway on NPQ induction was less at 20 mM NaHCO3 than at 1 mM NaHCO3. The suppression of NPQ induction by the inhibition of the AOX pathway was also observed during the induction phase of photosynthesis. In addition, the inhibition of the AOX pathway increased the accumulation of hydrogen peroxide (H2O2), suggesting that the AOX pathway functions as an antioxidant mechanism.

Conclusions

The inhibition of the AOX pathway resulted in the rapid accumulation of NADPH in the chloroplasts, which caused the over-reduction of the PSI acceptor side. Furthermore, the restriction of the photosynthetic linear electron flow due to the inhibition of the AOX pathway limited the generation of the thylakoid ΔpH and suppressed the induction of NPQ. Therefore, the mitochondrial AOX pathway protected the photosynthetic apparatus against photodamage by alleviating the over-reduction of the PSI acceptor side and accelerating the induction of NPQ in Rumex K-1 leaves.
Prevalence, genetic diversity and antiretroviral drugs resistance-associated mutations among untreated HIV-1-infected pregnant women in Gabon, central Africa
Authors: Caron Mélanie , Lekana-Douki Sonia Etenna , Makuwa Maria , Obiang-Ndong Guy-Patrick , Biba Olivia , Nkoghé Dieudonné , Kazanji Mirdad
Published: March 2012

Background

In Africa, the wide genetic diversity of HIV has resulted in emergence of new strains, rapid spread of this virus in sub-Saharan populations and therefore spread of the HIV epidemic throughout the continent.

Methods

To determine the prevalence of antibodies to HIV among a high-risk population in Gabon, 1098 and 2916 samples were collected from pregnant women in 2005 and 2008, respectively. HIV genotypes were evaluated in 107 HIV-1-positive samples to determine the circulating subtypes of strains and their resistance to antiretroviral drugs (ARVs).

Results

The seroprevalences were 6.3% in 2005 and 6.0% in 2008. The main subtype was recombinant CRF02_AG (46.7%), followed by the subtypes A (19.6%), G (10.3%), F (4.7%), H (1.9%) and D (0.9%) and the complex recombinants CRF06_cpx (1.9%) and CRF11_cpx (1.9%); 12.1% of subtypes could not be characterized. Analysis of ARVs resistance to the protease and reverse transcriptase coding regions showed mutations associated with extensive subtype polymorphism. In the present study, the HIV strains showed reduced susceptibility to ARVs (2.8%), particularly to protease inhibitors (1.9%) and nucleoside reverse transcriptase inhibitors (0.9%).

Conclusions

The evolving genetic diversity of HIV calls for continuous monitoring of its molecular epidemiology in Gabon and in other central African countries.
Diabetes mellitus type 2 in urban Ghana: characteristics and associated factors
Authors: Danquah Ina , Bedu-Addo George , Terpe Karl-Johann , Micah Frank , Amoako Yaw A , Awuku Yaw A , Dietz Ekkehart , van der Giet Markus , Spranger Joachim , Mockenhaupt Frank P
Published: March 2012

Background

Sub-Saharan Africa faces a rapid spread of diabetes mellitus type 2 (DM2) but its potentially specific characteristics are inadequately defined. In this hospital-based study in Kumasi, Ghana, we aimed at characterizing clinical, anthropometric, socio-economic, nutritional and behavioural parameters of DM2 patients and at identifying associated factors.

Methods

Between August 2007 and June 2008, 1466 individuals were recruited from diabetes and hypertension clinics, outpatients, community, and hospital staff. Fasting plasma glucose (FPG), serum lipids and urinary albumin were measured. Physical examination, anthropometry, and interviews on medical history, socio-economic status (SES), physical activity and nutritional behaviour were performed.

Results

The majority of the 675 DM2 patients (mean FPG, 8.31 mmol/L) was female (75%) and aged 40-60 years (mean, 55 years). DM2 was known in 97% of patients, almost all were on medication. Many had hypertension (63%) and microalbuminuria (43%); diabetic complications occurred in 20%. Overweight (body mass index > 25 kg/m2), increased body fat (> 20% (male), > 33% (female)), and central adiposity (waist-to-hip ratio > 0.90 (male), > 0.85 (female)) were frequent occurring in 53%, 56%, and 75%, respectively. Triglycerides were increased (≥ 1.695 mmol/L) in 31% and cholesterol (≥ 5.17 mmol/L) in 65%. Illiteracy (46%) was high and SES indicators generally low. Factors independently associated with DM2 included a diabetes family history (adjusted odds ratio (aOR), 3.8; 95% confidence interval (95%CI), 2.6-5.5), abdominal adiposity (aOR, 2.6; 95%CI, 1.8-3.9), increased triglycerides (aOR, 1.8; 95%CI, 1.1-3.0), and also several indicators of low SES.

