bluuebunny/crossref_metadata_2025 huggingface dataset:
The “Tiering” of Citizenship and Residency and the “Hierarchization” of Migrant Communities: The United Arab Emirates in Historical Context
Authors: Jamal Manal A.
Published: February 2015

The local population of the United Arab Emirates (UAE) constitutes less than 11.5 percent of the total population. In response to their growing numerical minority status, many Gulf Cooperation Council (GCC) states, including the UAE, have become more stringent about their citizenship, nationality, and employment policies. The natural questions to follow are: Why have UAE nationality and citizenship laws diverged from the anticipated “opening” of nationality and citizenship policies that some assumed would accompany globalization? In the specific context of the UAE, what factors have shaped and changed these policies over time?
Effect of maternal use of chewing gums containing xylitol on transmission of mutans streptococci in children: a meta‐analysis of randomized controlled trials
Authors: Lin Hsi‐Kuei , Fang Chia‐En , Huang Mao‐Suan , Cheng Hsin‐Chung , Huang Tsai‐Wei , Chang Hui‐Ting , Tam Ka‐Wai
Published: February 2015

Background

Mutans streptococci (MS) are the major causative bacteria involved in human dental decay. Habitual consumption of xylitol has been proved to reduce MS levels in saliva and plaque.

Aim

To evaluate the effect of the maternal use of xylitol gum on MS reduction in infants.

Design

A structured literature review and meta‐analysis. A random effects model was used to assess the relative risks of the incidence of MS in the saliva or plaque of children who were 6, 9, 12, 18, and 24 months old.

Results

We reviewed 11 RCTs derived from 5 research teams that included 601 mothers. Our results indicated that the incidence of MS in the saliva or plaque of the infants was significantly reduced in the xylitol group (risk ratio: 0.54; 95% confidence interval: 0.39–0.73, at 12–18 months) and (risk ratio: 0.56; 95% confidence interval: 0.40–0.79, at 36 months) compared with the control groups. The long‐term effect of maternal xylitol gum exposure on their children's dental caries was controversial.

Conclusion

Habitual xylitol consumption by mothers with high MS levels was associated with a significant reduction in the mother–child transmission of salivary MS.
Determinants of the gender unemployment gap in Italy and the United Kingdom: A comparative investigation
Authors: BAUSSOLA Maurizio , MUSSIDA Chiara , JENKINS Jamie , PENFOLD Matthew
Published: February 2015

The authors analyse the gender unemployment gap in Italy and the United Kingdom by investigating the determinants of labour market flows, on the basis of multinomial logit model estimates, and identifying the contribution of a single transition from each state – employment, unemployment, inactivity – to the gap. Using this methodology, labour markets in Italy and the United Kingdom are compared, based on both countries' labour force survey data for the period 2004–13. Decomposition of the gender unemployment gap, using a transition probability matrix approach, shows that while women are disadvantaged in Italy, the reverse is true in the United Kingdom.
Controlled Synthesis of Layered Rare‐Earth Hydroxide Nanosheets Leading to Highly Transparent (Y0.95Eu0.05)2O3 Ceramics
Authors: Lu Bin , Li Ji‐Guang , Suzuki Tohru S. , Estili Mehdi , Liu Weigang , Sun Xudong , Sakka Yoshio
Published: February 2015

Chemical precipitation at the freezing temperature of ~4°C has directly yielded layered rare‐earth hydroxide [LRH, Ln2(OH)5NO3·nH2O, Ln = Y0.95Eu0.05] nanosheets (up to 7 nm thick) for the Y/Eu binary system, with the interlayer NO3− exchangeable with SO42−. Calcining the sulfate derivative at 1100°C for 4 h produces well‐dispersed and readily sinterable Ln2O3 red phosphor powders (~14.8 m2/g) that can be densified into highly transparent ceramics via optimized vacuum sintering at the relatively low temperature of 1700°C for 4 h (average grain size ~14 μm; in‐line transmittance ~80% at the 613 nm Eu3+ emission or ~99% of the theoretical transmittance of Y2O3 single crystal). Our systematic studies also found that (1) the extent of SO42− exchange and the interlayer distance of LRH are both affected by the SO42−/Ln3+ molar ratio (R), and an almost complete exchange is achievable at R = 0.25 as expected from the chemical formula (one SO42− replaces two NO3− for charge balance). The optimal R value for sintering, however, was found to be 0.03; (2) The Ln3+ concentration for LRH synthesis substantially affects properties of the resultant oxides, and hard agglomeration has been significantly reduced at the optimized Ln3+ concentration of 0.05–0.075 mol/L; (3) Sulfate exchange significantly alters the thermal decomposition pathway of LRH, and was found essential to produce well‐dispersed and highly sinterable oxide powders; (4) Both the oxide powders and transparent ceramics exhibit the typical red emission of Eu3+ at ~613 nm (the 5D0→7F2 transition) under charge‐transfer (CT) excitation. Red‐shifted CT band center, stronger excitation/emission, and shorter fluorescence lifetime were, however, observed for the transparent ceramics.
The effects of providing periodontal disease risk information on psychological outcomes – a randomized controlled trial
Authors: Asimakopoulou Koula , Newton Jonathon Tim , Daly Blánaid , Kutzer Yvonne , Ide Mark
Published: February 2015

Aim

In a two arm randomized controlled trial this study compared the effects of a routine periodontal assessment consultation versus a routine consultation + individualized risk assessment communication intervention on patient thoughts and emotions about periodontal disease.

