bluuebunny/crossref_metadata_2025 huggingface dataset:
Multiple myeloma: 2014 Update on diagnosis, risk‐stratification, and management
Authors: Rajkumar S. Vincent
Published: September 2014

Disease overview: Multiple myeloma accounts for approximately 10% of hematologic malignancies. Diagnosis: The diagnosis requires 10% or more clonal plasma cells on bone marrow examination or a biopsy proven plasmacytoma plus evidence of associated end‐organ damage. If end‐organ damage is not present, the presence of 60% or more clonal plasma cells in the marrow is also considered as myeloma. Risk stratification: In the absence of concurrent trisomies, patients with 17p deletion, t(14;16), and t(14;20) are considered to have high‐risk myeloma. Patients with t(4;14) translocation are considered intermediate‐risk. All others are considered as standard‐risk. Risk‐adapted intial therapy: Standard‐risk patients can be treated with lenalidomide plus low‐dose dexamethasone (Rd), or a bortezomib‐containing triplet such as bortezomib, cyclophosphamide, dexamethasone (VCD). Intermediate‐risk and high‐risk patients require a bortezomib‐based triplet regimen. In eligible patients, initial therapy is given for approximately 4 months followed by autologous stem cell transplantation (ASCT). Standard risk patients can opt for delayed ASCT if stem cells can be cryopreserved. In patients who are not candidates for transplant, initial therapy is given for approximately 12 to 18 months. Maintenance therapy: After initial therapy, lenalidomide maintenance is considered for standard risk patients who are not in very good partial response or better, while maintenance with a bortezomib‐based regimen should be considered in patients with intermediate or high risk myeloma. Management of refractory disease: Patients with indolent relapse can be treated first with 2‐drug or 3‐drug combinations. Patients with more aggressive relapse often require therapy with a combination of multiple active agents. Am. J. Hematol. 89:998–1009, 2014. © 2014 Wiley Periodicals, Inc.
A genome‐wide CNV analysis of schizophrenia reveals a potential role for a multiple‐hit model
Authors: Rudd Danielle S. , Axelsen Michael , Epping Eric A. , Andreasen Nancy C. , Wassink Thomas H.
Published: September 2014

Schizophrenia is a chronic and severe psychiatric disorder that is highly heritable. While both common and rare genetic variants contribute to disease risk, many questions still remain about disease etiology. We performed a genome‐wide analysis of copy number variants (CNVs) in 166 schizophrenia subjects and 52 psychiatrically healthy controls. First, overall CNV characteristics were compared between cases and controls. The only statistically significant finding was that deletions comprised a greater proportion of CNVs in cases. High interest CNVs were then identified as conservative using the following filtering criteria: (i) known deleterious CNVs; (ii) CNVs >1 Mb that were novel (not found in a database of control individuals); and (iii) CNVs <1 Mb that were novel and that overlapped the coding region of a gene of interest. Cases did not harbor a higher proportion of conservative CNVs in comparison to controls. However, similar to previous reports, cases had a slightly higher proportion of individuals with clinically significant CNVs (known deleterious or conservative CNVs >1 Mb) or with multiple conservative CNVs. Two case individuals with the highest burden of conservative CNVs also share a recurrent 15q11.2 BP1‐2 deletion, indicating a role for a potential multiple‐hit CNV model for schizophrenia. In total, we report three 15q11.2 BP1‐2 deletion individuals with schizophrenia, adding to a growing body of evidence that this CNV is involved in disease etiology. © 2014 Wiley Periodicals, Inc.
Evaluating the role of a galanin enhancer genotype on a range of metabolic, depressive and addictive phenotypes
Authors: Richardson Tom G. , Minica Camelia , Heron Jon , Tavare Jeremy , MacKenzie Alasdair , Day Ian , Lewis Glyn , Hickman Matthew , Vink Jacqueline M. , Gelernter Joel , Kranzler Henry R. , Farrer Lindsay A , Munafò Marcus , Wynick David
Published: September 2014

There is a large body of pre‐clinical and some clinical data to link the neuropeptide galanin to a range of physiological and pathological functions that include metabolism, depression, and addiction. An enhancer region upstream of the human GAL transcriptional start site has previously been characterised. In‐vitro transfection studies in rat hypothalamic neurons demonstrated that the CA allele was 40% less active than the GG allele in driving galanin expression. Our hypothesis was to investigate the effect of this galanin enhancer genotype on a range of variables that relate to the known functions of the galaninergic system in the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort of young adults (N = 169–6,078). Initial findings showed a positive relationship of cannabis usage (OR = 2.070, P = 0.007, N = 406 (individuals who had used cannabis at least once within the last 12 months, total sample size 2731) with the GG haplotype, consistent with the previous published data linking galanin with an increased release of dopamine. As our sample size was relatively small we replicated the analysis in a larger cohort of 2,224 African Americans and 1,840 European Americans, but no discernible trend across genotypes was observed for the relationship with cannabis usage. Further, we found no association of the galanin enhancer genotype with any of the other pathophysiological parameters measured. These findings emphasise that preclinical data does not always predict clinical outcomes in cohort studies, noting that association studies are subject to multiple confounders. © 2014 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics published by Wiley Periodicals, Inc.
Precipitation regionalization of the Brazilian Amazon
Authors: Santos Eliane Barbosa , Lucio Paulo Sérgio , Silva Cláudio Moisés Santos e
Published: September 2014