Conclusions

In this study from urban Ghana, DM2 affects predominantly obese patients of rather low socio-economic status and frequently is accompanied by hypertension and hyperlipidaemia. Prevention and management need to account for a specific risk profile in this population.
Genetic population structure of the malaria vector Anopheles baimaii in north-east India using mitochondrial DNA
Authors: Sarma Devojit K , Prakash Anil , O'Loughlin Samantha M , Bhattacharyya Dibya R , Mohapatra Pradumnya K , Bhattacharjee Kanta , Das Kanika , Singh Sweta , Sarma Nilanju P , Ahmed Gias U , Walton Catherine , Mahanta Jagadish
Published: March 2012

Background

Anopheles baimaiiis a primary vector of human malaria in the forest settings of Southeast Asia including the north-eastern region of India. Here, the genetic population structure and the basic population genetic parameters ofAn. baimaiiin north-east India were estimated using DNA sequences of the mitochondrial cytochrome oxidase sub unit II (COII) gene.

Methods

Anopheles baimaiiwere collected from 26 geo-referenced locations across the seven north-east Indian states and the COII gene was sequenced from 176 individuals across these sites. Fifty-seven COII sequences ofAn. baimaiifrom six locations in Bangladesh, Myanmar and Thailand from a previous study were added to this dataset. Altogether, 233 sequences were grouped into eight population groups, to facilitate analyses of genetic diversity, population structure and population history.

Results

A star-shaped median joining haplotype network, unimodal mismatch distribution and significantly negative neutrality tests indicated population expansion inAn. baimaiiwith the start of expansion estimated to be ~0.243 million years before present (MYBP) in north-east India. The populations ofAn. baimaiifrom north-east India had the highest haplotype and nucleotide diversity with all other populations having a subset of this diversity, likely as the result of range expansion from north-east India. The north-east Indian populations were genetically distinct from those in Bangladesh, Myanmar and Thailand, indicating that mountains, such as the Arakan mountain range between north-east India and Myanmar, are a significant barrier to gene flow. Within north-east India, there was no genetic differentiation among populations with the exception of the Central 2 population in the Barail hills area that was significantly differentiated from other populations.

Conclusions

The high genetic distinctiveness of the Central 2 population in the Barail hills area of the north-east India should be confirmed and its epidemiological significance further investigated. The lack of genetic population structure in the other north-east Indian populations likely reflects large population sizes ofAn. baimaiithat, historically, were able to disperse through continuous forest habitats in the north-east India. Additional markers and analytical approaches are required to determine if recent deforestation is now preventing ongoing gene flow. Until such information is acquired,An. baimaiiin north-east India should be treated as a single unit for the implementation of vector control measures.
Kinetic study of batch and fed-batch enzymatic saccharification of pretreated substrate and subsequent fermentation to ethanol
Authors: Gupta Rishi , Kumar Sanjay , Gomes James , Kuhad Ramesh Chander
Published: March 2012

Background

Enzymatic hydrolysis, the rate limiting step in the process development for biofuel, is always hampered by its low sugar concentration. High solid enzymatic saccharification could solve this problem but has several other drawbacks such as low rate of reaction. In the present study we have attempted to enhance the concentration of sugars in enzymatic hydrolysate of delignified Prosopis juliflora, using a fed-batch enzymatic hydrolysis approach.

Results

The enzymatic hydrolysis was carried out at elevated solid loading up to 20% (w/v) and a comparison kinetics of batch and fed-batch enzymatic hydrolysis was carried out using kinetic regimes. Under batch mode, the actual sugar concentration values at 20% initial substrate consistency were found deviated from the predicted values and the maximum sugar concentration obtained was 80.78 g/L. Fed-batch strategy was implemented to enhance the final sugar concentration to 127 g/L. The batch and fed-batch enzymatic hydrolysates were fermented with Saccharomyces cerevisiae and ethanol production of 34.78 g/L and 52.83 g/L, respectively, were achieved. Furthermore, model simulations showed that higher insoluble solids in the feed resulted in both smaller reactor volume and shorter residence time.

