bluuebunny/crossref_metadata_2025 huggingface dataset:
Computation of Standard Errors
Authors: Dowd Bryan E. , Greene William H. , Norton Edward C.
Published: November 2013

Objectives

We discuss the problem of computing the standard errors of functions involving estimated parameters and provide the relevant computer code for three different computational approaches using two popular computer packages.

Study Design

We show how to compute the standard errors of several functions of interest: the predicted value of the dependent variable for a particular subject, and the effect of a change in an explanatory variable on the predicted value of the dependent variable for an individual subject and average effect for a sample of subjects.

Empirical Application

Using a publicly available dataset, we explain three different methods of computing standard errors: the delta method, Krinsky–Robb, and bootstrapping. We provide computer code for Stata 12 and LIMDEP 10/NLOGIT 5.

Conclusions

In most applications, choice of the computational method for standard errors of functions of estimated parameters is a matter of convenience. However, when computing standard errors of the sample average of functions that involve both estimated parameters and nonstochastic explanatory variables, it is important to consider the sources of variation in the function's values.
Reduction of Elevated Cytokine Levels in Acute/Acute‐on‐Chronic Liver Failure Using Super‐Large Pore Albumin Dialysis Treatment: An In Vitro Study
Authors: Dominik Adrian , Stange Jan , Pfensig Claudia , Borufka Luise , Weiss‐Reining Helga , Eggert Martin
Published: November 2013

The removal of small water soluble toxins and albumin‐bound toxins in acute liver failure patients (ALF) or acute‐on‐chronic liver failure (AocLF) patients has been established using extracorporeal liver support devices (e.g. Molecular Adsorbents Recirculating System; MARS). However, reduction of elevated cytokines in ALF/AocLF using MARS is still not efficient enough to lower patients' serum cytokine levels. New membranes with larger pores or higher cut‐offs should be considered in extracorporeal liver support devices based on albumin dialysis in order to address these problems, as the introduction of super‐large pore membranes could counterbalance high production rates of cytokines and further improve detoxification in vivo. Using an established in vitro two compartment albumin dialysis model, three novel membranes of different pore sizes were compared with the MARS Flux membrane for cytokine removal and detoxification qualities in vitro. Comparing the membranes, no improvement in the removal of water soluble toxins was found. Albumin‐bound toxins were removed more efficiently using novel large (Emic2) to super‐large pore sized membranes (S20; HCO Gambro). Clearance of cytokines IL‐6 and tumor necrosis factor‐α was drastically improved using super‐large pore membranes. The Emic2 membrane predominantly removed IL‐6. In vitro data suggest that the usage of larger pore sized membranes in albumin dialysis can efficiently reduce elevated cytokine levels and liver failure toxins. Using large to super‐large pore membranes might exert effects on patients' serum cytokine levels. Combined with increased detoxification this could lead to higher survival in ALF/AocLF. Promising membranes for clinical evaluation have been identified.
Keeping the Arctic ‘Cold’: The Rise of Plurilateral Diplomacy?
Authors: Bjola Corneliu
Published: November 2013

At a time when the Arctic region faces significant climatic transformations, a triple governance gap threatens to fuel major diplomatic tensions among regional actors over natural resources, navigation rights and fishery management. This article argues that a plurilateral diplomatic approach could help close these gaps by establishing an effective ‘web of contracts’ involving institutional networks defined around the Arctic Council as the central node of Arctic governance and NATO, the International Maritime Organization (IMO) and the United Nations Development Programme (UNDP) / the Global Environment Facility (GEF) as supporting agencies. In so doing, the article makes a twofold contribution to the literature on global governance. It explains how governance gaps could be closed in a manner that does not require extensive institutional frameworks or rigid legal mandates, and it highlights the role of institutional networks in sustaining regional and global governance.
Identity and War
Authors: Kaldor Mary
Published: November 2013

This article makes two arguments. First, sectarian identity (ethnic, tribal or religious) is an outcome of war rather than a cause of war, even though such identities make (selective) use of memory. The implication of this proposition is that war should be interpreted less as an external contest of will between two sides but rather as a one‐sided and/or parallel effort to construct unidimensional political identities as a basis for power. Power derived from identity so constructed is likely to be authoritarian and repressive. Second, different methods of communication provide the basis for different modalities of power and this matters; power diffuses through all forms of communication. But the language of violence is much less amenable to freedom and human emancipation than other nonviolent forms of communication. The arguments are elaborated through a critique of the work of the German legal theorist Carl Schmitt and his notion of the friend–enemy distinction as a basis of political authority. The article concludes by arguing that in a global era, when traditional inter‐state war is declining, there are greater possibilities for multiple identities and a layering of political authority, even though there are also efforts to resurrect the friend–enemy distinction in many ‘new wars’ and, above all, in the war on terror.
Does dominance of crossing retinal ganglion cells make the eyes cross? The temporal retina in the origin of infantile esotropia – a neuroanatomical and evolutionary analysis
Authors: ten Tusscher Marcel P. M.
Published: November 2013

