bluuebunny/crossref_metadata_2025 huggingface dataset:
Serum high‐mobility group box 1 protein correlates with cognitive decline after gastrointestinal surgery
Authors: LIN G.‐X. , WANG T. , CHEN M.‐H. , HU Z.‐H. , OUYANG W.
Published: April 2014

Background

Accumulating evidence has indicated that inflammation may act as a potential mechanism underlying post‐operative cognitive dysfunction (POCD). High‐mobility group box 1 (HMGB1), as a known late mediator of inflammation, is involved in the development of post‐operative complications. Thus, we sought to determine the role of HMGB1 in reflecting POCD following major gastrointestinal surgery.

Methods

Fifty‐three elderly patients undergoing gastrointestinal surgery were recruited, and 50 patients completed the study. Serum HMGB1 and interleukin (IL)‐6 levels were measured pre‐operatively and at 6 h, day 1 and day 3 post‐operatively. Neuropsychological tests were administered before and 1 week after surgery. POCD was determined using a Z score ≥ 1.96.

Results

Seventeen (34%, 17/50) patients developed POCD at 1 week. The POCD group had higher serum HMGB1 levels at day 1 (12.15 ± 3.12 vs. 9.91 ± 3.15 ng/ml, P = 0.021) and day 3 (11.04 ± 2.88 vs. 8.52 ± 3.31 ng/ml, P = 0.011). IL‐6 levels at 6 h (51.18 ± 15.22 vs. 39.20 ± 14.32 pg/ml, P = 0.009) and day 1 (41.59 ± 11.08 vs. 33.81 ± 11.42 pg/ml, P = 0.026) were significantly higher in POCD patients. Serum values of IL‐6 at 6 h, HMGB1 at day 1 and levels of education showed positive correlations with Z scores. HMGB1 at day 3 and IL‐6 at 6 h were independent risk factors.

Conclusions

Serum HMGB1 and IL‐6 levels increase significantly after major gastrointestinal surgery in elderly patients and such elevations are associated with the occurrence of cognitive decline after surgery.
A Time Series Approach to Examining Regional Economic Resiliency to Hurricanes
Authors: Ewing Bradley T. , Liang Daan , Cui Yuepeng
Published: April 2014

Hurricanes disrupt business processes and activities, energy distribution and consumption, and services of infrastructure and lead to a reallocation of resources and their uses. This research models the relationship among economic and engineering measures of the state of the built environment in order to provide insight into a region's ability to withstand and recover from a future hurricane. As such, we provide a quantitative approach to modeling and measuring a region's economic resiliency. The findings have implications for developing strategies for long‐term sustainability of economic regions.
The Effect of Urbanization and Industrialization on Energy Use in Emerging Economies: Implications for Sustainable Development
Authors: Sadorsky Perry
Published: April 2014

This article investigates the impact of two important socio‐economic variables—urbanization and industrialization—on energy consumption in a panel of emerging economies. The results indicate that income increases energy consumption in both the long run and the short run. In the long run, urbanization decreases energy consumption, while industrialization increases it. Long‐run dynamics are important as evidenced by the estimated coefficient on the error correction term. These results have implications for sustainable development. Economic growth policies designed to increase income and industrialization will increase energy consumption. Since most energy needs in emerging economies are currently met by the burning of fossil fuels, economic growth and industrialization policies will be at odds with sustainable development.
Serum immunoglobulin free light chain levels are higher in girls than boys during eosinophilic oesophagitis
Authors: Knipping Karen , Colson Diana , Soulaines Pascale , Redegeld Frank , Garssen Johan , Dupont Christophe
Published: April 2014

Aim

Eosinophilic oesophagitis (EO) is an emerging worldwide disease, closely associated with male gender and allergic disorders. This study investigated the distribution of allergy markers in a cohort of children with EO.

Methods

We analysed allergy markers in 91 children (62 males and 29 females) with EO and a control group of 45 age‐matched children who had non‐EO gastrointestinal allergic symptoms. The markers analysed were serum cow's milk‐specific and hen's egg‐specific IgE, thymic stromal lymphopoietin (TSLP), thymus‐regulated and activation‐regulated chemokine (TARC/CCL17) and immunoglobulin free light chain (Ig‐fLC).

Results

In the EO group, cow's milk‐specific IgE levels were detectable in 41.9% of males and 62.1% of females and hen's egg‐specific levels in 25% of males and 26.9% of females. There was no gender difference in increased TSLP or TARC levels. Kappa Ig‐fLC were increased in 5.6% of males and 20.8% of females (p = 0.058) and lambda Ig‐fLC in 1.9% of males and 33.3% of females (p = 0.000). No gender differences were found in the control group.