Conclusion

Fed-batch enzymatic hydrolysis is an efficient procedure for enhancing the sugar concentration in the hydrolysate. Restricting the process to suitable kinetic regimes could result in higher conversion rates.
Reproductive aging-associated common genetic variants and the risk of breast cancer
Authors: He Chunyan , Chasman Daniel I , Dreyfus Jill , Hwang Shih-Jen , Ruiter Rikje , Sanna Serena , Buring Julie E , Fernández-Rhodes Lindsay , Franceschini Nora , Hankinson Susan E , Hofman Albert , Lunetta Kathryn L , Palmieri Giuseppe , Porcu Eleonora , Rivadeneira Fernando , Rose Lynda M , Splansky Greta L , Stolk Lisette , Uitterlinden André G , Chanock Stephen J , Crisponi Laura , Demerath Ellen W , Murabito Joanne M , Ridker Paul M , Stricker Bruno H , Hunter David J
Published: March 2012

Introduction

A younger age at menarche and an older age at menopause are well established risk factors for breast cancer. Recent genome-wide association studies have identified several novel genetic loci associated with these two traits. However, the association between these loci and breast cancer risk is unknown.

Methods

In this study, we investigated 19 and 17 newly identified single nucleotide polymorphisms (SNPs) from the ReproGen Consortium that have been associated with age at menarche and age at natural menopause, respectively, and assessed their associations with breast cancer risk in 6 population-based studies among up to 3,683 breast cancer cases and 34,174 controls in white women of European ancestry. In addition, we used these SNPs to calculate genetic risk scores (GRSs) based on their associations with each trait.

Results

After adjusting for age and potential population stratification, two age at menarche associated SNPs (rs1079866 and rs7821178) and one age at natural menopause associated SNP (rs2517388) were associated with breast cancer risk (p values, 0.003, 0.009 and 0.023, respectively). The odds ratios for breast cancer corresponding to per-risk-allele were 1.14 (95% CI, 1.05 to 1.24), 1.08 (95% CI, 1.02 to 1.15) and 1.10 (95% CI, 1.01 to 1.20), respectively, and were in the direction predicted by their associations with age at menarche or age at natural menopause. These associations did not appear to be attenuated by further controlling for self-reported age at menarche, age at natural menopause, or known breast cancer susceptibility loci. Although we did not observe a statistically significant association between any GRS for reproductive aging and breast cancer risk, the 4th and 5th highest quintiles of the younger age at menarche GRS had odds ratios of 1.14 (95% CI, 1.01 to 1.28) and 1.13 (95% CI, 1.00 to 1.27), respectively, compared to the lowest quintile.

Conclusions

Our study suggests that three genetic variants, independent of their associations with age at menarche or age at natural menopause, were associated with breast cancer risk and may contribute modestly to breast cancer risk prediction; however, the combination of the 19 age at menarche or the 17 age at natural menopause associated SNPs did not appear to be useful for identifying a high risk subgroup for breast cancer.
Effect of Postdiagnosis Weight Change on Hot Flash Status Among Early-Stage Breast Cancer Survivors
Authors: Caan Bette J. , Emond Jennifer A. , Su H. Irene , Patterson Ruth E. , Flatt Shirley W. , Gold Ellen B. , Newman Vicky A. , Rock Cheryl L. , Thomson Cynthia A. , Pierce John P.
Published: March 2012

Purpose

Hot flashes (HF) affect a large proportion of breast cancer (BC) survivors and can negatively affect their quality of life. Treatments other than estrogen replacement to alleviate HF are needed. Body weight is related to hot flashes, but little is known about the effect of weight change on HF.

Patients and Methods

We used data from 3,088 women previously treated for early-stage BC who were enrolled onto the Women's Healthy Eating and Living study to examine the association between weight change after a breast cancer diagnosis and the odds of reporting HF.

Results

Overall, 36.1% of participants reported moderate to severe HF at study entry. At 2 years postdiagnosis, 69.2% of women remained within 10%, 4.8% lost at least 10%, and 26.0% gained at least 10% of their prediagnosis weight. Those who gained at least 10% of their prediagnosis weight had a greater risk of reporting HF than women who remained weight stable in that same period (odds ratio [OR], 1.33; 95% CI, 1.11 to 1.60; P = .003). Weight loss of at least 10% of prediagnosis weight was associated with a nonsignificant reduced risk (OR, 0.72; 95% CI, 0.47 to 1.08; P = .118) of reporting HF. However, the trend of weight change (weight loss and weight gain) on HF was significant both when examined categorically (P = .03) and continuously (P < .001).