A closer look at the evolution of the eye and the brain provides a possible explanation for both the origin of infantile esotropia and its motor characteristics. In the course of evolution, the eyes have moved from a lateral to a frontal position. Consequently, the monocular visual fields started to overlap resulting in a binocular visual field. In lateral‐eyed animals, the retinae project to the contralateral visual cortices only. These projections are also found in binocular mammals and birds with binocular visual fields but in addition there are uncrossed projections from the temporal retinae to the visual cortex. The partial chiasmal decussation and the corpus callosum provide the necessary structure that allows binocular vision to develop. Disruption of normal binocular development causes a loss of binocularity in the primary visual cortex and beyond. Beyond the primary visual cortex, the contralateral eye dominates while the temporal retinal signal appears to lose influence. Loss or absence of binocular vision in infantile esotropia may be caused by inadequate retinotopic matching between the nasal and temporal retinal signals like in albinism with an abnormal or asymmetric chiasmal decussation or agenesis of the corpus callosum. Dominance of the crossing retinal signal might also explain the motor characteristics of infantile esotropia (asymmetric OKN, latent nystagmus, DVD). A normal binocular cortical signal will predominate over the evolutionary older, originally non‐binocular, retinal projections to the superior colliculi (CS) and the accessory optic system (AOS). A suppressed temporal retinal signal paves the way for the re‐emergence of eye movements driven by one eye, as in lateral‐eyed non‐binocular animals.
Differential satellite cell density of type I and II fibres with lifelong endurance running in old men
Authors: Mackey A. L. , Karlsen A. , Couppé C. , Mikkelsen U. R. , Nielsen R. H. , Magnusson S. P. , Kjaer M.
Published: November 2013

Aim

To investigate the influence of lifelong endurance running on the satellite cell pool of type I and type II fibres in healthy human skeletal muscle.

Methods

Muscle biopsies were collected from 15 healthy old trained men (O‐Tr) who had been running 43 ± 16 (mean ± SD) kilometres a week for 28 ± 9 years. Twelve age‐matched untrained men (O‐Un) and a group of young trained and young untrained men were recruited for comparison. Frozen sections were immunohistochemically stained for Pax7, type I myosin and laminin, from which fibre area, the number of satellite cells, and the relationship between these variables were determined.

Results

In O‐Un and O‐Tr, type II fibres were smaller and contained fewer satellite cells than type I fibres. However, when expressed relative to fibre area, the difference in satellite cell content between fibre types was eliminated in O‐Tr, but not O‐Un. A strong positive relationship between fibre size and satellite cell content was detected in trained individuals. In line with a history of myofibre repair, a greater number of fibres with centrally located myonuclei were detected in O‐Tr.

Conclusion

Lifelong endurance training (i) does not deplete the satellite cell pool and (ii) is associated with a similar density of satellite cells in type I and II fibres despite a failure to preserve the equal fibre type distribution of satellite cells observed in young individuals. Taken together, these data reveal a differential regulation of satellite cell content between fibre types, in young and old healthy men with dramatically different training histories.
The role of magnetic resonance imaging (MRI) in focal therapy for prostate cancer: recommendations from a consensus panel
Authors: Muller Berrend G. , Fütterer Jurgen J. , Gupta Rajan T. , Katz Aaron , Kirkham Alexander , Kurhanewicz John , Moul Judd W. , Pinto Peter A. , Rastinehad Ardeshir R. , Robertson Cary , de la Rosette Jean , Sanchez‐Salas Rafael , Jones J. Stephen , Ukimura Osamu , Verma Sadhna , Wijkstra Hessel , Marberger Michael
Published: November 2013

Objective

To establish a consensus on the utility of multiparametric magnetic resonance imaging (mpMRI) to identify patients for focal therapy.

Methods

Urological surgeons, radiologists, and basic researchers, from Europe and North America participated in a consensus meeting about the use of mpMRI in focal therapy of prostate cancer.

The consensus process was face‐to‐face and specific clinical issues were raised and discussed with agreement sought when possible. All participants are listed among the authors.

Topics specifically did not include staging of prostate cancer, but rather identifying the optimal requirements for performing MRI, and the current status of optimally performed mpMRI to (i) determine focality of prostate cancer (e.g. localising small target lesions of ≥0.5 mL), (ii) to monitor and assess the outcome of focal ablation therapies, and (iii) to identify the diagnostic advantages of new MRI methods.

In addition, the need for transperineal template saturation biopsies in selecting patients for focal therapy was discussed, if a high quality mpMRI is available. In other words, can mpMRI replace the role of transperineal saturation biopsies in patient selection for focal therapy?

Results

Consensus was reached on most key aspects of the meeting; however, on definition of the optimal requirements for mpMRI, there was one dissenting voice.

mpMRI is the optimum approach to achieve the objectives needed for focal therapy, if made on a high quality machine (3T with/without endorectal coil or 1.5T with endorectal coil) and judged by an experienced radiologist.

Structured and standardised reporting of prostate MRI is paramount.

State of the art mpMRI is capable of localising small tumours for focal therapy.

State of the art mpMRI is the technique of choice for follow‐up of focal ablation.

Conclusions

The present evidence for MRI in focal therapy is limited.

mpMRI is not accurate enough to consistently grade tumour aggressiveness.

Template‐guided saturation biopsies are no longer necessary when a high quality state of the art mpMRI is available; however, suspicious lesions should always be confirmed by (targeted) biopsy.
Using Cone Beam Computed Tomography Angle for Predicting the Outcome of Horizontal Bone Augmentation
Authors: Garaicoa Carlos , Suarez Fernando , Fu Jia‐Hui , Chan Hsun‐Liang , Monje Alberto , Galindo‐Moreno Pablo , Wang Hom‐Lay
Published: November 2013

Background

The aim of this study was to assess the influence of ridge morphology on the amount of horizontal bone augmentation achieved with the sandwich bone augmentation (SBA) technique in the reconstruction of buccal dehiscence defects on dental implants.