Materials and Methods

Adults (N = 102) with moderate/advanced chronic periodontitis referred to a Periodontology Department of a large UK dental school, completed psychological measures before a periodontal assessment and again at the end of the visit. Intervention participants received an individualized calculation of their periodontal disease risk using PreViser Risk Calculator in addition to their routine assessment consultation.

Results

In routine care, patients’ thoughts about periodontal disease seriousness (p < 0.001) and susceptibility (p < 0.03) increased post‐consultation and participants felt more positive (p < 0.02) about periodontal disease. These effects were also seen in intervention participants. Additionally, the individualized risk communication intervention led to patients reporting i) periodontal disease treatment as more effective than they did pre‐consultation (p < 0.001), ii) feeling more confident in their ability to adhere to treatment as seen in increases in self‐efficacy (p < 0.05) and iii) higher intentions to adhere to periodontal management (p < 0.03).

Conclusions

Individualized periodontal disease risk communication influences psychological variables that underpin adherence with periodontal instructions.
Phenotypic and genetic associations between reading comprehension, decoding skills, and ADHD dimensions: evidence from two population‐based studies
Authors: Plourde Vickie , Boivin Michel , Forget‐Dubois Nadine , Brendgen Mara , Vitaro Frank , Marino Cecilia , Tremblay Richard T. , Dionne Ginette
Published: February 2015

Background

The phenotypic and genetic associations between decoding skills and ADHD dimensions have been documented but less is known about the association with reading comprehension. The aim of the study is to document the phenotypic and genetic associations between reading comprehension and ADHD dimensions of inattention and hyperactivity/impulsivity in early schooling and compare them to those with decoding skills.

Methods

Data were collected in two population‐based samples of twins (Quebec Newborn Twin Study – QNTS) and singletons (Quebec Longitudinal Study of Child Development – QLSCD) totaling ≈ 2300 children. Reading was assessed with normed measures in second or third grade. Teachers assessed ADHD dimensions in kindergarten and first grade.

Results

Both decoding and reading comprehension were correlated with ADHD dimensions in a similar way: associations with inattention remained after controlling for the other ADHD dimension, behavior disorder symptoms and nonverbal abilities, whereas associations with hyperactivity/impulsivity did not. Genetic modeling showed that decoding and comprehension largely shared the same genetic etiology at this age and that their associations with inattention were mostly explained by shared genetic influences.

Conclusion

Both reading comprehension and decoding are uniquely associated with inattention through a shared genetic etiology.
Time Discounting in Strategic Contests
Authors: Deck Cary , Jahedi Salar
Published: February 2015

In many contests, such as political campaigns or R&D expenditures, there is at least some trade‐off between immediate money outlay and potential future benefits. This timing aspect has mostly been ignored by the contest literature. If contestants exhibit a strong present bias, such as that shown by past individual choice experiments, then benefits that are deferred to the future will lead to a significant drop in investment. This paper uses controlled laboratory experiments to explore how the timing of prize payment impacts behavior in a contest with a unique Nash equilibrium strategy. We find no evidence that people significantly discount future prizes in our contests, despite the fact that we do replicate present bias in a separate individual choice experiment.
Agents Monitoring Their Manager: A Hard‐Times Theory of Producer Cooperation
Authors: Hueth Brent , Marcoul Philippe
Published: February 2015

We model the producer cooperative as a firm where a single class of individuals supplies an essential input and monitors managerial behavior. We show how this contractual structure reduces the incidence of equilibrium credit rationing, even assuming a cost disadvantage relative to a firm where these roles are specialized. Our model provides an explanation for producer and worker buyouts in the face of exit by investor owners, and, more generally, for cooperative entry in low‐return economic environments not serviced by investor‐financed firms. Further, our model predicts that a cooperative firm is less prone to monitor‐manager collusion, and that it monitors excessively in high‐return environments.
Unbundling Ownership and Control
Authors: Ferreira Daniel , Ornelas Emanuel , Turner John L.
Published: February 2015

We study control contests under asymmetric information. Using a mechanism design approach, we fully characterize the optimal control contest mechanism. The optimal mechanism requires increasing the number of shares owned by the incumbent insider if he remains in control, while giving him a golden parachute that includes both shares and cash if he is deposed. The model underscores a novel explanation for the prevalence and persistence of the separation of ownership from control: efficiency in control contests is more easily achieved when ownership of cash flow rights is not concentrated in the hands of insiders.
Ensuring consistent reporting of clinical pharmacy services to enhance reproducibility in practice: an improved version of DEPICT
Authors: Rotta Inajara , Salgado Teresa M. , Felix Daniel C. , Souza Thais T. , Correr Cassyano J. , Fernandez‐Llimos Fernando
Published: February 2015

Rationale, aims and objectives

DEPICT (Descriptive Elements of Pharmacist Intervention Characterization Tool) was created in response to the frequently reported issue of poor intervention description across studies assessing the impact of clinical pharmacy activities. The aim of this study was to create an improved version of DEPICT (i.e. DEPICT 2) to better characterize clinical pharmacy services in order to ensure consistent reporting, therefore enhancing reproducibility of interventions in practice.

Method

A qualitative approach through a thematic content analysis was performed to identify components of pharmacist interventions described in 269 randomized controlled trials. A preliminary version of DEPICT 2 was applied independently by two authors to a random sample of 85 of the 269 RCTs and reliability determined by the prevalence‐adjusted bias‐adjusted kappa (PABAK) or the intraclass correlation coefficient (ICC). The final version of DEPICT 2 was compared against DEPICT 1.

Results

The final version of DEPICT 2 comprised 146 items and 11 domains. The inter‐rater agreement analysis showed that DEPICT presented good to optimal reproducibility, with a mean PABAK value of 0.87 (95% CI 0.85–0.89) and a mean ICC value of 0.88 (95% CI 0.62–1.14). The mean difference between items checked in the two versions (DEPICT 2 – DEPICT 1) was 10.58 (95% CI 9.55–11.61), meaning that approximately 11 more components were identified in the new version of DEPICT.