Conclusion

Our findings suggest that serum TSLP might be a potential marker of EO and TARC of non‐EO gastrointestinal food allergies. In EO, serum Ig‐fLC appeared higher in females, adding another gender difference to the biology of EO.
Human polymorphonuclear leukocytes produce cytokines in response to Leishmania major promastigotes
Authors: Keyhani Alireza , Riazi‐Rad Farhad , Pakzad Saeed Reza , Ajdary Soheila
Published: April 2014

Polymorphonuclear leukocytes (PMN) release cytokines that may influence the development of the subsequent adaptive immune response. Little is known about cytokines produced by human PMN in response to Leishmania (L.). In this study, mRNA expression of Interleukin (IL)‐12p40, IL‐12p35, Interferon (IFN)‐γ, transforming growth factor (TGF)‐β, IL‐1, and IL‐4 in PMN of volunteers stimulated with L. major promastigotes has been investigated by real‐time PCR and the results were confirmed by flow cytometer. The results showed that L. major did not induce mRNA expression of IL12p40, IL12p35, IFN‐γ, and TGF‐β in PMN, while IL‐1 and IL‐4 mRNA were induced. Flow cytometry results confirmed no IFN‐γ production by PMN with or without stimulation. IL‐12p70 was present in untreated and L. major‐treated PMN, and these cells release IL‐12 following incubation with L. major. Significant amount of IL‐1 even without treatment with promastigotes was detected in PMN. Moreover, the proportion of PMN, which produce IL‐1 in response to L. major, was increased compared with the percent of unstimulated IL‐1‐producing PMN. The results showed the accumulation of small amounts of IL‐4 in PMN after stimulation. In conclusion, our results indicate that IL‐12 and IL‐1 are pre‐stored in human PMN, nor L. major induces IL‐1 and IL‐4, but not IL‐12, IFN‐γ, nor TGF‐β expression in these cells.
Safety of switching from vitamin K antagonists to dabigatran or rivaroxaban in daily care – results from the Dresden NOAC registry
Authors: Beyer‐Westendorf Jan , Gelbricht Vera , Förster Kati , Ebertz Franziska , Röllig Denise , Schreier Thomas , Tittl Luise , Thieme Christoph , Hänsel Ulrike , Köhler Christina , Werth Sebastian , Kuhlisch Eberhard , Stange Thoralf , Röder Ingolf , Weiss Norbert
Published: April 2014

Aim

Vitamin‐K antagonists (VKA) and non‐vitamin‐K dependent oral anticoagulants (NOAC) have been approved for anticoagulation in venous thromboembolism (VTE) and atrial fibrillation and patients previously treated with VKA are switched to NOAC therapy. Safety data for this switching are urgently needed.

Methods

Using data from a large regional prospective registry of daily care NOAC patients, we evaluated the safety of switching anticoagulation from VKA to dabigatran or rivaroxaban. Switching procedures and cardiovascular and bleeding events occurring within 30 days after switching were centrally adjudicated.

Results

Between 1 October 2011 and 18 June 2013, 2231 patients were enrolled. Of these, 716 patients were switched from VKA to NOAC. Only 410 of the 546 evaluable patients (75.1%) had a recorded INR measurement within the 10 days preceding or following the end of VKA treatment (mean INR 2.4). As of day 30, major bleeding complications were rare (0.3%; 95% CI 0.0, 1.0) with an overall bleeding rate of 12.2% (95% CI 9.8, 14.8). Major cardiovascular events occurred in 0.8% (95% CI 0.3, 1.8). There was no significant difference in outcome event rates between the subgroups of patients with or without INR testing.

Conclusion

In daily care, only 75% of VKA patients have an INR measurement documented before NOAC are started. On average, NOAC are started within 2 to 5 days after the last intake of VKA. However, at 30 days follow‐up cardiovascular events or major bleedings were rare both in patients with and without INR testing. However, switching procedures need to be further evaluated in larger cohorts of patients.
Evaluation of the effect of naproxen on the pharmacokinetics and pharmacodynamics of apixaban
Authors: Frost Charles , Shenker Andrew , Gandhi Mohit D. , Pursley Janice , Barrett Yu Chen , Wang Jessie , Zhang Donglu , Byon Wonkyung , Boyd Rebecca A. , LaCreta Frank
Published: April 2014

Aim

To assess pharmacokinetic and pharmacodynamic interactions between naproxen (a non‐steroidal anti‐inflammatory drug) and apixaban (an oral, selective, direct factor‐Xa inhibitor).

Method

In this randomized, three period, two sequence study, 21 healthy subjects received a single oral dose of apixaban 10 mg, naproxen 500 mg or co‐administration of both. Blood samples were collected for determination of apixaban and naproxen pharmacokinetics and pharmacodynamics (anti‐Xa activity, international normalized ratio [INR] and arachidonic acid–induced platelet aggregation [AAI‐PA]). Adverse events, bleeding time and routine safety assessments were also evaluated.

Results

Apixaban had no effect on naproxen pharmacokinetics. However, following co‐administration, apixaban AUC(0,∞), AUC(0,t) and Cmax were 54% (geometric mean ratio 1.537; 90% confidence interval (CI) 1.394, 1.694), 55% (1.549; 90% CI 1.400, 1.713) and 61% (1.611; 90% CI 1.417, 1.831) higher, respectively. Mean (standard deviation [SD]) anti‐Xa activity at 3 h post‐dose was approximately 60% higher following co‐administration compared with apixaban alone, 4.4 [1.0] vs. 2.7 [0.7] IU ml−1, consistent with the apixaban concentration increase following co‐administration. INR was within the normal reference range after all treatments. AAI‐PA was reduced by approximately 80% with naproxen. Co‐administration had no impact beyond that of naproxen. Mean [SD] bleeding time was higher following co‐administration (9.1 [4.1] min) compared with either agent alone (5.8 [2.3] and 6.9 [2.6] min for apixaban and naproxen, respectively).