The Brazilian Amazon is a large territory, where different weather systems act, contributing to non‐homogeneity of the rainfall seasonal distribution in the region. The aim of this study is to determine sub‐regions of homogeneous precipitation in the Amazon, linking them to the main atmospheric systems that affect the rainfall in the region. For this, hierarchical cluster analysis was applied on a data set composed by 305 rain gauges. The results suggest that the Brazilian Amazon has six pluvial homogeneous regions.
Enhanced luminescence and white light emission from Eu3+‐co‐doped K3Ca2(SO4)3Cl:Dy3+ phosphor with near visible ultraviolet excitation for white LEDs
Authors: Baig N. , Dhoble N. S. , Park K. , Kokode N. S. , Dhoble S. J.
Published: September 2014

The luminescent properties of europium (Eu)‐ and dysprosium (Dy)‐co‐doped K3Ca2(SO4)3Cl halosulfate phosphors were analyzed. This paper reports the photoluminescence (PL) properties of K3Ca2(SO4)3Cl microphosphor doped with Eu and Dy and synthesized using a cost‐effective wet chemical method. The phosphors were characterized by X‐ray diffraction and scanning electron microscopy. The CIE coordinates were calculated to display the color of the phosphor. PL emission of the prepared samples show peaks at 484 nm (blue), 575 nm (yellow), 594 nm (orange) and 617 nm (red). The emission color of the Eu,Dy‐co‐doped K3Ca2(SO4)3Cl halophosphor depends on the doping concentration and excitation wavelength. The addition of Eu in K3Ca2(SO4)3Cl:Dy greatly enhances the intensity of the blue and yellow peaks, which corresponds to the 4 F9/2 → 6H15/2 and 4 F9/2 → 6H13/2 transitions of Dy3+ ions (under 351 nm excitation). The Eu3+/Dy3+ co‐doping also produces white light emission for 1 mol% of Eu3+, 1 mol% of Dy3+ in the K3Ca2(SO4)3Cl lattice under 396 nm excitation, for which the calculated chromaticity coordinates are (0.35, 0.31). Thus, K3Ca2(SO4)3Cl co‐doped with Eu/Dy is a suitable candidate for NUV based white light‐emitting phosphors technology. Copyright © 2014 John Wiley & Sons, Ltd.
Determinants of outcome following laparoscopic peritoneal lavage for perforated diverticulitis
Authors: Radé F , Bretagnol F , Auguste M , Di Guisto C , Huten N , de Calan L
Published: September 2014

Background

Laparoscopic peritoneal lavage has been proposed for generalized peritonitis from perforated diverticulitis to avoid a stoma. Reports of its feasibility and safety are promising. This study aimed to establish determinants of failure to enable improved selection of patients for this approach.

Methods

The study included all patients with perforated sigmoid diverticulitis who underwent emergency laparoscopic peritoneal lavage from January 2000 to December 2013. Factors predicting failure of laparoscopic treatment were analysed from data collected retrospectively.

Results

For patients undergoing emergency sigmoid resection (72 of 361), mortality and morbidity rates were 13 and 35 per cent respectively. In all, 71 patients had laparoscopic lavage, with mortality and morbidity rates of 6 and 28 per cent respectively. Reintervention was necessary in 11 patients (15 per cent) for unresolved sepsis. Age 80 years or more, American Society of Anesthesiologists grade III or above, and immunosuppression were associated with reintervention.

Conclusion

Elderly patients and those with immunosuppression or severe systemic co-morbidity are at risk of reintervention after laparoscopic lavage.
Excess adiposity and gastrointestinal cancer
Authors: Coe P O , O'Reilly D A , Renehan A G
Published: September 2014

Background

Excess adiposity is a risk factor for incidence of several gastrointestinal cancers, but it is unclear how these epidemiological observations translate into clinical practice.

Methods

Critical appraisals and updated analyses of published systematic reviews were undertaken to quantify cancer risk associations better and to assess the impact of weight-reducing strategies (surgical and non-surgical) on cancer prevention.

Results and conclusion

A large volume of evidence demonstrates that body mass index (BMI), as an approximation for general adiposity, is a risk factor for the development of oesophageal adenocarcinoma, and colorectal, hepatocellular, gallbladder and pancreatic cancers. A smaller volume of evidence demonstrates that indices of increased central adiposity (such as waist circumference) are associated with increased risk of oesophageal adenocarcinoma and colorectal cancer, but these indices are not necessarily better predictors of risk compared with BMI. Several biological mechanisms may explain these associations but each hypothesis has several caveats and weaknesses. There are few data that convincingly demonstrate significant reductions in risk of gastrointestinal cancers following weight-reducing strategies. In turn, there are many methodological pitfalls in this literature, which prevent conclusive interpretation. The lack of robust intermediary obesity-related biomarkers is an additional unresolved challenge for prevention trials. Novel underpinning mechanisms (for example, local ectopic fat) and more accurate methods to measure these intermediaries are sought and explored as the most optimistic research strategies for the future.
Impact of extranodal extension on prognosis in lymph node-positive gastric cancer
Authors: Lee I-S , Park Y-S , Ryu M-H , Song M J , Yook J-H , Oh S-T , Kim B-S
Published: September 2014

Background

The TNM classification system is used widely for tumour staging, and directs the treatment and prognosis of patients with cancer. The aim of this study was to assess the prognostic value of extranodal extension (ENE) in patients with early gastric cancer.

