bluuebunny/crossref_metadata_2025 huggingface dataset:
The Role of Modified Mediterranean Diet and Quantum Therapy in Type Diabetes Mellitus Primary Prevention
Authors: Stagnaro Sergio , Caramel Simone
Published: January 2013

The Authors provide an overview of useful treatments such as ‘Modified Mediterranean Diet’, CoQ10, melatonin, carnitine and ‘Quantum Therapy’, testing their effects in Type 2 Diabetes Mellitus (T2DM) primary prevention, performed possibly in the three first stages of T2DM. This is done through ‘Quantum Biophysical Semeiotics’ biological evaluation, clinically monitoring the results and efficiency of ongoing therapies aimed at improving mitochondrial and endothelial function, when it is impaired in any biological systems. This clinical method allows physicians to bedside assess tissue acidosis, before and during different preventive therapies, testing their respective efficacy and utility.All the investigated treatments have firstly ameliorated and then normalized tissue microcirculatory pattern, showing a physiological functioning. Furthermore the tested ‘Quantum therapy’ generates virtuous genetic feedbacks.‘Quantum Biophysical Semeiotics’ theory is an extension of medical semeiotics. It is grounded on a multidisciplinary approach that involves chemistry and biology, genetics and neuroscience, chaos theory and quantum physics.It is based on the method of ‘Auscultatory Percussion’, through which by means of the common stethoscope, it is possible to listen to the signs that the body gives us when appropriately stimulated.The stimuli are used to induce consistent behavior in precise and welldefined biological systems of the human body, thus giving local qualitative information on the state of health or disease, whether potential, being developed but not yet evident by usual clinical trial, effective or even in chronic phase. The 'Quantum Biophysical Semeiotics’ theory provides very detailed case studies based on the latency time, duration, and intensity of the reflexes, which play a central role in such a diagnostic method.
In Vitro Membrane Stabilizing and Thrombolytic Activities of Ophirrhiza mungos, Mussaenda macrophylla, Gmelina philippensis and Synedrella nodiflora Growing in Bangladesh
Authors: Islam Farhana , Chowdhury Sharmin Reza , Sharmin Tasnuva , Uddin Md. Gias , Kaisar Mohammad A. , Rashid Mohammad A.
Published: January 2013

The methanol extracts and their pet-ether, carbon tetrachloride, chloroform and aqueous soluble partitionates of Ophirrhiza mungos, Mussaenda macrophylla, Gmelina philippensis and Synedrella nodiflorawere subjected to assays for membrane stabilizing and thrombolytic activities. The extractives inhibited heat- as well as hypotonic solution-induced haemolysis of human erythrocytes in vitro. The pet-ether soluble fraction of O. mungos, M. macrophylla and S. nodiflora demonstrated 61.16 % & 24.75%, 52.55% & 23.35% and 60.24% & 22.85% inhibition of hemolysis of RBC caused by hypotonic solution and heat, whereas the carbon tetrachloride soluble fraction of G. philippensis showed 49.05% and 21.25% inhibition of hypotonic and heat induced hemolysis of RBC, respectively. Here, acetyl salicylic acid was used as reference standard at 0.10 mg/mL. Among the four plants, the carbon tetrachloride soluble fraction of O. mungos, methanol extract of M. macrophylla, carbon tetrachloride soluble fraction of G. philippensis and chloroform soluble fraction of S. nodiflora revealed highest thrombolytic activity with clot lysis value of 50.09%, 49.50%, 47.14% and 46.37%, respectively. Standard streptokinase and water were used as positive and negative controls which showed 65.00% and 3.84% lysis of clot, respectively.
Investigation of Measurement Methods of Antioxidant Activity and Involved Mechanisms
Authors: Ardestani Samira Berenji , Sahari Mohammad Ali
Published: January 2013

Bioactive food components are active ingredients in food or dietary supplements proven to have a role in health and they are safe for human consumption. These compounds exert their antioxidant effects by different mechanisms such as hydrogen atom transfer (HAT) or single electron transfer (SET) and their efficiencies can be evaluated by several methods such as ferric reducing ability of plasma (FRAP), trolox equivalent antioxidant capacity (TEAC), dipheny-picrylhydrazil (DPPH), Folin-Ciocaltue method (FCM), etc. In this review, these mechanisms and methods will be discussed in details.
Situación de las poblaciones de corzo andaluz (Capreolus capreolus) en las sierras occidentales de Málaga
Authors: Duarte Jesús , Farfán Miguel A. , Vargas J. Mario
Published: January 2013