Methods

Cone beam computed tomography (CBCT) was used to assess bone width changes in 26 patients who participated in a randomized controlled trial conducted in 2008 to 2011. The amount of horizontal bone gain was evaluated at four different levels (3, 6, 9, and 12 mm apical to the alveolar crest) and three different time points (T1: baseline, T2: at time of graft placement, and T3: 6 months later). Different morphological characteristics of the alveolar ridge were also evaluated to determine their influence on horizontal bone augmentation. A total of 78 CBCT scans were assessed.

Results

Comparison of the changes in ridge morphology at all measurement locations showed an overall ridge width gain of 2.30 ± 2.20 mm after 6 months. The use of membranes and the angulation of the concavity played a role in influencing the outcomes of the SBA technique. Critical crest angulation (CA) is 150° for bone gain at 9 mm apical to the crest. When CA is smaller than 150°, the horizontal bone gain was 4.3 ± 2.2 mm; if CA is greater than 150°, the gain was significantly lower at 1.3 ± 1.7 mm (p = .001).

Conclusions

SBA is a reliable and predictable technique to gain horizontal ridge width with simultaneous implant placement. Crest ridge angulation can be used as a tool to predict bone gain at 9 mm apical to the bone crest.
Characteristics and perspectives of night‐eating behaviour in a severely obese population
Authors: Cleator J. , Judd P. , James M. , Abbott J. , Sutton C. J. , Wilding J. P. H.
Published: November 2013

What is already known about this subject

Night‐eating syndrome (NES) can be a feature of severe obesity.

NES is a dysfunction of circadian rhythm and is associated with impaired sleep.

What this study adds

Night eaters with severe obesity are more likely to be low in mood and unemployed compared with non‐night eaters.

Night eaters with severe obesity describe compulsive and uncontrolled eating.

Research interest in night‐eating syndrome (NES) has grown in recent years in line with increased rates of obesity. This study used a mixed‐methods approach to investigate its characteristics in severe obesity. Eighty‐one individuals (mean [standard deviation] age 44.6 [11.6] years, [body mass index] 50.0 [10.7] kg m−2; 43% men) from a hospital‐based UK obesity clinic were interviewed for NES based on 2003 criteria. Full and partial NES were combined into one night‐eating behaviour (NEB) group (n = 31). Demographic and clinical characteristics were compared with those of non‐NEB individuals (n = 50). NEB characteristics were also identified through exploratory thematic analysis of interview data. NEB individuals had lower mood (P = 0.01) and were less likely to be employed (P = 0.03). Differences in mean age and reported sleep duration were not significant. Thematic analysis of patient perceptions of NEB highlighted the potential heterogeneity of NEB development: NEB developed in childhood, adolescence and adulthood. Individuals reported long‐standing and current sleep difficulties, negative affect and conflictful relationships. Night eating was solitary, compulsive and uncontrolled, and daytime eating patterns were chaotic. Accounts of awareness of night eating were conflicting. Severely obese night eaters are characterized by low mood and lack of employment. Further studies are required to explore behavioural and cognitive influences on night eating in severe obesity.
Natural dyeing and antibacterial activity of atmospheric‐plasma‐treated nylon 6 fabric
Authors: Haji Aminoddin , Mousavi Shoushtari Ahmad , Mirafshar Maryam
Published: November 2013

Atmospheric plasma treatment as an environmentally friendly method was employed to modify the surface properties and improve the absorption of natural cationic dye on to nylon 6 fabric. Nylon fabric was treated in atmospheric air plasma, and the surface characteristics of the fabric were evaluated using attenuated total reflection Fourier Transform‐infrared analysis, scanning electron microscopy, and a wicking test. The effects of plasma treatment and mordanting with copper sulfate on the dye uptake of the samples were investigated. Plasma‐treated and mordanted samples showed the highest colour strength when dyed. The antibacterial activity of samples was evaluated according to AATCC test method 100‐2004. Premordanting with copper sulfate showed a synergistic effect on the antibacterial properties of the dyed fabric. The plasma‐treated and copper‐sulfate‐mordanted sample showed acceptable antibacterial activity against both gram‐negative and gram‐positive bacteria when dyed with an extract from Berberis vulgaris, berberine.
A preliminary study on pressure‐plate evaluation of forelimb toe–heel and mediolateral hoof balance on a hard vs. a soft surface in sound ponies at the walk and trot
Authors: Oosterlinck M. , Royaux E. , Back W. , Pille F.
Published: November 2013

Reasons for performing study

Thus far, pressure‐plate analysis has been limited to measurements on a hard surface, whereas equine athletes routinely perform on a deformable substrate.

Objectives

To explore pressure‐plate analysis on arena footing.

Study design

Nonrandomised crossover study using noninvasive techniques.

Methods

Five sound, unshod ponies were walked and trotted over a pressure plate in 2 different conditions. In the first session, the plate was covered with only a 5 mm rubber mat, and in the second session, with an additional 50 mm layer of sand and synthetic fibres. Limb loading and timing variables (peak vertical force, vertical impulse, peak vertical pressure, hoof contact area and stance phase duration) were obtained. Toe–heel and mediolateral hoof balance of the vertical force were calculated throughout stance (126 Hz).