Methods

All patients who underwent gastrectomy with lymphadenectomy for primary gastric cancer with lymph node metastases between January 2003 and June 2006 were reviewed. Histological slides of metastatic nodes were reviewed by two gastrointestinal pathologists. The association of ENE with clinicopathological characteristics was assessed. The disease-specific survival rate was calculated by the Kaplan–Meier method, and a multivariable Cox regression model was used to identify independent prognostic factors.

Results

Some 1143 patients were included. ENE was associated with advanced pT and pN category, larger tumour size and lymphovascular/perineural invasion. In multivariable analysis, pT category, pN category, ENE, lymphovascular invasion and perineural invasion were found to be independent prognostic factors in node-positive gastric carcinoma. The 5-year survival rate of patients with ENE was 48·1 per cent, compared with 78·2 per cent for patients without ENE (P < 0·001). In the subgroup of patients with early gastric cancer, ENE was associated with a worse 5-year survival rate in patients with early (T1) gastric cancer: 75 per cent in patients with ENEversus 96·9 per cent in those without (P < 0·001).

Conclusion

ENE is an independent prognostic factor in patients with early and advanced gastric cancer.
Serum fatty acid profiles and potential biomarkers of ankylosing spondylitis determined by gas chromatography–mass spectrometry and multivariate statistical analysis
Authors: Chen Rui , Han Su , Dong Daming , Wang Yansong , Liu Qingpeng , Xie Wei , Li Mi , Yao Meng
Published: September 2014

Ankylosing spondylitis (AS) is a common chronic inflammatory rheumatic disease. Early and accurate detection is essential for effective disease treatment. Recently, research has focused on genomics and proteomics. However, the associated metabolic variations, especially fatty acid profiles, have been poorly discussed. In this study, the gas chromatography–mass spectrometry (GC‐MS) approach and multivariate statistical analysis were used to investigate the metabolic profiles of serum free fatty acids (FFAs) and esterified fatty acids (EFAs) in AS patients. The results showed that significant differences in most of the FFA (C12:0, C16:0, C16:1, C18:3, C20:4, C20:5, C22:5 and C22:6) and EFA (C12:0, C16:1, C18:0, C18:1, C18:2, C18:3, C20:4 and C22:6) concentrations were found between the AS patients and healthy controls (p < 0.05). Principal component analysis and partial least squares discriminant analysis were performed to classify the AS patients and controls. Additionally, FFAs C20:4, C12:0, C18:3 and EFAs C22:6, C12:0 were confirmed as potential biomarkers to identify AS patients and healthy controls. The present study highlights that differences in the serum FFA and EFA profiles of AS patients reflect the metabolic disorder. Moreover, FFA and EFA biomarkers appear to have clinical applications for the screening and diagnosis of AS. Copyright © 2014 John Wiley & Sons, Ltd.
Simultaneous quantification of two steroidal glycosides after oral gavage of Marsdenia tenacissima extract in rats using a LC‐MS/MS method
Authors: Wang Wei , Sun Wei , Dong Lei , Qu Xiaotong , Shi Jin , Li Ke‐Jun , Li Bing , Ma Da‐Peng
Published: September 2014

A specific, sensitive and accurate analytical LC‐MS/MS assay was developed for the simultaneous determination of two steroidal glycosides, tenacissoside H and tenacissoside I, in rat plasma. An Agilent ZORBAX SB‐C18 column was used with an isocratic mobile phase system composed of methanol–water–formic acid (70:30:0.1, v/v/v) at a flow rate of 0.3 mL/min. The analysis was performed on a positive ionization electrospray mass spectrometer via selected reaction monitoring mode scan. One‐step protein precipitation with acetonitrile was chosen to extract the analytes from plasma. The lower limits of quantification were 0.9 ng/mL for tenacissoside H and tenacissoside I. The intra‐ and inter‐day precisions were 2.03–11.56 and 3.76–11.62%, respectively, and the accuracies were <110.28% at all quality control levels. The validated method was applied to a pharmacokinetic study in rats after oral gavage of Marsdenia tenacissima extract. Copyright © 2014 John Wiley & Sons, Ltd.
A proposed novel function of the psoas minor revealed through cadaver dissection
Authors: Neumann Donald A. , Garceau Luke R.
Published: September 2014

There is sparse information about the anatomy and function of the psoas minor, specifically the extent and frequency to which the muscle attaches into the iliac fascia that drapes over the iliopsoas. This information may help clarify the function of the psoas minor, especially regarding the possibility of controlling the position and mechanical stability of the underlying iliopsoas. This descriptive, semiquantitative cadaveric study sought to clarify the gross anatomic detail of the psoas minor, particularly the muscle's distal attachments. Thirty‐two embalmed cadaver hips were examined. Hips that presented with a psoas minor underwent further anatomic measurements. The psoas minor was present in 65.6% of the 32 hips. All of the psoas minor tendons attached firmly into iliac fascia, while 90.5% also had a firm bony attachment to the pelvis. On average, the muscle belly occupied the proximal 37.5 ± 6.0% of the entire musculotendinous unit, while the muscle belly's average anatomical cross‐sectional area was 52.5 ± 34.3 mm2. The psoas minor's firm and consistent distal tendinous attachment into the iliac fascia may allow this muscle to partially control the position and mechanical stability of the underlying iliopsoas as it crosses the femoral head and adjacent regions. This hypothesized function may be clinically related to inflammation and pathology involving the iliopsoas tendon and adjacent tissues in the anterior region of the hip. Further study is now warranted to determine the clinical relevancy and biomechanical validity of this proposed function of the psoas minor. Clin. Anat. 28:243–252, 2015. © 2014 Wiley Periodicals, Inc.
An efficient method for calculating the moments of multidimensional growth processes in population balance systems
Authors: Dürr Robert , Kienle Achim
Published: September 2014

