bluuebunny/crossref_metadata_2025 huggingface dataset:
Dopamine transporter imaging is associated with long‐term outcomes in Parkinson's disease
Authors: Ravina Bernard , Marek Kenneth , Eberly Shirley , Oakes David , Kurlan Roger , Ascherio Alberto , Beal Flint , Beck James , Flagg Emily , Galpern Wendy R. , Harman Jennifer , Lang Anthony E. , Schwarzschild Michael , Tanner Caroline , Shoulson Ira
Published: September 2012

Dopamine (DA) transporter (DAT) imaging has been studied as a diagnostic tool for degenerative parkinsonism. Our aim was to measure the prognostic value of imaging for motor and nonmotor outcomes in Parkinson's disease (PD). We prospectively evaluated a Parkinson's cohort after enrollment in a de novo clinical trial with a battery of motor (UPDRS), cognitive (Montreal Cognitive Assessment), and behavioral measures. DAT imaging with [123I][β]‐CIT and single‐photon emission computerized tomography (SPECT) was performed at baseline and after 22 months. In total, 491 (91%) of the 537 subjects had evidence of DA deficiency on their baseline scan, consistent with PD, and were included in the analyses. The cohort was followed for 5.5 (0.8) years, with a mean duration of diagnosis of 6.3 (1.2). Lower striatal binding at baseline was independently associated with higher risk for clinical milestones and measures of disease severity, including motor‐related disability, falling and postural instability, cognitive impairment, psychosis, and clinically important depressive symptoms. Subjects in the bottom quartile for striatal binding, compared to the top quartile, had an odds ratio (95% confidence interval) of 3.3 (1.7, 6.7) for cognitive impairment and 12.9 (2.6, 62.4) for psychosis. Change from baseline in imaging after 22 months was also independently associated with motor, cognitive, and behavioral outcomes. DAT imaging with [123I][β]‐CIT and SPECT, shortly after the diagnosis of PD, was independently associated with clinically important long‐term motor and nonmotor outcomes. These results should be treated as hypothesis generating and require confirmation. © 2012 Movement Disorder Society
Evaluation of a porcine whole‐limb heterotopic autotransplantation model
Authors: Kiermeir David Manuel , Meoli Martino , Müller Sabine , Abderhalden Susanne , Vögelin Esther , Constantinescu Mihai Adrian
Published: September 2012

Background:

Recently performed vascularized composite tissue allotransplantations (CTAs) stimulate the ongoing research in the area of whole‐limb transplantation. A reliable in vivo animal model is required for investigations in vascularized whole‐limb CTA. The model should allow in vivo assessment in whole‐limb preservation, allograft and xenograft response, and host immunomodulation. The goal of this study is to describe and evaluate the in vivo feasibility and reproducibility of a whole‐limb porcine model as a basis for future research in this field.

Materials and methods:

In seven large white pigs, one forelimb was amputated under anesthesia and autotransplanted heterotopically with an arc of rotation of 180° and partially placed in a subcutaneous pocket. Clinical parameters were monitored and muscle biopsies were analyzed using ultrastructural morphological assessment of mitochondria quality after an observation period of 7 days.

Results:

All animals could fully mobilize postoperatively without restrictions. At sacrifice, the anastomosed pedicle vessels of the limb were patent in six animals. In one pig, venous thrombosis could be observed. Muscle response was triggered following direct electrostimulation in six replanted limbs. The replanted extremities gained 12.97% weight within 7 days postreplantation compared with the amputation baseline values (P = 0.464 while maintaining normal compartment pressures at sacrifice (8.25 ± 5.31 cmH2O, P = 0.60). The ultrastructural evaluation of mitochondria morphology revealed intact mitochondria without signs of ischemia/reperfusion damage.

Conclusion:

This porcine model proved feasible, reliable, and reproducible for whole‐limb autotransplantation. It presents significant potential in future preclinical research of whole‐limb CTA transplantation. © 2012 Wiley Periodicals, Inc., Microsurgery, 2013.
An a priori error estimate for the finite element modelling of electromagnetic waves interacting with a periodic diffraction grating
Authors: Lord N.H. , Mulholland A.J.
Published: September 2012

An a priori error estimate using a so called α,β‐ periodic transformation to study electromagnetic waves in a periodic diffraction grating is derived. It has been reported for single scattering that there is an instability in numerical methods for high wavenumbers. To address this problem, the analytical solution of the scattering problem when the domain is scatterer free and an unknown function called the α,β‐quasi periodic solution are used to transform the associated Helmholtz problem. The well‐posedness of the resulting continuous problem is analysed before approximating its solution using a finite element discretization. To guarantee the uniqueness of this approximate solution, an a priori error estimate is derived. Finally, numerical results are presented that suggest that the α,β‐quasi periodic method converges at a far lower number of degrees of freedom than the α,0‐quasi periodic method reported previously; especially for high wavenumbers. This is particularly true when the incident wave only undergoes a small perturbation because of the presence of the scatterer. Copyright © 2012 John Wiley & Sons, Ltd.
Validation of questionnaire‐based long‐term dietary exposure to polychlorinated biphenyls using biomarkers
Authors: Bergkvist Charlotte , Åkesson Agneta , Glynn Anders , Michaëlsson Karl , Rantakokko Panu , Kiviranta Hannu , Wolk Alicja , Berglund Marika
Published: September 2012

Scope

The health consequences of lifelong low‐level exposure to polychlorinated biphenyls (PCBs) via food are largely unknown, mainly due to the lack of large population‐based prospective studies addressing this issue. We validated long‐term food frequency questionnaire (FFQ)‐based dietary PCB exposure against concentrations of six PCB congeners in serum.