Results

Peak vertical force, vertical impulse, peak vertical pressure and stance phase duration were decreased on the soft substrate, while hoof contact area increased. At impact, there was more even load distribution between the toe and heel region on the soft vs. hard surface. At mid‐stance, there was more loading of the toe region on the soft compared with the hard surface. At impact, there was more even load distribution between lateral and medial on the soft vs. hard surface at walk, but not at trot.

Conclusions

Comparison of observed vs. expected impulse indicated that the main factor involved in the lower loading on the soft surface is the dampening effect of the soft substrate, although definitive conclusions require concurrent force‐plate analysis. The pressure plate permitted quantitative evaluation of hoof balance of the vertical force on a deformable surface at the walk and trot and proved that there is more even load distribution on arena footing.
Toward Relationship‐Directed Parenting: An Example of North American Born Second‐Generation Korean‐American Mothers and their Partners
Authors: Kim Lana , Knudson‐Martin Carmen , Tuttle Amy
Published: November 2013

Historically, parenting has been constructed hierarchically; however, contemporary parenting models frequently emphasize parenting as relationship (Siegel & Hartzell [2004] Parenting from the inside out: How a deeper self‐understanding can help you raise children who thrive; Tuttle, Knudson‐Martin, & Kim [2012] Family Process, 51, 73–89). Drawing on interviews with 20 North American born second‐generation Korean–American mothers and their partners, and sensitized by TP‐CRO, a social constructionist framework for conceptualizing parent–child relational orientations, this grounded theory analysis identified three main processes that facilitate relational connection as a parenting orientation rather than the rule‐directed approach historically associated with first‐generation immigrant Asian families. These include: (a) emphasizing dominant culture values; (b) inviting open communication; and (c) promoting mutuality. Results also show how parents integrate collectivist cultural values of their first generation immigrant parents' traditional culture into North American parenting ideals with which they primarily identify. The study demonstrates the usefulness of the TP‐CRO for understanding parent–child relationships within multicultural parenting contexts and offers suggestions for working with second‐generation Korean families.
Effect of submillimeter size holes on the fatigue limit of a high strength tool steel
Authors: Shyam A. , Blau P. , Jordan T. , Yang N.
Published: November 2013

The very high cycle fatigue and small fatigue crack growth behaviour of a generic tool steel material for diesel fuel injector application are described. The small crack growth tests for the tool steel material with and without the hardening heat treatment revealed the mechanisms of crack propagation and threshold behaviour. Based on the small fatigue crack propagation threshold value, an elastic plastic fracture mechanics methodology for the prediction of the endurance limit of specimens with submillimeter holes is proposed. The advantages of the new methodology are discussed in relation to existing methodologies for endurance limit prediction of specimens with small holes.
Association of knee‐extension strength with instrumental activities of daily living in community‐dwelling older adults
Authors: Kojima Narumi , Kim Hunkyung , Saito Kyoko , Yoshida Hideyo , Yoshida Yuko , Hirano Hirohiko , Obuchi Shuichi , Shimada Hiroyuki , Suzuki Takao
Published: November 2013

Aim

The purpose of the present study was to investigate the relationship between knee‐extension (KE) strength and instrumental activities of daily living (IADL), and to examine the risk of IADL disability in relation to KE strength in community‐dwelling older adults.

Methods

The participants were 1235 community‐dwelling older adults (261 men and 974 women) in Tokyo who underwent a comprehensive health survey in 2009. The health survey included measurement of KE strength and a questionnaire on the Tokyo Metropolitan Institute of Gerontology (TMIG)‐IADL. Pearson product‐moment correlation coefficients and partial correlation coefficients were calculated separately for each sex for four parameters representing quadriceps muscle strength and TMIG‐IADL. Pearson's χ2‐test of independence and the Cochran–Armitage test of trend were also carried out to determine the relationship between KE strength and IADL disability.

Results

In women, all correlations between the quadriceps muscle strength parameters and the TMIG‐IADL score were statistically significant (P < 0.0005). The significance persisted remained even after factors regarding cognition or depression were taken into consideration. Furthermore, the percentage of female participants with IADL disability was dependent on KE strength; there was an inverse trend between KE strength and the percentage of people with IADL disability. In men, no significant relationship was found between KE strength and IADL.

Conclusions

KE strength and IADL correlated positively, and the percentage of people with IADL disability decreased with increasing KE strength in women. Geriatr Gerontol Int 2014; 14: 674–680.
Advanced Method for Evaluation of Gastric Cancer Risk By Serum Markers: Determination of True Low‐Risk Subjects for Gastric Neoplasm
Authors: Boda Tomoyuki , Ito Masanori , Yoshihara Masaharu , Kitamura Yoko , Matsuo Taiji , Oka Shiro , Tanaka Shinji , Chayama Kazuaki
Published: November 2013

Background

Patients with negative anti‐Helicobacter pylori antibody titer and high pepsinogen (PG) level (group A) are regarded as having a low risk for gastric cancer. However, gastric cancer cases are occasionally observed in this group. We aimed to elucidate the clinical features of gastric neoplasm in group A patients and reviewed advanced methods for mass screening.

