bluuebunny/crossref_metadata_2025 huggingface dataset:
Supporting student self-study: The educational design of podcasts in a collaborative learning context
Authors: Taylor Lucy , McGrath-Champ Susan , Clarkeburn Henriikka
Published: February 2012

One activity-rich way to utilize collaborative learning, team-based learning (TBL), can present students and teachers with both opportunities and challenges. TBL requires students to prepare for each class, where they are then assessed for their ‘readiness’ to apply the concepts learned during their pre-class preparation. This study addresses two aspects of TBL in an aim to better support and facilitate student learning and engagement: (1) supporting students during their pre-class preparation by providing metadata on the often-difficult required readings, and (2) offering students communication from the teacher, or ‘expert’ – something students often perceive as missing in active learning classes. Short, supportive podcasts are provided to students to give context to their out-of-class preparation and to allow them to hear directly from the teacher. Results suggest that the intervention of supportive podcasts successfully addresses these two issues and may benefit other collaborative classrooms that face similar challenges.
Learning spaces in mobile learning environments
Authors: Sølvberg Astrid M. , Rismark Marit
Published: February 2012

Mobile learning (m-learning) environments open a wide range of new and exciting learning opportunities, and envision students who are continually on the move, learn across space and time, and move from topic to topic and in and out of interaction with technology. In this article we present findings from a study of how students manoeuvre and study within an m-learning environment. The students in the study were enthusiastic about the new learning options provided by the mobile technologies, and they reported that the learning environment offered new study opportunities. One major asset was the flexibility of being able to study at any time and any place. The students engaged in learning activities within three learning spaces: attending lectures, on-campus activities and off-campus activities. Each learning space had different features when it came to how the students worked with the course material. Interactions between the participants, how they used the mobile technologies and their perceptions of the student role also differed across the learning spaces. To realize the valuable affordances provided by m-learning environments, educators will need to undertake complex pedagogical reasoning in their planning and teaching and must take into account how students act within various learning spaces.
Twitter as a teaching practice to enhance active and informal learning in higher education: The case of sustainable tweets
Authors: Kassens-Noor Eva
Published: February 2012

With the rise of Web 2.0, a multitude of new possibilities on how to use these online technologies for active learning has intrigued researchers. While most instructors have used Twitter for in-class discussions, this study explores the teaching practice of Twitter as an active, informal, outside-of-class learning tool. Through a comparative experiment in a small classroom setting, this study asks whether the use of Twitter aids students in learning of a particular subject matter. And if so, in which learning contexts Twitter offers advantages over more traditional teaching methods. This exploratory study showed potential opportunities and pitfalls that Twitter could bring to the e-learning community in higher education.
Postpolitical correctness?
Authors: Bylund Jonas
Published: February 2012

During the recent symposium ‘ Is Planning Past Politics?’, the notion of postpolitics and the question what the proper political could be in relation to planning became the main topic. The issue concerning the practices of politics in planning is pertinent, particularly when democratic politics is not necessarily seen to derive its legitimacy only through institutional and procedural arrangements. However, this article identifies a danger in the binary of postpolitics/proper political that it might develop into a kind of ‘postpolitical correctness’.
Tracking Motor Improvement at the Subtask Level During Robot-Aided Neurorehabilitation of Stroke Patients
Authors: Panarese Alessandro , Colombo Roberto , Sterpi Irma , Pisano Fabrizio , Micera Silvestro
Published: February 2012

Background. Robot-aided neurorehabilitation can provide intensive, repetitious training to improve upper-limb function after stroke. To be more effective, motor therapy ought to be progressive and continuously challenge the patient’s ability. Current robotic systems have limited customization capability and require a physiotherapist to assess progress and adapt therapy accordingly. Objective. The authors aimed to track motor improvement during robot-assistive training and test a tool to more automatically adjust training. Methods. A total of 18 participants with chronic stroke were trained using a multicomponent reaching task assisted by a shoulder–elbow robotic assist. The time course of motor gains was assessed for each subtask of the practiced exercise. A statistical algorithm was then tested on simulated data to validate its ability to track improvement and subsequently applied to the recorded data to determine its performance compared with a therapist. Results. Patients’ recovery of motor function exhibited a time course dependent on the particular component of the executed task, suggesting that differential training on a subtask level is needed to continuously challenge the neuromuscular system and boost recovery. The proposed algorithm was tested on simulated data and was proven to track overall patient’s progress during rehabilitation. Conclusions. Tuning of the training program at the subtask level may accelerate the process of motor relearning. The algorithm proposed to adjust task difficulty opens new possibilities to automatically customize robotic-assistive training.
Impact reconstruction from damage to pedal and motorcycle helmets
Authors: McIntosh Andrew S , Patton Declan A
Published: February 2012

Pedal and motorcycle helmets offer a high level of protection to the wearer’s head. There is a need to review and assess the performance offered by helmets, so that helmet design and test standards can be optimized. One input into this process is crash reconstruction. Helmeted crash cases can be collected and examined, leading to insights into impact severity, helmet performance and injury outcomes. However, it is unclear to what extent residual helmet damage reflects the impact characteristics. This paper addresses this issue using controlled laboratory impact tests.

