bluuebunny/crossref_metadata_2025 huggingface dataset:
Trauma Among Street-Involved Youth
Authors: Bender Kimberly A. , Thompson Sanna J. , Ferguson Kristin M. , Yoder Jamie R. , Kern Leah
Published: March 2013

Previous research documents that street-involved youth experience rates of trauma and posttraumatic stress disorder (PTSD) that are significantly higher than their housed counterparts. Trauma and PTSD are of particular concern for homeless youth as they can negatively affect youths’ ability to function adaptively and to transition off the streets. This mixed-methods study investigates the intricacies of trauma experienced by homeless youth across three U.S. cities. Qualitative interviews were conducted with a sample of 145 homeless youth in Los Angeles ( n = 50), Denver ( n = 50), and Austin ( n = 45) to explore youths’ perspectives on the definition of trauma and the contexts associated with victimization. Quantitative standardized assessments investigated youths’ trauma experiences before and after becoming homeless. Trauma screening identified high rates of trauma incidents (78%), with 28% of participants meeting criteria for PTSD. Participants reported various traumatic experiences that occurred before leaving home and while on the streets, and high rates of polyvictimization. Qualitative themes describe particular people and places most vulnerable on the streets. Implications for services to prevent and treat trauma among homeless youth are discussed.
Open Ankle Arthrodesis With a Fibular-Sparing Technique
Authors: Smith Jeremy T. , Chiodo Christopher P. , Singh Samrendu K. , Wilson Michael G.
Published: March 2013

Background:

Many ankle arthrodesis techniques excise the fibula or require a fibular osteotomy. Advantages of fibular preservation include increased surface area for bony union, preservation of the peroneal groove, prevention of valgus drift in cases of delayed union, and facilitation of future ankle arthroplasty. The goal of this study was to evaluate fusion rate and clinical outcomes of a novel open fibular-sparing ankle arthrodesis technique.

Methods:

A total of 50 consecutive ankle arthrodeses using this technique were included in this study. These consisted of 46 patients with an average age of 52 (range, 30 to 71) years. Outcomes assessed postoperatively included radiographs, complications, patient satisfaction, and functional scoring.

Results:

At an average of 28 (range, 19 to 56) months postoperatively, 38 patients (42 ankles) were available for review. Of the 42 cases, 39 (93%) achieved union at an average of 12 weeks postoperatively. Of patients, 86% reported being “completely satisfied” with the outcome. Average AOFAS Ankle-Hindfoot Scale was 84 ± 12 and average Foot Function Index pain subscale was 1 ± 0.9. Two ankles (5%) were fused in excessive varus; no patient required revision surgery for malalignment.

Conclusion:

This method of open ankle arthrodesis preserved the fibula and had a high fusion rate with good patient outcome scores.

Level of Evidence:

Level IV, retrospective case series.
Working as playing? Consumer labor, guild and the secondary industry of online gaming in China
Authors: Zhang Lin , Fung Anthony YH
Published: March 2013

China has become one of the biggest consumers and producers of online games in the world; however, little is known about a burgeoning secondary industry emerging out of the socioeconomic interaction between gamers and the online gaming industry. Through the lens of online gaming guilds—the intermediary institutions between the industry and gamers—this article discusses how the Chinese information economy’s dependence on consumer labor and the gamers’ entrepreneurial resourcefulness have produced a secondary industry. As the secondary industry has evolved, the gaming industry has come to depend on the productive play of consumers. This changing regime of value has given rise to bio-political control of consumer labor and, along with state control, is drawing gamers into the tug-of-war between entrepreneurial invention and labor exploitation. By depicting the complex negotiations between capital and labor, and community and commerce, on both subjective and institutional levels, this article re-examines and explicates the Western debate over consumer digital cultural production and its social, economic, and political implications.
Archaeologies and geographies of the post-industrial past: landscape, memory and the spectral
Authors: Hill Lisa
Published: March 2013

Located at the interface between contemporary archaeology, cultural and historical geography, this essay explores the ‘more-than-representational’ nature of memory as embodied and haunted by the spectral. Focusing on the post-industrial landscape of the Royal Forest of Dean, I narrate a walk undertaken in November 2008 with local resident, Ron Beard, as we sought to re-trace an old miners’ path. Histories of the landscape unfolded as we walked. Yet they also revealed a haunting sense of loss, a fragmented remembering and forgetting that was unsettled by ghosts from the past. For memory is born of strange and uncanny associations, inexplicable connections between times and places that erupt into the present without warning. As such, memory demands new ways of writing; narratives that better cope with our fragile and contingent recollections, disclosing the haunting presence-absence of the spectral in all its shapes, apparitions and phantasms. I begin by pursuing the idea that memory is more-than-representational. I go on to explore the recurrent manifestation of the spectral, which disturbs, displaces and conditions our understanding of space and time, absence and presence. Developing the argument that alternative styles of writing are needed to reveal the true nature of memory and our haunting engagements with the past − while at the same time accepting Wylie’s assertion that spectral geographies should themselves be spectral − I consider the work of Walter Benjamin and W.G. Sebald, which, through devices such as literary montage, biography and phantasmagoria, successfully unsettles, disrupts and enlivens. Taking stylistic inspiration from these great writers, the ‘Long Path’ is narrated in a non-conventional academic style that seeks itself to displace settled orders of space and time, to reveal the revenant trace of the spectre.
Linaclotide: A new drug for the treatment of chronic constipation and irritable bowel syndrome with constipation
Authors: Corsetti Maura , Tack Jan
Published: March 2013

Introduction

Linaclotide is the first member of a novel class of drugs to be extensively evaluated for the treatment of chronic constipation (CC) and irritable bowel syndrome with constipation (IBS‐C).