Conclusion

Prevention of weight gain after a BC diagnosis—a modifiable behavior—may offer a viable intervention for relief of HF. Effects of intentional weight loss in BC survivors requires further study.
Modeling HIV-associated neurocognitive disorders in mice: new approaches in the changing face of HIV neuropathogenesis
Authors: Jaeger Laura B. , Nath Avindra
Published: March 2012

It is well established that infection with the human immunodeficiency virus (HIV) leads to immune suppression. Less well known is the fact that long-term, progressive HIV disease is associated with the development of cognitive deficits. Since the introduction of combined antiretroviral therapy (cART), the clinical presentation of HIV infection has evolved into a chronic illness with very low levels of viral replication and chronic immune activation, with compliant affected individuals surviving for decades with a high quality of life. Despite these advances, many HIV-infected individuals develop some degree of neurodegeneration and cognitive impairment. The underlying pathophysiological mechanisms are not well understood, and there are no effective treatments. Thus, there is an unmet need for animal models that enable the study of HIV-associated neurocognitive disorders (HAND) and the testing of new therapeutic approaches to combat them. Here, we review the pros and cons of existing mouse models of HIV infection for addressing these aims and propose a detailed strategy for developing a new mouse model of HIV infection.
Effect of patient positioning on the duration of venous reflux in duplex ultrasound for venous insufficiency
Authors: Bonfield M , Cramp F , Robinson T
Published: March 2012

Introduction

There is currently little research regarding optimum patient position for venous insufficiency assessment although standing is considered the gold standard in many professional guidelines. Some patients are unable to stand for the examination and scanning patients in a standing position is physically challenging for the sonographer. This pilot study aimed to evaluate the effect of varying patient positioning on the duration of venous reflux.

Method

Venous reflux duration was measured in symptomatic participants with suspected venous insufficiency. Measurements were taken in the standing position (gold standard) and four alternative positions: 25° reverse-Trendelenburg (RT) tilt, sitting on the edge of the examination couch, 10° RT tilt and 0° RT tilt. The mean reflux duration measured in each different position was compared with the gold standard.

Results

Complete measurements were obtained from 16 patients (8 men and 8 women). For an incompetent vein, statistical analysis demonstrated a significant difference only between the standing position and the 0° position ( U = 19.0; exact P < 0.01 [2-tailed]).

Conclusion

Results suggest that several alternative positions could be used for assessing incompetent veins as long as the patient is not lying supine with 0° tilt. This would offer much greater flexibility, which may be of benefit to both patients and sonographers.
Experimental Research on the Load-Bearing Capacity of Partially Encased Steel Columns Under Fire Conditions
Authors: Correia António , Rodrigues João , Korzen Manfred
Published: March 2012

The composite steel and concrete columns are known to have enhanced fire behaviour when compared with bare steel columns. However there are still aspects that must be clarified, as the influence of the building surrounding structure on the fire resistance of the columns. In this paper, the results of fire resistance tests on partially encased steel columns carried out with two different experimental systems are compared. In one of the experimental systems, the building surrounding structure is materialised by a steel restraining frame, and in the other is performed by the so-called substructuring method. Due to the concept of hybrid substructuring, the entire building is decomposed in two parts: one is represented by the building element under test, whereas the remaining building is simulated numerically in a computer. The main conclusion drawn from this work was that the surrounding structure has a major influence in the development of axial forces in the test columns. Moreover, it was observed that the higher the non-dimensional axial restraint ratio the lower the critical time of the columns.
Review of Kinemax total knee replacements performed at the NHS treatment centre, Weston-Super-Mare
Authors: Hickey B. A. , Kempshall P. J. , Metcalfe A. J. , Forster M. C.
Published: March 2012