Two pedal cycle and three motorcycle helmet models were tested with an ‘M’ size headform in impact energy attenuation tests from 1 m, 2 m and 2.5 m. Headform acceleration, impact force and post-impact deformation were measured. The dynamic deformations were measured with three methods: video, kinetic energy and an analytical approach using impact force and liner yield stress.

All five models offered highly repeatable performance in terms of impact energy attenuation and acceleration management in radial impacts across the impact severities. The results showed that the Standards Australia certified helmets provided impact protection to the head in impacts that greatly exceeded the impact energy attenuation performance requirements of those standards.

The residual and dynamic deformation measurements were correlated with drop height and headform acceleration for pedal cycle helmets. The results indicate that the residual deformation observed in a pedal cycle helmet collected from a crash can be used to estimate the impact severity and, after undertaking exemplar impact tests on the same model helmet, the head impact acceleration. However, the residual deformation measured on the three motorcycle helmets was not correlated with the drop height, which indicated that, within the limits of this study, estimating crash severity from motorcycle helmet damage is not reliable.
Imaging in ankylosing spondylitis
Authors: Østergaard Mikkel , Lambert Robert G.W.
Published: February 2012

Imaging is an integral part of the management of patients with ankylosing spondylitis and axial spondyloarthritis. Characteristic radiographic and/or magnetic resonance imaging (MRI) findings are key in the diagnosis. Radiography and MRI are also useful in monitoring the disease. Radiography is the conventional, albeit quite insensitive, gold standard method for assessment of structural damage in spine and sacroiliac joints, whereas MRI has gained a decisive role in monitoring disease activity in clinical trials and practice. MRI may also, if ongoing research demonstrates a sufficient reliability and sensitivity to change, become a new standard method for assessment of structural damage. Ultrasonography allows visualization of peripheral arthritis and enthesitis, but has no role in the assessment of axial manifestations. Computed tomography is a sensitive method for assessment of structural changes in the spine and sacroiliac joints, but its clinical utility is limited due to its use of ionizing radiation and lack of ability to assess the soft tissues. It is exciting that with continued dedicated research and the rapid technical development it is likely that even larger improvements in the use of imaging may occur in the decade to come, for the benefit of our patients.
Clinical significance of bone changes in osteoarthritis
Authors: Neogi Tuhina
Published: February 2012

Osteoarthritis (OA), the most common form of arthritis, is now understood to involve all joint tissues, with active anabolic and catabolic processes. Knee OA in particular is considered to be a largely mechanically-driven disease. As bone adapts to loads by remodeling to meet its mechanical demands, bone alterations likely play an important role in OA development. Subchondral bone changes in bone turnover, mineralization, and volume result in altered apparent and material density of bone that may adversely affect the joint’s biomechanical environment. Subchondral bone alterations such as bone marrow lesions (BMLs) and subchondral bone attrition (SBA) both tend to occur more frequently in the more loaded knee compartments, and are associated with cartilage loss in the same region. Recently, MRI-based 3D bone shape has been shown to track concurrently with and predict OA onset.

The contributions of structural abnormalities to the clinical manifestations of knee OA are becoming better understood as well. While a structure-symptom discordance in knee OA is thought to exist, such observations do not take into account all potential factors that can contribute to between-person differences in the pain experience. Using novel methodology, pain fluctuation has been associated with changes in BMLs, synovitis and effusion. SBA has also been associated with knee pain, but the relationship of osteophytes to pain has been conflicting.

Understanding the pathophysiologic sequences and consequences of OA pathology will guide rational therapeutic targeting. Importantly, rational treatment targets require understanding what structures contribute to pain as pain is the reason patients seek medical care.
Molecular distinctions between pediatric and adult mature B-cell non-Hodgkin lymphomas identified through genomic profiling
Authors: Deffenbacher Karen E. , Iqbal Javeed , Sanger Warren , Shen Yulei , Lachel Cynthia , Liu Zhongfeng , Liu Yanyan , Lim Megan S. , Perkins Sherrie L. , Fu Kai , Smith Lynette , Lynch James , Staudt Louis M. , Rimsza Lisa M. , Jaffe Elaine , Rosenwald Andreas , Ott German K. , Delabie Jan , Campo Elias , Gascoyne Randy D. , Cairo Mitchell S. , Weisenburger Dennis D. , Greiner Timothy C. , Gross Thomas G. , Chan Wing C.
Published: February 2012