Multidimensional growth processes play an important role in many fields of applications, such as crystallization processes and cell culture engin‐ eering. The numerical solution of the corresponding multivariate population balance equations is quite challenging as standard discretization‐based methods are not efficient for high dimensional problems. For this reason, the distribution dynamics is often characterized by its moments. However, the moment dynamics generally cannot be calculated in closed form. Existing approximation techniques cannot be implemented efficiently in the multivariate framework, in particular for high dimensional problems. This contribution presents an alternative methodology for the efficient approximate computation of moments for multidimensional growth processes using Monomial Cubatures and the Method of Characteristics (MOC). The procedure will be shown to reproduce the moments accurately for one‐ and two‐dimensional examples which feature nonlinear growth rates and coupling to a continuous phase, respectively. Furthermore numerical effort and accuracy will be analyzed for a five‐dimensional benchmark problem.
Stability improvement of multimachine power system via new coordinated design of PSSs and SVC
Authors: Ali E. S. , Abd‐Elazim S. M.
Published: September 2014

In this article, the assessment of new coordinated design of power system stabilizers (PSSs) and static var compensator (SVC) in a multimachine power system via statistical method is proposed. The coordinated design problem of PSSs and SVC over a wide range of loading conditions is handled as an optimization problem. The bacterial swarming optimization (BSO), which synergistically couples the bacterial foraging with the particle swarm optimization (PSO), is used to seek for optimal controllers parameters. By minimizing the proposed objective function, in which the speed deviations between generators are involved; stability performance of the system is enhanced. To compare the capability of PSS and SVC, both are designed independently, and then in a coordinated manner. Simultaneous tuning of the BSO‐based coordinated controller gives robust damping performance over wide range of operating conditions and large disturbance in compare to optimized PSS controller based on BSO (BSOPSS) and optimized SVC controller based on BSO (BSOSVC). Moreover, a statistical T test is executed to validate the robustness of coordinated controller versus uncoordinated one. © 2014 Wiley Periodicals, Inc. Complexity 21: 256–266, 2015
Evaluation of the stability and pharmacokinetics of cabazitaxel‐loaded intravenous lipid microspheres: Beneficial effect of cholesterol
Authors: Shao Yanjie , Li Shuang , Tian Bin , Su Linlin , Zhang Chungang , Wang Yueqi , Tang Xing , Wang Yanjiao
Published: September 2014

In this work, we describe the evaluation of the stability and pharmacokinetics of cabazitaxel‐loaded lipid microspheres (CTX‐LM) prepared by high‐pressure homogenization. Investigation of the physicochemical stability under different homogenization cycles and diverse sterilization times confirmed that 8 cycles at 800 bar and 121°C for 8 min were the optimal technological parameters. The beneficial effect of cholesterol on the physical stability of CTX‐LM was confirmed and its mechanism of action was identified. The stability of CTX‐LM using an aqueous isotonic glucose solution as a diluting agent was greater compared with using 0.9% NaCl solution as a result of an electric charge effect. CTX‐LM are stable under freeze‐thaw conditions and should not be exposed to high temperatures and protected from light during storage. Furthermore, all the changes in parameters were within an acceptable range at 4°C within 9 months, which supported the good long‐term stability of CTX‐LM. Finally, to compare the pharmacokinetics of CTX‐LM with cabazitaxel‐solution in vivo, a rapid, accurate UPLC‐MS/MS method was developed and used to determine cabazitaxel in rat plasma after a single intravenous administration of 4 mg/kg. An obviously larger area under the curve (AUC) of CTX‐LM was observed than that of CTX‐solution, which will improve the antitumor efficacy of cabazitaxel.

Practical applications: As a novel semisynthetic taxane, cabazitaxel has shown antitumour activity in a broad range of cell‐lines and tumor models and has been approved in combination with prednisone for the treatment of patients with castration‐resistant metastatic prostate cancer. However, serious undesirable effects in humans, such as anaphylactoid hypersensitivity reactions and peripheral neuropathy were produced by the addition of polysorbate 80 to commercial products. In this paper, CTX‐LM was prepared by high‐pressure homogenization in order to overcome the above drawbacks. The good stability and markedly higher AUC of CTX‐LM may hasten their passage from a pre‐clinical phase to a clinical trial phase and allow their production on a large scale.

In this paper, cabazitaxel lipid microspheres exhibited a great stability and had a higher AUC than cabazitaxel solution.
Nickel‐Catalyzed Kumada Coupling of Benzyl Chlorides and Vinylogous Derivatives
Authors: Soler‐Yanes Rita , Guisán‐Ceinos Manuel , Buñuel Elena , Cárdenas Diego J.
Published: September 2014

Conditions for the fast Ni‐catalyzed Kumada‐type cross‐coupling of functionalized benzyl and allyl chlorides with alkylmagnesium reagents were discovered. The use of Ni(acac)2–TMEDA (acac = acetylacetonate, TMEDA = N,N,N′,N′‐tetramethyl‐1,2‐ethylenediamine) allows the presence of reactive functional groups on the electrophile. On the other hand, the use of diallyl ether was shown to provide fast coupling at low temperature with a low catalyst loading. The reaction seems to follow a radical pathway.
Recent shifts in coastline change and shoreline stabilization linked to storm climate change
Authors: Johnson Jennifer M. , Moore Laura J. , Ells Kenneth , Murray A. Brad , Adams Peter N. , MacKenzie Richard A. , Jaeger John M.
Published: September 2014