Aim

To provide a comprehensive overview of the current state of knowledge on linaclotide, its pharmacological properties, mode of action and efficacy in clinical trials to date.

Methods

We conducted a systematic review of the literature.

Results

The survey revealed that linaclotide is a minimally absorbed, 14‐amino acid peptide which acts in the intestinal lumen on guanylate cyclase‐C (GC‐C). This results in generation of cyclic guanosine monophosphate (cGMP), which stimulates chloride secretion, resulting in increased luminal fluid secretion and an acceleration of intestinal transit. In animal models, linaclotide also decreased visceral hypersensitivity. Linaclotide softened stool and increased transit in CC and in IBS‐C. Phase II and phase III clinical studies established efficacy of linaclotide in CC (linaclotide 145 µg daily approved in the United States for CC) and in IBS‐C (linaclotide 290 µg daily US Food and Drug Administration‐approved for IBS‐C, with favourable recommendation for the European Medicines Agency Committee for Medicinal Products for Human Use (CHMP). Linaclotide showed a favourable safety profile, and the main treatment‐emerging adverse event was diarrhea, leading to discontinuation rates of up to 5%. Linaclotide is an important addition to the therapeutic possibilities for treating IBS‐C and CC.
A new approach for eradication of residual lymphoma cells by host nonreactive anti–third-party central memory CD8 T cells
Authors: Lask Assaf , Ophir Eran , Or-Geva Noga , Cohen-Fredarow Adva , Afik Ran , Eidelstein Yaki , Reich-Zeliger Shlomit , Nathansohn Bar , Edinger Matthias , Negrin Robert S. , Hagin David , Reisner Yair
Published: February 2013

Key Points

Anti–third-party Tcm kill malignant B cells in a T-cell receptor–independent mechanism while sparing naive B cells.
Porcine CD8αdim/-NKp46high NK cells are in a highly activated state
Authors: Mair Kerstin H , Müllebner Andrea , Essler Sabine E , Duvigneau J Catharina , Storset Anne K , Saalmüller Armin , Gerner Wilhelm
Published: March 2013

Natural Killer (NK) cells play a crucial role in the early phase of immune responses against various pathogens. In swine so far only little information about this lymphocyte population exists. Phenotypical analyses with newly developed monoclonal antibodies (mAbs) against porcine NKp46 recently revealed that in blood NKp46-and NKp46+cells with NK phenotype exist with comparable cytotoxic properties. In spleen a third NKp46-defined population with NK phenotype was observed that was characterised by a low to negative CD8α and increased NKp46 expression. In the current study it is shown that this NKp46highphenotype was correlated with an increased expression of CD16 and CD27 compared to the CD8α+NKp46-and NKp46+NK-cell subsets in spleen and blood. Additionally NKp46highNK cells expressed elevated levels of the chemokine receptor CXCR3 on mRNA level. Functional analyses revealed that splenic NKp46highNK cells produced much higher levels of Interferon-γ and Tumor Necrosis Factor-α upon stimulation with cytokines or phorbol-12-myristate-13-acetate/Ionomycin compared to the other two subsets. Furthermore, cross-linking of NKp46 by NKp46-specific mAbs led to a superior CD107a expression in the NKp46highNK cells, thus indicating a higher cytolytic capacity of this subset. Therefore porcine splenic NKp46highNK cells represent a highly activated subset of NK cells and may play a profound role in the immune surveillance of this organ.
Evolution of land plant genes encoding L-Ala-D/L-Glu epimerases (AEEs) via horizontal gene transfer and positive selection
Authors: Yang Zefeng , Wang Yifan , Zhou Yong , Gao Qingsong , Zhang Enying , Zhu Lei , Hu Yunyun , Xu Chenwu
Published: March 2013

Background

The L-Ala-D/L-Glu epimerases (AEEs), a subgroup of the enolase superfamily, catalyze the epimerization of L-Ala-D/L-Glu and other dipeptides in bacteria and contribute to the metabolism of the murein peptide of peptidoglycan. Although lacking in peptidoglycan, land plants possess AEE genes that show high similarity to those in bacteria.

Results

Similarity searches revealed that the AEE gene is ubiquitous in land plants, from bryophytas to angiosperms. However, other eukaryotes, including green and red algae, do not contain genes encoding proteins with an L-Ala-D/L-Glu_epimerase domain. Homologs of land plant AEE genes were found to only be present in prokaryotes, especially in bacteria. Phylogenetic analysis revealed that the land plant AEE genes formed a monophyletic group with some bacterial homologs. In addition, land plant AEE proteins showed the highest similarity with these bacterial homologs and shared motifs only conserved in land plant and these bacterial AEEs. Integrated information on the taxonomic distribution, phylogenetic relationships and sequence similarity of the AEE proteins revealed that the land plant AEE genes were acquired from bacteria through an ancient horizontal gene transfer (HGT) event. Further evidence revealed that land plant AEE genes had undergone positive selection and formed the main characteristics of exon/intron structures through gaining some introns during the initially evolutionary period in the ancestor of land plants.