Burkitt lymphoma (BL) predominates in pediatric patients, whereas diffuse large B-cell lymphoma (DLBCL) is uncommon. In contrast to adults, BL and DLBCL are treated similarly in children and both entities have superior outcomes in children compared with adults. Gene expression profiling (GEP) and miRNA expression profiling clearly differentiated pediatric DLBCL from BL, forming distinct clusters regardless of patient age. However, pathway analysis of GEP data identified minor differences between corresponding pediatric and adult tumors. Predominance (6:1) of the germinal center B-cell subtype to activated B-cell subtype was found among pediatric DLBCL. Two cases were molecularly classified as primary mediastinal B-cell lymphoma. We observed frequent abnormalities in 8q24 in pediatric DLBCL, including MYC rearrangement in 31% (5 of 16) and gain or amplification in 50% (6 of 12) nonrearranged cases. MYC rearrangement was present in 96% (23 of 24) BL cases. Array-based CGH analysis identified abnormalities that are shared between adult and pediatric DLBCL (+12q15, +19q13, −6q), and abnormalities unique to the pediatric cases (−4p14, −19q13.32, +16p11.2), suggesting distinct pathogenetic mechanisms relative to age. Elucidation of the underlying target genes may provide insight into factors that modulate outcome and could provide potential novel therapeutic targets with less toxicity for pediatric patients with B-cell non-Hodgkin lymphoma.
Recent advances in the pathogenesis and clinical evaluation of pulmonary fibrosis
Authors: Margaritopoulos G.A. , Romagnoli M. , Poletti V. , Siafakas N.M. , Wells A.U. , Antoniou K.M.
Published: February 2012

Interstitial lung diseases (ILDs) are a group of heterogeneous disorders, either idiopathic or associated with injurious or inflammatory causes, in which the major site of damage is the lung interstitium. For a long time, knowledge regarding pathogenesis was trivial and there were difficulties in diagnosing and subsequently treating these diseases.

During the past decade, however, there has been an impressive development in the field of ILDs. Idiopathic pulmonary fibrosis, the most common and fatal form of ILD, was initially believed to be due to an inflammatory response to unknown lung injury, whereas nowadays it is believed to be the result of multiple injuries at different sites of the lung followed by aberrant repair.

The integration of clinical, radiological and histological data, namely a multidisciplinary team (MDT) approach, has provided grounds for a more accurate diagnosis of ILDs, and helped the identification of different entities and development of different therapeutic approaches. However, because of the complexity of ILDs, even this approach may fail to establish a confident diagnosis.

How should the clinician behave in this case and what are the pitfalls of the MDT approach? In addition, since diagnosis is the major predictor of prognosis, are there any other tools available to predict prognosis?
Pulmonary hypertension: the science behind the disease spectrum
Authors: Wilkins M.R.
Published: February 2012

Pulmonary hypertension (PH) is a complex, multifactorial disorder divided into five major subtypes according to pathological, pathophysiological and therapeutic characteristics. Although there are distinct differences between the PH categories, a number of processes are common to the pathology of all subtypes.

Vasoconstriction, as a result of endothelial dysfunction and an imbalance in the levels of vasoactive mediators, is a well-characterised contributory mechanism. Excessive cell proliferation and impaired apoptosis in pulmonary vessels leading to structural remodelling is most evident in pulmonary arterial hypertension (PAH), and several factors have been implicated, including mitochondrial dysfunction and mutations in bone morphogenetic protein receptor type 2. Inflammation plays a key role in the development of PH, with increased levels of many cytokines and chemokines in affected patients. Exciting insights into the role of angiogenesis and bone marrow-derived endothelial progenitor cells in disease progression have also recently been revealed. Furthermore, there is increasing interest in changes in the right ventricle in PH and the role of metabolic abnormalities.

Despite considerable progress in our understanding of the molecular mechanisms of PH, further research is required to unravel and integrate the molecular changes into a better understanding of the pathophysiology of PH, particularly in non-PAH, to put us in a better position to use this knowledge for improved treatments.
How to detect disease progression in pulmonary arterial hypertension
Authors: Vachiéry J-L. , Yerly P. , Huez S.
Published: February 2012

Pulmonary arterial hypertension (PAH) is a rapidly progressive disease, ultimately leading to right heart failure and death. Accumulating evidence indicates that intervention early in disease progression results in better outcomes than delaying treatment.

In this review we will discuss the assessments and strategies that can be used to monitor disease progression and guide clinical management. Many tools, such as symptoms, functional classification, exercise capacity, haemodynamic measures, findings on cardiac imaging and levels of biomarkers, have shown to be prognostic for survival both at diagnosis and during treatment. However, attempts to define goal thresholds have produced a variety of results.

Several groups have developed risk calculators to estimate individual patients' mortality risk, but the accuracy of these tools across different patient populations remains unknown. What is clear is the importance of regularly assessing a range of parameters and then tailoring treatment goals to each patient. In addition, the use of a multidisciplinary team approach is crucial in order to support patients through all aspects of managing their condition.

There is still an urgent need for prospective collaborative initiatives to assess novel goals and improve treatment strategies that would allow physicians to personalise and optimise clinical management for their patients with PAH.
State-of-the-art chronic thromboembolic pulmonary hypertension diagnosis and management
Authors: Jenkins D. , Mayer E. , Screaton N. , Madani M.
Published: February 2012

Chronic thromboembolic pulmonary hypertension (CTEPH) is a debilitating disease caused by chronic obstruction of pulmonary artery branches following episodes of pulmonary embolism and incomplete thrombus resolution. The prognosis of patients with CTEPH is poor unless an early diagnosis is made and treatment is initiated.

Chest radiography and echocardiography are used in the initial assessment of suspected pulmonary hypertension. A diagnosis of CTEPH may be confirmed by the presence of a mismatched wedge-shaped perfusion deficit during ventilation/perfusion scintigraphy or characteristic findings during multi-slice computed tomography (CT) angiography, including a mosaic perfusion pattern, dilatation of proximal pulmonary arteries and right heart chambers, and the presence of vascular stenosis or obstruction.