Conclusion

Co‐administration of naproxen with apixaban results in higher apixaban exposure and appears to occur through increased apixaban bioavailability. The effects on anti‐Xa activity, INR and inhibition of AAI‐PA observed in this study were consistent with the individual pharmacologic effects of apixaban and naproxen.
Pharmacokinetic tools for the dose adjustment of ciclosporin in haematopoietic stem cell transplant patients
Authors: Woillard Jean‐Baptiste , Lebreton Vincent , Neely Michael , Turlure Pascal , Girault Stéphane , Debord Jean , Marquet Pierre , Saint‐Marcoux Franck
Published: April 2014

Aims

Ciclosporin A (CsA) is used in the prophylaxis and treatment of acute and chronic graft vs. host disease after haematopoietic stem cell (HSCT) transplantation. Our objective was to build and compare three independent Bayesian estimators of CsA area under the curve (AUC) using a limited sampling strategy (LSS), to assist in dose adjustment.

Methods

The Bayesian estimators were developed using in parallel: two independent parametric modelling approaches (nonmem® and iterative two stage (ITS) Bayesian modelling) and the non‐parametric adaptive grid method (Pmetrics®). Seventy‐two full pharmacokinetic profiles (at pre‐dose and 0.33, 0.66, 1, 2, 3, 4, 6, 8 and 12h after dosing) collected from 40 HSCT patients given CsA were used to build the pharmacokinetic models, while 15 other profiles (n = 7) were kept for validation. For each Bayesian estimator, AUCs estimated using the full profiles were compared with AUCs estimated using three samples.

Results

The pharmacokinetic profiles were well fitted using a two compartment model with first order elimination, combined with a gamma function for the absorption phase with ITS and Pmetrics or an Erlang distribution with nonmem. The derived Bayesian estimators based on a C0‐C1 h‐C4 h sampling schedule (best LSS) accurately estimated CsA AUC(0,12 h) in the validation group (n = 15; nonmem: bias (mean ± SD)/RMSE 2.05% ± 13.31%/13.02%; ITS: 4.61% ± 10.56%/11.20%; Pmetrics: 0.30% ± 10.12%/10.47%). The dose chosen confronting the three results led to a pertinent dose proposal.

Conclusions

The developed Bayesian estimators were all able to predict ciclosporin AUC(0,12 h) in HSCT patients using only three blood with minimal bias and may be combined to increase the reliability of CsA dose adjustment in routine.
A comparison of medical and pharmacy students' knowledge and skills of pharmacology and pharmacotherapy
Authors: Keijsers Carolina J. P. W. , Brouwers Jacobus R. B. J. , de Wildt Dick J. , Custers Eugene J. F. M. , ten Cate Olle Th J. , Hazen Ankie C. M. , Jansen Paul A. F.
Published: April 2014

Aim

Pharmacotherapy might be improved if future pharmacists and physicians receive a joint educational programme in pharmacology and pharmacotherapeutics. This study investigated whether there are differences in the pharmacology and pharmacotherapy knowledge and skills of pharmacy and medical students after their undergraduate training. Differences could serve as a starting point from which to develop joint interdisciplinary educational programmes for better prescribing.

Methods

In a cross‐sectional design, the knowledge and skills of advanced pharmacy and medical students were assessed, using a standardized test with three domains (basic pharmacology knowledge, clinical or applied pharmacology knowledge and pharmacotherapy skills) and eight subdomains (pharmacodynamics, pharmacokinetics, interactions and side‐effects, Anatomical Therapeutic Chemical Classification groups, prescribing, prescribing for special groups, drug information, regulations and laws, prescription writing).

Results

Four hundred and fifty‐one medical and 151 pharmacy students were included between August 2010 and July 2012. The response rate was 81%. Pharmacy students had better knowledge of basic pharmacology than medical students (77.0% vs. 68.2% correct answers; P < 0.001, δ = 0.88), whereas medical students had better skills than pharmacy students in writing prescriptions (68.6% vs. 50.7%; P < 0.001, δ = 0.57). The two groups of students had similar knowledge of applied pharmacology (73.8% vs. 72.2%, P = 0.124, δ = 0.15).

Conclusions

Pharmacy students have better knowledge of basic pharmacology, but not of the application of pharmacology knowledge, than medical students, whereas medical students are better at writing prescriptions. Professional differences in knowledge and skills therefore might well stem from their undergraduate education. Knowledge of these differences could be harnessed to develop a joint interdisciplinary education for both students and professionals.
The experience of gender dysphoria for pre‐pubescent children and their families: a review of the literature
Authors: Gregor Claire , Davidson Sarah , Hingley‐Jones Helen
Published: April 2014

In recent years, the experience of gender dysphoria has gained public prominence through an explosion of sensationalized interest in the popular media. However, childhood gender dysphoria remains poorly understood and both parents and children often find themselves having to educate professionals around them. This not only creates a sense of disconnect between family and professionals, but also means that social workers can often be unaware of the myriad of competing perspectives that seek to explain gender variance. This review of the literature seeks to provide interested social workers with an overview of gender dysphoria, current research in the field and theoretical paradigms, with a view to promoting understanding and better practice with families in this little understood field.
De novo EEF1A2 mutations in patients with characteristic facial features, intellectual disability, autistic behaviors and epilepsy
Authors: Nakajima J. , Okamoto N. , Tohyama J. , Kato M. , Arai H. , Funahashi O. , Tsurusaki Y. , Nakashima M. , Kawashima H. , Saitsu H. , Matsumoto N. , Miyake N.
Published: April 2014