Conclusions

The results of this study clearly demonstrated that the ancestor of land plants acquired an AEE gene from bacteria via an ancient HGT event. Other findings illustrated that adaptive evolution through positive selection has contributed to the functional adaptation and fixation of this gene in land plants.
Mutational profiling reveals PIK3CA mutations in gallbladder carcinoma
Authors: Deshpande Vikram , Nduaguba Afamefuna , Zimmerman Stephanie M , Kehoe Sarah M , MacConaill Laura E , Lauwers Gregory Y , Ferrone Cristina , Bardeesy Nabeel , Zhu Andrew X , Hezel Aram F
Published: March 2013

Background

The genetics of advanced biliary tract cancers (BTC), which encompass intra- and extra-hepatic cholangiocarcinomas as well as gallbladder carcinomas, are heterogeneous and remain to be fully defined.

Methods

To better characterize mutations in established known oncogenes and tumor suppressor genes we tested a mass spectrometric based platform to interrogate common cancer associated mutations across a panel of 77 formalin fixed paraffin embedded archived BTC cases.

Results

Mutations among three genes, KRAS, NRAS and PIK3CA were confirmed in this cohort. Activating mutations in PIK3CA were identified exclusively in GBC (4/32, 12.5%). KRAS mutations were identified in 3 (13%) intra-hepatic cholangiocarcinomas and 1 (33%) perihillar cholangiocarcinoma but were not identified in gallbladder carcinomas and extra-hepatic cholangiocarcinoma.

Conclusions

The presence of activating mutations in PIK3CA specifically in GBC has clinical implications in both the diagnosis of this cancer type, as well as the potential utility of targeted therapies such as PI3 kinase inhibitors.
Variation of C peptide decay rate in diabetic patients with positive glutamic acid decarboxylase antibody: better discrimination with initial fasting C peptide
Authors: Li Xia , Huang Gan , Lin Jian , Yang Lin , Zhou Zhiguang
Published: March 2013

Background

Diabetic patients with positive glutamic acid decarboxylase antibody (GAD-Ab) could be classified as autoimmune diabetes, which is discriminated into acute-onset classical type 1 diabetes (T1DM) and latent autoimmune diabetes in adults (LADA). However, whether the decay rate of beta cell function is relevant with the mode of onset (acute or latent-onset) is unclear. We aimed to investigate whether initial C peptide levels could help differentiate variation of C peptide decay rate.

Methods

Five hundred and twenty-seven newly diagnosed GAD-Ab positive diabetic patients were followed up to assess the natural course of beta cell function. Beta cell function failure was defined as fasting C peptide and postprandial C peptide levels less than 100 pmol/L and 150 pmol/L respectively.

Results

All these diabetic patients were discriminated according to initial fasting C peptide of 300 pmol/L, that is B+ (larger than 300 pmol/L) and B- (less than 300 pmol/L) group. The proportion of developing beta cell function failure was 13.1% in B+ group and 90.5% in B- group, which suggested that fasting C peptide levels made a good distinction of the heterogeneity in autoimmune diabetes. Receiver operator characteristic (ROC) analysis suggested that the fasting C peptide level of 300 pmol/L was optimal for determining beta cell function failure with sensitivity of 90.5% and specificity of 86.9%.

Conclusions

Initial level of fasting C peptide is a good indicator for predicting beta cell function failure in GAD-Ab positive diabetic patients.
Guava leaf extracts promote glucose metabolism in SHRSP.Z-Leprfa/Izm rats by improving insulin resistance in skeletal muscle
Authors: Guo Xiangyu , Yoshitomi Hisae , Gao Ming , Qin Lingling , Duan Ying , Sun Wen , Xu Tunhai , Xie Peifeng , Zhou Jingxin , Huang Liansha , Liu Tonghua
Published: March 2013

Background

Metabolic syndrome (MS) and type 2 diabetes mellitus (T2DM) have been associated with insulin-resistance; however, the effective therapies in improving insulin sensitivity are limited. This study is aimed at investigating the effect of Guava Leaf (GL) extracts on glucose tolerance and insulin resistance in SHRSP.Z-Leprfa/Izm rats (SHRSP/ZF), a model of spontaneously metabolic syndrome.

Methods

Male rats at 7 weeks of age were administered with vehicle water or treated by gavage with 2 g/kg GL extracts daily for six weeks, and their body weights, water and food consumption, glucose tolerance, and insulin resistance were measured.

Results

Compared with the controls, treatment with GL extracts did not modulate the amounts of water and food consumption, but significantly reduced the body weights at six weeks post treatment. Treatment with GL extracts did not alter the levels of fasting plasma glucose and insulin, but significantly reduced the levels of plasma glucose at 60 and 120 min post glucose challenge, also reduced the values of AUC and quantitative insulin sensitivity check index (QUICKI) at 42 days post treatment. Furthermore, treatment with GL extracts promoted IRS-1, AKT, PI3Kp85 expression, then IRS-1, AMKP, and AKT308, but not AKT473, phosphorylation, accompanied by increasing the ratios of membrane to total Glut 4 expression and adiponectin receptor 1 transcription in the skeletal muscles.