Prior to possible surgery, pulmonary angiography remains the definitive diagnostic technique, indicating the site and accessibility of the obstruction. However, many centres utilise CT and magnetic resonance imaging following recent advances in these noninvasive techniques. Haemodynamic evaluationviaright heart catheterisation is also mandatory, as pulmonary vascular resistance is the most important determinant of both prognosis and the risk associated with pulmonary endarterectomy surgery.

Accurate CTEPH diagnosis and characterisation of its extent and distribution are imperative to allow the prompt initiation of treatment, particularly surgical pulmonary endarterectomy in eligible patients.
Performance evaluation of unified medical language system®'s synonyms expansion to query PubMed
Authors: Griffon Nicolas , Chebil Wiem , Rollin Laetitia , Kerdelhue Gaetan , Thirion Benoit , Gehanno Jean-François , Darmoni Stéfan Jacques
Published: February 2012

Background

PubMed is the main access to medical literature on the Internet. In order to enhance the performance of its information retrieval tools, primarily non-indexed citations, the authors propose a method: expanding users' queries using Unified Medical Language System' (UMLS) synonyms i.e. all the terms gathered under one unique Concept Unique Identifier.

Methods

This method was evaluated using queries constructed to emphasize the differences between this new method and the current PubMed automatic term mapping. Four experts assessed citation relevance.

Results

Using UMLS, we were able to retrieve new citations in 45.5% of queries, which implies a small increase in recall. The new strategy led to a heterogeneous 23.7% mean increase in non-indexed citation retrieved. Of these, 82% have been published less than 4 months earlier. The overall mean precision was 48.4% but differed according to the evaluators, ranging from 36.7% to 88.1% (Inter rater agreement was poor: kappa = 0.34).

Conclusions

This study highlights the need for specific search tools for each type of user and use-cases. The proposed strategy may be useful to retrieve recent scientific advancement.
A new method of lower extremity immobilization in radiotherapy
Authors: Zheng Xuhai , Dai Tangzhi , Shu Xiaochuan , Pu Yuanxue , Feng Gang , Li Xuesong , Liao Dongbiao , Du Xiaobo
Published: February 2012

We developed a new method for immobilization of the fix lower extremities by using a thermoplastic mask, a carbon fiber base plate, a customized headrest, and an adjustable angle holder. The lower extremities of 11 patients with lower extremity tumors were immobilized by this method. CT simulation was performed for each patient. For all 11 patients, the device fit was suitable and comfortable and had good reproducibility, which was proven in daily radiotherapy.
Effectiveness of Chinese herbal medicine in treating liver fibrosis: a systematic review and meta-analysis of randomized controlled trials
Authors: Cheung Fan , Feng Yibin , Wang Ning , Yuen Man-Fung , Tong Yao , Wong Vivian Taam
Published: February 2012

Background

The studies on the effectiveness of Chinese herbal medicines (CHM) in treating liver fibrosis (LF) were not consistent. This study aims to systematically review the effectiveness of CHM on treating LF patients.

Methods

Databases including MEDLINE, AMED, EMBASE, The Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, TCMOnline, Chinese Biomedical Literature Database, and Chinese Medical Current Contents were searched up to March 2011. Randomized controlled trials (RCTs) involving LF patients receiving CHM, Western medicine, combined CHM and Western medicine compared with placebo, Western medicine or no intervention were included. LF markers including serum hyaluronic acid (HA), laminin (LN), procollagen type III (PC-III), type IV collagen (IV-C), matrix metalloproteinase (MMP), and tissue inhibitors of metalloproteinase (TIMP) were measured as primary outcomes. Liver biochemistry, including alanine aminotransferase (ALT) and aspartarte aminotransferase (AST), and improvement of related clinical symptoms were measured as secondary outcomes. Risk of bias of allocation sequence, allocation concealment, blinding, incomplete outcome data, selective outcome reporting, and other biases were assessed.

Results

Twenty-three RCTs with 2123 participants were analyzed in subgroups of types of comparison and study quality. Fifteen studies were graded as good quality. CHM alone and combined with Western medicine showed significant improvements in HA, LN, PC-III and IV-C compared with Western medicine alone. However, there were no significant differences observed between CHM and placebo treatments.

Conclusion

The current inconclusive results in determining the effectiveness of CHM treatment on LF, due to the poor methodological quality and high heterogeneity of the studies, suggests that large RCTs using standardized Chinese medicine syndrome diagnosis and CHM formulae with longer follow-up are required for further evaluation.
Frequency of disease-associated and other nuclear autoantibodies in patients of the German network for systemic scleroderma: correlation with characteristic clinical features
Authors: Mierau Rudolf , Moinzadeh Pia , Riemekasten Gabriela , Melchers Inga , Meurer Michael , Reichenberger Frank , Buslau Michael , Worm Margitta , Blank Norbert , Hein Rüdiger , Müller-Ladner Ulf , Kuhn Annegret , Sunderkötter Cord , Juche Aaron , Pfeiffer Christiane , Fiehn Christoph , Sticherling Michael , Lehmann Percy , Stadler Rudolf , Schulze-Lohoff Eckhard , Seitz Cornelia , Foeldvari Ivan , Krieg Thomas , Genth Ekkehard , Hunzelmann Nicolas
Published: February 2012

Introduction

In the present study, we analysed in detail nuclear autoantibodies and their associations in systemic sclerosis (SSc) patients included in the German Network for Systemic Scleroderma Registry.