Conclusions

DEPICT 2 is a reliable tool to characterize components of clinical pharmacy services, which should be used to ensure consistent reporting of interventions to allow their reproducibility in practice.
Risk factors of hepatocellular carcinoma development in non‐cirrhotic patients with sustained virologic response for chronic hepatitis C virus infection
Authors: Toyoda Hidenori , Kumada Takashi , Tada Toshifumi , Kiriyama Seiki , Tanikawa Makoto , Hisanaga Yasuhiro , Kanamori Akira , Kitabatake Shusuke , Ito Takanori
Published: February 2015

Background and Aim

Hepatocellular carcinoma (HCC) can develop in patients with chronic hepatitis C after they have achieved a sustained virologic response (SVR) to antiviral therapy, that is eradication of hepatitis C virus (HCV). Thus, surveillance for HCC remains necessary after SVR. We investigated factors that are predictive of HCC in HCV‐infected patients who achieved SVR.

Methods

The incidence and risk factors for HCC were evaluated in 522 patients who achieved SVR with interferon‐based antiviral therapy for HCV. Patients maintained regular follow‐up every 6 months for HCC surveillance. The FIB‐4 index and aspartate aminotransferase to platelet count ratio index were calculated based on laboratory data at the time that SVR was documented (SVR24).

Results

Patients continued follow‐up visits for 1.0–22.9 years (median, 7.2 years) after SVR. HCC developed in 18 patients. The incidence of HCC was 1.2% at 5 years and 4.3% at 10 years. The use of peginterferon or ribavirin for treatment and a history of antiviral therapy prior to the course when SVR was achieved were not associated with the incidence of HCC after SVR. The presence of diabetes mellitus (risk ratio 2.08; P = 0.0451) and FIB‐4 index calculated at the time of SVR24 (risk ratio 1.73; P = 0.0198) were associated with a higher likelihood of HCC after SVR by multivariate analysis.

Conclusions

Patients with diabetes mellitus and patients with the elevation of FIB‐4 index at SVR24 are at higher risk of HCC after SVR. Surveillance for HCC should be continued in this patient subpopulation.
Creatinine modified Child–Turcotte–Pugh and integrated model of end‐stage liver disease scores as predictors of spontaneous bacterial peritonitis‐related in‐hospital mortality: Applicable or not
Authors: Hassan Elham Ahmed , Abdel Rehim Abeer Sharaf ELdin
Published: February 2015

Background and Aims

Despite intensive management, spontaneous bacterial peritonitis (SBP) is associated with poor prognosis especially in hospitalized patients. Therefore, the aim of this study was to determine prognostic factors for SBP‐related in‐hospital mortality, and to evaluate the predictive power of Child–Pugh (CP), model of end‐stage liver disease (MELD), creatinine modified Child–Turcotte–Pugh (CrCTP), and integrated MELD (iMELD) for identifying the best score to predict mortality.

Methods

Predictors of SBP‐related in‐hospital mortality were assessed using regression analysis over 100 cirrhotic patients. Predictive abilities of CP, MELD, CrCTP, and iMELD were compared using the area under receiver operating characteristic curve (AUC).

Results

SBP‐related in‐hospital mortality was 22%. Age, serum creatinine, bilirubin, sodium, CrCTP, MELD, and iMELD were associated with mortality. Using AUC, CrCTP, and iMELD was significantly better than CP and MELD in predicting in‐hospital mortality, where iMELD had the highest AUC (0.862). The cut‐off with the best ability to predict in‐hospital mortality was 43.5 for iMELD.

Conclusion

Age, serum creatinine, bilirubin, and sodium were associated with SBP‐related in‐hospital mortality. The incorporation of these variables into CP and MELD significantly improves their predictive ability. iMELD followed by CrCTP provided useful prognostic information for critically ill patients with SBP.
Preservation of quality of life with doxorubicin drug‐eluting bead transarterial chemoembolization for unresectable hepatocellular carcinoma: Longitudinal prospective study
Authors: Xing Minzhi , Webber Grant , Prajapati Hasmukh J , Chen Zhengjia , El‐Rayes Bassel , Spivey James R , Pillai Anjana A , Kim Hyun S
Published: February 2015

Background and Aim

The study aims to determine the effects of doxorubicin drug‐eluting bead transarterial chemoembolization (DEB‐TACE) therapies on health‐related quality of life (HRQOL) in patients with unresectable hepatocellular carcinoma (HCC).

Methods

This is a single‐center, prospective study assessing HRQOL of consecutive patients with unresectable HCC who underwent DEB‐TACE. Longitudinal assessment of HRQOL scores via Short‐Form‐36 (SF‐36) was performed. Baseline HRQOL scores were evaluated for significant change (P < 0.05) pre‐therapy, post‐therapy, and at 6‐ and 12‐month follow‐up. Analysis of overall survival (OS) from HCC diagnosis and OS from first DEB‐TACE was performed. Paired t‐tests were used to compare HRQOL domain scores.