Methods and results

Dietary PCB exposure was estimated in the Swedish Mammography Cohort by constructing a recipe‐based database of CB‐153, an indicator for total PCBs in food. The Spearman rank correlation (adjusted for within‐person variability) was assessed between concurrent (2004–2006), past (1997), and long‐term (mean of 1997 and 2004–2006) FFQ‐based dietary PCB exposure, respectively, and the following serum PCB congeners, CB‐118, CB‐138, CB‐153, CB‐156, CB‐170, and CB‐180, in women (56–85 years of age, n = 201). The correlation between FFQ‐based dietary PCB exposure and serum CB‐153 was 0.41 (p < 0.001) for the concurrent (median 1.6 ng/kg body weight) and 0.34 (p < 0.05) for the past (median 2.6 ng/kg body weight) exposure assessment. Long‐term validity of FFQ‐based PCB estimates and the six serum PCB congeners ranged from 0.30 to 0.58 (p < 0.05).

Conclusion

FFQ‐based PCB exposure estimates show acceptable validity in relation to PCB concentrations in serum, justifying their use in large‐scale epidemiological studies.
Gender Disparities in Health Care
Authors: Kent Jennifer A. , Patel Vinisha , Varela Natalie A.
Published: September 2012

The existence of disparities in delivery of health care has been the subject of increased empirical study in recent years. Some studies have suggested that disparities between men and women exist in the diagnoses and treatment of health conditions, and as a result measures have been taken to identify these differences. This article uses several examples to illustrate health care gender bias in medicine. These examples include surgery, peripheral artery disease, cardiovascular disease, critical care, and cardiovascular risk factors. Additionally, we discuss reasons why these issues still occur, trends in health care that may address these issues, and the need for acknowledgement of the current system's inequities in order to provide unbiased care for women in the future. Mt Sinai J Med 79:555–559, 2012. © 2012 Mount Sinai School of Medicine
Meyerhoff Scholars Program: A Strengths‐Based, Institution‐Wide Approach to Increasing Diversity in Science, Technology, Engineering, and Mathematics
Authors: Maton Kenneth I. , Pollard Shauna A. , McDougall Weise Tatiana V. , Hrabowski Freeman A.
Published: September 2012

The Meyerhoff Scholars Program at the University of Maryland, Baltimore County is widely viewed as a national model of a program that enhances the number of underrepresented minority students who pursue science, technology, engineering, and mathematics PhDs. The current article provides an overview of the program and the institution‐wide change process that led to its development, as well as a summary of key outcome and process evaluation research findings. African American Meyerhoff students are 5× more likely than comparison students to pursue a science, technology, engineering, and mathematics PhD. Program components viewed by the students as most beneficial include financial scholarship, being a part of the Meyerhoff Program community, the Summer Bridge program, study groups, and summer research. Qualitative findings from interviews and focus groups demonstrate the importance of the Meyerhoff Program in creating a sense of belonging and a shared identity, encouraging professional development, and emphasizing the importance of academic skills. Among Meyerhoff students, several precollege and college factors have emerged as predictors of successful entrance into a PhD program in the science, technology, engineering, and mathematics fields, including precollege research excitement, precollege intrinsic math/science motivation, number of summer research experiences during college, and college grade point average. Limitations of the research to date are noted, and directions for future research are proposed. Mt Sinai J Med 79:610–623, 2012 © 2012 Mount Sinai School of Medicine
A theoretical and experimental comparison of different techniques for B1 mapping at very high fields
Authors: Pohmann Rolf , Scheffler Klaus
Published: September 2012

With the increasing use of ultrahigh‐field MR with multiple transmit channels, mapping of the B1+ field has become a critical factor in many studies, leading to the publication of a large number of sequences for the measurement of the flip angle in recent years. In this article, the accuracy, precision and practicability of some of the most prominent of these techniques are investigated both theoretically, using error propagation computations and Monte‐Carlo simulations, and experimentally for different settings. For an exemplary experiment, which is typical for high‐field applications, the flip angle uncertainty is calculated and measured for two‐ and three‐dimensional acquisitions for techniques based on both magnitude and phase data. Simulated and measured results show good agreement. An experimental assessment of T1 and B0 dependence yields weak variations with these parameters for only a few of the sequences. Measurements on human scanners show crucial influences of specific absorption rate limitations, especially at ultrahigh field. Copyright © 2012 John Wiley & Sons, Ltd.
Fraction of unsaturated fatty acids in visceral adipose tissue (VAT) is lower in subjects with high total VAT volume – a combined 1H MRS and volumetric MRI study in male subjects
Authors: Machann Jürgen , Stefan Norbert , Schabel Christoph , Schleicher Erwin , Fritsche Andreas , Würslin Christian , Häring Hans‐Ulrich , Claussen Claus D. , Schick Fritz
Published: September 2012

Visceral adipose tissue (VAT) is thought to play an important role in the pathogenesis of obesity and insulin resistance. However, little is known about the composition of VAT with regard to the amount of mono‐ (MUFAs) and polyunsaturated fatty acids (PUFAs) in triglycerides. Volume‐selective MRS was performed in addition to MRI for the quantification of VAT. Analysis comprised proton signals from the vinyl‐H group (H–C = C–H), including protons from MUFA + PUFA, and diallylic‐H, i.e. methylene‐interrupted PUFAs. The methyl (−CH3) resonance, which is the only peak with a defined number of protons/triglyceride (n = 9), served as reference.