Materials and Methods

A total of 271 gastric epithelial neoplasm patients were enrolled. We classified them according to the H. pylori‐PG system and determined the number of patients in each group. After excluding true H. pylori‐negative cases from group A (group A'), we examined the differences between group A' and group non‐A.

Results

Group A included 30 (11%) patients, and only three of these were true negative for H. pylori. All patients in group A' (n = 27) exhibited endoscopic atrophy in the gastric corpus. Serologically, these patients showed low gastrin, low PG II and high PG I/II ratio, indicative of post‐eradication. Histologically, 24 (89%) of these had little inflammation, and 26 (96%) were negative for H. pylori by immunohistochemistry. No difference was observed in the incidence of metachronous gastric tumors between group A' and group non‐A. The discriminant function using gastrin and PGs could distinguish these 27 patients from true H. pylori‐negative controls with 85% sensitivity and 84% specificity.

Conclusions

Group A included a certain number of patients with atrophic gastritis who were potentially at risk of gastric neoplasm development. Although evaluation of corpus atrophy is necessary for the identification of these patients, the discriminant function may be useful.
Infrared LED irradiation photobiomodulation of oxidative stress in human dental pulp cells
Authors: Montoro L. A. , Turrioni A. P. S. , Basso F. G. , de Souza Costa C. A. , Hebling J.
Published: November 2013

Aim

To investigate the effect of infrared light‐emitting diode (LED) irradiation on the oxidative stress induced in human dental pulp cells (HDPCs) by lipopolysaccharide (LPS).

Methodology

Human dental pulp cells (HDPCs) were harvested from sound primary teeth that were near exfoliation. Cells were seeded (105 cells cm−2) using α‐MEM supplemented with 10% FBS and after 24 h, were placed in contact with LPS (10 μg mL−1 of culture medium). Immediately afterwards, HDPCs were subjected to a single irradiation with an infrared LED (855 nm) delivering different doses of energy (0, 2, 4, 8, 15 or 30 J cm−2). For each dose, there was a control group without LPS application. Twenty‐four hours after irradiation, groups were tested for nitric oxide (NO) quantification, cell viability (MTT assay) and qualitative assessment of reactive oxygen species (ROS). Data were submitted to Kruskal–Wallis and Mann–Whitney tests (α = 0.05).

Results

Lipopolysaccharide (LPS)‐induced stress resulted in significant increase in NO production by HDPC without causing damage to cell respiratory metabolism. Irrespective of energy dose delivered, NO production was significantly reduced when LPS‐stressed cells were irradiated with infrared LED (2 J cm−2, P = 0.003; 95% CI = 5.84–27.71; 4 J cm−2, P = 0.001; 95% CI = 7.52–26.39; 8 J cm−2, P = 0.0195; 95% CI = −2.86–16.01; 15 J cm−2, P = 0.0001; 95% CI = 12.10–30.96; 30 J cm−2, P = 0.007; 95% CI = 5.84–24.71). The highest decrease in NO production was observed when 15 J cm−2 was delivered to cells. Infrared LED irradiation resulted in a decrease in ROS production, whilst HDPC metabolism was not significantly affected.

Conclusion

Biomodulation of oxidative stress of HPDC can be achieved by irradiation with a single dose of infrared LED. Within the range investigated, 15 J cm−2 resulted in the least production of NO.
Translational Perspectives on Perfusion–Diffusion Mismatch in Ischemic Stroke
Authors: Campbell Bruce C. V. , Macrae I. Mhairi
Published: November 2013

Magnetic resonance imaging has tremendous potential to illuminate ischemic stroke pathophysiology and guide rational treatment decisions. Clinical applications to date have been largely limited to trials. However, recent analyses of the major clinical studies have led to refinements in selection criteria and improved understanding of the potential implications for the risk vs. benefit of thrombolytic therapy. In parallel, preclinical studies have provided complementary information on the evolution of stroke that is difficult to obtain in humans due to the requirement for continuous or repeated imaging and pathological verification. We review the clinical and preclinical advances that have led to perfusion–diffusion mismatch being applied in phase 3 randomized trials and, potentially, future routine clinical practice.
Rituximab‐induced interleukin‐15 reduction associated with clinical improvement in rheumatoid arthritis
Authors: Díaz‐Torné César , Ortiz de Juana M. Angels , Geli Carme , Cantó Elisabet , Laiz Ana , Corominas Héctor , Casademont Jordi , de Llobet Josep M. , Juárez Cándido , Díaz‐López César , Vidal Sílvia
Published: November 2013