Methods

Sera of 863 patients were analysed according to a standardised protocol including immunofluorescence, immunoprecipitation, line immunoassay and immunodiffusion.

Results

Antinuclear antibodies (ANA) were detected in 94.2% of patients. In 81.6%, at least one of the autoantibodies highly associated with SSc or with overlap syndromes with scleroderma features was detected, that is, anti-centromere (35.9%) or anti-topoisomerase I (30.1%), followed in markedly lower frequency by antibodies to PM-Scl (4.9%), U1-ribonucleoprotein (U1-RNP) (4.8%), RNA polymerases (RNAPs) (3.8%), fibrillarin (1.4%), Ku (1.2%), aminoacyl-transfer RNA synthetases (0.5%), To (0.2%) and U11-RNP (0.1%). We found that the simultaneous presence of SSc-associated autoantibodies was rare (1.6%). Furthermore, additional autoantibodies were detected in 55.4% of the patients with SSc, of which anti-Ro/anti-La, anti-mitochondrial and anti-p25/p23 antibodies were most frequent. The coexistence of SSc-associated and other autoantibodies was common (43% of patients). SSc-associated autoantibodies disclosed characteristic associations with clinical features of patients, some of which were previously not acknowledged.

Conclusions

This study shows that five autoantigens (that is, centromere, topoisomerase I, PM-Scl, U1-RNP and RNAP) detected more than 95% of the known SSc-associated antibody responses in ANA-positive SSc patients and characterise around 79% of all SSc patients in a central European cohort. These data confirm and extend previous data underlining the central role of the determination of ANAs in defining the diagnosis, subset allocation and prognosis of SSc patients.
Fluid management and risk factors for renal dysfunction in patients with severe sepsis and/or septic shock
Authors: Muller Laurent , Jaber Samir , Molinari Nicolas , Favier Laurent , Larché Jérôme , Motte Gilles , Lazarovici Sonia , Jacques Luc , Alonso Sandrine , Leone Marc , Constantin Jean Michel , Allaouchiche Bernard , Suehs Carey , Lefrant Jean-Yves ,   the AzuRéa Group
Published: February 2012

Introduction

The causative role of new hydroxyethyl starch (HES 130/0.4) in renal dysfunction frequency (a > 50% increase in serum creatinine or need for renal replacement therapy (RRT)) remains debated. Using the database of a multicenter study focusing on patients with severe sepsis and septic shock, the present study aimed at identifying factors associated with the occurrence of renal dysfunction.

Methods

Among the 435 patients in a multicenter study of patients with severe sepsis and septic shock in 15 Southern French ICUs, 388 patients surviving after 24 hour, without a history of renal failure were included. Factors associated with renal dysfunction and RRT were isolated using a multivariate analysis with logistic regression.

Results

Renal dysfunction was reported in 117 (33%) patients. Ninety patients required RRT. Among study participants, 379 (98%) were administered fluids in the first 24 hours of management: HES 130/0.4 only (n = 39), crystalloids only (n = 63), or both HES 130/0.4 and crystalloids (n = 276). RRT was independently associated with the need for vasopressors and the baseline value of serum creatinine in the first 24 hours. Multivariate analysis indicated that male gender, SAPS II score, being a surgical patient, lack of decrease in SOFA score during the first 24 hours, and the interventional period of the study were independently associated with renal dysfunction. Mortality increased in the presence of renal dysfunction (48% versus 24%, P < 0.01).

Conclusions

Despite being used in more than 80% of patients with severe sepsis and/or septic shock, the administration of HES 130/0.4 in the first 24 hours of management was not associated with the occurrence of renal dysfunction.
Editorial: Nyet to NETs,n? A pause for healthy skepticism
Authors: Nauseef William M
Published: February 2012

Discussion of Parker et al. that challenges the evidence for the antimicrobial capacity of neutrophil extracellular traps (NETs) in vitro.
Lipid-Induced Endoplasmic Reticulum Stress in Liver Cells Results in Two Distinct Outcomes: Adaptation with Enhanced Insulin Signaling or Insulin Resistance
Authors: Achard Caroline S. , Laybutt D. Ross
Published: February 2012