As part of the national initiative to reduce waiting times for joint replacement surgery in Wales, the Cardiff and Vale NHS Trust referred 224 patients to the NHS Treatment Centre in Weston-Super-Mare for total knee replacement (TKR). A total of 258 Kinemax TKRs were performed between November 2004 and August 2006. Of these, a total of 199 patients (232 TKRs, 90%) have been followed up for five years. This cohort was compared with 258 consecutive TKRs in 250 patients, performed at Cardiff and Vale Orthopaedic Centre (CAVOC) over a similar time period. The five year cumulative survival rate was 80.6% (95% confidence interval (CI) 74.0 to 86.0) in the Weston-Super-Mare cohort and 95.0% (95% CI 90.2 to 98.2) in the CAVOC cohort with revision for any reason as the endpoint. The relative risk for revision at Weston-Super-Mare compared with CAVOC was 3.88 (p < 0.001). For implants surviving five years, the mean Oxford knee scores (OKS) and mean EuroQol (EQ-5D) scores were similar (OKS: Weston-Super-Mare 29 (2 to 47) vs CAVOC 29.8 (3 to 48), p = 0.61; EQ-5D: Weston-Super-Mare 0.53 (-0.38 to 1.00) vs CAVOC 0.55 (-0.32 to 1.00), p = 0.79). Patients with revised TKRs had significantly lower Oxford knee and EQ-5D scores (p < 0.001).

The results show a higher revision rate for patients operated at Weston-Super-Mare Treatment Centre, with a reduction in functional outcome and quality of life after revision. This further confirms that patients moved from one area to another for joint replacement surgery fare poorly.
Impact of arthroscopy of the hip for femoroacetabular impingement on quality of life at a mean follow-up of 3.2 years
Authors: Malviya A. , Stafford G. H. , Villar R. N.
Published: March 2012

The benefit of arthroscopy of the hip in the treatment of femoroacetabular impingement (FAI) in terms of quality of life (QoL) has not been reported. We prospectively collected data on 612 patients (257 women (42%) and 355 men (58%)) with a mean age at the time of surgery of 36.7 years (14 to 75) who underwent arthroscopy of the hip for FAI under the care of a single surgeon. The minimum follow-up was one year (mean 3.2 years (1 to 7)). The responses to the modified Harris hip score were translated using the Rosser Index Matrix in order to provide a QoL score. The mean QoL score increased from 0.946 (-1.486 to 0.995) to 0.974 (0.7 to 1) at one year after surgery (p < 0.001). The mean QoL score in men was significantly higher than in women, both before and one year after surgery (both p < 0.001). However, the mean change in the QoL score was not statistically different between men and women (0.02 (-0.21 to 0.27) and 0.04 (-0.16 to 0.87), respectively; p = 0.12). Linear regression analysis revealed that the significant predictors of a change in QoL score were pre-operative QoL score (p < 0.001) and gender (p = 0.04). The lower the pre-operative score, the higher the gain in QoL post-operatively (ρ = -0.66; p < 0.001). One year after surgery the QoL scores in the 612 patients had improved in 469 (76.6%), remained unchanged in 88 (14.4%) and had deteriorated in 55 (9.0%).
Corrigenda/Errata
Authors: Scott J.
Published: March 2012

Koh Y-G, Moon H-K, Kim Y-C, Park Y-S, Jo S-B, Kwon S-K. Comparison of medial and lateral meniscal transplantation with regard to extrusion of the allograft, and its correlation with clinical outcome.
Exam Corner –April 2012
Authors: Khanduja V.
Published: March 2012

The FRCS (Tr & Orth) examination has three components: MCQs, Vivas and Clinical Examination. The Vivas are further divided into four sections comprising Basic Science, Adult Pathology, Hands and Children’s Orthopaedics and Trauma. The Clinical Examination section is divided into Upper and Lower limb cases. The aim of this section in the Journal is to focus specifically on the trainees preparing for the exam and to cater to all the sections of the exam. The vision is to complete the cycle of all relevant exam topics (as per the syllabus) in four years.
Health Dynamics and the Evolution of Health Inequality over the Life Course: The Importance of Neighborhood and Family Background
Authors: Johnson Rucker C.
Published: March 2012