Conclusions

These data indicated that GL extracts improved glucose metabolism and insulin sensitivity in the skeletal muscles of rats by modulating the insulin-related signaling.
Characterizing microclimate in urban malaria transmission settings: a case study from Chennai, India
Authors: Cator Lauren J , Thomas Shalu , Paaijmans Krijn P , Ravishankaran Sangamithra , Justin Johnson A , Mathai Manu T , Read Andrew F , Thomas Matthew B , Eapen Alex
Published: March 2013

Background

Environmental temperature is an important driver of malaria transmission dynamics. Both the parasite and vector are sensitive to mean ambient temperatures and daily temperature variation. To understand transmission ecology, therefore, it is important to determine the range of microclimatic temperatures experienced by malaria vectors in the field.

Methods

A pilot study was conducted in the Indian city of Chennai to determine the temperature variation in urban microclimates and characterize the thermal ecology of the local transmission setting. Temperatures were measured in a range of probable indoor and outdoor resting habitats of Anopheles stephensi in two urban slum malaria sites. Mean temperatures and daily temperature fluctuations in local transmission sites were compared with standard temperature measures from the local weather station. The biological implications of the different temperatures were explored using temperature-dependent parasite development models to provide estimates of the extrinsic incubation period (EIP) of Plasmodium vivax and Plasmodium falciparum.

Results

Mean daily temperatures within the urban transmission sites were generally warmer than those recorded at the local weather station. The main reason was that night-time temperatures were higher (and hence diurnal temperature ranges smaller) in the urban settings. Mean temperatures and temperature variation also differed between specific resting sites within the transmission environments. Most differences were of the order of 1-3°C but were sufficient to lead to important variation in predicted EIPs and hence, variation in estimates of transmission intensity.

Conclusions

Standard estimates of environmental temperature derived from local weather stations do not necessarily provide realistic measures of temperatures within actual transmission environments. Even the small differences in mean temperatures or diurnal temperature ranges reported in this study can lead to large variations in key mosquito and/or parasite life history traits that determine transmission intensity. Greater effort should be directed at quantifying adult mosquito resting behaviour and determining the temperatures actually experienced by mosquitoes and parasites in local transmission environments. In the absence of such highly resolved data, the approach used in the current study provides a framework for improved thermal characterization of transmission settings.
Combination treatment with ABT-737 and chloroquine in preclinical models of small cell lung cancer
Authors: Zinn Rebekah L , Gardner Eric E , Dobromilskaya Irina , Murphy Sara , Marchionni Luigi , Hann Christine L , Rudin Charles M
Published: March 2013

Background

New therapies are urgently needed for patients with small cell lung cancer (SCLC). Chemotherapy and targeted therapies, including the Bcl-2 inhibitor ABT-737, may induce tumor cell autophagy. Autophagy can promote survival of cancer cells under stress and comprise a pathway of escape from cytotoxic therapies.

Methods

We explored the combination of ABT-737 and chloroquine, an inhibitor of autophagy, in preclinical models of SCLC. These included cell culture analyses of viability and of autophagic and apoptotic pathway induction, as well as in vivo analyses of efficacy in multiple xenograft models.

Results

Combination treatment of SCLC lines with ABT-737 and chloroquine decreased viability and increased caspase-3 activation over treatment with either single agent. ABT-737 induced several hallmarks of autophagy. However, knockdown of beclin-1, a key regulator of entry into autophagy, diminished the efficacy of ABT-737, suggesting either that the effects of chloroquine were nonspecific or that induction but not completion of autophagy is necessary for the combined effect of ABT-737 and chloroquine. ABT-737 and chloroquine in SCLC cell lines downregulated Mcl-1 and upregulated NOXA, both of which may promote apoptosis. Treatment of tumor-bearing mice demonstrated that chloroquine could enhance ABT-737-mediated tumor growth inhibition against NCI-H209 xenografts, but did not alter ABT-737 response in three primary patient-derived xenograft models.

Conclusion

These data suggest that although ABT-737 can induce autophagy in SCLC, autophagic inhibition by choroquine does not markedly alter in vivo response to ABT-737 in relevant preclinical models, arguing against this as a treatment strategy for SCLC.
Organic electrochemical transistors based on a dielectrophoretically aligned nanowire array
Authors: Choi WooSeok , An Taechang , Lim Geunbae
Published: March 2013

In this study, we synthesized an organic electrochemical transistor (OECT) using dielectrophoresis of a carbon nanotube-Nafion (CNT-Nafion) suspension. Dielectrophoretically aligned nanowires formed a one-dimensional submicron bundle between triangular electrodes. The CNT-Nafion composite nanowire bundles showed p-type semiconductor characteristics. The drain-source current decreased with increasing gate voltage. The nanowire bundles showed potential as pH sensor because the drain-source current ratio varied linearly according to the gate voltage in pH buffers.
Hydroxychloroquine effectiveness in reducing symptoms of hand osteoarthritis (HERO): study protocol for a randomized controlled trial
Authors: Kingsbury Sarah R , Tharmanathan Puvan , Adamson Joy , Arden Nigel K , Birrell Fraser , Cockayne Sarah , Dickson John , Doherty Michael , Dziedzic Krysia S , Grainger Andrew , Hewitt Catherine E , O’Neill Terence W , Scott David L , Vincent Tonia L , Wakefield Richard J , Watt Fiona E , Torgerson David J , Conaghan Philip G
Published: March 2013

Background

Osteoarthritis (OA) is the most common type of arthritis, causing significant joint pain and disability. It is already a major cause of healthcare expenditure and its incidence will further increase with the ageing population. Current treatments for OA have major limitations and new analgesic treatments are needed. Synovitis is prevalent in OA and is associated with pain. Hydroxychloroquine is used in routine practice for treating synovitis in inflammatory arthritides, such as rheumatoid arthritis. We propose that treating patients with symptomatic hand OA with hydroxychloroquine will be a practical and safe treatment to reduce synovitis and pain.