Eukaryotic elongation factor 1, alpha‐2 (eEF1A2) protein is involved in protein synthesis, suppression of apoptosis, and regulation of actin function and cytoskeletal structure. EEF1A2 gene is highly expressed in the central nervous system and Eef1a2 knockout mice show the neuronal degeneration. Until now, only one missense mutation (c.208G > A, p.Gly70Ser) in EEF1A2 has been reported in two independent patients with neurological disease. In this report, we described two patients with de novo mutations (c.754G > C, p.Asp252His and c.364G > A, p.Glu122Lys) in EEF1A2 found by whole‐exome sequencing. Common clinical features are shared by all four individuals: severe intellectual disability, autistic behavior, absent speech, neonatal hypotonia, epilepsy and progressive microcephaly. Furthermore, the two patients share the similar characteristic facial features including a depressed nasal bridge, tented upper lip, everted lower lip and downturned corners of the mouth. These data strongly indicate that a new recognizable disorder is caused by EEF1A2 mutations.
ASSESSING RETURNS TO EDUCATION AND LABOR SHOCKS IN MEXICAN REGIONS AFTER NAFTA
Authors: Mollick André Varella , Cabral René
Published: April 2014

This article examines Mexico's (real) wage movements across its 32 subnational entities for post‐North American Free Trade Agreement years. Employing dynamic panel data methods, we obtain the following results. First, education (or labor productivity) has slightly higher wage effects in the Border‐North region. Second, allowing for foreign capital and labor to respond to wages, returns to education have higher effects in South‐Center Mexico, the region with (average) lower education levels. Third, convergence rates become lower with endogenous foreign capital and migration flows: wages move faster in the South‐Center region than in Border‐North. Overall, migration flows have greater effects on wages than foreign direct investment inflows. (JEL F15, F21, F22, F43, O47)
DISENTANGLING DEMAND‐ENHANCING AND TRADE‐COST EFFECTS OF MAXIMUM RESIDUE REGULATIONS
Authors: XIONG BO , BEGHIN JOHN
Published: April 2014

Maximum residue level (MRL) regulations in plant products can create unnecessary trade barriers on one hand and enhance demand via risk mitigation or quality assurance on the other. We stipulate a generalized gravity equation model to disentangle the effects of MRLs on the import demand and foreign exporters' supply. Applying the framework to the MRLs on pesticides imposed by high‐income Organization for Economic Co‐operation and Development countries, we find that the MRLs jointly enhance the import demand and hinder foreign exporters' supply. In addition, exporters from the less and least developed countries are more constrained by the MRLs than their competitors from the developed world. (JEL F14, Q17)
Cannabinoid receptor type 1 receptors on GABAergic vs. glutamatergic neurons differentially gate sex‐dependent social interest in mice
Authors: Terzian Ana Luisa B. , Micale Vincenzo , Wotjak Carsten T.
Published: April 2014

Abnormalities in social behavior are found in almost all psychiatric disorders, such as anxiety, depression, autism, and schizophrenia. Thus, comprehension of the neurobiological basis of social interaction is important for a better understanding of numerous pathologies and improved treatments. Several findings have suggested that an alteration of cannabinoid receptor type 1 (CB1) receptor function could be involved in the pathophysiology of such disorders. However, the role of CB1 receptors is still unclear, and their localisation on different neuronal subpopulations may produce distinct outcomes. To dissect the role of CB1 receptors in different neuronal populations, we used male knockout mice and their respective control littermates [total deletion (CB1−/−); specific deletion on cortical glutamatergic neurons (Glu‐CB1−/−) or on GABAergic interneurons (GABA‐CB1−/−), and wild‐type (WT) mice treated with the CB1 antagonist/inverse agonist SR141716A (3 mg/kg). Mice were required to perform different social tasks – direct social interaction and social investigation. Direct interaction of two male mice was not modified in any group; however, when they were paired with females, Glu‐CB1−/− mice showed reduced interaction. Also, exploration of the male stimulus subject in the three‐chamber social investigation test was almost unaffected. The situation was completely different when a female was used as the stimulus subject. In this case, Glu‐CB1−/− mice showed reduced interest in the social stimulus, mimicking the phenotype of CB1−/− or WT mice treated with SR141716A. GABA‐CB1−/− mice showed the opposite phenotype, by spending more time investigating the social stimulus. In conclusion, we provide evidence that CB1 receptors specifically modulate the social investigation of female mice in a neuronal subtype‐specific manner.
Retinal ganglion cells projecting to the accessory optic system in optokinetic blind albinotic rats are direction‐selective
Authors: Krause Martin , Distler Claudia , Hoffmann Klaus‐Peter
Published: April 2014

The optokinetic deficits in albinotic rats and ferrets are caused by the loss of direction selectivity in the accessory optic system (AOS). However, the underlying mechanisms for this loss are still not clear. Here we tested the hypothesis that, in albino rats, the retinal input to the AOS lacks direction selectivity and, as a consequence, neurons in the AOS are direction non‐selective. We investigated ON‐center direction‐selective retinal ganglion cells, the major input to the AOS, in pigmented Long Evans and albino Wistar rats using extracellular in vitro patch‐clamp techniques. To visualise putative AOS‐projecting direction‐selective ganglion cells, we retrogradely labeled them by injection of the infrared‐sensitive dye indocyanine green into the medial terminal nucleus of the AOS. The present study is the first to present physiological evidence for retinal ON‐center direction‐selective ganglion cells in rat. Our results show that, in albinotic and pigmented rats, ON‐center retinal ganglion cells projecting to the AOS are similarly direction‐selective, suggesting that the optokinetic deficit must be caused by the abolition of direction selectivity in the AOS itself.
The highs and lows of beta activity in cortico‐basal ganglia loops
Authors: Brittain John‐Stuart , Sharott Andrew , Brown Peter
Published: April 2014