We have monitored the presence of roe deer in 25 municipalities in the occidental mountians of Málaga. We estimated roe deer abundance (pellet groups counts/km) and relative density (deer/km2) by means of distance sampling and defecation rate conversion. We also analyzed the relationships between roe deer abundance and habitat vegetation and coverages by means of GLM models. Results are presented by hidrological basins. We found that roe deer relative density varied between 0.18 to 2.49 deer/km2. The highest values were found in the Hozgarganta river and the Genal river valley. The lowest was in the mountains around the Guadalhorce river basin. Roe deer abundance was positively related to the vicinity of roe deer population in the Cádiz mountains and to the coverage of mixed forests of oaks, pines and chestnuts. Roe deer abundance was negatively related to urban landuses, farmlands and dense pine forests. Our results are coherent with the hyphotesis of an expanding roe deer population in the Málaga mountains.
Analyzing inclusive schooling for students with disabilities in international contexts: Outline of a model
Authors: Winzer Margret , Mazurek Kas
Published: January 2013

Conceptual and methodological difficulties confound comparative studies of the inclusive agenda for persons with disabilities. This paper, based on the authors' previous analyses of various aspects of inclusive schooling in international contexts, introduces a model to assist in the observation and analysis of the subtle and multi-aspect phenomena of inclusive schooling in its varied manifestations. With attention to inclusive schooling's premises, progress, implementation, and impact around the world, the model details five interlocking areas: core philosophy; dimensions of time; cultural parameters; school transformation; and policy and outcomes. These five parameters are best viewed as a set of intermeshed, overlapping, and embedded dimensions. Factors salient to comparative analyses are outlined in the paper; brief examples from national agendas add nuances to the discussion.
Family Functioning, Social Opportunities and Health as Predictors of Stress in Families of Children with Developmental Disability in the United Arab Emirates
Authors: Dukmak Samir J. , Aburezeq Ibtehal M.
Published: January 2013

A significant number of individuals all over the world experience various types of developmental disabilities. Families of these individuals are likely to be impacted by these disabilities in different ways. This research examines the UAE parents' adaptation and stress to the developmental disabilities that their children have as well as examines the impact of these disabilities on three family factors: family functioning, family social opportunities, and family general health. The relationships between these factors were investigated and also those between these factors and several child and family characteristics. The results revealed that parents who had better general health had also better family functioning, and had less stress. Child age was found to be associated with parents' stress, as stress decreases when the child gets older. The results also showed that parents' educational level was associated with their social opportunities. Further, parents' stress level was found to be linked to their children's behavior problems. Finally, the results of the study explored that the type of child's developmental disability impacted family social opportunities.
Early identification for special education: Implications for research and development in the Pacific Rim
Authors: Cook Bryan , Gerber Michael , Hong Li-Yu , Mannan Hasheem , Zhang Weng-jing
Published: January 2013

Early identification and intervention for children with disabilities can significantly improve longer term outcomes, but in developing nations like many in the Pacific Rim, such programs and practices can be expensive and must compete against other needs. We argue that early identification and intervention by schools leads not only to life improvements for children with disabilities and their families but also to substantial additions to a nation's human capital. Therefore, national investment in special education and prevention systems that provide the earliest possible identification and effective interventions can not only offset the lifetime family and social costs of disabilities, but also can add importantly to general well-being. Moreover, new knowledge and technologies relevant to applied problems in early identification are rapidly emerging, potentially increasing the precision and lowering the costs involved. The bottleneck, however, is the inadequate supply of highly skilled professionals in the special and general education systems – from university doctoral training down to typical classroom teaching. Based on extant literature, we articulate some development principles to help developing education systems in choosing how they may best invest in early identification and intervention.
Engineering Hierarchical Nanostructures by Elastocapillary Self‐Assembly
Authors: De Volder Michaël , Hart A. John
Published: January 2013