Twenty male subjects participated in this prospective study and underwent MRS of VAT on a 3‐T whole‐body unit. Spectra were recorded by a single‐voxel stimulated echo acquisition mode (STEAM) technique (TE/TM/TR = 20/10/4000 ms; volume of interest between 20 × 25 × 20 and 30 × 30 × 20 mm³; 48–80 acquisitions depending on the size of the volume of interest; bandwidth, 1200 Hz). Post‐processing was performed by a Java‐based magnetic resonance user interface (jMRUI; AMARES). The volume of VAT was quantified in a separate session on a 1.5‐T imager a few days prior to the MRS session by T1‐weighted imaging. The relative amount of VAT was calculated as a percentage of body weight (%VAT). Ratios of vinyl‐H to –CH3 and diallylic‐H to –CH3 were calculated.

All spectra recorded from VAT were of high quality, enabling reliable quantification of the mentioned resonances. %VAT and vinyl‐H/CH3 varied over a broad range (2.8–8.3% and 0.45–0.64, respectively). A strong negative correlation between %VAT and vinyl‐H/CH3 was found (r = −0.92), whereas diallylic‐H/CH3 alone was clearly less well correlated with %VAT (r = −0.21).

The composition of VAT shows strong interindividual variations. The greater the total amount of VAT, the less unsaturated the fatty acids. This is a preliminary result in mainly obese male subjects, and it remains to be determined whether this correlation holds for other cohorts of different age, gender and body mass index. Furthermore, changes in VAT composition during weight loss or different forms of diet have yet to be examined. Copyright © 2012 John Wiley & Sons, Ltd.
Understanding the decision‐making processes for arts sponsorship
Authors: Daellenbach Kate
Published: September 2012

Corporate support is a significant revenue stream for non‐profit organisations, yet little is known of the actual decision paths companies take when making these decisions and what characterises these paths. This study seeks to develop a greater understanding of decision processes for companies considering sponsorship of the arts. A multiple‐case study approach was taken, with participants from arts organisations and paired sponsoring companies, resulting in the finding of three decision paths: one characterised as high‐level and intuitive, one as driven at a lower‐level, and a third initially instigated by a third party. Analysis of these paths highlights the importance of existing relationships as well as a ‘fit’ between both parties. In addition, the company's orientation towards more commercial or philanthropic goals is found to be a key element determining the path taken, and the role of individual informed intuition is highlighted as crucial in moving decisions forward. This study extends knowledge in sponsorship and corporate philanthropy, into a decision making and arts sponsorship context. The findings also offer a useful perspective for non‐profit arts managers as they pitch their event to the business sector.

Copyright © 2012 John Wiley & Sons, Ltd.
Cytomegalovirus retinitis as an adverse immunological effect of pulses of vincristine and dexamethasone in maintenance therapy for childhood acute lymphoblastic leukemia
Authors: Moritake Hiroshi , Kamimura Sachiyo , Kojima Hitomi , Shimonodan Hidemi , Harada Masako , Sugimoto Takako , Nao‐i Nobuhisa , Nunoi Hiroyuki
Published: September 2012

We describe a 5‐year‐old female with acute lymphoblastic leukemia (ALL) who suffered from cytomegalovirus (CMV) retinitis during maintenance therapy consisting of 6‐mercaptopurine (6‐MP) and methotrexate (MTX) with pulses of vincristine (VCR) and dexamethasone (DEX). Administration of anticytomegaloviral drugs led to a complete regression of active retinitis. Her low CD4 positive T cells and serum immunoglobulin G (IgG) recovered when maintenance therapy was resumed without VCR and DEX. The patient has been in complete remission (CR) for more than 5 months after completion of maintenance therapy without recurrence of CMV retinitis. Pediatr Blood Cancer 2013;60:329–331. © 2012 Wiley Periodicals, Inc.
Seizure freedom is not adversely affected by early discontinuation of concomitant anti‐epileptic drugs in the EULEV cohort of levetiracetam users
Authors: Droz‐Perroteau Cécile , Marchal Cécile , Dureau‐Pournin Caroline , Lassalle Régis , Jové Jérémy , Robinson Philip , Lavernhe Gilles , Vespignani Hervé , Moore Nicholas , Fourrier‐Réglat Annie ,   on behalf of the Eulev Study group
Published: September 2012

Purpose

Fear of discontinuing concomitant anti‐epileptic drugs (AEDs) may lead to potentially unnecessary and perhaps unsafe polypharmacy. The effect of withdrawing concomitant AEDs on epilepsy control was therefore studied in long‐term users of levetiracetam.

Methods

The EULEV cohort followed patients initiating levetiracetam in France in 2005 or 2006 for one year. In those maintaining levetiracetam throughout the study period, the association of a reduction in the number of concomitant AEDs during the first six months with seizure‐freedom during the last six months of follow‐up was investigated using logistic regression.

Results

Of the 356 patients continuing levetiracetam for at least 1 year, 140 (39.3%) were seizure‐free during the last six months of follow‐up. Partial symptomatic or generalised idiopathic epilepsy were associated with greater seizure‐freedom than partial cryptogenic disease. Factors associated with seizures were: longer disease duration, initial incapacity, increased number of seizures in the six months preceding levetiracetam initiation, and number of consultations for epilepsy in the six months preceding levetiracetam initiation. There was a trend for the association between the early reduction in the number of concomitant AEDs and seizure‐free status later during follow‐up, which however did not reach statistical significance in the final propensity score‐adjusted multivariate model (OR = 1.8, 95%CI [0.8;4.0]).