Methods/design

HERO is an investigator-initiated, multicentre, randomized, double-blind, placebo-controlled trial. A total of 252 subjects with symptomatic hand OA will be recruited across primary and secondary care sites in the UK and randomized on a 1:1 basis to active treatment or placebo for 12 months. Daily medication dose will range from 200 to 400 mg according to ideal body weight. The primary endpoint is change in average hand pain during the previous two weeks (measured on a numerical rating scale (NRS)) between baseline and six months. Secondary endpoints include other self-reported pain, function and quality-of-life measures and radiographic structural change at 12 months. A health economics analysis will also be performed. An ultrasound substudy will be conducted to examine baseline levels of synovitis. Linear and logistic regression will be used to compare changes between groups using univariable and multivariable modelling analyses. All analyses will be conducted on an intention-to-treat basis.

Discussion

The HERO trial is designed to examine whether hydroxychloroquine is an effective analgesic treatment for OA and whether it provides any long-term structural benefit. The ultrasound substudy will address whether baseline synovitis is a predictor of therapeutic response. This will potentially provide a new treatment for OA, which could be of particular use in the primary care setting.

Trial registration

ISRCTN91859104.
Outcome of surgical treatment for proximal long segment post intubation tracheal stenosis
Authors: Bagheri Reza , Majidi Mohammadreza , Khadivi Ehsan , attar Alireza Sharifian , Tabari Azadeh
Published: March 2013

Background

Post intubation long segment tracheal stenosis is a serious problem which usually requires multiple methods of treatment. The aim of this study was to evaluate the results of surgical treatment in long segment post intubation tracheal stenosis.

Methods

Between 2004 to 2008, 20 patients with proximal long segment tracheal stenosis and resection of over 40% of tracheal length, were analyzed in terms of age, sex, clinical symptoms, etiology of stenosis, length of stenosis and resection, role of suprahyoeid release with bilateral hyoeid bone cutting maneuver, post operative complications and life quality 3 year after surgery.

Results

M/F was 2/5, with the average age of 23.5 ± 0.5 years. Average length of stenosis was 4.2 ± 0.4 cm and the average length of resected segment was 5.2 ± 0.4 cm. Early postoperative complications occurred in 4 patients (20%), 5 patients (25%) had late stenosis and 4 of them were treated with multiple dilation and one patient needed tracheostomy and prolonged T. tube. We didn’t have any mortality. 80% of patients had excellent surgical results in follow up period.

Conclusion

Surgery is the best method of treatment in long and multi segment tracheal stenosis.
Incidence and pattern of technical complications in balloon-guided osteoplasty for depressed tibial plateau fractures: a pilot study in 20 consecutive patients
Authors: Mauffrey Cyril , Fader Ryan , Hammerberg E Mark , Hak David J , Stahel Philip F
Published: March 2013

Background

Inflation bone tamps are becoming increasingly popular as a reduction tool for depressed tibial plateau fractures. A number of recent publications have addressed the technical aspects of balloon inflation osteoplasty. However, no study has yet been published to describe the technical limitations, intraoperative complications, and surgical bailout strategies for this new technology.

Methods

Observational retrospective study of all patients managed with inflatable bone tamps for depressed tibial plateau fractures between October 1, 2010 and December 1, 2012. The primary outcome parameter was the rate of complications, which were stratified into “minor” and “major” depending on the necessity for altering the surgical plan intraoperatively, and based on the risk for patient harm. This study was approved by the Institutional Review Board of the State of Colorado.

Results

A consecutive series of 20 patients were managed by balloon inflation osteoplasty for depressed tibial plateau fractures during the 15 months study period. The mean age was 42.8 years (range 20–79), with 9 females and 11 males. A total of 13 patients sustained an adverse intraoperative event (65%), with three patients sustaining multiple technical complications. Minor events (n = 8) included the burst of a balloon with extrusion of contrast dye, and the unintentional posterior wall displacement during balloon inflation. Major events (n = 5) included the intra-articular injection of calcium phosphate in the knee joint, and the inability to elevate the depressed articular fragment with the inflatable bone tamp.

Conclusion

The observed intraoperative complication rate of 65% reflects a steep learning curve for the use of inflation bone tamps to reduce depressed tibial plateau fractures. Specific surgical bailout options are provided in this article, based on our early anecdotal experience in a pilot series of 20 consecutive cases. Patients should be advised on the benefits and risks of this new technology as part of the shared decision-making process during the informed consent.
Evaluation of reference genes for reverse transcription quantitative PCR analyses of fish-pathogenic Francisella strains exposed to different growth conditions
Authors: Brudal Espen , Winther-Larsen Hanne Cecilie , Colquhoun Duncan John , Duodu Samuel
Published: March 2013

Background

Reverse transcription quantitative PCR has become a powerful technique to monitor mRNA transcription in response to different environmental conditions in many bacterial species. However, correct evaluation of data requires accurate and reliable use of reference genes whose transcription does not change during the course of the experiment. In the present study exposure to different growth conditions was used to validate the transcription stability of eight reference gene candidates in three strains from two subspecies of Francisella noatunensis, a pathogen causing disease in both warm and cold water fish species.