This paper investigates the extent and ways in which childhood family and neighborhood quality influence later-life health outcomes. The study analyzes the health trajectories of children born between 1950 and 1970 followed through 2005. Data from the Panel Study of Income Dynamics (PSID) spanning four decades are linked with information on neighborhood attributes and school quality resources that prevailed at the time these children were growing up.There are several key findings. First, estimates of sibling and child neighbor correlations in health are used to bound the proportion of inequality in health status in childhood through mid-life that are attributable to childhood family and neighborhood quality. Estimates based on four-level hierarchical random effects models (neighborhoods, families, individuals, over time) consistently show a significant scope for both childhood family and neighborhood background (including school quality). The results imply substantial persistence in health status across generations that are linked in part to low intergenerational economic mobility. Sibling correlations are large throughout at least the first 50 years of life: roughly three-fifths of adult health disparities may be attributable to family and neighborhood background. Childhood neighbor correlations in adult health are also substantial (net of the similarity arising from similar family characteristics), suggesting that disparities in neighborhood background account for more than one-third of the variation in health status in mid life.Second, exposure to concentrated neighborhood poverty during childhood has significant deleterious impacts on adult health. The results reveal that even a large amount of selection on unobservable factors does not eliminate the significant effect of child neighborhood poverty on health status later in life. Thus, racial differences in adult health can be accounted for by childhood family, neighborhood, and school quality factors, while contemporaneous economic factors account for relatively little of this gap.
Taiwan, Tourism, and Trademarks: Protecting Aboriginal Culture
Authors: Lee Anny , Wu Stacy
Published: March 2012

The Taiwanese government has long used and endorsed aboriginal culture (e.g., in the form of theme parks, cartoons, music, and films) to grow local industries and attract tourism. By showcasing indigenous culture on the world stage, Taiwan's entertainment and tourism industries have developed in mainstream society a sense of pride in its living native treasures. The conscious effort to diversify what it means to be Taiwanese has resulted, somewhat ironically, in a sort of communal identity. Accordingly, some scholars believe that indigenous culture should belong to the public domain. Indeed, the injection of aboriginal culture into the mainstream has had positive and negative effects. On the one hand, the entry of indigenous culture into the mainstream has provided formerly overlooked minority groups with new resources and societal leverage, as well as educated the Taiwanese people about diversity. On the other hand, the capitalization of traditional culture by non-aboriginal entities can be detrimental to aboriginal self-sufficiency and preservation efforts. This paper examines the different levels of protection of traditional culture for aboriginal tribes. Part II discusses the legislations currently in place for the benefits of the aborigines, and the recent controversy surrounding government procedures in defining the legal statuses of the aboriginal tribes. Part III looks at the efficacy of domestic legislation vis-à-vis international treaties. Part IV describes the role of intellectual property rights in a private settlement between a film production company and the Seediq tribe.
Deterrence of Antitrust Violations: Do Actions for Damages Matter in Japan?
Authors: Vande Walle Simon
Published: March 2012

There is considerable debate about the role private litigation should play in the enforcement of antitrust law. This article focuses on one of the most controversial private enforcement mechanisms – damages actions – and assesses whether and how much such actions have contributed to deterring antitrust violations in Japan. It does so by answering two questions: (1) how much have damages actions contributed to the detection of antitrust violations?, and (2) how much have damages actions contributed to an increase in the sanctions for antitrust violations? Based on original data concerning damages actions between 1990 and 2010, the article argues that damages actions have somewhat contributed to deterring certain antitrust violations, bid-rigging in particular, but that an almost equivalent measure of deterrence could have been generated more efficiently by imposing higher penalties through public enforcement.
The universe of Hsp90
Authors: Stankiewicz Marta , Mayer Matthias P.
Published: March 2012

Molecular chaperones are key components in the maintenance of cellular homeostasis and survival, not only during stress but also under optimal growth conditions. Among the ATP-dependent chaperones, heat shock proteins (Hsp90) proteins play a special role. While Hsp90s can interact with unfolded and misfolded proteins, their main (and in eukaryotic cells essential) function appears to involve interactions with a limited number of protein clients at late steps of maturation or in “alter-native” conformations for regulating their stability and activity. Because Hsp90 clients are hubs of diverse signaling networks and participate in nearly every cellular function, Hsp90s interconnect many regulatory circuits and link them to environmental impacts. The availability and activity of Hsp90 may thus influence complex physiological and pathophysiological processes, such as differentiation, development, aging, cancer, neurodegeneration, and infectious diseases. Furthermore, through homeostatic effects on differentiation and development, Hsp90s act as capacitors of phenotypic evolution. In this review, we discuss recent insights in the structure and chaperone cycle of Hsp90s, the mechanisms underlying Hsp90 binding to clients, and potential reasons why client proteins specifically require the assistance of Hsp90s. Moreover, the current views on Hsp90-cochaperone interactions and regulation of Hsp90 proteins via posttranslational modifications are summarized. The second half of this article is devoted to the role of Hsp90 proteins in health and disease, aging, and evolution.
Development of a host blood meal database: de novo sequencing of hemoglobin from nine small mammals using mass spectrometry
Authors: Laskay Ünige A. , Burg Jennifer , Kaleta Erin J. , Vilcins Inger-Marie E. , Telford III Sam R. , Barbour Alan G. , Wysocki Vicki H.
Published: March 2012