Conclusions

Taking into account the various risk factors for seizures, the early reduction of concomitant AEDs was not associated with worse seizure rates during follow‐up in real‐life users of levetiracetam. Copyright © 2012 John Wiley & Sons, Ltd.
Prostate epithelial AR inactivation leads to increased intraprostatic androgen synthesis
Authors: McNamara Keely M. , Nakamura Yasuhiro , Sasano Hironobu , Handelsman David J. , Simanainen Ulla
Published: September 2012

BACKGROUND

Regulation of steroid synthesis within the prostate is not well understood. In this study, we examined androgen synthesis and metabolism in the mouse prostate.

METHODS

Using LC–MSMS steroid assays, immunohistochemistry and real‐time PCR we examined the role of prostate epithelial AR in regulating 5αR expression and subsequent androgen metabolism by analyzing natural differences in epithelial AR expression between lobes as well as in the prostate epithelial AR knockout (PEARKO) mouse model. Subsequently, the role of intraprostatic androgen metabolism and epithelial AR in the generation and progression of prostate epithelial pathology was examined using long‐term exogenous testosterone (T) + estradiol (E2) exposure.

RESULTS

Epithelial AR and 5αR2 expression as well as intraprostatic DHT followed the same lobe‐specific pattern being lower in anterior than the other lobes (n = 6–8, P < 0.05). Lobe‐specific 5αR2 expression was similar in PEARKO and wild‐type (WT) prostate. However, PEARKO prostate had higher intraprostatic DHT content with significantly increased 5αR2 expression localized in abnormal epithelium. T + E2 treatment induced epithelial pathology was more common in PEARKO prostate compared to WT (20% vs. 2%), and was associated with increased 5αR2 expression (n = 6, P < 0.001).

CONCLUSIONS

We suggest that androgen synthesis via 5αR2 expression is driven by its own product (DHT) acting on adjacent stromal cells in a paracrine loop leading to increased in situ androgen levels in the PEARKO prostate. This may form part of a feed‐forward loop that promotes the development of epithelial pathology. Prostate 73: 316–327, 2013. © 2012 Wiley Periodicals, Inc.
Studies on Prokinetic, Laxative and Spasmodic Activities ofPhyllanthus emblicain Experimental Animals
Authors: Mehmood Malik Hassan , Rehman Abdul , Rehman Najeeb‐ur , Gilani Anwarul‐Hassan
Published: September 2012

This study was aimed to provide pharmacological basis for the medicinal use ofPhyllanthus emblicafruit in indigestion and constipation using thein‐vivoandin‐vitroassays. The crude extract of the dried fruits ofPhyllanthus emblica(Pe.Cr) and its fractions were tested positive for alkaloids, saponins, tannins, terpenes, flavonoids, sterols and coumarins. Pe.Cr at the doses of 100 and 300 mg/kg exhibited the prokinetic and laxative activities in mice, which were found partially sensitive to atropine. In isolated guinea‐pig ileum and rabbit jejunum, the crude extract and its aqueous fraction (Pe.Aq) caused concentration‐dependent and partially atropine‐sensitive stimulatory effects followed by relaxation at higher tested concentrations, being more efficacious in guinea pig, while more potent in rabbit tissues. The petroleum fraction (0.003–0.1 mg/mL) exhibited fully atropine‐sensitive contractions in both guinea‐pig and rabbit tissues. However, the ethyl acetate and chloroform fractions (0.003–1.0 mg/mL) showed only spasmolytic activity when studied in spontaneously contracting rabbit jejunum. This study showed that thePhyllanthus emblicapossesses prokinetic and laxative activities in mice along with spasmodic effect in the isolated tissues of guinea pig and rabbit, mediated partially through activation of muscarinic receptors; thus, this study provides a rationale for the medicinal use ofPhyllanthus emblicafruits in indigestion and constipation. Copyright © 2012 John Wiley & Sons, Ltd.
Antipyretic and Anti‐inflammatory Effects of Asiaticoside in Lipopolysaccharide‐treated Rat through Up‐regulation of Heme Oxygenase‐1
Authors: Wan JingYuan , Gong Xia , Jiang Rong , Zhang Zhuo , Zhang Li
Published: September 2012

Asiaticoside (AS), a triterpenoid isolated from Centella asiatica, has been found to exhibit antioxidant and anti‐inflammatory activities in several experimental animal models. However, the underlying mechanisms remain elusive. In this study, we provide experimental evidences that AS dose‐dependently inhibited lipopolysaccharide (LPS)‐induced fever and inflammatory response, including serum tumor necrosis factor (TNF)‐α and interleukin (IL)‐6 production, liver myeloperoxidase (MPO) activity, brain cyclooxygenase‐2 (COX‐2) protein expression and prostaglandin E2 (PGE2) production. Interestingly, AS increased serum IL‐10 level, liver heme oxygenase‐1 (HO‐1) protein expression and activity. Furthermore, we found that the suppressive effects of AS on LPS‐induced fever and inflammation were reversed by pretreatment with ZnPPIX, a HO‐1 activity inhibitor. In summary, our results suggest that AS has the antipyretic and anti‐inflammatory effects in LPS‐treated rat. These effects could be associated with the inhibition of pro‐inflammatory mediators, including TNF‐α and IL‐6 levels, COX‐2 expression and PGE2 production, as well as MPO activity, which might be mediated by the up‐regulation of HO‐1. Copyright © 2012 John Wiley & Sons, Ltd.
Model guided adaptive design and analysis in computer experiment
Authors: Yu Qingzhao , Li Bin , Fang Zhide , Peng Lu
Published: September 2012