Results

Relative transcription levels for genes encoding DNA gyrase (gyrA), RNA polymerase beta subunit (rpoB), DNA polymerase I (polA), cell division protein (ftsZ), outer membrane protein (fopA), riboflavin biosynthesis protein (ribC), 16S ribosomal RNA (16S rRNA) and DNA helicases (uvrD) were quantified under exponential, stationary and iron-restricted growth conditions. The suitability of selected reference genes for reliable interpretation of gene expression data was tested using the virulence-associated intracellular growth locus subunit C (iglC) gene.

Conclusion

Although the transcription stability of the reference genes was slightly different in the three strains studied, fopA, ftsZ and polA proved to be the most stable and suitable for normalization of gene transcription in Francisella noatunensis ssp.
Use of a physiologically-based pharmacokinetic model to simulate artemether dose adjustment for overcoming the drug-drug interaction with efavirenz
Authors: Siccardi Marco , Olagunju Adeniyi , Seden Kay , Ebrahimjee Farid , Rannard Steve , Back David , Owen Andrew
Published: March 2013

Purpose

To treat malaria, HIV-infected patients normally receive artemether (80 mg twice daily) concurrently with antiretroviral therapy and drug-drug interactions can potentially occur. Artemether is a substrate of CYP3A4 and CYP2B6, antiretrovirals such as efavirenz induce these enzymes and have the potential to reduce artemether pharmacokinetic exposure. The aim of this study was to develop an in vitro in vivo extrapolation (IVIVE) approach to model the interaction between efavirenz and artemether. Artemether dose adjustments were then simulated in order to predict optimal dosing in co-infected patients and inform future interaction study design.

Methods

In vitro data describing the chemical properties, absorption, distribution, metabolism and elimination of efavirenz and artemether were obtained from published literature and included in a physiologically based pharmacokinetic model (PBPK) to predict drug disposition simulating virtual clinical trials. Administration of efavirenz and artemether, alone or in combination, were simulated to mirror previous clinical studies and facilitate validation of the model and realistic interpretation of the simulation. Efavirenz (600 mg once daily) was administered to 50 virtual subjects for 14 days. This was followed by concomitant administration of artemether (80 mg eight hourly) for the first two doses and 80 mg (twice daily) for another two days.

Results

Simulated pharmacokinetics and the drug-drug interaction were in concordance with available clinical data. Efavirenz induced first pass metabolism and hepatic clearance, reducing artemether Cmax by 60% and AUC by 80%. Dose increases of artemether, to correct for the interaction, were simulated and a dose of 240 mg was predicted to be sufficient to overcome the interaction and allow therapeutic plasma concentrations of artemether.

Conclusions

The model presented here provides a rational platform to inform the design for a clinical drug interaction study that may save time and resource while the optimal dose is determined empirically. Wider application of IVIVE could help researchers gain a better understanding of the molecular mechanisms underpinning variability in drug disposition.
Pannexin1 hemichannels are critical for HIV infection of human primary CD4+ T lymphocytes
Authors: Orellana J A , Velasquez S , Williams D W , Sáez J C , Berman J W , Eugenin E A
Published: March 2013

HIV is a major public health issue, and infection of CD4+ T lymphocytes is one of its key features. Whereas several cellular proteins have been identified that facilitate viral infection and replication, the role of hemichannels in these processes has not been fully characterized. We now show that the HIV isolates, R5 and X4, induced a transient-early (5–30 min) and a later, persistent (48–120 h) opening of Panx1 hemichannels, which was dependent on the binding of HIV to CD4 and CCR5/CXCR4 receptors. Blocking Panx1 hemichannels by reducing their opening or protein expression inhibited HIV replication in CD4+ T lymphocytes. Thus, our findings demonstrate that Panx1 hemichannels play an essential role in HIV infection.
Dwarfism and Increased Adiposity in the gh1 Mutant Zebrafish vizzini
Authors: McMenamin Sarah K. , Minchin James E.N. , Gordon Tiffany N. , Rawls John F. , Parichy David M.
Published: March 2013

Somatic growth and adipogenesis are closely associated with the development of obesity in humans. In this study, we identify a zebrafish mutant, vizzini, that exhibits both a severe defect in somatic growth and increased accumulation of adipose tissue. Positional cloning of vizzini revealed a premature stop codon in gh1. Although the effects of GH are largely through igfs in mammals, we found no decrease in the expression of igf transcripts in gh1 mutants during larval development. As development progressed, however, we found overall growth to be progressively retarded and the attainment of specific developmental stages to occur at abnormally small body sizes relative to wild type. Moreover, both subcutaneous (sc) and visceral adipose tissues underwent precocious development in vizzini mutants, and at maturity, the sizes of different fat deposits were greatly expanded relative to wild type. In vivo confocal imaging of sc adipose tissue (SAT) expansion revealed that vizzini mutants exhibit extreme enlargement of adipocyte lipid droplets without a corresponding increase in lipid droplet number. These findings suggest that GH1 signaling restricts SAT hypertrophy in zebrafish. Finally, nutrient deprivation of vizzini mutants revealed that SAT mobilization was greatly diminished during caloric restriction, further implicating GH1 signaling in adipose tissue homeostasis. Overall, the zebrafish gh1 mutant, vizzini, exhibits decreased somatic growth, increased adipose tissue accumulation, and disrupted adipose plasticity after nutrient deprivation and represents a novel model to investigate the in vivo dynamics of vertebrate obesity.
Stable incorporation vs. dynamic exchange of β subunits in a native calcium channel complex
Authors: Campiglio Marta , Biase Valentina Di , Tuluc Petronel , Flucher Bernhard E.
Published: February 2013