Oscillatory activity in the beta (13–30 Hz) frequency band is widespread in cortico‐basal ganglia circuits, and becomes prominent in Parkinson's disease (PD). Here we develop the hypothesis that the degree of synchronization in this frequency band is a critical factor in gating computation across a population of neurons, with increases in beta band synchrony entailing a loss of information‐coding space and hence computational capacity. Task and context drive this dynamic gating, so that for each state there will be an optimal level of network synchrony, and levels lower or higher than this will impair behavioural performance. Thus, both the pathological exaggeration of synchrony, as observed in PD, and the ability of interventions like deep brain stimulation (DBS) to excessively suppress synchrony can potentially lead to impairments in behavioural performance. Indeed, under physiological conditions, the manipulation of computational capacity by beta activity may itself present a mechanism of action selection and maintenance.
Network Closure or Structural Hole? The Conditioning Effects of Network–Level Social Capital on Innovation Performance
Authors: Tan Justin , Zhang Hongjuan , Wang Liang
Published: April 2014

This study contributes to the bonding–bridging debate in the social capital literature by examining the conditioning effects of collective social capital. Data generated from simulation reveals that network density, a measure of network–level social capital, negatively moderates the impacts of firm–level social capitals, measured separately by degree centrality and structural hole, on a firm's innovation performance. Specifically, in low–density networks, degree centrality and structural holes are complementary at enhancing innovation performance. In high–density networks, the positive impact of degree centrality weakens and structural holes turn out to be detrimental. The findings not only advance our understanding of the cross–level dynamics of social capital, but also provide a possible explanation for the mixed empirical results found in previous studies.
Venture Capital Contracting in Theory and Practice: Implications for Entrepreneurship Research
Authors: Burchardt Jens , Hommel Ulrich , Kamuriwo Dzidziso Samuel , Billitteri Carolina
Published: April 2014

This article provides a comprehensive theoretical and empirical literature review of venture capital contracts. This outlines the differences between theoretical and practical uses of contract designs; that is, (1) how does the choice of securities give rise to different adverse selection problems in terms of attracting different types of entrepreneurial companies; how does the choice of securities in conjunction with cash flow and control rights provisions affect (2) the effort levels by the entrepreneur and the investor; and (3) ultimately affect entrepreneurial outcomes. This article highlights the major discrepancies between theory and practice and points out potential avenues for further research.
Living the Dream? Assessing the “Entrepreneurship as Emancipation” Perspective in a Developed Region
Authors: Jennings Jennifer E. , Jennings P. Devereaux , Sharifian Manely
Published: April 2014

This paper seeks to stimulate additional research on the entrepreneurship–as–emancipation perspective. We extend extant work by specifying the practices within developed regions from which entrepreneurs arguably pursue liberation and then developing hypotheses pertaining to the incidence, determinants, and outcomes associated with departure from such norms. Our survey findings offer evidence to question not only the prevalence with which entrepreneurs in such contexts deviate from the status quo, but also the characteristics of those who enact greater departure. On average, women are not more likely to do so; moreover, they tend to be less satisfied overall when they do deviate highly.
Bilateral hypoplasia of the minor tubercle of the humerus with medial luxation of the biceps tendon in two Quarter Horses
Authors: Lund C. M. , Ragle C. A. , Rice H. C. , Wilkinson T. E.
Published: April 2014

Two Quarter Horses were examined at the Washington State University Veterinary Teaching Hospital with forelimb lameness. Case 1 was a 4‐year‐old female with a 4 month history of intermittent forelimb lameness that had partially responded to oral anti‐inflammatories. The horse was in full training and actively competing in cutting. Case 2 was a one‐year‐old filly bred for cutting that presented with a right forelimb lameness of 3 weeks’ duration, which was not responsive to oral anti‐inflammatories. The horse was not in training. On lameness examination, Case 1 was grade 1/5 (American Association of Equine Practitioners scale) lame in the left forelimb in a straight line on a hard surface, extension and flexion of the shoulder was resented and exacerbated the lameness. Case 2 was grade 3/5 lame in the right forelimb in a straight line on a hard surface, flexion and extension of the shoulder was resented and exacerbated the lameness. Both horses had a characteristic dished appearance to the dorsal aspect of the shoulder, with prominence of the proximal aspect of the humerus. Ultrasound and proximodistal oblique (skyline) radiographic views of the scapulohumeral joints demonstrated bilateral hypoplasia of the minor tubercle of the humerus with bilateral medial luxation of the proximal biceps tendon in both cases. To the authors' knowledge this is the first report of 2 cases of bilaterally affected horses, as well as the first report of the condition in the Quarter Horse breed.
Embryo transfer in competition horses: Managing mares and expectations
Authors: Campbell M. L. H.
Published: April 2014