Since cuspate coastlines are especially sensitive to changes in wave climate, they serve as potential indicators of initial responses to changing wave conditions. Previous work demonstrates that Cape Hatteras and Cape Lookout, North Carolina, which are largely unaffected by shoreline stabilization efforts, have become increasingly asymmetric over the past 30 years, consistent with model predictions for coastline response to increases in Atlantic Ocean summer wave heights and resulting changes in the distribution of wave‐approach angles. Historic and recent shoreline change observations for Cape Fear, North Carolina, and model simulations of coastline response to an increasingly asymmetric wave climate in the presence of beach nourishment, produce comparable differences in shoreline change rates in response to changes in wave climate. Results suggest that the effect of beach nourishment is to compensate for – and therefore to mask – natural responses to wave climate change that might otherwise be discernible in patterns of shoreline change alone. Therefore, this case study suggests that the effects of wave climate change on human‐modified coastlines may be detectable in the spatial and temporal patterns of shoreline stabilization activities. Similar analyses of cuspate features in areas where the change in wave climate is less pronounced (i.e. Fishing Point, Maryland/Virginia) and where local geology appears to exert control on coastline shape (i.e. Cape Canaveral, Florida), suggest that changes in shoreline configuration that may be arising from shifting wave climate are currently limited to sandy wave‐dominated coastlines where the change in wave climate has been most pronounced. However, if hurricane‐generated wave heights continue to increase, large‐scale shifts in patterns of erosion and accretion will likely extend beyond sensitive cuspate features as the larger‐scale coastline shape comes into equilibrium with changing wave conditions. Copyright © 2014 John Wiley & Sons, Ltd.
Effect of sofosbuvir and ribavirin treatment on peripheral and hepatic lipid metabolism in chronic hepatitis C virus, genotype 1–infected patients
Authors: Meissner Eric G. , Lee Yu‐Jin , Osinusi Anu , Sims Zayani , Qin Jing , Sturdevant Dan , McHutchison John , Subramanian Mani , Sampson Maureen , Naggie Susanna , Patel Keyur , Remaley Alan T. , Masur Henry , Kottilil Shyam
Published: September 2014

Hepatitis C virus (HCV) modulates intrahepatic cholesterol biosynthetic pathways to promote viral replication. Chronic HCV infection is associated with altered metabolism, including dyslipidemia and insulin resistance (IR), which contributes to disease progression and influences response to therapy. To further understand the impact of HCV infection on host metabolism, we examined changes in serum lipid profiles and intrahepatic expression of lipid‐related genes during interferon (IFN)‐free treatment of chronic HCV, genotype 1 infection with sofosbuvir and ribavirin (RBV), and explored associations with treatment outcome. Serum lipids (total cholesterol, low‐density lipoprotein [LDL], high‐density lipoprotein [HDL], and triglycerides [TGs]) and hemoglobin A1C (HbA1C) were measured during treatment, while gene expression of lipid‐related genes was assessed using paired pre‐ and end‐of‐treatment (EOT) liver biopsies from 8 patients (n = 7 sustained virologic response [SVR]; n = 1 relapse) and unpaired EOT liver biopsies from 25 patients (n = 17 SVR; n = 8 relapse). Serum LDL concentration and particle size increased early in therapy, whereas TG concentration and very‐low‐density lipoprotein particle size decreased concomitantly, irrespective of treatment outcome. Whereas LDL increased in patients regardless of treatment outcome, average LDL concentration was lower at baseline and post‐treatment in patients who relapsed. Analysis of paired liver biopsies revealed altered expression of genes associated with lipid transport, assembly, and signaling. In unpaired EOT liver biopsies, intrahepatic expression of fatty acid metabolism and lipid transport genes was lower in patients who experienced treatment relapse. Conclusion: Clearance of HCV using an IFN‐free antiviral regimen results in rapid changes in peripheral and intrahepatic metabolic pathways, implicating a direct effect of HCV replication on lipid homeostasis. (Hepatology 2015;61:790–801)
Role of oxygen in the polymerization and de‐polymerization of alginate produced by Azotobacter vinelandii
Authors: Flores Celia , Díaz‐Barrera Alvaro , Martínez Fabiola , Galindo Enrique , Peña Carlos
Published: September 2014

Microbial polymers have diverse chemical structures, which determine their functional properties. Many microbial sources produce either intracellular or extracellular biopolymers. For example, Azotobacter vinelandii is a non‐pathogenic soil bacterium that produces alginate, an extracellular polysaccharide. Alginates are used mainly in the food and pharmaceutical industries as stabilizing, thickening, gel‐ or film‐forming agents. Due to its characteristics of biocompatibility, biodegradability and non‐antigenicity, new applications for alginate are being discovered, such as biomaterial in the biomedical field and tissue engineering.