Voltage-gated calcium channels are multi-subunit membrane proteins which transduce depolarization into cellular functions like excitation-contraction coupling in muscle or neurotransmitter release in neurons. The auxiliary β subunits function in membrane targeting of the channel and modulation of its gating properties. However, whether β subunits can reversibly interact with, and thus differentially modulate channels in the membrane is still unresolved. Here we applied fluorescence recovery after photobleaching (FRAP) of GFP-tagged α1 and β subunits expressed in dysgenic myotubes to study the relative dynamics of these calcium channel subunits for the first time in a native functional signaling complex. Identical fluorescence recovery rates of both subunits indicate stable interactions, distinct rates dynamic interactions. Whereas the skeletal muscle β1a isoform formed stable complexes with CaV1.1 and CaV1.2, the non-skeletal muscle β2a and β4b isoforms dynamically interacted with both α1 subunits. Neither replacing the I–II loop of CaV1.1 with that of CaV2.1, nor deletions in the proximal I–II loop, known to change the orientation of β relative to the α1 subunit, altered the specific dynamic properties of the β subunits. In contrast, a single residue substitution in the α interaction pocket of β1aM293A increased the FRAP rate three-fold. Together these findings indicate that in skeletal muscle triads the homologous β1a subunit forms a stable complex, whereas the heterologous β2a and β4b subunits form dynamic complexes with the calcium channel. The distinct binding properties are not determined by differences in the I–II loop sequences of the α1 subunits but are intrinsic properties of the β subunit isoforms.
Bounded Rationality in Service Systems
Authors: Huang Tingliang , Allon Gad , Bassamboo Achal
Published: March 2013

The traditional operations management and queueing literature typically assumes that customers are fully rational. In contrast, in this paper we study canonical service models with boundedly rational customers. We capture bounded rationality using a model in which customers are incapable of accurately estimating their expected waiting time. We investigate the impact of bounded rationality from both a profit-maximizing firm's perspective and a social planner's perspective. For visible queues with the optimal price, bounded rationality results in revenue and welfare loss; with a fixed price, bounded rationality can lead to strict social welfare improvement. For invisible queues, bounded rationality benefits the firm when its level is sufficiently high. Ignoring bounded rationality, when present yet small, can result in significant revenue and welfare loss.
Engaging Supply Chains in Climate Change
Authors: Jira Chonnikarn (Fern) , Toffel Michael W.
Published: March 2013

Suppliers are increasingly being asked to share information about their vulnerability to climate change and their strategies to reduce greenhouse gas emissions. Their responses vary widely. We theorize and empirically identify several factors associated with suppliers being especially willing to share this information with buyers, focusing on attributes of the buyers seeking this information and of the suppliers being asked to provide it. We test our hypotheses using data from the Carbon Disclosure Project's Supply Chain Program, a collaboration of multinational corporations requesting such information from thousands of suppliers in 49 countries. We find evidence that suppliers are more likely to share this information when requests from buyers are more prevalent, when buyers appear committed to using the information, when suppliers belong to more profitable industries, and when suppliers are located in countries with greenhouse gas regulations. We find evidence that these factors also influence the comprehensiveness of the information suppliers share and their willingness to share the information publicly.
Fixed vs. Random Proportions Demand Models for the Assortment Planning Problem Under Stockout-Based Substitution
Authors: Honhon Dorothée , Seshadri Sridhar
Published: March 2013

We consider the problem of determining the optimal assortment of products to offer in a given product category when each customer is characterized by a type, which is a list of products he is willing to buy in decreasing order of preference. We assume consumer-driven, dynamic, stockout-based substitution and random proportions of each type. No efficient method to obtain the optimal solution for this problem is known to our knowledge. However, if the number of customers of each type is a fixed proportion of demand, there exists an efficient algorithm for solving for the optimal assortment. We show that the fixed proportions model gives an upper bound to the optimal expected profit for the random proportions model. This bound allows us to obtain a measure of the absolute performance of heuristic solutions. We also provide a bound for the component-wise absolute difference in expected sales between the two models, which is asymptotically tight as the inventory vector is made large, while keeping the number of products fixed. This result provides us with a lower bound to the optimal expected profit and a performance guarantee for the fixed proportions solution in the random proportions model.
Does pre-coating total knee tibial implants affect the risk of aseptic revision?
Authors: Bini S. A. , Chen Y. , Khatod M. , Paxton E. W.
Published: February 2013