Results

One hundred eighteen patients (83 male; median age 60 years) were enrolled. Patients had lower baseline scores within all eight HRQOL domains of the SF‐36 compared with US age‐adjusted healthy norms. No significant changes in all eight domains were observed post‐therapy and at 6‐ or 12‐month follow‐up compared with baseline (P > 0.05). No significant differences in all eight domains were observed between patients receiving ≥ 4 versus ≤ 3 DEB‐TACE (P > 0.05). Both groups were similar for age at HCC diagnosis, gender, ethnicity, HCC etiology, Child–Pugh class and Eastern Cooperative Oncology Group Performance Status (P > 0.05). Patients receiving staged DEB‐TACE demonstrated significantly greater median OS from HCC diagnosis (≥ 4 vs ≤ 3 DEB‐TACE procedures, 31.9 vs 23.7 months, P = 0.04) and from first DEB‐TACE (≥ 4 vs ≤ 3 DEB‐TACE, 29.1 vs 20.2 months, P = 0.03).

Conclusion

DEB‐TACE therapy for HCC demonstrated long‐term preservation of HRQOL. In addition, staged DEB‐TACE with four or more therapies does not significantly impact long‐term HRQOL compared with patients who received three or fewer therapies.
Intellectual functioning in relation to autism and ADHD symptomatology in children and adolescents with 22q11.2 deletion syndrome
Authors: Hidding E. , Swaab H. , de Sonneville L. M. J. , van Engeland H. , Sijmens‐Morcus M. E. J. , Klaassen P. W. J. , Duijff S. N. , Vorstman J. A. S.
Published: February 2015

Background

The 22q11.2 deletion syndrome (22q11DS; velo‐cardio‐facial syndrome) is associated with an increased risk of various disorders, including autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). With this study, we aimed to investigate the relation between intellectual functioning and severity of ASD and ADHD symptomatology in 22q11DS.

Method

A sample of 102 individuals (62 females) with 22q11DS aged 9 to 18.5 years were assessed using age appropriate Wechsler scales of intelligence as well as psychological and psychiatric assessment to evaluate the presence of ASD and ADHD symptomatology.

Results

Intelligence profiles were characterised by lower scores on the factor perceptual organisation and higher scores on the factor processing speed, with on subtest level higher scores on digit span and lower scores on arithmetic and vocabulary as compared with the mean factor or subtest score respectively. No differences in intelligence profiles were found between subgroups with and without ASD and/or ADHD. Low scores on coding were associated with higher severity of ASD symptomatology, while lower scores on block design were associated with more severe ADHD symptomatology.

Conclusions

On several sub‐domains of intelligence, poorer performance was associated with higher severity of ASD and ADHD symptomatology. The impact of developmental disorders in 22q11DS can be traced in specific domains of intellectual functioning as well as in severity of symptomatology.
Signal‐to‐noise ratio enhancement on SEM images using a cubic spline interpolation with Savitzky–Golay filters and weighted least squares error
Authors: KIANI M.A. , SIM K.S. , NIA M.E. , TSO C.P.
Published: February 2015

A new technique based on cubic spline interpolation with Savitzky–Golay smoothing using weighted least squares error filter is enhanced for scanning electron microscope (SEM) images. A diversity of sample images is captured and the performance is found to be better when compared with the moving average and the standard median filters, with respect to eliminating noise. This technique can be implemented efficiently on real‐time SEM images, with all mandatory data for processing obtained from a single image. Noise in images, and particularly in SEM images, are undesirable. A new noise reduction technique, based on cubic spline interpolation with Savitzky–Golay and weighted least squares error method, is developed. We apply the combined technique to single image signal‐to‐noise ratio estimation and noise reduction for SEM imaging system. This autocorrelation‐based technique requires image details to be correlated over a few pixels, whereas the noise is assumed to be uncorrelated from pixel to pixel. The noise component is derived from the difference between the image autocorrelation at zero offset, and the estimation of the corresponding original autocorrelation. In the few test cases involving different images, the efficiency of the developed noise reduction filter is proved to be significantly better than those obtained from the other methods. Noise can be reduced efficiently with appropriate choice of scan rate from real‐time SEM images, without generating corruption or increasing scanning time.
Rhesus monkey (Macaca mulatta) lipoprotein(a) and apolipoprotein(a): high frequency of small size apolipoprotein(a) isoforms
Authors: Enkhmaa Byambaa , Abbuthalha Adnan , Anuurad Erdembileg , Zhang Wei , Tarantal Alice F. , Berglund Lars
Published: February 2015

Background

Levels of lipoprotein(a), Lp(a), a genetically regulated independent cardiovascular risk factor present in humans and Old World monkeys, are impacted by the apolipoprotein(a), apo(a), gene. Allele‐specific apo(a) levels, taking both the apo(a) genotypic and phenotypic characteristics into account, are useful markers to determine atherosclerotic cardiovascular risk.

Methods

We determined (i) the genetic variability of apo(a), (ii) Lp(a) levels, and (iii) allele‐specific apo(a) levels in rhesus monkeys (n = 95).

Results

Lp(a) levels differed substantially between animals (range: 4–247 nmol/l) with a skewed distribution toward lower levels. Lp(a) and allele‐specific apo(a) levels were inversely related to the number of apo(a) Kringle 4 (K4) repeats. The median apo(a) size was 23 K4 repeats, and the prevalence of a small size apo(a) (≤22 K4) was 43%.