Computer experiments have become increasingly important in several different industries. These experiments save resources by exploring different designs without necessitating real hardware manufacturing. However, computer experiments usually require lengthy simulation times and powerful computational capacity. Therefore, it is often pragmatically impossible to run experiments on a complete design space. In this paper, we propose an adaptive sampling scheme that interactively works with predictive models to sequentially select design points for computer experiments. The selected samples are used to build predictive models, which in turn guide further sampling and predict the entire design space. For illustration, we use Bayesian additive regression trees (BART), multiple additive regression trees (MART), treed Gaussian process and Gaussian process to guide the proposed sampling method. Both real data and simulation studies show that our sampling method is effective in that (i) it can be used with different predictive models; (ii) it can select multiple design points without repeatedly refitting the predictive models, which makes parallel simulations possible and (iii) the predictive model built on its generated samples gives more accurate predictions on the unsampled points than the models built on samples from other methods such as random sampling, space‐filling designs and some adaptive sampling methods. © 2012 Wiley Periodicals, Inc. Statistical Analysis and Data Mining, 2012
An information criterion for marginal structural models
Authors: Platt Robert W. , Brookhart M. Alan , Cole Stephen R. , Westreich Daniel , Schisterman Enrique F.
Published: September 2012

Marginal structural models were developed as a semiparametric alternative to the G‐computation formula to estimate causal effects of exposures. In practice, these models are often specified using parametric regression models. As such, the usual conventions regarding regression model specification apply. This paper outlines strategies for marginal structural model specification and considerations for the functional form of the exposure metric in the final structural model. We propose a quasi‐likelihood information criterion adapted from use in generalized estimating equations. We evaluate the properties of our proposed information criterion using a limited simulation study. We illustrate our approach using two empirical examples. In the first example, we use data from a randomized breastfeeding promotion trial to estimate the effect of breastfeeding duration on infant weight at 1 year. In the second example, we use data from two prospective cohorts studies to estimate the effect of highly active antiretroviral therapy on CD4 count in an observational cohort of HIV‐infected men and women. The marginal structural model specified should reflect the scientific question being addressed but can also assist in exploration of other plausible and closely related questions. In marginal structural models, as in any regression setting, correct inference depends on correct model specification. Our proposed information criterion provides a formal method for comparing model fit for different specifications. Copyright © 2012 John Wiley & Sons, Ltd.
Maximizing an ROC‐type measure via linear combination of markers when the gold reference is continuous
Authors: Chang Yuan‐chin Ivan
Published: September 2012

Effectively combining many classification instruments or diagnostic measurements together to improve the classification accuracy of individuals is a common idea in disease diagnosis or classification. These ensemble‐type diagnostic methods can be constructed with respect to different kinds of performance criterions. Among them, the receiver operating characteristic (ROC) curve is the most popular criterion, which, together with some indexes derived from it, is commonly used to evaluate and summarize the performance of a classification instrument, such as a biomarker or a classifier. However, the usefulness of ROC curve and its related indexes relies on the existence of a binary label for each individual subject. In many disease diagnosis situations, such a binary variable may not exist, but only the continuous measurement of the true disease status is available. This true disease status is often referred to as the ‘gold standard’. The modified area under ROC curve (AUC)‐type measure defined by Obuchowski is a method proposed to accommodate such a situation. However, there is still no method for finding the optimal combination of diagnostic measurements, with respect to such an index, to have better diagnostic power than that of each individual measurement. In this paper, we propose an algorithm for finding the optimal combination with respect to such an extended AUC‐type measure such that the combined measurement can have more diagnostic power. We illustrate the performance of our algorithm by using some synthesized data and a diabetes data set. Copyright © 2012 John Wiley & Sons, Ltd.
First Anxiety, Afterwards Depression: Psychological Distress in Cancer Patients at Diagnosis and after Medical Treatment
Authors: Gil Francisco , Costa Gema , Hilker Ines , Benito Llucia
Published: September 2012

Objective

The purpose of this study was to assess psychosocial changes at two particular moments: at cancer diagnosis and 2–4 weeks after having finished treatment.

Material and methods

A total of 67 cancer outpatients were assessed in this study. The inclusion/exclusion criteria were as follows: ambulatory cancer patients aged 18 years or older and receiving medical treatment. Patients with a performance status <50 or with cognitive impairment (≥3 errors in the Pfeiffer Questionnaire) were excluded. The inclusion period ranged from 1 April 2005 to 30 April 2007. The scales used were the 14‐item Hospital Anxiety and Depression Scale (HADS), which has two subscales for anxiety (seven items) and for depression (seven items), the Quality of Life Short Form 36 Questionnaire, the Mental Adjustment Scale and the Medical Outcomes Study Questionnaire for measuring social support. All data were compared with sociodemographic and medical characteristics.

Results

Patients had higher levels of pre‐treatment versus post‐treatment anxiety (HADS‐Anxiety mean, 7.41 versus 6.69), whereas depression scores were higher post‐treatment versus pre‐treatment (HADS‐Depression mean, 3.14 versus 3.89). After medical treatment, patients were more fatigued, with lower performance status (Karnofsky Index), less social support and less quality of life, but no differences in coping styles were found. Women had higher levels of anxiety than men. Patients with psychiatric antecedents had higher levels of distress, but these differences were only observed after diagnosis and not after the treatment. In general, head and neck cancer patients had higher levels of distress, worse coping and worse social functioning.