Chronically elevated fatty acids contribute to insulin resistance through poorly defined mechanisms. Endoplasmic reticulum (ER) stress and the subsequent unfolded protein response (UPR) have been implicated in lipid-induced insulin resistance. However, the UPR is also a fundamental mechanism required for cell adaptation and survival. We aimed to distinguish the adaptive and deleterious effects of lipid-induced ER stress on hepatic insulin action. Exposure of human hepatoma HepG2 cells or mouse primary hepatocytes to the saturated fatty acid palmitate enhanced ER stress in a dose-dependent manner. Strikingly, exposure of HepG2 cells to prolonged mild ER stress activation induced by low levels of thapsigargin, tunicamycin, or palmitate augmented insulin-stimulated Akt phosphorylation. This chronic mild ER stress subsequently attenuated the acute stress response to high-level palmitate challenge. In contrast, exposure of HepG2 cells or hepatocytes to severe ER stress induced by high levels of palmitate was associated with reduced insulin-stimulated Akt phosphorylation and glycogen synthesis, as well as increased expression of glucose-6-phosphatase. Attenuation of ER stress using chemical chaperones (trimethylamine N-oxide or tauroursodeoxycholic acid) partially protected against the lipid-induced changes in insulin signaling. These findings in liver cells suggest that mild ER stress associated with chronic low-level palmitate exposure induces an adaptive UPR that enhances insulin signaling and protects against the effects of high-level palmitate. However, in the absence of chronic adaptation, severe ER stress induced by high-level palmitate exposure induces deleterious UPR signaling that contributes to insulin resistance and metabolic dysregulation.
Perinatal Maternal Dietary Supplementation of ω3-Fatty Acids Transiently Affects Bone Marrow Microenvironment, Osteoblast and Osteoclast Formation, and Bone Mass in Male Offspring
Authors: Fong Laura , Muhlhausler Beverly S. , Gibson Robert A. , Xian Cory J.
Published: February 2012

It is increasingly evident that micronutrient environment experienced before birth and in infancy is important for achieving optimal bone mass by adolescence and maintaining bone health. This study determined whether maternal supplementation with ω3-polyunsaturated fatty acids (n3FA) improved offspring bone growth and adult bone mass. Female rats were fed a diet containing 0.1% (control, n = 10) or 1% (n3FA, n = 11) docosahexanoic acid (DHA) during pregnancy and lactation. Offspring were weaned onto a control rat chow diet. Tibial growth plate and metaphysis structure, osteoblast/osteoclast density and differentiation, and gene expression were assessed in offspring at 3 wk (weaning), 6 wk (adolescent), and 3 months (adult). Maternal n3FA supplementation elevated offspring plasma n3FA levels at 3 and 6 wk. Although total growth plate heights were unaffected at any age, the resting zone thickness was increased in both male and female offspring at 3 wk. In n3FA males, but not females, bone trabecular number and thickness were increased at 3 wk but not other ages. The wk 3 n3FA males also exhibited an increased bone volume, an increased osteoblast but decreased osteoclast density, and lower expression of osteoclastogenic cytokines receptor activator of nuclear factor-κB ligand, TNF-α, and IL-6. No effects were seen at 6 wk or 3 months in either sex. Thus, perinatal n3FA supplementation is associated with increased bone formation, decreased resorption, and a higher bone mass in males, but not in females, at weaning; these effects do not persist into adolescence and adulthood and are unlikely to produce lasting improvements in bone health.
Protein Kinase C: A Putative New Target for the Control of Human Medullary Thyroid Carcinoma Cell Proliferation in Vitro
Authors: Molè Daniela , Gentilin Erica , Gagliano Teresa , Tagliati Federico , Bondanelli Marta , Pelizzo Maria Rosa , Rossi Martina , Filieri Carlo , Pansini Giancarlo , degli Uberti Ettore C. , Zatelli Maria Chiara
Published: February 2012

We investigate the role of protein kinase C (PKC) in the control of medullary thyroid carcinoma (MTC) cell proliferation by a PKC inhibitor, Enzastaurin, in human MTC primary cultures and in the TT cell line. We found that PKC inhibition reduces cell proliferation by inducing caspase-mediated apoptosis and blocks the stimulatory effect of IGF-I on calcitonin secretion. Enzastaurin reduces PKCβII (Thr500) phosphorylation, indicating a direct involvement of this isoform as well as the phosphorylated levels of Akt (Ser 473) and glycogen synthase kinase (Ser9), PKC pathway downstream targets and pharmacodynamic markers for PKC inhibition. PKCβII and PKCδ enzyme isoforms expression and localization were investigated. These data indicate that in vitro PKC is involved in the control of human MTC proliferation and survival by modulating apoptosis, with a mechanism that implicates PKCβII inhibition and translocation in different subcellular compartments. Targeting PKC may represent a useful therapeutic approach for controlling MTC proliferation.
Rab27a mediated protease release regulates neutrophil recruitment by allowing uropod detachment.
Authors: Singh Rajesh K. , Liao Wenjia , Tracey-White Dhani , Recchi Chiara , Tolmachova Tanya , Rankin Sara M. , Hume Alistair N. , Seabra Miguel C.
Published: February 2012

Neutrophil migration is vital for immunity and precedes effector functions such as pathogen killing. Here we report that this process is regulated by the Rab27a GTPase, a protein known to control granule exocytosis. Rab27a-deficient (Rab27a KO) neutrophils exhibit migration defects in vitro and in vivo, and live cell microscopy suggests that delayed uropod detachment causes the migratory defect. Surface expression of CD11b, a key adhesion molecule, is increased in chemokine-stimulated Rab27a KO neutrophils versus control, suggesting a turn-over delay caused by defect in elastase secretion from azurophilic granules at the rear of BM-PMNs. We suggest that Rab27a-dependent protease secretion regulates neutrophil migration via proteolysis-dependent de-adhesion of uropods, a mechanism that could be conserved in cell migration and invasion.
Halide-controlled Construction and Structural Determination of a Series of Thiolato-bridged 16-Nuclear Copper(I) Clusters from Benzothiazoline
Authors: Takino Yusuke , Yoshinari Nobuto , Tsuge Kiyoshi , Kawamoto Tatsuya , Konno Takumi
Published: February 2012