Conclusions

Distribution of Lp(a) and allele‐specific apo(a) levels in rhesus monkeys reflected the corresponding human patterns, but with a high prevalence of smaller apo(a) sizes.
Different contributions of calcium channel subtypes to electrical excitability of chromaffin cells in rat adrenal slices
Authors: Albiñana Elisa , Segura‐Chama Pedro , Baraibar Andres M. , Hernández‐Cruz Arturo , Hernández‐Guijo Jesus M.
Published: February 2015

We characterized the ionic currents underlying the cellular excitability and the Ca2+‐channel subtypes involved in action potential (AP) firing of rat adrenal chromaffin cells (RCCs) preserved in their natural environment, the adrenal gland slices, through the perforated patch‐clamp recording technique. RCCs prepared from adrenal slices exhibit a resting potential of −54 mV, firing spontaneous APs (2–3 spikes/s) generated by the opening of Na+ and Ca2+‐channels, and terminated by the activation of voltage and Ca2+‐activated K+‐channels (BK). Ca2+ influx via L‐type Ca2+‐channels is involved in reaching threshold potential for AP firing, and is responsible for activation of BK‐channels contributing to AP‐repolarization and afterhyperpolarization, whereas P/Q‐type Ca2+‐channels are involved only in the repolarization phase. BK‐channels carry total outward current during AP‐repolarization. Blockade of L‐type Ca2+‐channels reduces BK‐current ~60%, whereas blockade of N‐ or P/Q‐type produces little effect. This study demonstrates that Ca2+ influx through L‐type Ca2+‐channels plays a key role in modulating the threshold potential from RCCs in situ.

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This study demonstrates that Ca2+ influx through L‐type Ca2+ channels plays a key role in modulating the threshold potential for action potential firing and activating BK channels contributing to repolarization and afterhyperpolarization from rat adrenal chromaffin cells in situ.
Noise‐induced cochlear F‐actin depolymerization is mediated via ROCK2/p‐ERM signaling
Authors: Han Yu , Wang Xianren , Chen Jun , Sha Su‐Hua
Published: February 2015

Our previous work has suggested that traumatic noise activates Rho‐GTPase pathways in cochlear outer hair cells (OHCs), resulting in cell death and noise‐induced hearing loss (NIHL). In this study, we investigated Rho effectors, Rho‐associated kinases (ROCKs), and the targets of ROCKs, the ezrin‐radixin‐moesin (ERM) proteins, in the regulation of the cochlear actin cytoskeleton using adult CBA/J mice under conditions of noise‐induced temporary threshold shift (TTS) and permanent threshold shift (PTS) hearing loss, which result in changes to the F/G‐actin ratio. The levels of cochlear ROCK2 and p‐ERM decreased 1 h after either TTS‐ or PTS‐noise exposure. In contrast, ROCK2 and p‐ERM in OHCs decreased only after PTS‐, not after TTS‐noise exposure. Treatment with lysophosphatidic acid, an activator of the Rho pathway, resulted in significant reversal of the F/G‐actin ratio changes caused by noise exposure and attenuated OHC death and NIHL. Conversely, the down‐regulation of ROCK2 by pretreatment with ROCK2 siRNA reduced the expression of ROCK2 and p‐ERM in OHCs, exacerbated TTS to PTS, and worsened OHC loss. Additionally, pretreatment with siRNA against radixin, an ERM protein, aggravated TTS to PTS. Our results indicate that a ROCK2‐mediated ERM‐phosphorylation signaling cascade modulates noise‐induced hair cell loss and NIHL by targeting the cytoskeleton.

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We propose the following cascade following noise trauma leading to alteration of the F‐actin arrangement in the outer hair cell cytoskeleton: Noise exposure reduces the levels of GTP‐RhoA and subsequently diminishes levels of RhoA effector ROCK2 (Rho‐associated kinase 2). Phosphorylation of ezrin‐radixin‐moesin (ERM) by ROCK2 normally allows ERM to cross‐link actin filaments with the plasma membrane. Noise‐decreased levels of ROCK results in reduction of phosphorylation of ERM that leads to depolymerization of actin filaments. Lysophosphatidic acid (LPA), an agonist of RhoA, binds to the G‐protein‐coupled receptor (GPCR) leading to activation of RhoA through Gα12/13 and RhoGEF. Administration of LPA rescues the noise‐diminished F/G‐actin ratio.
Neuroprotective role of Nrf2 for retinal ganglion cells in ischemia‐reperfusion
Authors: Xu Zhenhua , Cho Hongkwan , Hartsock Matthew J. , Mitchell Katherine L. , Gong Junsong , Wu Lijuan , Wei Yanhong , Wang Shuang , Thimmulappa Rajesh K. , Sporn Michael B. , Biswal Shyam , Welsbie Derek S. , Duh Elia J.
Published: February 2015

Retinal ischemia plays a critical role in multiple vision‐threatening diseases and leads to death of retinal neurons, particularly ganglion cells. Oxidative stress plays an important role in this ganglion cell loss. Nrf2 (NF‐E2‐related factor 2) is a major regulator of the antioxidant response, and its role in the retina is increasingly appreciated. We investigated the potential retinal neuroprotective function of Nrf2 after ischemia‐reperfusion (I/R) injury. In an experimental model of retinal I/R, Nrf2 knockout mice exhibited much greater loss of neuronal cells in the ganglion cell layer than wild‐type mice. Primary retinal ganglion cells isolated from Nrf2 knockout mice exhibited decreased cell viability compared to wild‐type retinal ganglion cells, demonstrating the cell‐intrinsic protective role of Nrf2. The retinal neuronal cell line 661W exhibited reduced cell viability following siRNA‐mediated knockdown of Nrf2 under conditions of oxidative stress, and this was associated with exacerbation of increase in reactive oxygen species. The synthetic triterpenoid CDDO‐Im (2‐Cyano‐3,12‐dioxooleana‐1,9‐dien‐28‐imidazolide), a potent Nrf2 activator, inhibited reactive oxygen species increase in cultured 661W under oxidative stress conditions and increased neuronal cell survival after I/R injury in wild‐type, but not Nrf2 knockout mice. Our findings indicate that Nrf2 exhibits a retinal neuroprotective function in I/R and suggest that pharmacologic activation of Nrf2 could be a therapeutic strategy.