We report the successful de novo sequencing of hemoglobin using a mass spectrometry-based approach combined with automatic data processing and manual validation for nine North American species with currently unsequenced genomes. The complete α and β chain of all nine mammalian hemoglobin samples used in this study were successfully sequenced. These sequences will be appended to the existing database containing all known hemoglobins to be used for identification of the mammalian host species that provided the last blood meal for the tick vector of Lyme disease, Ixodes scapularis.
Biochemical characterization and structural modeling of human cathepsin E variant 2 in comparison to the wild-type protein
Authors: Puizdar Vida , Zajc Tajana , Žerovnik Eva , Renko Miha , Pieper Ursula , Eswar Narayanan , Šali Andrej , Dolenc Iztok , Turk Vito
Published: March 2012

Cathepsin E splice variant 2 appears in a number of gastric carcinomas. Here we report detecting this variant in HeLa cells using polyclonal antibodies and biotinylated inhibitor pepstatin A. An overexpression of GFP fusion proteins of cathepsin E and its splice variant within HEK-293T cells was performed to show their localization. Their distribution under a fluorescence microscope showed that they are colocalized. We also expressed variants 1 and 2 of cathepsins E, with propeptide and without it, in Escherichia coli. After refolding from the inclusion bodies, the enzymatic activity and circular dichroism spectra of the splice variant 2 were compared to those of the wild-type mature active cathepsins E. While full-length cathepsin E variant 1 is activated at acid pH, the splice variant remains inactive. In contrast to the active cathepsin E, the splice variant 2 predominantly assumes β-sheet structure, prone to oligomerization, at least under in vitro conditions, as shown by atomic force microscopy as shallow disk-like particles. A comparative structure model of splice variant 2 was computed based on its alignment to the known structure of cathepsin E intermediate (Protein Data Bank code 1TZS) and used to rationalize its conformational properties and loss of activity.
Characterization of RNA damage under oxidative stress in Escherichia coli
Authors: Liu Min , Gong Xin , Alluri Ravi Kumar , Wu Jinhua , Sablo Tene’ , Li Zhongwei
Published: March 2012

We have examined the level of 8-hydroxyguanosine (8-oxo-G), an oxidized form of guanosine, in RNA in Escherichia coli under normal and oxidative stress conditions. The level of 8-oxo-G in RNA rises rapidly and remains high for hours in response to hydrogen peroxide (H2O2) challenge in a dose-dependent manner. H2O2 induced elevation of 8-oxo-G content is much higher in RNA than that of 8-hydroxydeoxyguanosine (8-oxo-dG) in DNA. Under normal conditions, the 8-oxo-G level is low in RNA isolated from the ribosome and it is nearly three times higher in non-ribosomal RNAs. In contrast, 8-oxo-G generated by a short exposure to H2O2 is almost equally distributed in various RNA species, suggesting that although ribosomal RNAs are normally less oxidized, they are not protected against exogenous H2O2. Interestingly, highly folded RNA is not protected from oxidation because 8-oxo-G generated by H2O2 treatment in vitro increases to approximately the same levels in tRNA and rRNA in both native and denatured forms. Lastly, increased RNA oxidation is closely associated with cell death by oxidative stress. Our data suggests that RNA is a primary target for reactive oxygen species and RNA oxidation is part of the paradox that cells have to deal with under oxidative stress.
Uncommon membrane distribution of Shiga toxin glycosphingolipid receptors in toxin-sensitive human glomerular microvascular endothelial cells
Authors: Betz Josefine , Bauwens Andreas , Kunsmann Lisa , Bielaszewska Martina , Mormann Michael , Humpf Hans-Ulrich , Karch Helge , Friedrich Alexander W. , Müthing Johannes
Published: March 2012