It is well established that alginate is first synthesized as a polymannuronate from its cytosolic precursor. However, the mechanisms involved in the polymerization, modification (acetylation, epimerization and depolymerization) and translocation of alginate have been poorly elucidated. Two of the most important parameters in alginate production by A. vinelandii are dissolved oxygen tension (DOT) and the oxygen supply conditions, as these impact both the polymer concentration and its composition, particularly its molecular weight (MW). Several studies have revealed that increased alginate molecular weight occurs in oxygen limited conditions, specifically at oxygen concentrations near zero. This article reviews recent studies examining the influence of oxygen, under limitation (microaerophilic) and non‐limitation conditions (measured as DOT and oxygen transfer rate, OTR), on the polymerization and degradation of alginate produced by A. vinelandii. This review also provides evidence for understanding these processes at the cellular level and the effect of oxygen on alginate biosynthesis. © 2014 Society of Chemical Industry
Neuroanatomical circuitry mediating the sensory impact of nicotine in the central nervous system
Authors: Dehkordi Ozra , Rose Jed E. , Asadi Sadegh , Manaye Kebreten F. , Millis Richard M. , Jayam‐Trouth Annapurni
Published: September 2014

Direct actions of nicotine in the CNS appear to be essential for its reinforcing properties. However, activation of nicotinic acetylcholine receptors (nAChRs) on afferent sensory nerve fibers is an important component of addiction to, and withdrawal from, cigarette smoking. The aim of the present study was to identify the neuroanatomical substrates activated by the peripheral actions of nicotine and to determine whether these sites overlap brain structures stimulated by direct actions of nicotine. Mouse brains were examined by immunohistochemistry for c‐Fos protein after intraperitoneal injection of either nicotine hydrogen tartrate salt (NIC; 30 and 40 μg/kg) or nicotine pyrrolidine methiodide (NIC‐PM; 20 and 30 μg/kg). NIC‐PM induced c‐Fos immunoreactivity (IR) at multiple brain sites. In the brainstem, c‐Fos IR was detected in the locus coeruleus, laterodorsal tegmental nucleus, and pedunculotegmental nucleus. In the midbrain, c‐Fos IR was observed in areas overlapping the ventral tegmental area (VTA), which includes the paranigral nucleus, parainterfascicular nucleus, parabrachial pigmental area, and rostral VTA. Other structures of the nicotine brain‐reward circuitry activated by NIC‐PM included the hypothalamus, paraventricular thalamic nucleus, lateral habenular nucleus, hippocampus, amygdala, accumbens nucleus, piriform cortex, angular insular cortex, anterior olfactory nucleus, lateral septal nucleus, bed nucleus of stria terminalis, cingulate and medial prefrontal cortex, olfactory tubercle, and medial and lateral orbital cortex. NIC, acting through central and peripheral nAChRs, produced c‐Fos IR in areas that overlapped NIC‐PM‐induced c‐Fos‐expressing sites. These neuroanatomical data are the first to demonstrate that the CNS structures that are the direct targets of nicotine are also anatomical substrates for the peripheral sensory impact of nicotine. © 2014 Wiley Periodicals, Inc.
Big data, big results: Knowledge discovery in output from large‐scale analytics
Authors: McCormick Tyler H. , Ferrell Rebecca , Karr Alan F. , Ryan Patrick B.
Published: September 2014

Observational healthcare data, such as electronic health records and administrative claims databases, provide longitudinal clinical information at the individual level. These data cover tens of millions of patients and present unprecedented opportunities to address such issues as post‐market safety of medical products. Analyzing patient‐level databases yields population‐level inferences, or ‘results’, such as the strength of association between medical product exposure and subsequent outcomes, often with thousands of drugs and outcomes. In this article, by contrast, we study ‘big results’, which are the product of applying thousands of alternative analysis strategies to five large patient databases. These results were produced by the Observational Medical Outcomes Partnership. All together, there are more than 6 million results, comprising risk assessments for 399 medical product–outcome pairs analyzed across five observational databases using seven statistical methods, each of which has between a few dozen and a few hundred variants representing parameters or ‘tuning variables’. We focus on the value of knowledge discovery methods and the challenges in extracting clinically relevant knowledge from big results. We believe our analyses are both scientifically and methodologically valuable as they reveal information about how methods/algorithms perform under various circumstances, as well as provide a basis for comparison of these methods.
Considering the size and strength of beam‐column joints in the design of RC frames
Authors: Costa Ricardo Joel Teixeira , Providência Paulo , Dias Alfredo
Published: September 2014

Some experimental research studies have reported that longitudinal reinforcement in beams and columns exhibits larger strains inside the joint than at the joint periphery (defined as the intersection of the outer surfaces of beam and column). This may explain why several technical specifications and state‐of‐the‐art programs recommend basing the design of beams and columns on internal force values larger than those at the joint periphery. These results and procedures are questionable and are investigated in this paper. The non‐linear finite element analysis presented here for reinforced concrete frames under gravity and quasi‐static monotonic lateral loads examines (i) the stress fields in reinforcement inside interior, exterior and roof exterior joints, and (ii) the load‐carrying capacity of representative sub‐frame models incorporating such joints. The results prove that it is actually safe, with respect to the joint load capacity, to base the design of longitudinal reinforcement in beams and columns on the internal force values at the joint periphery. This result also contributes to the recommendation to use real‐size beam‐column joint models in the analysis procedure.
Accuracy of prenatal ultrasound in detecting jejunal and ileal atresia: systematic review and meta‐analysis
Authors: Virgone C. , D'Antonio F. , Khalil A. , Jonh R. , Manzoli L. , Giuliani S.
Published: September 2014

Objective

The accuracy of prenatal ultrasound examination in detecting jejunal and ileal atresia has been reported in the literature to be highly variable, at 25–90%. The aim of this systematic review was to evaluate the accuracy of prenatal ultrasound in detecting non‐duodenal small bowel atresia (ND‐SBA).