Embryo transfer (ET) is an accepted and successful technique for obtaining foals from mares without interrupting their competition careers. Recent research, however, suggests that the potential of factors including heat, exercise, repeated embryo flushing and repeated manipulation of the reproductive cycle using exogenous hormones to have a negative impact on fertility may have been underestimated. This paper reviews the evidence base for involvement of these factors in repeated failures to recover embryos from nongeriatric competition mares without obvious clinical or pathological indications of reproductive abnormalities. It concludes that, for some mares at least, a cessation of exercise for the periovulatory period and the period between ovulation and embryo flushing, combined with careful management of flushing‐induced endometritis, and minimal hormonal manipulation of the reproductive cycle, may be necessary to optimise embryo recovery rates. Mare owners may have been encouraged to requestETfor their mares following high‐profile examples in the media of elite mares that have produced foals byETwhilst competing. The veterinarian should educate mare owners about the multiple factors that may affect the chances of recovering an embryo from their mares, and should manage the expectations of mare owners so that they do not approachETprogrammes in the expectation that there will be no disruption to their training and competition plans.
Mutation‐dependent effects on mRNA and protein expressions in cultured keratinocytes of Hailey–Hailey disease
Authors: Matsuda Mitsuhiro , Hamada Takahiro , Numata Sanae , Teye Kwesi , Okazawa Hiromi , Imafuku Shinichi , Ohata Chika , Furumura Minao , Hashimoto Takashi
Published: April 2014

Hailey–Hailey disease (HHD) is a dominantly inherited skin disease caused by mutations in ATP2C1 gene, which encodes secretory pathway Ca2+/Mn2+‐ATPase protein 1. The precise mechanism remains unclear. In this study, to understand molecular basis of HHD, we examined expression of mRNA and protein in cultured keratinocytes derived from three HHD patients with different mutations. We showed that reduced expression of mRNA and protein in patient with p.Gln504X, but not in patients with p.Pro307His and c.1308+1G>A. RT‐PCR analysis for patient with c.1308+1G>A revealed in‐frame exon skipping. Reduction of mRNA and protein in p.Gln504X was considered to be caused by nonsense‐mediated mRNA decay. p.Pro307His located adjacent to Ca2+‐binding residue may induced conformational change, which leads to defective Ca2+ transport. In‐frame shorter transcript caused by c.1308+1G>A may have slightly reduced activity, which accounted for mild phenotype of the patient. These results clarified the pathogenic effects of different causative mutations in development of skin lesions.
Production and function of pigment epithelium‐derived factor in isolated skin keratinocytes
Authors: Chen Lin , DiPietro Luisa A.
Published: April 2014

Pigment epithelium‐derived factor (PEDF) is a multifunctional factor with potent anti‐angiogenic activity that may play a role in skin homoeostasis and wound healing. Analysis of PEDF levels demonstrated that PEDF levels are high in normal skin but quite low in early wounds. As previous studies have suggested that keratinocytes can produce PEDF, we investigated how conditions that mimic those found at sites of injury influence PEDF production by keratinocytes in vitro. Both injury by mechanical disruption (scratch assay) and treatment of human keratinocytes with inflammatory cytokines (IL‐1β, IL‐6 and TNF‐α) inhibited PEDF expression. We next examined how PEDF affects keratinocyte functions that are important in tissue repair. Treatment of keratinocytes with exogenous PEDF enhanced keratinocyte adhesion, therefore impairing migration, while having no effect on cell proliferation. The results suggest that modulation of PEDF levels may play a pivotal role in skin homoeostasis and the response of keratinocytes to injury or inflammatory insults.
The Implementation and Use of Benchmarking in Local Government: A Case Study of the Translation of a Management Accounting Innovation
Authors: Siverbo Sven
Published: April 2014

Benchmarking is a management accounting innovation (MAI) that can be used for performance measurement and management in both the private and the public sectors. Although public sector accounting researchers have reported some success with the use of benchmarking, frequently charged problems exist in implementing and using this management technique. To look beyond the technical and institutional explanations, this paper takes a translation approach and presents a case study of a local government benchmarking network. We conclude that there is a link between benchmarking implementation problems and initiators’ failure to build a strong network of benchmarking allies. Implementation is facilitated if actors, other than the initiators, recognize the possibility of making benchmarking more relevant and less cost focused. However, even when a network of actors has a favourable attitude towards benchmarking, benchmarking may still appear as an unruly ‘actant’. Furthermore, the perception of implementation failure and success is heterogeneous and connected to various actors’ adoption of benchmarking. We also conclude that there is a connection between the use of benchmarking and 1) actors’ possibilities to use benchmarking in the struggle for resources and 2) the perception of benchmarking information as ‘factual’ or ‘factual enough’. However, the perception of benchmarking information as ‘factual’ or ‘factual enough’ seems not only a matter of correct or incorrect ratios but also of whether such information serves actors’ interests. A final conclusion is that the use of benchmarking increases when actors other than the initiators complement the original idea and ‘counter interest’ the initiators.
Role of Internal Audit in Australian Local Government Governance: A Step in the Right Direction
Authors: Pilcher Robyn
Published: April 2014

While the functions of local government are many and varied, the primary role is to provide effective performance which arguably will coincide with good governance for its municipality. Internal audit and relevant controls play a key role in ensuring that good governance. The introduction of accrual accounting in local government certainly has added complexity and additional risks, with cases of fraud, corruption and high risk investments in several Australian local councils being reported periodically by the media. Those cases have been accompanied by proposed governance reforms including the introduction of an internal audit function to address the issues raised. Although seen as an essential part of the governance process, the results here suggest there is still some confusion as to the role of the internal audit and its perceived effectiveness in Australian local government.
A brief history of macromolecular crystallography, illustrated by a family tree and its Nobel fruits
Authors: Jaskolski Mariusz , Dauter Zbigniew , Wlodawer Alexander
Published: April 2014