Rituximab therapy alters all aspects of B‐cell participation in the disturbed immune response of rheumatoid arthritis patients. To determine the impact of B‐cell depletion on other immune compartments, we analysed levels of soluble and surface interleukin‐15 (IL‐15) along with the frequency of IL‐15‐related subsets after rituximab treatment. We then studied the correlation of observed changes with clinical activity. Heparinized blood samples from 33 rheumatoid arthritis patients were collected on days 0, 30, 90 and 180 after each of three rituximab cycles. Serum cytokine levels were determined by ELISA. Interleukin‐15 trans‐presentation was analysed by cytometry. Flow cytometry with monoclonal antibodies was performed to analyse circulating cell subsets. Interleukin‐15 was detected in the serum of 25 patients before initiating the treatment. Rituximab then progressively reduced serum IL‐15 (138 ± 21 pg/ml at baseline, 48 ± 18 pg/ml after third cycle, P = 0·03) along with IL‐17 (1197 ± 203 pg/ml at baseline, 623 ± 213 pg/ml after third cycle, P = 0·03) and tended to increase the frequency of circulating regulatory T cells (3·1 ± 1 cells/μl at baseline, 7·7 ± 2 cells/μl after third cycle). Rituximab also significantly decreased IL‐15 trans‐presentation on surface monocytes of patients negative for IL‐15 serum (mean fluorescence intensity: 4·82 ± 1·30 at baseline, 1·42 ± 0·69 after third cycle P = 0·05). Reduction of serum IL‐15 was associated with decrease in CD8+ CD45RO+/RA+ ratio (1·17 ± 0·21 at baseline, 0·36 ± 0·06 at third cycle, P = 0·02). DAS28, erythrocyte sedimentation rate and C‐reactive protein correlated significantly with CD8+ CD45RO+/RA+ ratio (R = 0·323, R = 0·357, R = 0·369 respectively, P < 0·001). Our results suggest that sustained clinical improvement after rituximab treatment is associated with IL‐15/memory T‐cell‐related mechanisms beyond circulating B cells.
Advances in antivirals for non‐influenza respiratory virus infections
Authors: Hayden Frederick G.
Published: November 2013

Progress in the development of antivirals for non‐influenza respiratory viruses has been slow with the result that many unmet medical needs and few approved agents currently exist. This commentary selectively reviews examples of where specific agents have provided promising clinical benefits in selected target populations and also considers potential therapeutics for emerging threats like the SARS and Middle East respiratory syndrome coronaviruses. Recent studies have provided encouraging results in treating respiratory syncytial virus infections in lung transplant recipients, serious parainfluenza virus and adenovirus infections in immunocompromised hosts, and rhinovirus colds in outpatient asthmatics. While additional studies are needed to confirm the efficacy and safety of the specific agents tested, these observations offer the opportunity to expand therapeutic studies to other patient populations.
Influenza vaccines: an Asia–Pacific perspective
Authors: Jennings Lance C.
Published: November 2013

This article provides an overview of some aspects of seasonal, pre‐pandemic and pandemic influenza vaccines and initiatives aimed to increase influenza vaccine use within the Asia–Pacific region. Expanding the use of influenza vaccines in the Asia–Pacific region faces many challenges. Despite the recent regional history for the emergence of novel viruses, SARS, the H5N1 and H7N9, and the generation of and global seeding of seasonal influenza viruses and initiatives by WHO and other organisations to expand influenza awareness, the use of seasonal influenza vaccines remains low. The improvement in current vaccine technologies with the licensing of quadrivalent, live‐attenuated, cell culture‐based, adjuvanted and the first recombinant influenza vaccine is an important step. The development of novel influenza vaccines able to provide improved protection and with improved manufacturing capacity is also advancing rapidly. However, of ongoing concern are seasonal influenza impact and the low use of seasonal influenza vaccines in the Asia–Pacific region. Improved influenza control strategies and their implementation in the region are needed. Initiatives by the World Health Organization (WHO), and specifically the Western Pacific Regional Office of WHO, are focusing on consistent vaccine policies and guidelines in countries in the region. The Asian‐Pacific Alliance for the Control of Influenza (APACI) is contributing through the coordination of influenza advocacy initiates.
Performance evaluation of a two‐echelon supply chain with stochastic demand, lost sales, and Coxian‐2 phase replenishment times
Authors: Vidalis Michael , Vrisagotis Vassilios , Varlas George
Published: November 2013

This paper deals with a two‐echelon supply chain comprising a retailer and manufacturer. The retailer faces Poisson demand and follows a (S, s) continuous review inventory policy. The manufacturer produces and ships the retailer's orders with random delay that follows the Coxian‐2 distribution. Assuming lost sales at the retailer and infinite capacity at the manufacturer, we try to explore the performance of the supply chain system. The system is modeled as a continuous‐time Markov process with discrete space. The structure of the transition matrices of these specific systems is categorized as block‐partitioned, and a computational algorithm generates the matrices for different values of system characteristics. The proposed algorithm allows the calculation of performance measures—fill rate, cycle times, average inventory (work in progress [WIP])—from the derivation of the steady‐state probabilities. Moreover, expressions for the holding costs and shortage costs are derived.
Nutritional and Sensory Characteristics of Bread‐Coated Hake Fillets as Affected by Cooking Conditions
Authors: Pérez‐Palacios Trinidad , Casal Susana , Petisca Catarina , Ferreira Isabel M.P.L.V.O.
Published: November 2013

The influence of deep‐frying at different combinations of temperature (160, 180 and 200C) and time (2, 4 and 6 min) and the cooking process (deep‐frying in sunflower/olive oil and oven‐baking) on quality characteristics (moisture and lipid content, instrumental texture and color, fatty acid composition and sensory traits) of bread‐coated hake fillets was studied. The relationships between these quality characteristics were also analyzed. The effect of temperature and time of deep‐frying was not so relevant in quality parameters, whereas the cooking process influenced significantly. Deep‐frying in olive oil and oven‐baking were more adequate from a nutritional point of view, whereas deep‐frying in sunflower gave preferred sensory characteristics. Significant correlations were found between most studied parameters, i.e., overall acceptability correlated positively to lightness (L*), yellowness (b*), polyunsaturated acids and sunflower oil flavor. These findings are considerable to maintain sensory attributes in bread‐coated hake fillets and enhance nutritional properties.