Treatment of [Cu(CH3CN)4]+ with 2-(4-dimethylaminophenyl)benzothiazoline in the presence of halide ions (X = Cl−, Br−, and I−) gave [Cu16L12X]3+ (L = (C6H4NMe2)CH=N(C6H4)S−) with a spherical Cu16S12 structure, while similar treatment in the absence of halide ions afforded [Cu8L8]2+ with a cyclic Cu8S8 structure.
The value of computed tomography scans in the diagnosis and management following invasive arterial investigation
Authors: Walker Stuart , Beasley Anthony
Published: February 2012

We report a patient who was known to have an abdominal aortic aneurysm and was being assessed for endovascular repair by calibrated angiogram, who developed back pain and cardiovascular collapse, where a computed tomography scan proved essential in establishing the correct diagnosis – bleed from an accessory renal artery branch.
Spontaneous axillary artery aneurysm: a case report and review of the literature
Authors: Malik Manmeet K , Kraev Alexander I , Hsu Ekai K , Clement Michael-Hunter C , Landis Gregg S
Published: February 2012

Degenerative arterial aneurysms can occur in any vascular territory. However, they are exceedingly rare in the axillary artery. Complications of axillary artery aneurysms may result in acute vascular insufficiency and neurological deficits. Prompt treatment should be employed in the management of this condition. We report a case of an atraumatic degenerative axillary artery aneurysm that was treated with transaxillary open surgical bypass.
Supervised exercise therapy for intermittent claudication: current status and future perspectives
Authors: Lauret Gert-Jan , van Dalen Daniëlle C W , Willigendael Edith M , Hendriks Erik J M , de Bie Rob A , Spronk Sandra , Teijink Joep A W
Published: February 2012

Intermittent claudication (IC) has a high prevalence in the older population and is closely associated with cardiovascular and cerebrovascular disease. High mortality rates are reported due to ongoing atherosclerotic disease. Because of these serious health risks, treatment of IC should address reduction of cardiovascular events (and related morbidity/mortality) and improvement of the poor health-related quality of life (QoL) and functional capacity. In several randomized clinical trials and systematic reviews, supervised exercise therapy (SET) is compared with non-supervised exercise, usual care, placebo, walking advice or vascular interventions. The current evidence supports SET as the primary treatment for IC. SET improves maximum walking distance and health-related QoL with a marginal risk of co-morbidity or mortality. This is also illustrated in contemporary international guidelines. Community-based SET appears to be at least as efficacious as programs provided in a clinical setting. In the Netherlands, a national integrated care network (ClaudicatioNet) providing specialized care for patients with IC is currently being implemented. Besides providing a standardized form of SET, the specialized physical therapists stimulate medication compliance and perform lifestyle coaching. Future research should focus on the influence of co-morbidities on prognosis and effect of SET outcome and the potential beneficial effects of SET combined with a vascular intervention.
Validation of motion correction techniques for liver CT perfusion studies
Authors: Chandler A , Wei W , Anderson E F , Herron D H , Ye Z , Ng C S
Published: February 2012

Objectives: Motion in images potentially compromises the evaluation of temporally acquired CT perfusion (CTp) data; image registration should mitigate this, but first requires validation. Our objective was to compare the relative performance of manual, rigid and non-rigid registration techniques to correct anatomical misalignment in acquired liver CTp data sets.

Methods: 17 data sets in patients with liver tumours who had undergone a CTp protocol were evaluated. Each data set consisted of a cine acquisition during a breath-hold (Phase 1), followed by six further sets of cine scans (each containing 11 images) acquired during free breathing (Phase 2). Phase 2 images were registered to a reference image from Phase 1 cine using two semi-automated intensity-based registration techniques (rigid and non-rigid) and a manual technique (the only option available in the relevant vendor CTp software). The performance of each technique to align liver anatomy was assessed by four observers, independently and blindly, on two separate occasions, using a semi-quantitative visual validation study (employing a six-point score). The registration techniques were statistically compared using an ordinal probit regression model.

Results: 306 registrations (2448 observer scores) were evaluated. The three registration techniques were significantly different from each other (p=0.03). On pairwise comparison, the semi-automated techniques were significantly superior to the manual technique, with non-rigid significantly superior to rigid (p<0.0001), which in turn was significantly superior to manual registration (p=0.04).