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Oxidative stress is thought to be an important mediator of retinal ganglion cell death in ischemia‐reperfusion injury. We found that the transcription factor NF‐E2‐related factor 2 (Nrf2), a major regulator of oxidative stress, is an important endogenous neuroprotective molecule in retinal ganglion cells in ischemia‐reperfusion, exerting a cell‐autonomous protective effect.  The triterpenoid 2‐Cyano‐3,12‐dioxooleana‐1,9‐dien‐28‐imidazolide (CDDO‐Im) reduces neurodegeneration following ischemia‐reperfusion in an Nrf2‐dependent fashion. This suggests that Nrf2‐activating drugs including triterpenoids could be a therapeutic strategy for retinal neuroprotection.
Inverted formin 2‐related Charcot‐Marie‐Tooth disease: extension of the mutational spectrum and pathological findings in Schwann cells and axons
Authors: Roos Andreas , Weis Joachim , Korinthenberg Rudolf , Fehrenbach Henry , Häusler Martin , Züchner Stephan , Mache Christoph , Hubmann Holger , Auer‐Grumbach Michaela , Senderek Jan
Published: February 2015

Abstract

Mutations in the gene encoding inverted formin FH2 and WH2 domain‐containing protein (INF2), a Cdc42 effector involved in the regulation of actin dynamics, cause focal segmental glomerulosclerosis (FSGS) and intermediate Charcot‐Marie‐Tooth neuropathy combined with FSGS (FSGS–CMT). Here, we report on six patients from four families with sensorimotor polyneuropathy and FSGS. Nerve conduction velocities were moderately slowed, and amplitudes of sensory and motor potentials were decreased. One patient had internal hydrocephalus and was intellectually disabled. Molecular genetic testing revealed two known and two novel missense mutations in the second and fourth exons of the INF2 gene. Investigations of one nerve biopsy confirmed the diagnosis of intermediate‐type CMT and revealed occasional abnormal in‐ and outfoldings of myelin sheaths and expansions of the endoplasmic reticulum in axons and Schwann cells. While earlier reports suggested that mutations causing FSGS‐CMT are restricted to exons 2 and 3 of the INF2 gene, we found one CMT‐FSGS causing mutation (p.Glu184Lys) in exon 4 extending the critical region of INF2 for rapid CMT‐FSGS molecular genetic diagnosis. Study of a nerve biopsy showed abnormalities that might be related to the known role of the INF2‐binding partner CDC42 in myelination.
Crimp morphology in the ovine anterior cruciate ligament
Authors: Zhao Lei , Thambyah Ashvin , Broom Neil
Published: February 2015

While the crimp morphology in ligaments and tendons has been described in detail in the literature, its relative distribution within the tissue has not been studied, especially in relation to the complex multi‐bundle arrangement as is found in the anterior cruciate ligament (ACL). In this study, the crimp morphology of the ovine ACL was examined topologically and with respect to its double‐bundle structure. The crimp morphologies were compared with the knee in three knee positions, namely stance, maximum extension and maximum flexion. As a control, the crimp morphology of the ACL free from its bony attachments was determined. In the control samples, the anterior‐medial (AM) bundle contained a combination of coarse and fine crimp, whereas the posterior‐lateral (PL) bundle manifested only a coarse crimp. Using the extent of crimp loss observed when subjecting the knee to the respective positions, and comparing with the controls, the crimp morphologies show that the AM bundle of the ACL is most active in the stance position, whereas for the maximum extension and flexion positions the PL bundle is most active. We propose that these differences in crimp morphologies have relevance to ACL design and function.
Long bone histology of the stem salamander Kokartus honorarius (Amphibia: Caudata) from the Middle Jurassic of Kyrgyzstan
Authors: Skutschas Pavel , Stein Koen
Published: February 2015

Kokartus honorarius from the Middle Jurassic (Bathonian) of Kyrgyzstan is one of the oldest salamanders in the fossil record, characterized by a mixture of plesiomorphic morphological features and characters shared with crown‐group salamanders. Here we present a detailed histological analysis of its long bones. The analysis of a growth series demonstrates a significant histological maturation during ontogeny, expressed by the progressive appearance of longitudinally oriented primary vascular canals, primary osteons, growth marks, remodelling features in primary bone tissues, as well as progressive resorption of the calcified cartilage, formation of endochondral bone and development of cartilaginous to bony trabeculae in the epiphyses. Apart from the presence of secondary osteons, the long bone histology of Kokartus is very similar to that of miniaturized temnospondyls, other Jurassic stem salamanders, miniaturized seymouriamorphs and modern crown‐group salamanders. We propose that the presence of secondary osteons in Kokartus honorarius is a plesiomorphic feature, and the loss of secondary osteons in the long bones of crown‐group salamanders as well as in those of miniaturized temnospondyls is the result of miniaturization processes. Hitherto, all stem salamander long bong histology (Kokartus, Marmorerpeton and ‘salamander A’) has been generally described as having paedomorphic features (i.e. the presence of Katschenko's Line and a layer of calcified cartilage), these taxa were thus most likely neotenic forms. The absence of clear lines of arrested growth and annuli in long bones of Kokartus honorarius suggests that the animals lived in an environment with stable local conditions.
Use of EchoNavigator, a Novel Echocardiography‐Fluoroscopy Overlay System, for Transseptal Puncture and Left Atrial Appendage Occlusion
Authors: GAFOOR SAMEER , SCHULZ PHILIPP , HEUER LUISA , MATIC PREDRAG , FRANKE JENNIFER , BERTOG STEFAN , REINARTZ MARKUS , VASKELYTE LAURA , HOFMANN ILONA , SIEVERT HORST
Published: February 2015