Practical Applications

The effect of the cooking method on nutritional and sensory traits in bread‐coated hake fillets as well as the proved relationships between these quality characteristics are of major relevance to establish healthier nutritional recommendations about this type of products while keeping consumer's acceptance.
A temporal assessment of flooding fatalities in Pakistan (1950–2012)
Authors: Paulikas M.J. , Rahman M.K.
Published: November 2013

Pakistan is a developing nation that has historically been subjected to high flooding fatality events due to its socioeconomic characteristics, population geography, and landscape attributes. Flooding in Pakistan has historically resulted from heavy rain events or periodic landfalling tropical cyclones that have afflicted the nation throughout its history. This study aggregates flooding events in Pakistan over a 62‐year period to identify peak years and seasonal cycles of when flood‐related fatalities have historically been highest in the nation. Seasonally, Pakistan is especially prone to flood disasters during the summer monsoon months, and also during the months of November and December, when tropical cyclone activity periodically impacts the nation. Some of the earlier flooding events have not been well documented with respect to specific months or dates of occurrence, and have therefore been excluded from the seasonal analysis portion of the study. Over the past 60 years, exceptionally high numbers of flood‐related fatalities occurred in the years 1950, 1965, and 2010; peak fatality flood years are mostly attributed to single catastrophic events caused primarily by large‐scale river floods or landfalling tropical cyclones.
Regional intensity‐duration‐frequency curves for Jeddah region, Saudi Arabia, using ordinary and L‐moments approaches
Authors: Awadallah A.G.
Published: November 2013

The frequency analysis of rainfall in the Jeddah region, Saudi Arabia, has been disputed both on grounds of the methodology, statistical model and the resulting rainfall estimates. Frequency analysis of available rainfall records for Jeddah region, Saudi Arabia, is performed to develop regional intensity‐duration‐frequency (IDF) curves. The data cover nearly 40 years of records for 10 stations. Only three stations comprise short duration records of 10 min accuracy. The homogeneity of the region is first assessed using tests relying on the coefficients of variation of ordinary moments and also the discordancy and the heterogeneity measures based on L‐moments. The best fitting distribution to all region stations is selected comparing several approaches: namely the ordinary and L‐moment ratio diagrams, the goodness‐of‐fit measures based on L‐moments, the log‐log and the mean excess function plots, and finally the Akaike and Bayesian Information Criteria. The gamma distribution can be used for fitting the whole region. Jeddah region is thus divided into two homogeneous rainfall regions and two sets of rainfall IDF curves are developed for 2‐, 5‐, 10‐, 25‐, 50‐ and 100‐year return periods. The approach proposed by this study helps develop IDF curves derived using a regional approach in which several methods are investigated yielding converging results.
Pathogenic mutation of UBQLN2 impairs its interaction with UBXD8 and disrupts endoplasmic reticulum‐associated protein degradation
Authors: Xia Yuxing , Yan Linda H , Huang Bo , Liu Mujun , Liu Xionghao , Huang Cao
Published: November 2013

Protein aggregation is a common feature of several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration. How protein aggregates are formed and contribute to neurodegeneration, however, is not clear. Mutation of Ubiquilin 2 (UBQLN2) has recently been linked to ALS and frontotemporal lobar degeneration. Therefore, we examined the effect of ALS‐linked UBQLN2 mutation on endoplasmic reticulum‐associated protein degradation (ERAD). Compared to its wild‐type counterpart, mutated UBQLN2 caused greater accumulation of the ERAD substrate Hong Kong variant of α‐1‐antitrypsin, although ERAD was disturbed by both UBQLN2 over‐expression and knockdown. Also, UBQLN2 interacted with ubiquitin regulatory X domain‐containing protein 8 (UBXD8) in vitro and in vivo, and this interaction was impaired by pathogenic mutation of UBQLN2. As UBXD8 is an endoplasmic membrane protein involved in the translocation of ubiquitinated ERAD substrates, UBQLN2 likely cooperates with UBXD8 to transport defective proteins from the endoplasmic reticulum to the cytosol for degradation, and this cell‐protective function is disturbed by pathogenic mutation of UBQLN2.

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Endoplasmic reticulum‐associated protein degradation (ERAD) is important machinery for cells to maintain protein homeostasis. We found that ERAD is disturbed by pathogenic Ubiquilin 2 mutation that is recently linked to amyotrophic lateral sclerosis (ALS). Impaired ERAD is likely involved in Ubiquilin 2 pathogenesis.
Perineural invasion and expression of nerve growth factor can predict the progression and prognosis of oral tongue squamous cell carcinoma
Authors: Shen Wei‐Ren , Wang Yi‐Ping , Chang Julia Yu‐Fong , Yu Shang‐Yang , Chen Hsin‐Ming , Chiang Chun‐Pin
Published: November 2013

Background

Perineural invasion (PNI) and nerve growth factor (NGF) expression are found to be significantly associated with the progression and/or prognosis of several human cancers.

Methods

Immunohistochemical staining for S‐100 and NGF proteins was performed to assess the PNI and NGF expression level in 116 oral tongue squamous cell carcinoma (OTSCC) specimens, respectively.