Methods

MEDLINE, EMBASE and The Cochrane Library, including The Cochrane Database of Systematic Reviews (CDSR), Database of Abstracts of Reviews of Effects (DARE) and The Cochrane Central Register of Controlled Trials (CENTRAL), were searched electronically. The overall detection rate of jejunal or ileal atresia using ultrasound was reported. The accuracy of using polyhydramnios and dilated loops of bowel as diagnostic signs was also explored.

Results

Sixteen studies involving 640 fetuses were included in this review. The detection rate of ND‐SBA by prenatal ultrasound was highly variable, with values ranging from 10 to 100%, with an overall prediction of 50.6% (95% CI, 38.0–63.2%). When analyzed separately, the detection rates of jejunal and ileal atresia were 66.3%, (95% CI, 33.9–91.8%) and 25.9% (95% CI, 4.0–58.0%), respectively. Both dilated loops of bowel and polyhydramnios as diagnostic signs for ND‐SBA provided a low overall detection rate.

Conclusions

The diagnostic performance of prenatal ultrasound in identifying ND‐SBA is extremely variable. Large studies are needed in order to identify objective and combined criteria for the diagnosis of these anomalies. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.
Double Cube Polycationic Clusters and CuI Between Covalent and Ionic Bonding in Cu(Sb7Te8)[GaCl4]6
Authors: Eich Andreas , Beck Johannes
Published: September 2014

The reaction of antimony telluride with antimony trichloride in a GaCl3‐rich copper(I) tetrachloridogallate melt in the presence of antimony(III) oxide yields Cu(Sb7Te8)[GaCl4]6 (1) as dark‐orange, moisture sensitive crystals. SbCl3 acts as the oxidant, GaCl3 as the reaction medium, which provides the weakly coordinating [GaCl4]– anions. The discrete, double cube shaped (Sb7Te8)5+ clusters show only small distortions from ideal D3d symmetry. A remarkable structural feature is the linear coordination of Cu+ by the Cl atoms of two neighboring [GaCl4]– ions forming a [{CuCl2}–·2GaCl3] entity [d(Cu–Cl) = 2.188(1) Å], which fixes the Cu+ ion in the center of the large cube‐shaped CuCl8 coordination sphere. Single crystal diffraction at different temperatures between 100 and 223 K revealed a large thermal vibration of the Cu+ cation. A solid state phase transition, as observed for the isotypic Na+ and Ag+ congeners, was not found for 1.
Mycobacterium tuberculosis PE25/PPE41 protein complex induces necrosis in macrophages: Role in virulence and disease reactivation?
Authors: Tundup Smanla , Mohareer Krishnaveni , Hasnain Seyed E.
Published: September 2014

Necrotic cell death during TB infection is an important prerequisite for bacterial dissemination and virulence. The underlying mechanisms and the bacterial factors involved therein are not well understood. The Mycobacterium tuberculosis (M. tuberculosis) co‐operonic PE25/PPE41 protein complex, similar to ESAT‐6/CFP‐10, belonging to the PE/PPE and ESAT‐6 families of genes has co‐expanded and co‐evolved in the genomes of pathogenic mycobacteria. We report a novel role of this highly immunogenic PE25/PPE41 protein complex in inducing necrosis, but not apoptosis, in macrophages. We propose that these protein complexes of M. tuberculosis, secreted by similar/unique transport system (Type VII), have an important role in M. tuberculosis virulence and disease reactivation.
Top‐down, bottom‐up, or both? Toward an integrative perspective on operations strategy formation
Authors: Kim Yoon Hee , Sting Fabian J. , Loch Christoph H.
Published: September 2014

Operations strategy is formed via complex processes that transpire in multiple directions at multiple organizational levels. While most previous studies focus on the “macro‐level” process of strategy formation from the dominant top‐down perspective, this study investigates the “micro‐level” process of strategy formation that governs interactions among competitive priorities, objectives, and action plans within operations. Using 111 (59 top‐down and 52 bottom‐up) action plans collected from six German manufacturing plants, we build on Kim and Arnold's (1996) framework and propose an integrated process model of operations strategy formation that encompasses both top‐down planning and bottom‐up learning. We also identify a contingency factor that affects their balance: centralized versus decentralized organizational structure. Finally, based on the analysis of their respective strategic content, we provide evidence concerning the complementary roles of top‐down and bottom‐up action plans in operations strategy.
Management of Chlorine Gas-Related Injuries From the Graniteville, South Carolina, Train Derailment
Authors: Mackie Emily , Svendsen Erik , Grant Stephen , Michels Jill E. , Richardson William H.
Published: September 2014

A widely produced chemical, chlorine is used in various industries including automotive, electronics, disinfectants, metal production, and many others. Chlorine is usually produced and transported as a pressurized liquid; however, as a gas it is a significant pulmonary irritant. Thousands of people are exposed to chlorine gas every year, and while large-scale exposures are uncommon, they are not rare. Symptoms are usually related to the concentration and length of exposure, and although treatment is largely supportive, certain specific therapies have yet to be validated with randomized controlled trials. The majority of those exposed completely recover with supportive care; however, studies have shown the potential for persistent inflammation and chronic hyperreactivity. This case report describes an incident that occurred in Graniteville, South Carolina, when a train derailment exposed hundreds of people to chlorine gas. This report reviews the events of January 6, 2005, and the current treatment options for chlorine gas exposure.(Disaster Med Public Health Preparedness. 2014;0:1-6)
Bragg accelerator optimization
Authors: Hanuka Adi , Schächter Levi
Published: September 2014