Conclusions

Cancer patients require special consideration before and after treatment. Anxiety is the symptom that characterizes diagnosis, whereas depression is more common after medical treatment. The head and neck cancer patients were the group with the highest complexity. Copyright © 2012 John Wiley & Sons, Ltd.
Online communication on climate change and climate politics: a literature review
Authors: Schäfer Mike S.
Published: September 2012

The study of climate change communication has become an important research field. As stakeholders such as scientists, politicians, corporations, or NGOs increasingly turn to the Internet and social media for providing information and mobilizing support, and as an increasing number of people use these media, online communication on climate change and climate politics has become a relevant topic. This article reviews the available scholarly literature on the role of online and social media in climate communication. It analyzes how stakeholders use online communication strategically, showing, for example, that climate scientists and scientific institutions do not seem to be major players in online debates about climate change and climate politics. Furthermore, it highlights the characteristics of online climate communication, outlining, for example, that although (or because) many stakeholders participate online, this does not lead to robust scientific information or better debates. Eventually, the review assesses what is known about the uses and effects of online climate communication, showing that impacts on the broader public seem to be limited so far. Research desiderata are identified in the end, and directions for further studies are shown.WIREs Clim Change2012, 3:527–543. doi: 10.1002/wcc.191

This article is categorized under:

Perceptions, Behavior, and Communication of Climate Change > Communication
MOLCAS—a software for multiconfigurational quantum chemistry calculations
Authors: Aquilante Francesco , Pedersen Thomas Bondo , Veryazov Valera , Lindh Roland
Published: September 2012

At variance, with most of the quantum chemistry software presently available, MOLCAS is a package that is specialized in multiconfigurational wave function theory (MC‐WFT) rather than density functional theory (DFT). Given the much higher algorithmic complexity of MC‐WFT versus DFT, an extraordinary effort needs to be made from the programming point of view to achieve state‐of‐the‐art performance for large‐scale calculations. In particular, a robust and efficient implementation of the Cholesky decomposition techniques for handling two‐electron integrals has been developed which is unique to MOLCAS. Together with this ‘Cholesky infrastructure’, a powerful and multilayer graphical and scripting user interface is available, which is an essential ingredient for the setup of MC‐WFT calculations. These two aspects of the MOLCAS software constitute the focus of the present report. © 2012 John Wiley & Sons, Ltd.

This article is categorized under:

Software > Quantum Chemistry
What does Pirahã grammar have to teach us about human language and the mind?
Authors: Everett Daniel L.
Published: September 2012

Pirahã is a language isolate of the Brazilian Amazon. Among the lessons it has to teach us about human language and the mind, two are highlighted here. The first is that recursion is not a necessary condition for human syntax, because there is no evidence for recursive sentential syntax in the language. This is a stark counterexample to the claims of Chomsky and others. The second lesson is that the influence of culture on Pirahã grammar, coupled with much established and newer research, indicates that the idea of an innate, universal grammar has little if any role to play in our understanding of the nature, origins, and use of human language. WIREs Cogn Sci 2012 doi: 10.1002/wcs.1195

This article is categorized under:

Linguistics > Linguistic Theory
Psychology of spatial cognition
Authors: Tommasi Luca , Laeng Bruno
Published: September 2012

In this overview, focusing on memory and higher cognitive processes, we cover some of the most relevant results that emerged from research on spatial cognition in animals and in humans in the last 3 decades. In particular, we discuss how representations of distance and direction are used to localize oneself with respect to the external world, to determine the position of objects with respect to each other, and to compute the position of invisible goals. The role of landmarks and environmental geometry as cues for extracting spatial information in such abilities is compared, and the reliance upon self‐centered and external frames of reference is discussed. Moreover, the contribution of working memory and processing strategies in forming representations of spatial relations in humans is presented. Finally, implications for some neighboring fields of the cognitive sciences will be outlined.WIREs Cogn Sci2012. doi: 10.1002/wcs.1198

This article is categorized under:

Psychology > Memory
Harnessing the power of cell‐penetrating peptides: activatable carriers for targeting systemic delivery of cancer therapeutics and imaging agents
Authors: MacEwan Sarah R. , Chilkoti Ashutosh
Published: September 2012

Targeted delivery of cancer therapeutics and imaging agents aims to enhance the accumulation of these molecules in a solid tumor while avoiding uptake in healthy tissues. Tumor‐specific accumulation has been pursued with passive targeting by the enhanced permeability and retention effect, as well as with active targeting strategies. Active targeting is achieved by functionalization of carriers to allow specific interactions between the carrier and the tumor environment. Functionalization of carriers with ligands that specifically interact with overexpressed receptors on cancer cells represents a classic approach to active tumor targeting. Cell‐penetrating peptides (CPPs) provide a non‐specific and receptor‐independent mechanism to enhance cellular uptake that offers an exciting alternative to traditional active targeting approaches. While the non‐specificity of CPP‐mediated internalization has the intriguing potential to make this approach applicable to a wide range of tumor types, their promiscuity is, however, a significant barrier to their clinical utility for systemically administered applications. Many approaches have been investigated to selectively turn on the function of systemically delivered CPP‐functionalized carriers specifically in tumors to achieve targeted delivery of cancer therapeutics and imaging agents. WIREs Nanomed Nanobiotechnol 2013, 5:31–48. doi: 10.1002/wnan.1197

This article is categorized under:

Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease

Biology-Inspired Nanomaterials > Peptide-Based Structures
Free energy v.s. Sasaki-Einstein volume for infinite families of M2-brane theories
Authors: Amariti Antonio , Franco Sebastián
Published: September 2012

Abstract

We investigate infinite families of 3d
$ \mathcal{N} = {2} $
superconformal Chern-Simons quivers with an arbitrarily large number of gauge groups arising on M2-branes over toric CY4’s. These theories have the same matter content and superpotential of those on D3-branes probing cones over L

a,b,a
Sasaki-Einstein manifolds. For all these infinite families, we explicitly show the correspondence between the free energy F on S
3 and the volume of the 7-dimensional base of the associated CY4, even before extremization. Symmetries of the toric diagram are exploited for reducing the dimensionality of the space over which the volume of the Sasaki-Einstein manifold is extremized. Similarly, the space of trial R-charges of the gauge theory is constrained using symmetries of the quiver. Our results add to those existing in the literature, providing further support for the correspondence. We develop a lifting algorithm, based on the Type IIB realization of these theories, that takes from CY3’s to CY4’s and we use it to efficiently generate the models studied in the paper. Finally, we show that in all the infinite families we consider F
2 can be expressed, even off-shell, as a quartic function in R-charges associated to certain 5-cycles. This suggests that a quartic formula on R-charges, analogous to a similar cubic function for the central charge a in 4d, exists for all toric toric CY4’s and we present some ideas regarding its general form.
Relationship between Preoperative Volume and Weight of the Right Liver Lobe Graft, with and without the Middle Hepatic Vein, in Living‐Donor Transplantation
Authors: Peron Gilberto , Salzedas Netto Alcides A. , Mancero Jorge Padilla , Ribeiro Marcelo Augusto Fontenelle , Copstein José Luis , de Oliveira e Silva Adávio , D’Albuquerque Luiz Augusto Carneiro , Gonzalez Adriano Miziara
Published: September 2012

Background

The aim of this study was to assess the relationship between the preoperative volume of the right liver lobe (as determined by computed tomography) and the intraoperative graft weight with or without the middle hepatic vein.

Methods

Sixty‐three patients who underwent liver transplantation were included in this study. The preoperative volumes of both the left and the right liver lobe were measured in all patients using computed tomography. The intraoperative weight of the right liver lobe was also measured with (group 1, n = 29) and without (group 2, n = 34) the middle hepatic vein. The results were compared with respect to gender, age, body weight, height, body mass index (BMI), weights of the left and right liver lobes as measured by computed tomography, and intraoperative weight of the right liver lobe.

Results

A 21.64 % difference was observed between the weight of the right liver lobe as measured by computed tomography and the weight of the right lobe without the hepatic vein as measured intraoperatively (group 2). Moreover, a 12.38 % difference was observed between the weight of the right liver lobe as measured by computed tomography and the weight of the right lobe plus the middle hepatic vein as measured intraoperatively (group 1).

Conclusions

The weight of the right liver lobe graft in a living‐donor transplantation is less than that calculated by preoperative computed tomography, and the inclusion of the middle hepatic vein in the right liver lobe graft resulted in a statistically significant decrease in this difference.
Cost‐comparison of Laparoscopic and Open Surgery for Mid or Low Rectal Cancer after Preoperative Chemoradiotherapy: Data from a Randomized Controlled Trial
Authors: Son Hae‐Jung , Lee Hoo‐Yeon , Park Ji Won , Choi Hyo Seong , Jeong Seung‐Yong , Oh Jae Hwan
Published: September 2012

Background

The purpose of the present study was to compare the direct costs of laparoscopic surgery (LS) and open surgery (OS) in the treatment of mid or low rectal cancer after preoperative chemoradiotherapy in patients in Korea.

Methods and results

The records of 130 LS patients and 125 OS patients were reviewed. Hospital stay after surgery and overall complication rates within three months of surgery were not significantly different. The LS group had significantly higher median costs than the OS group ($7,467.30 vs. $5,667.00; P < 0.001). The median hospital costs during hospitalization for surgery were higher in the LS group ($7,436.60 vs. $5,626.60; P < 0.001), but hospital costs for management of early postoperative complications were similar. The higher direct costs of LS were mainly due to the more expensive consumables and equipment needed for LS.

Conclusions

Further study is needed to determine whether the higher direct costs of LS for rectal cancer are balanced by advantages of LS over OS, such as better short‐term outcomes and cosmetic effect.
Long‐term clinical outcomes in type 1 Gaucher disease following 10 years of imiglucerase treatment
Authors: Weinreb Neal J. , Goldblatt Jack , Villalobos Jacobo , Charrow Joel , Cole J. Alexander , Kerstenetzky Marcelo , vom Dahl Stephan , Hollak Carla
Published: September 2012

Objective

We studied the effect of long‐term alglucerase/imiglucerase (Ceredase®/Cerezyme®, Genzyme, a Sanofi company, Cambridge, MA, USA) treatment on hematological, visceral, and bone manifestations of Gaucher disease type 1 (GD1).

Methods

The International Collaborative Gaucher Group (ICGG) Gaucher Registry identified GD1 patients treated with alglucerase/imiglucerase who had dose and clinical data at first infusion and after 10 years of follow‐up. Data for hemoglobin, platelet count, organ volumes, bone pain, and bone crisis were analyzed. Tests of the null hypothesis (no change from first infusion to 10 years) were performed using t tests for within‐patient absolute change in continuous measurements and McNemar/chi‐square tests for change in distributions using categorical values. An alpha level of 0.05 designated statistical significance.