Membrane microdomain association of the glycosphingolipids (GSLs) globotriaosylceramide (Gb3Cer) and globotetraosylceramide (Gb4Cer), the highly and less effective receptors, respectively, for Shiga toxins (Stxs), is assumed as a functional requirement for Stx-mediated cytotoxicity. In a previous study, we demonstrated predominant localization of Stx receptors in cholesterol-enriched membrane microdomains of moderately Stx-sensitive human brain microvascular endothelial cells (HBMECs) by means of detergent-resistant membranes (DRMs). Here we report a different preferential distribution of Stx receptors in non-DRM fractions of human glomerular microvascular endothelial cells (GMVECs), the major targets of Stxs in the human kidney. Full structural characterization of Stx receptors using electrospray ionization (ESI) mass spectrometry revealed Gb3Cer and Gb4Cer lipoforms with ceramide moieties mainly composed of C24:0/C24:1 or C16:0 fatty acid and sphingosine (d18:1) in GMVECs comparable to those previously found in HBMECs. Thin-layer chromatography immunostaining demonstrated an approximately 2-fold higher content of Gb3Cer and a 1.4-fold higher content of Gb4Cer in GMVECs than in HBMECs. However, this does not explain the remarkable higher cytotoxic action of Stx1 and Stx2 toward GMVECs as compared with HBMECs. Our finding opens new questions on the microdomain association of Stx receptors and the functional role of GSLs in the membrane assembly of GMVECs.
Asymptotische Störkompensation mittels dualer Zustandsregler für lineare Deskriptorsysteme
Authors: Deutscher Joachim
Published: March 2012

Gegenstand dieses Beitrags ist die asymptotische Störkompensation für lineare Deskriptorsysteme mittels Ausgangsregler, wobei die Regelgrößen nicht als messbar vorausgesetzt werden. Durch Lösung dieser Problemstellung mittels des dualen Zugangs zur Zustandsregelung werden direkt Regler bestimmt, die eine klassische Zustandsdarstellung besitzen. Der Entwurf erfolgt ohne eine Transformation auf Weierstrass-Kronecker-Normalform und lässt sich auch auf nicht impulssteuerbare und impulsbeobachtbare Deskriptorsysteme anwenden. Zur Lösung der hergeleiteten Entwurfsgleichungen wird ein parametrisches Verfahren angegeben. Ein einfaches mechanisches Beispielsystem dient zur Veranschaulichung der theoretischen Ergebnisse.
Zwei-Freiheitsgrade-Regelung linearer Systeme mit Stellgrößen- und Stellratenbegrenzungen
Authors: Kefferpütz Klaus , Ackermann Carlo , Adamy Jürgen
Published: March 2012

In diesem Artikel wird eine schnelle Führungsregelung für lineare Regelstrecken unter Stellgrößen- und Stellratenbeschränkungen vorgestellt. Dazu wird ein auch für nichtlineare Systeme anwendbarer inversionsbasierter Vorsteuerungsentwurf mit einem weich-strukturvariablen Regler kombiniert. Die Formulierung eines konvexen Optimierungsproblems erlaubt den effizienten Reglerentwurf.
Role of leptin in the pancreatic β-cell: effects and signaling pathways
Authors: Marroquí Laura , Gonzalez Alejandro , Ñeco Patricia , Caballero-Garrido Ernesto , Vieira Elaine , Ripoll Cristina , Nadal Angel , Quesada Ivan
Published: March 2012

Leptin plays an important role in the control of food intake, energy expenditure, metabolism, and body weight. This hormone also has a key function in the regulation of glucose homeostasis. Although leptin acts through central and peripheral mechanisms to modulate glucose metabolism, the pancreatic β-cell of the endocrine pancreas is a critical target of leptin actions. Leptin receptors are present in the β-cell, and their activation directly inhibits insulin secretion from these endocrine cells. The effects of leptin on insulin occur also in the long term, since this hormone inhibits insulin gene expression as well. Additionally, β-cell mass can be affected by leptin through changes in proliferation, apoptosis, or cell size. All these different functions in the β-cell are triggered by leptin as a result of the large diversity of signaling pathways that this hormone is able to activate in the endocrine pancreas. Therefore, leptin can participate in glucose homeostasis owing to different levels of modulation of the pancreatic β-cell population. Furthermore, it has been proposed that alterations in this level of regulation could contribute to the impairment of β-cell function in obesity states. In the present review, we will discuss all these issues with special emphasis on the effects and pathways of leptin signaling in the pancreatic β-cell.