We present the first steps of a design of the optimal parameters for a full Bragg X-Ray free electron laser (BX-FEL). Aiming towards a future source of coherent X-ray radiation, operating in the strong Compton regime, we envisage the system to be the seed for an advanced light source or compact medical X-ray source. Here we focus on the design of the accelerator parameters: maximum gradient, optimal accelerated charge, maximum efficiency, and ‘wake coefficient’, which relates to the decelerating electric field generated due to the motion of a charged-line or train of charged-lines. Specifically, we demonstrate that the maximum efficiency has optimal value and given the fluence of the materials, the maximum accelerated charge in the train is constant. These two results might be important in any future design.
Effect of the commercial product Lumance™, a combination of partly esterified organic acids and plant extracts, on the productive performance of broiler chickens
Authors: Taha T.M.A. , Zakaria H. , Jalal M. , Bauwens S.
Published: September 2014

The present study was conducted to determine the effect of dietary supplementation of organic acids combined with synergistic components, using a commercial product Lumance™ (Innovad NV, Belgium) containing esterified butyrins, propionic acid and sorbic acid, with medium chain fatty acids (capric, caprylic, and lauric acid) and plant extracts, on the productive performance and mortality of growing broiler chickens. A total of 492, one day old broiler chicks (Ross 308) were randomly allocated to four experimental treatments either with an unsupplemented control or 0.05, 0.1 or 0.15% organic acid mixture in a pelleted corn/soyabean meal diet, which were offered ad libitum until 35 days of age. Results showed that birds in the 0.1% supplemented diet group gave significantly higher (P < 0.05) body weights during the first two weeks of age and increased weight gain during the first three weeks of age. The inclusion had no effect on broiler mortality.
“Extreme Confusion and Disorder”? The Japanese Economy in the Great Kantō Earthquake of 1923
Authors: Hunter Janet
Published: September 2014

Contemporary concerns about the difficulties faced by the Japanese economy following the Great Kantō Earthquake of 1923 soon appeared to be unfounded as the economy recovered relatively quickly. This paper suggests that despite its limited impact on Japan's longer-term economic trajectory this disaster can tell us a great deal about the ways in which individuals, organizations, and officialdom respond to a devastating event, and help us better understand the process of transition from immediate relief to longer-term recovery, not just in Japan, but more broadly. It analyzes the impact of the disaster on market transactions, showing that the scale and nature of market disruption went far beyond direct physical destruction; that the collective and individual responses of government, producers, traders, and consumers had the potential to make matters worse, rather than better; and that the existence of integrated markets spread the effects of the disaster across the Japanese archipelago. It also suggests that reestablishing market stability following the crisis was one of the keys to longer-term recovery, and that further research will help us understand the causal factors in that process.
Lu Xun on Our Minds: The Post-Socialist Reappraisal; Chou,Memory, Violence, Queues: Lu Xun Interprets China; Davies,Lu Xun's Revolution: Writing in a Time of Violence; Cheng,Literary Remains: Death, Trauma, and Lu Xun's Refusal to Mourn
Authors: von Kowallis Jon Eugene
Published: September 2014

That American academic publishers within a short time have put out three monographs this substantial on Lu Xun (1881–1936), often referred to as the founder of modern Chinese literature, is indicative of a new enthusiasm for Lu Xun in the United States and elsewhere in the West. In Japan, South Korea, and of course the People's Republic of China, the study of Lu Xun has been an academic enterprise of considerable standing for some time already. Not that American scholars have failed to make substantial contributions to Lu Xun studies in the past, but such contributions have been relatively far between. Fortunately, there is little overlap between these three exciting new studies.
Mythologizing the Global with the ‘Korean Original Musical’
Authors: CHAMBERS CLAIRE MARIA
Published: September 2014

Because South Korea's national sovereignty is a matter of cultural production, Seoul boasts an energetic programme of world-class performances that educate both foreigners and Koreans about the nation's struggle to assert its subjectivity throughout centuries of invasion, colonization and displacement. Three musicals re-present episodes from Korea's mythical past in ways that demonstrate a ‘primordial’ uniqueness of Korean global presence. The Celestial Clock addresses a Korean audience, unfolding outdoors against the backdrop of Gyeonghuigung Palace. Miso: The Original Korean Musical – Love Songs from Chunhyang, a showcase for traditional performing arts, uses pantomime and subtitles to guide an international audience through a popular legend; and Miso II: Land of the Gods stages Korean mythical history in breathtaking spectacle. The musicals, by arguing for the ‘always already’ global viability of Korean national sovereignty, also work to destabilize current ‘mythologies’ of what it means for a state to achieve ‘global’ status.
Editorial: Theatre, Transnationalism and Economy: A Collaboration with Theatre Survey
Authors: CANNING CHARLOTTE M.
Published: September 2014

This special issue is unique in that it is the first time that this journal has collaborated with another to share the same set of questions ramified through the two journals’ different missions. Editor Esther Kim Lee and I proposed to link Theatre Research International and Theatre Survey in order to explore how the ‘2008 worldwide economic crisis brought scholars of theatre and performance to re-examine how neoliberalism, economic nomadism, and transnationalism affect artistic practices’, as we wrote in the call for papers. The response was impressive and demonstrated that performance scholars around the globe are thinking about these pressing issues in contiguous and contradictory ways.