Structural heart disease requires a coordinated effort to join echocardiographic and fluoroscopic data. Various methods have been used, including echocardiography, CT, and MRI. We report on the use of EchoNavigator (Philips Inc., Amsterdam, Netherlands), a novel echocardiographic‐fluoroscopic fusion system. This new system allows real‐time integration and marking of important structures that track on fluoroscopy even with movement of the C‐arm. In this article, we describe potential uses for this system in respect to transseptal puncture and left atrial appendage closure.
The Dark Side of Leadership: Towards a Mid‐Range Theory of Hubris and Greed in Entrepreneurial Contexts
Authors: Haynes Katalin Takacs , Hitt Michael A. , Campbell Joanna Tochman
Published: February 2015

Much of the research on entrepreneurial behaviour and leadership has emphasized their importance and potentially valuable outcomes, along with the challenges involved in each. Although entrepreneurial activities are essential in all types of organizations, this research focuses on the potential dark side of strategic leaders. Specifically, we examine the potential for and the outcomes of the display of greed and hubris in different entrepreneurial contexts. We present a theoretical model of moderated mediation, focused on the effects of greedy and hubristic behaviour by entrepreneurial leaders on the firm's human and social capital, and consequently venture success. However, the negative relationship manifests differently in the presence of certain firm‐level characteristics. We examine the implications of the dark side of entrepreneurial leadership and recommend several avenues for future research. In so doing, this work contributes to the development of a mid‐range theory of the dark side of entrepreneurial leadership.
Data‐analytic strategies for examining the effectiveness of daily interventions
Authors: Lischetzke Tanja , Reis Dorota , Arndt Charlotte
Published: February 2015

Interest in the use of ecological momentary interventions – that is, interventions that are implemented in participants' everyday lives – to change experiences and behaviours has grown rapidly in recent years. In particular, EMIs in which the intervention is delivered on a daily basis (daily interventions) can be easily combined with daily diary studies to analyse intervention effects on dependent variables (DVs) that fluctuate over time. This article first provides a typology of research designs to classify daily intervention studies according to (1) the type of assessment of the DV (global assessment on a small number of fixed occasions, daily assessment, and repeated assessment within days) and (2) the type of control (within‐subjects vs. between‐subjects designs) used in the studies. We then demonstrate how multilevel models can be used to examine the effects of a daily intervention on the mean levels of the DV. We differentiate between general effectiveness, differential effectiveness, and conditional effectiveness and show how these effects are represented in the models. As an illustration, we apply some of the models to data from a daily intervention workplace study (N = 51 full‐time employees) that focused on the effects of savouring exercises on calm mood and vigour.

Practitioner points

In work and organizational psychology, a recent trend in intervention study designs is to implement an intervention on a daily basis and incorporate a daily diary assessment approach.

To examine intervention effectiveness in pre‐/post‐designs, multilevel models are the method of choice because they circumvent the shortcomings of ANOVA approaches.

In intervention studies with daily assessments, multilevel models can be applied to examine the intervention's general effectiveness and differential effectiveness (i.e., Who benefits more from the intervention?).

Daily intervention studies with repeated assessments within days allow researchers to examine conditional effectiveness (i.e., On which days is the intervention more effective?).
Lacosamide as adjunctive therapy in treatment‐resistant epilepsy in childhood
Authors: Gulati Pratima , Cannell Patricia , Ghia Twinkle , Bint Lewis , Walsh Peter , Ghosh Soumya , Nagarajan Lakshmi
Published: February 2015

Aims

Lacosamide (LCM) is a novel anti‐epileptic drug (AED) that enhances the slow inactivation of voltage‐gated sodium channels. Its efficacy as adjunctive therapy for focal seizures is confirmed in adult placebo controlled trials with >50% reduction in seizure frequency in up to 50% patients. There is paucity of data on its efficacy and tolerance in treatment‐resistant epilepsy in childhood (TREC). This study aims to assess efficacy and tolerance of LCM as adjunct therapy in TREC.

Methods

Audit of medical records and seizure diaries in children with TREC on LCM. A response (RR) was defined as ≥50% reduction in seizure frequency.

Results

Forty children (age range: 2–19 years) with TREC received LCM as add‐on therapy. All had abnormal electroencephalograms, and 36 had abnormal neuroimaging. All children failed >2 AED trials, nine had trialled the ketogenic diet, five had failed the vagal nerve stimulator and 11 had failed resective epilepsy surgery. Median dose and duration of LCM therapy were 5.7 mg/kg/day and 10.5 months, respectively. RR was seen in 20% with persistence of RR in 8/36, 8/30 and 8/26 children on LCM at 3‐, 6‐ and 9‐month follow‐up. Two children became seizure free. Retention on LCM was 65% at 9 months. LCM was well tolerated with minor side effects in seven children; no child discontinued LCM because of side effects.

Conclusion

LCM is a well‐tolerated AED with RR in 20%: in 5%, it resulted in seizure freedom. LCM may be useful even in TREC when seizures have not responded to intervention with multiple modalities.
Correlating liposomal adjuvant characteristics to in-vivo cell-mediated immunity using a novel M
ycobacterium tuberculosis fusion protein: a multivariate analysis study
Authors: Kastner Elisabeth , Hussain M Jubair , Bramwell Vincent W , Christensen Dennis , Perrie Yvonne
Published: February 2015

Objective

In this study, we have used a chemometrics-based method to correlate key liposomal adjuvant attributes with in-vivo immune responses based on multivariate analysis.