Results

The PNI rate increased from 22% of the original pathological report, through 39% after reevaluation of hematoxylin and eosin‐stained tissue sections, to 51% with the help of anti‐S‐100 immunostaining. The positive PNI was significantly associated with larger tumor size (P = 0.033), positive lymph node metastasis (P = 0.001), advanced clinical stage (P < 0.001), greater tumor thickness (P < 0.001), close or positive section margin (P = 0.013), and higher grade of cancer invasion front pattern (P < 0.001). Moreover, the high NGF expression level was significantly correlated with larger tumor size (P = 0.009), positive lymph node metastasis (P = 0.004), advanced clinical stage (P < 0.001), greater tumor thickness (P = 0.005), close or positive section margin (P = 0.030), and the positive PNI (P = 0.009). In addition, OTSCC patients with positive PNI or high NGF expression level had significantly worse overall survival than those with negative PNI or low NGF expression level, respectively.

Conclusions

Anti‐S‐100 immunostaining is an effective technique to detect occult PNI. Both the positive PNI and NGF expression level are valuable biomarkers that can predict the progression of OTSCC and prognosis of OTSCC patients.
Balanced‐Budget Rules, Elasticity of Substitution, and Macroeconomic (In)Stability
Authors: XUE JIANPO , K. YIP CHONG
Published: November 2013

This paper examines the relation between factor substitution and (local) stability of equilibria in a one‐sector real business cycle model under balanced‐budget rules. We show that under non‐unitary elasticity of factor substitution, the Schmitt‐Grohé‐Uribe indeterminacy result can be altered. Using the two‐step normalization procedure, we highlight two opposing effects of factor substitution, namely, the efficiency effect and the distribution effect, on aggregate stability. With endogenous distortionary taxes and gross substitutability between capital and labor, the existing literature overlooks the distribution effect and finds that balanced‐budget rules are likely to deliver indeterminacy. However, if capital stock is relatively more abundant, a higher elasticity of substitution generates a source of stability due to the distribution effect. Our calibration shows that the distribution effect is always the dominating force.
Molecular Characterization of Southern Rice Blacked‐Streaked Dwarf Virus (SRBSDV) from Vietnam
Authors: Xue Jin , Li Jing , Zhang Heng‐Mu , Yang Jian , Lv Ming‐Fang , Gao Bi‐Da , Chen Jian‐Ping
Published: November 2013

Southern rice black‐streaked dwarf virus (SRBSDV) is a novel putative member of the genus Fijivirus, family Reoviridae. We report here the genomic sequences of a Vietnamese isolate (SRBSDV‐V). The total genome of SRBSDV‐V has 29 115 nucleotides (nt), nine nt shorter than SRBSDV‐GD or ‐HN, but similar in organization to these two Chinese isolates. Nucleotide diversities among SRBSDV isolates were much lower than those among the corresponding ORFs of the available RBSDV isolates and there was a lower purifying selection pressure on SRBSDV than RBSDV, providing first molecular evidence for the view that SRBSDV is of recent origin. In studies of all available SRBSDV sequences, there was no obvious correlation between geographic distances and phylogenetic distribution. A high frequency of genetic recombination was found among both Chinese and Vietnam SRBSDV isolates, suggesting that recombination may play an important role in the molecular variation and evolution of SRBSDV.
Demographic model of admixture predicts symmetric introgression when a species expands into the range of another: A comment on Currat et al. (2008)
Authors: ZHANG Da‐Yong
Published: November 2013

A recent model by Currat et al. indicates that when one species colonizes an area already occupied by a closely related species, massive introgression of neutral genes should take place primarily in the direction from the local to the invasive species. Here, I show that this model relies on an assumption that might not capture the true dynamics of how species exchange migrants during admixture. As an alternative, I formulate a new model, based on a different and perhaps more biologically realistic assumption of interbreeding, that demonstrates symmetric introgression as compared to the large and asymmetric introgression predicted by the original model. The new model indicates that asymmetry is not a default property of introgressions, thus necessitating alternative explanations for the common observation of massive asymmetric introgression including sex‐biased dispersal.
Assessing the cost‐effectiveness of finding cases of hepatitis C infection inUKmigrant populations and the value of further research
Authors: Miners A. H. , Martin N. K. , Ghosh A. , Hickman M. , Vickerman P.
Published: November 2013

summary

Hepatitis C (HCV) infection can cause cirrhosis, liver cancer and death in the absence of treatment. Many people living in theUKbut born overseas are believed to be infected withHCValthough many are unlikely to know they are infected. The aim of this study is to assess the potential for a case‐finding approach to be cost‐effective and to estimate the value of further research. An economic evaluation and value of information analysis was undertaken by developing a model ofHCVdisease progression and by populating it with evidence from the published literature. They were performed from aUKNational Health Services cost perspective, and outcomes were expressed in terms of quality‐adjusted life‐years (QALYs). The comparator intervention was defined as the background rate of testing (i.e. no intervention). The base case results generated an incremental cost‐effectiveness ratio (ICER) of about £23 200 per additionalQALY. However, theICERwas shown to be particularly sensitive toHCVseroprevalence, the intervention effect / cost and the probability of treatment uptake. The value of information analysis suggested that approximately £4 million should be spent on further research. This evaluation demonstrates that testingUKmigrants forHCVcould be cost‐effective. However, further research, particularly to refine estimates of the probability of treatment uptake once identified, the utility associated with sustained virological response and the cost of the intervention, would help to increase the robustness of this conclusion.