As a contribution to the celebration of the year 2014, declared by the United Nations to be ‘The International Year of Crystallography’, the FEBS Journal is dedicating this issue to papers showcasing the intimate union between macromolecular crystallography and structural biology, both in historical perspective and in current research. Instead of a formal editorial piece, by way of introduction, this review discusses the most important, often iconic, achievements of crystallographers that led to major advances in our understanding of the structure and function of biological macromolecules. We identified at least 42 scientists who received Nobel Prizes in Physics, Chemistry or Medicine for their contributions that included the use of X‐rays or neutrons and crystallography, including 24 who made seminal discoveries in macromolecular sciences. Our spotlight is mostly, but not only, on the recipients of this most prestigious scientific honor, presented in approximately chronological order. As a summary of the review, we attempt to construct a genealogy tree of the principal lineages of protein crystallography, leading from the founding members to the present generation.
High‐Dose Extended‐Release Lansoprazole (Dexlansoprazole) and Amoxicillin Dual Therapy for Helicobacter pylori Infections
Authors: Attumi Taraq A. , Graham David Y.
Published: April 2014

Background

Helicobacter pylori infections have become increasingly difficult to treat.

Aim

To examine whether amoxicillin and high‐dose dexlansoprazole would reliably achieve an H. pylori eradication rate of ≥90%.

Methods

An open‐label prospective pilot study of H. pylori eradication in treatment‐naïve subjects with active H. pylori infection (positive by two tests). Therapy: amoxicillin 1 g and dexlansoprazole 120 mg each twice a day at approximately 12‐hour intervals for 14 days. Success was accessed by urea breath test. An effective therapy was defined as a per‐protocol treatment success of 90% or greater; treatment success of 80% or less was prespecified as an unacceptable result.

Results

After 13 subjects were entered (12 men, one woman; average age of 54 years), the prespecified stopping rule of six treatment failures was achieved (i.e., the 95% confidence interval excluded achieving the required 90% success rate even if the proposed study of 50 completed patients were entered) and enrollment was stopped. Per‐protocol and intention‐to‐treat treatment success were both 53.8%; (7/13); 95% CI = 25–80%. Compliance was 100%. Three patients (23%) reported side effects, all of which were mild and none interrupted therapy.

Conclusion

Theoretically, dual PPI plus amoxicillin should reliably eradicate H. pylori provided nearly neutral intragastric pH can be maintained. Clearly, dexlansoprazole, despite being administered at high dose and twice a day (i.e., total daily dose 240 mg), failed to achieve an intragastric milieu consistent with dual PPI plus amoxicillin therapy being an effective anti‐H. pylori regimen.
Children's mental health policies in the United States: perspectives from advocates and state leaders
Authors: Cooper Janice L. , Aratani Yumiko
Published: April 2014

Background

Previous research suggests a disconnect on both policy and practice between advocates and state leaders in child mental health.

Aim

To compare advocates' and state leader's perspectives and understanding on the three main themes in children's mental health policies: (i) state's initiatives to empower and engage families and youth in policy and practice; (ii) state's fiscal support for family and youth driven services; and (iii) policy challenges to improving children's mental health services and outcomes.

Study design

This study draws on data from national surveys of State Children's Mental Health Directors (2006) and of state affiliates of Mental Health America (2007).

Results

The findings from 38 responses representing 19 states suggest differences between state leaders and advocates on their understanding of family and youth engagement, service access, quality and fiscal supports. While state directors and advocates seem to have similar understanding on the existence of states' efforts related to evidence‐based practices, many advocates are unaware of the specifics of the strategies that states undertook or funded. Advocates also did not know which types of settings were eligible for reimbursement for children's services.

Conclusions

Advocates lack some information that is vital to fulfilling their role. Policymakers seem unaware of key challenges that families face and therefore appear to be without critical information that fuels the agenda for advocates. The challenge for both set of actors is how to get beyond this information asymmetry to advance efforts to improve mental health.
Imatinib: a novel treatment approach for generalized morphea
Authors: Coelho‐Macias Vasco , Mendes‐Bastos Pedro , Assis‐Pacheco Fernando , Cardoso Jorge
Published: April 2014

Background

Morphea is a rare chronic inflammatory disease that involves skin and subcutaneous tissues, causing skin sclerosis. Generalized morphea is characterized by extensive cutaneous involvement and poor response to therapy. Although the pathophysiology for morphea is not completely understood, abnormal signaling through the platelet‐derived growth factor and transforming growth factor beta axes seems to play a major role in the inflammatory response and sclerotic process. Imatinib, a tyrosine kinase inhibitor, interferes with both transforming growth factor beta and platelet‐derived growth factor signaling pathways. Recent studies proved imatinib's efficacy in the prevention and regression of fibrosis associated with systemic sclerosis, nephrogenic sclerosis, and bleomycin‐related fibrosis.

Observations

We present the case of a 50‐year‐old Caucasian man with a generalized morphea diagnosed 10 years ago, with multiple ulcers, who was treated with imatinib over the course of 12 months. At the end of the treatment, most of the skin ulcerations had healed, and cutaneous thickness was reduced as demonstrated by skin biopsy and ultrasound evaluation. The patient also experienced an improvement in articular mobility, sustained by a 20° increase in left knee extension.