Results

As of October 2011, 557 nonsplenectomized and 200 splenectomized patients met the inclusion criteria. The majority of GD1 patients had at least one N370S allele. Compared with nonsplenectomized patients at first infusion, splenectomized patients had lower percentages of anemia (26.0 % vs. 42.8 %) and thrombocytopenia (14.2 % vs. 76.3 %), similar percentages of moderate or severe hepatomegaly (81.2 % vs. 80.0 %), and higher percentages of bone pain (88.9 % vs. 52.4 %) and bone crises (38.3 % vs. 16.0 %). After 10 years, both groups showed significant (p < 0.05) improvements in mean hemoglobin levels, platelet count, liver, and spleen (nonsplenectomized) volumes, and bone crises. Initial dosing in both groups ranged from <15 U/kg to ≤90 U/kg every 2 weeks. After 10 years, the majority was receiving 15 to ≤45 U/kg every 2 weeks.

Conclusion

Ten years of imiglucerase treatment results in sustainable improvements in all GD1 parameters.
Dynamic changes of lipid profile in Romanian patients with Gaucher disease type 1 under enzyme replacement therapy: a prospective study
Authors: Zimmermann Anca , Grigorescu‐Sido Paula , Rossmann Heidi , Lackner Karl J. , Drugan Cristina , Al Khzouz Camelia , Bucerzan Simona , Naşcu Ioana , Zimmermann Tim , Leucuţa Daniel , Weber Matthias M.
Published: September 2012

Background

Dyslipidemia in Gaucher disease includes reduced total, low‐density lipoprotein (LDL)‐, and high‐density lipoprotein (HDL)‐cholesterol (C). No prospective analysis of lipid profile changes in treatment‐naïve patients under enzyme replacement therapy (ERT) is available.

Methods

We analyzed lipid profile changes during ERT in a prospective controlled manner. Twelve treatment‐naïve patients, Gaucher disease type 1 (GD1), 29.5 ± 12.9 years, 4M/8F. Diagnosis was made by enzymatic measurement and mutational analysis. Total‐, LDL‐, and HDL‐C, triglycerides (TG), and LDL subfractions were assessed before the start of ERT with imiglucerase and biannually for 3 years. Patients were matched with healthy controls before and after 3 years of ERT.

Results

At baseline, we found severely reduced HDL‐C concentrations (23.6 ± 5.4 mg/dl) and enhanced LDL/HDL ratios (3.1 ± 0.7). HDL‐C increased after 6 months (29.2 ± 5.7,p = 0.023), LDL/HDL ratio decreased after 30 months (2.5 ± 0.5,p = 0.039). TG, even not consistently enhanced at baseline (128 ± 31.3 mg/dl), yet higher than in controls (p < 0.001), decreased after 18 months, being comparable with controls after 3 years of ERT. Small, dense LDL (mg/dl) increased continuously without significant difference to controls. After 3 years of ERT, only reduced HDL‐C concentrations persisted as a potentially atherogenic alteration; however, mean concentrations markedly improved (42.9 ± 8.3 mg/dl,p < 0.001). Lipid parameters correlated with six markers of disease severity.

Conclusions

This is the first prospective controlled study regarding lipid profile dynamics during ERT (glucocerebrosidase) in initially treatment‐naïve GD1 patients. The most important changes were reduced HDL‐C and enhanced LDL/HDL ratio. Their dynamics during ERT and correlations with markers of disease activity suggest that they can be considered markers of disease severity and follow‐up in Gaucher patients under treatment.
Molecular characterization of 355 mucopolysaccharidosis patients reveals 104 novel mutations
Authors: Pollard Laura M. , Jones Julie R. , Wood Tim C.
Published: September 2012

Mucopolysaccharidosis (MPS) disorders are heterogeneous and caused by deficient lysosomal degradation of glycosaminoglycans, resulting in distinct but sometimes overlapping phenotypes. Molecular analysis was performed for a total of 355 MPS patients with MPSI (n = 15), MPSII (n = 218), MPSIIIA (n = 86), MPSIIIB (n = 20), MPSIVA (n = 6) or MPSVI (n = 10). This analysis revealed 104 previously unreported mutations: seven in IDUA (MPSI), 61 in IDS (MPSII), 19 in SGSH (MPSIIIA), 11 in NAGLU (MPSIIIB), two in GALNS (MPSIVA) and four in ARSB (MPSVI). The intergenic comparison of the mutation data for these disorders has revealed interesting differences. Whereas IDUA, IDS, NAGLU and ARSB demonstrate similar levels of mutation heterogeneity (0.6–0.675 different mutations per total alleles), SGSH and GALNS have lower levels of mutation heterogeneity (0.282 and 0.455, respectively), due to more recurrent mutations. The type of mutation also varies significantly by gene. SGSH, GALNS and ARSB mutations are usually missense (76.5 %, 81.8 % and 85 %), while IDUA has many more nonsense mutations (56 %) than the other genes (≤20%). The mutation spectrum is most diverse for IDS, including intergenic inversions and multi‐exon deletions. By testing 102 mothers of MPSII patients, we determined that 22.5 % of IDS mutations are de novo. We report the allele frequency of common mutations for each gene in our patient cohort and the exonic distribution of coding sequence alterations in the IDS, SGSH and NAGLU genes, which reveals several potential “hot‐spots”. This further molecular characterization of these MPS disorders is expected to assist in the diagnosis and counseling of future patients.