We evaluated the impact of pre-coating the tibial component with polymethylmethacrylate (PMMA) on implant survival in a cohort of 16 548 primary NexGen total knee replacements (TKRs) in 14 113 patients. In 13 835 TKRs a pre-coated tray was used while in 2713 TKRs the non-pre-coated version of the same tray was used. All the TKRs were performed between 2001 and 2009 and were cemented. TKRs implanted with a pre-coated tibial component had a lower cumulative survival than those with a non-pre-coated tibial component (p = 0.01). After adjusting for diagnosis, age, gender, body mass index, American Society of Anesthesiologists grade, femoral coupling design, surgeon volume and hospital volume, pre-coating was an independent risk factor for all-cause aseptic revision (hazard ratio 2.75, p = 0.006). Revision for aseptic loosening was uncommon for both pre-coated and non-pre-coated trays (rates of 0.12% and 0%, respectively). Pre-coating with PMMA does not appear to be protective of revision for this tibial tray design at short-term follow-up.

Cite this article: Bone Joint J 2013;95-B:367–70.
Primary total knee replacement in patients with mental disability improves their mental health and knee function
Authors: Clement N. D. , MacDonald D. , Burnett R.
Published: February 2013

We assessed the effect of mental disability on the outcome of total knee replacement (TKR) and investigated whether mental health improves post-operatively. Outcome data were prospectively recorded over a three-year period for 962 patients undergoing primary TKR for osteoarthritis. Pre-operative and one year Short-Form (SF)-12 scores and Oxford knee scores (OKS) were obtained. The mental component of the SF-12 was stratified into four groups according to level of mental disability (none ≥ 50, mild 40 to 49, moderate 30 to 39, severe < 30). Patients with any degree of mental disability had a significantly greater subjective physical disability according to the SF-12 (p = 0.06) and OKS (p < 0.001). The improvement in the disease-specific score (OKS) was not affected by a patient’s mental health (p = 0.33). In contrast, patients with mental disability had less of an improvement in their global physical health (SF-12) (p < 0.001). However, patients with any degree of mental disability had a significant improvement in their mental health post-operatively (p < 0.001).

Despite a similar improvement in their disease-specific scores and improvement in their mental health, patients with mental disability were significantly more likely to be dissatisfied with their TKR at one year (p = 0.001). Patients with poor mental health do benefit from improvements in their mental health and knee function after TKR, but also have a higher rate of dissatisfaction.

Cite this article: Bone Joint J 2013;95-B:360–6.
Comparison of unipedicular and bipedicular balloon kyphoplasty for the treatment of osteoporotic vertebral compression fractures
Authors: Rebolledo B. J. , Gladnick B. P. , Unnanuntana A. , Nguyen J. T. , Kepler C. K. , Lane J. M.
Published: February 2013

This is a prospective randomised study comparing the clinical and radiological outcomes of uni- and bipedicular balloon kyphoplasty for the treatment of osteoporotic vertebral compression fractures. A total of 44 patients were randomised to undergo either uni- or bipedicular balloon kyphoplasty. Self-reported clinical assessment using the Oswestry Disability Index, the Roland-Morris Disability questionnaire and a visual analogue score for pain was undertaken pre-operatively, and at three and twelve months post-operatively. The vertebral height and kyphotic angle were measured from pre- and post-operative radiographs. Total operating time and the incidence of cement leakage was recorded for each group.

Both uni- and bipedicular kyphoplasty groups showed significant within-group improvements in all clinical outcomes at three months and twelve months after surgery. However, there were no significant differences between the groups in all clinical and radiological outcomes. Operating time was longer in the bipedicular group (p < 0.001). The incidence of cement leakage was not significantly different in the two groups (p = 0.09).

A unipedicular technique yielded similar clinical and radiological outcomes as bipedicular balloon kyphoplasty, while reducing the length of the operation. We therefore encourage the use of a unipedicular approach as the preferred surgical technique for the treatment of osteoporotic vertebral compression fractures.

Cite this article: Bone Joint J 2013;95-B:401–6.
The three-dimensional relationship between acetabular rim morphology and the severity of femoral cam lesions
Authors: Masjedi M. , Nightingale C. L. , Azimi D. Y. , Cobb J. P.
Published: February 2013

We examined the relationship between the size of the femoral cam in femoroacetabular impingement (FAI) and acetabular pathomorphology to establish if pincer impingement exists in patients with a femoral cam.

CT scans of 37 symptomatic impinging hips with a femoral cam were analysed in a three-dimensional study and were compared with 34 normal hips. The inclination and version of the acetabulum as well as the acetabular rim angle and the bony acetabular coverage were calculated. These measurements were correlated with the size and shape of the femoral cams.

While the size of the femoral cam varied characteristically, the acetabular morphology of the two groups was similar in terms of version (normal mean 23° (sd 7°); cam mean 22° (sd 9°)), inclination (normal mean 57° (sd 5°); cam mean 56° (sd 5°)), acetabular coverage (normal mean 41% (sd 5%); cam mean 42% (sd 4%)) and the mean acetabular rim angle (normal mean 82° (sd 5°); cam mean 83° (sd 4°)).

We found no correlation between acetabular morphology and the severity of cam lesion and no evidence of either global or focal over-coverage to support the diagnosis of ‘mixed’ FAI. The femoral cam may provoke edge loading but removal of any acetabular bearing surface when treating cam FAI might induce accelerated wear.

Cite this article: Bone Joint J 2013;95-B:314–19.