Conclusions

Although controlled studies are necessary to access the antifibrotic effect of imatinib in morphea, the present report shows its potential role in the treatment of this condition.
A seminar on gardens for the health of the skin
Authors: Ryan Terence J. , Matts Paul J. , Snyder Brad , Orr Vanya
Published: April 2014

This is a report on a seminar held on January 12, 2013, at the Regional Dermatology Training Centre in Tanzania, sponsored by the International Society of Dermatology as part of its Taskforce Program for Skin Care for All: Community Dermatology. There were four themes: (i) Gardens attached to health centers increase their attractiveness and result in increased attendance and, thus, increase the utilization of effective skin care interventions. Literature on the positive effect of greenery surrounding health centers on health and the environment is reviewed. (ii) Adding an expert on agriculture to the staff of health centers in Rwanda has provided nutrition and safe medicines. (iii) In southern India, these interventions are channeled through the empowerment of tribal women in an area noted for anxiety due to unemployment in the tea and forestry industry. The gardens are used for teaching about nutrition and herbal medicines, and the women are further attracted by childcare facilities. (iv) Measuring barrier function defects gives early warning of malnutrition of the skin after damage by trauma or by ultraviolet radiation. Higher cost research techniques may help to provide the science required to produce its evidence base. In conclusion, Gardens for health should be adopted as policy by skin care providers.
Factors influencing the adaptation to skilled nursing facilities among older Korean adults
Authors: Choi Jin Yi , Sok Sohyune R
Published: April 2014

This study was conducted to identify the factors that influence the level of adaptation of older Korean adults to skilled nursing facilities. The subjects were 500 adults aged 65 or older who were living in six different skilled nursing facilities in Seoul and Gyeong‐gi‐do, South Korea. The measures were a demographic form, Health Self‐Rating Scale, Activities of Daily Living Scale, Self‐Efficacy Instrument, Korean Simple Depression Scale, Quality of the Facility Scale and Facility Adaptation Scale. The analyses showed that the prediction model was significant (F = 128.624, P < 0.001). The value of the adjusted R2 was 0.435, which corresponds to the explanatory power of 43.5%. The factor that was found to have the greatest influence on the adaptation of older Korean adults to skilled nursing facilities was activities of daily living (β = −0.564), followed by self‐efficacy (β = 0.321), quality of the facility (β = 0.164), depression (β = 0.133), decision to enter a skilled nursing facility (β = 0.122), perceived health status (β = 0.064) and age (β = −0.010). This cross‐sectional study provides preliminary evidence that the level of adaptation of older Korean adults to skilled nursing facilities is related to their activities of daily living, self‐efficacy, depression, decision to enter a skilled nursing facility, perceived health status and age, and to the quality of the facility.
Metallothionein overexpression of bladder biopsies associated with tissue hypoxia in patients with interstitial cystitis/painful bladder syndrome
Authors: Lee Jane‐Dar , Lee Ming‐Huei
Published: April 2014

Objective

To study the relationship between hypoxia and metallothionein expression in bladder biopsies of interstitial cystitis/painful bladder syndrome patients.

Methods

The study group consisted of 41 patients with interstitial cystitis/painful bladder syndrome, and the control group consisted of 12 volunteers without any interstitial cystitis/painful bladder syndrome symptoms. All biopsy specimens were analyzed for both proteins of hypoxia‐inducible factor‐1α and metallothionein expression by immunoblotting, immunostaining and confocal laser scanning microscopy. Data were analyzed using the Mann–Whitney U‐test.

Results

An increased expression of hypoxia‐inducible factor‐1α and metallothionein was noted in the study group compared with the control group (P < 0.05). Both proteins of hypoxia‐inducible factor‐1α and metallothionein mainly distributed over bladder urothelium by immunohistochemical staining, and showed co‐localization under confocal microscopy.

Conclusions

High expression and co‐localization of metallothionein and hypoxia‐inducible factor‐1 alpha in the bladder mucosa of patients with interstitial cystitis suggest that overexpression of metallothionein is associated with the bladder hypoxia related to this disease.
Signal‐regulatory protein α from the NOD mouse binds human CD47 with an exceptionally high affinity – implications for engraftment of human cells
Authors: Kwong Lai Shan , Brown Marion H. , Barclay A. Neil , Hatherley Deborah
Published: April 2014

One common way to study human leucocytes and cancer cells in an experimental in vivo situation is to use mice that have been genetically engineered to lack an immune system and prevent human cell rejection. These mice lack CD132 and either RAG2 or the catalytic subunit of the DNA‐dependent protein kinase, to make the mice deficient in lymphocytes and natural killer cells. The NOD mouse strain provides a better background for engraftment than other strains due to stronger engagement of the signal‐regulatory protein‐α (SIRPα) inhibitory receptor with human CD47 (hCD47) resulting in a ‘don't‐eat‐me’ signal. To determine the molecular parameters that determine this major functional effect in the NOD mouse we measured the affinity of hCD47 for SIRPα from various mouse strains. Human CD47 bound SIRPα from the NOD mouse with an affinity 65 times greater than SIRPα from other mouse strains. This is due mainly to the NOD SIRPα lacking two amino acids in domain 1 compared with other mouse strains. Remarkably the SIRPα(NOD) binds hCD47 with 10 times the affinity of the syngeneic hCD47/hSIRPα interaction. This affinity is outside the normal range for affinities for leucocyte surface protein interactions and raises questions as to what is the optimal affinity of this interaction for engraftment and what other xenogeneic interactions involved in homeostasis may also not be optimal.