Methods

The liposomal adjuvant composed of the cationic lipid dimethyldioctadecylammonium bromide (DDA) and trehalose 6,6-dibehenate (TDB) was modified with 1,2-distearoyl-sn-glycero-3-phosphocholine at a range of mol% ratios, and the main liposomal characteristics (liposome size and zeta potential) was measured along with their immunological performance as an adjuvant for the novel, postexposure fusion tuberculosis vaccine, Ag85B–ESAT-6-Rv2660c (H56 vaccine). Partial least square regression analysis was applied to correlate and cluster liposomal adjuvants particle characteristics with in-vivo derived immunological performances (IgG, IgG1, IgG2b, spleen proliferation, IL-2, IL-5, IL-6, IL-10, IFN-γ).

Key findings

While a range of factors varied in the formulations, decreasing the 1,2-distearoyl-sn-glycero-3-phosphocholine content (and subsequent zeta potential) together built the strongest variables in the model. Enhanced DDA and TDB content (and subsequent zeta potential) stimulated a response skewed towards a cell mediated immunity, with the model identifying correlations with IFN-γ, IL-2 and IL-6.

Conclusion

This study demonstrates the application of chemometrics-based correlations and clustering, which can inform liposomal adjuvant design.
Magnetic resonance imaging of the lentiform nuclei in dogs with portosystemic shunts
Authors: Mortera‐Balsa V. , Penderis J. , Wessmann A. , Gonçalves R. , Lowrie M. , Gutierrez‐Quintana R.
Published: February 2015

OBJECTIVES

To develop and evaluate a method to quantify the T1‐weighted magnetic resonance imaging signal intensity of the lentiform nuclei in dogs, and to determine if there is any significant difference in this signal intensity between dogs with portosystemic shunts and a control group.

MATERIALS AND METHODS

A retrospective blinded study was performed to investigate the reliability and use of a quantitative method for assessing the T1‐weighted magnetic resonance imaging signal intensity of the lentiform nuclei in dogs with and without portosystemic shunts. The lentiform nuclei index (mean lentiform nucleus signal intensity/mean white matter signal intensity) was calculated for nine dogs with portosystemic shunts and a control group of 14 dogs.

RESULTS

The intra‐ and inter‐observer intraclass correlation coefficients were considered excellent (>0 · 75), suggesting that the lentiform nuclei index is a reliable method. The dogs with portosystemic shunts had a higher lentiform nuclei index than the control group (P = 0 · 0127).

CLINICAL SIGNIFICANCE

This method of quantifying the T1‐weighted magnetic resonance imaging signal intensity of the lentiform nuclei was reliable and showed that dogs with portosystemic shunts tend to have increased signal intensity. Further prospective studies are necessary to investigate the clinical significance and applications of these findings.
A Comprehensive Review of Metabolic Syndrome Affecting Erectile Dysfunction
Authors: Kaya Ecem , Sikka Suresh C. , Gur Serap
Published: February 2015

Introduction

Metabolic syndrome (MetS) is the most important public health issue threatening the health of men and women all over the world. Its current prevalence (i.e., approximately 30%) is continuously increasing. MetS by itself is considered a risk factor for erectile dysfunction (ED).

Aim

To focus on the definition epidemiology, pathogenesis, and possible mechanistic links between MetS and ED in order to provide guidelines for treating such individuals.

Methods

The search strategies yielded total records screened from PubMed.

Main Outcome Measures

Regardless of the definition, MetS consists of insulin resistance, hypertension, dyslipidemia, and obesity. MetS is not an end disease but is a disorder of energy utilization and storage.

Results

The prevalence of ED in patients with MetS is almost twice than in those without MetS, and about 40% of patients with ED have MetS. An important mechanism linking MetS and ED is hypogonadism.

Conclusions

Recognizing through ED, underlying conditions such as hypogonadism, diabetes and MetS might be a useful motivation for men to improve their health-related choices. The clinical management of MetS can be done by therapeutic interventions that include lifestyle modifications, hormone replacement alone or in combination with phosphodiesterase 5 inhibitors, and other pharmacological treatments.
Trait Sexual Motivation Questionnaire: Concept and Validation
Authors: Stark Rudolf , Kagerer Sabine , Walter Bertram , Vaitl Dieter , Klucken Tim , Wehrum-Osinsky Sina
Published: February 2015

Introduction

Trait sexual motivation defines a psychological construct that reflects the long-lasting degree of motivation for sexual activities, which is assumed to be the result of biological and sociocultural influences. With this definition, it shares commonalities with other sexuality-related constructs like sexual desire, sexual drive, sexual needs, and sexual compulsivity.

Aim

The Trait Sexual Motivation Questionnaire (TSMQ) was developed in order to measure trait sexual motivation with its different facets.

Methods

Several steps were conducted: First, items were composed assessing sexual desire, the effort made to gain sex, as well as specific sexual behaviors. Factor analysis of the data of a first sample (n = 256) was conducted. Second, the factor solution was verified by a confirmatory factor analysis in a second sample (n = 498) and construct validity was demonstrated. Third, the temporal stability of the TSMQ was tested in a third study (n = 59).

Main Outcome Measure

Questionnaire data.

Results

The exploratory and confirmatory factor analyses revealed that trait sexual motivation is best characterized by four subscales: Solitary Sexuality, Importance of Sex, Seeking Sexual Encounters, and Comparison with Others. It could be shown that the test quality of the questionnaire is high. Most importantly for the trait concept, the retest reliability after 1 year was r = 0.87.

Conclusion

Our results indicate that the TSMQ is indeed a suitable tool for measuring long-lasting sexual motivation with high test quality and high construct validity. A future differentiation between trait and state sexual motivation might be helpful for clinical as well as forensic research.