Conclusion: Semi-automated registration techniques achieved superior alignment of liver anatomy compared with the manual technique. We hope this will translate into more reliable CTp analyses.
Advance Selling When Consumers Regret
Authors: Nasiry Javad , Popescu Ioana
Published: February 2012

We characterize the effect of anticipated regret on consumer decisions and on firm profits and policies in an advance selling context where buyers have uncertain valuations. Advance purchases trigger action regret if valuations turn out to be lower than the price paid, whereas delaying purchase may cause inaction regret from missing a discount or facing a stockout. Consumers whom we describe as emotionally rational act strategically in response to the firm's policies and in anticipation of regret. In this context, regret explains two types of behavioral patterns: inertia (delayed purchase) and frenzies (buying early at negative surplus). We show how firms should optimally respond to consumer regret and also characterize a normative regret threshold above which they should not advance sell. Action regret reduces profits as well as the value of advance selling and booking limit policies for price-setting firms; inaction regret has the opposite effects. These effects are diminished by capacity constraints and are reversed for firms facing price pressure in the advance period (owing, e.g., to competition or market heterogeneity). Regret heterogeneity explains premium advance selling for the capacity-constrained firm, which may benefit from larger shares of regretful buyers. Finally, we show how the negative effects of regret on profits can be mitigated by regret-priming marketing campaigns and by offering refunds or options or allowing resales. Our results highlight the importance of assessing the relative strength of regret within and across market segments and of accounting for these factors in pricing and marketing policies.

This paper was accepted by Christian Terwiesch, operations management.
Information Environment and Equity Risk Premium Volatility Around the World
Authors: Lau Sie Ting , Ng Lilian , Zhang Bohui
Published: February 2012

This paper examines whether and how differences in investors' information environments (measured by a country's information disclosure, accounting standards, and financial transparency) are related to cross-country differences in the market risk premium volatility. We use the vector-autoregressive and implied cost of capital methods to extract time variation in risk premiums for 41 developed and emerging markets worldwide. Consistent with theoretical predictions, countries with better information environments tend to experience a lower risk premium volatility, even after controlling for various country variables that are potentially associated with variation in risk premiums. Our analysis of two exogenous events, specifically the 1997 Asian financial crisis and 2008 global financial crisis, further corroborates our key finding that information environments play an important role in explaining market risk premium variability.

This paper was accepted by Wei Xiong, finance.
In-Season Transshipments Among Competitive Retailers
Authors: Çömez Nagihan , Stecke Kathryn E. , Çakanyıldırım Metin
Published: February 2012

A decentralized system of competing retailers that order and sell the same product in a sales season is studied. When a customer demand occurs at a stocked-out retailer, that retailer requests a unit to be transshipped from another retailer who charges a transshipment price. If this request is rejected, the unsatisfied customer may go to another retailer with a customer overflow probability. Each retailer decides on the initial order quantity from a manufacturer and on the acceptance/rejection of each transshipment request. For two retailers, we show that retailers' optimal transshipment policies are dynamic and characterized by chronologically nonincreasing inventory holdback levels. We analytically study the sensitivity of holdback levels to explain interesting findings, such as smaller retailers and geographically distant retailers benefit more from transshipments. Numerical experiments show that retailers substantially benefit from using optimal transshipment policies compared to no sharing. The expected sales increase in all but a handful of over 3,000 problem instances. Building on the two-retailer optimal policies, we suggest an effective heuristic transshipment policy for a multiretailer system.
Managing Opportunistic Supplier Product Adulteration: Deferred Payments, Inspection, and Combined Mechanisms
Authors: Babich Volodymyr , Tang Christopher S.
Published: February 2012

Recent cases of product adulteration by foreign suppliers have compelled many manufacturers to rethink approaches to deterring suppliers from cutting corners, especially when manufacturers cannot fully monitor and control the suppliers' actions. In this paper, we study three mechanisms for dealing with product adulteration problems: (a) the deferred payment mechanism—the buyer pays the supplier after the deferred payment period only if no adulteration has been discovered by the customers; (b) the inspection mechanism—the buyer pays the supplier immediately, contingent on product passing the inspection; and (c) the combined mechanism—a combination of the deferred payment and inspection mechanisms. We show that the inspection mechanism cannot completely deter the suppliers from product adulteration, whereas the deferred payment mechanism can. Surprisingly, the combined mechanism is redundant: either the inspection or the deferred payment mechanisms perform just as well. Finally, we identify four factors that determine the dominance of deferred payment mechanism over the inspection mechanism: (a) the inspection cost relative to inspection accuracy, (b) the buyer's liability for adulterated products, (c) the difference in financing rates for the buyer and the supplier relative to the defects discovery rate by customers, and (d) the difference in production costs for adulterated and unadulterated product. We find that the deferred payment mechanism is preferable to inspection if the threats of adulteration (either incentive to adulterate or the consequences) are low.
Key Factors in the Market for Remanufactured Products
Authors: Subramanian Ravi , Subramanyam Ramanath
Published: February 2012

Measures to extend the economic lives of products—such as remanufacturing carried out by closed-loop supply chains—are receiving increased attention because of various economic and regulatory factors. In this paper, we examine drivers of price differentials between new and remanufactured products using data on purchases made on eBay. Our analysis shows that seller reputation significantly explains the price differentials between new and remanufactured products. We also find that products remanufactured by original equipment manufacturers or their authorized factories are purchased at relatively higher prices than products remanufactured by third parties. However, in the presence of these reputation signals (seller reputation and remanufacturer identity), we find that stronger warranties are not significantly associated with higher prices paid for remanufactured products. Our work contributes to the closed-loop supply chain research stream in operations management by empirically examining market factors that have not been studied before.