Surfaces coated with nanoscale filaments such as silicon nanowires and carbon nanotubes are potentially compelling for high‐performance battery and capacitor electrodes, photovoltaics, electrical interconnects, substrates for engineered cell growth, dry adhesives, and other smart materials. However, many of these applications require a wet environment or involve wet processing during their synthesis. The capillary forces introduced by these wet environments can lead to undesirable aggregation of nanoscale filaments, but control of capillary forces can enable manipulation of the filaments into discrete aggregates and novel hierarchical structures. Recent studies suggest that the elastocapillary self‐assembly of nanofilaments can be a versatile and scalable means to build complex and robust surface architectures. To enable a wider understanding and use of elastocapillary self‐assembly as a fabrication technology, we give an overview of the underlying fundamentals and classify typical implementations and surface designs for nanowires, nanotubes, and nanopillars made from a wide variety of materials. Finally, we discuss exemplary applications and future opportunities to realize new engineered surfaces by the elastocapillary self‐assembly of nanofilaments.
Intelligent Setting Control for Clinker Calcination Process
Authors: Qiao Jinghui , Chai Tianyou , Wang Hong
Published: January 2013

In the process of clinker calcination, the target value of the raw meal decomposition rate (RMDR) is different in the easy and difficult calcination stages because the boundary conditions of raw meal (i.e., raw meal flow, raw meal ingredients, and particle size) change frequently, where RMDR cannot be guaranteed to be within its desirable range. To solve this problem, an intelligent setting control method is proposed in this paper for a clinker calcination process. The proposed approach is realized by on‐line adjustment of the setpoints of control loops in line with the changes of raw meal boundary conditions. This method consists of five modules, namely an RMDR target value setting model, a control loop pre‐setting model, a feedback compensation model based on the fuzzy rules, a feedforward compensation model based on the fuzzy rules, and a soft measurement model for RMDR. Successful application to the clinker calcination process of the Jiuganghongda Cement Plant in China has been made, where the efficiency of the proposed method has been validated by the results of the practical application.
Randomized clinical trial of enhanced recovery versus standard care after laparoscopic sleeve gastrectomy
Authors: Lemanu D P , Singh P P , Berridge K , Burr M , Birch C , Babor R , MacCormick A D , Arroll B , Hill A G
Published: January 2013

Background

Optimized perioperative care within an enhanced recovery after surgery (ERAS) protocol is designed to reduce morbidity after surgery, resulting in a shorter hospital stay. The present study evaluated this approach in the context of sleeve gastrectomy for patients with morbid obesity.

Methods

Patients were allocated to perioperative care according to a bariatric ERAS protocol or a control group that received standard care. These groups were also compared with a historical group of patients who underwent laparoscopic sleeve gastrectomy at the same institution between 2006 and 2010, selected using matched propensity scores. The primary outcome was median length of hospital stay. Secondary outcomes included readmission rates, postoperative morbidity, postoperative fatigue and mean cost per patient.

Results

Of 116 patients included in the analysis, 78 were allocated to the ERAS (40) or control (38) group and there were 38 in the historical group. There were no differences in baseline characteristics between groups. Median hospital stay was significantly shorter in the ERAS group (1 day) than in the control (2 days; P < 0·001) and historical (3 days; P < 0·001) groups. It was also shorter in the control group than in the historical group (P = 0·010). There was no difference in readmission rates, postoperative complications or postoperative fatigue. The mean cost per patient was significantly higher in the historical group than in the ERAS (P = 0·010) and control (P = 0·018) groups.

Conclusion

The ERAS protocol in the setting of bariatric surgery shortened hospital stay and was cost-effective. There was no increase in perioperative morbidity. Registration number: NCT01303809 (http://www.clinicaltrials.gov).
Use of surgical-site infection rates to rank hospital performance across several types of surgery
Authors: van Dishoeck A M , Koek M B G , Steyerberg E W , van Benthem B H B , Vos M C , Lingsma H F
Published: January 2013

Background

Comparing and ranking hospitals based on health outcomes is becoming increasingly popular, although case-mix differences between hospitals and random variation are known to distort interpretation. The aim of this study was to explore whether surgical-site infection (SSI) rates are suitable for comparing hospitals, taking into account case-mix differences and random variation.

Methods

Data from the national surveillance network in the Netherlands, on the eight most frequently registered types of surgery for the year 2009, were used to calculate SSI rates. The variation in SSI rate between hospitals was estimated with multivariable fixed- and random-effects logistic regression models to account for random variation and case mix. ‘Rankability’ (as the reliability of ranking) of the SSI rates was calculated by relating within-hospital variation to between-hospital variation.

Results

Thirty-four hospitals reported on 13 629 patients, with overall SSI rates per surgical procedure varying between 0 and 15·1 per cent. Statistically significant differences in SSI rate between hospitals were found for colonic resection, caesarean section and for all operations combined. Rankability was 80 per cent for colonic resection but 0 per cent for caesarean section. Rankability was 8 per cent in all operations combined, as the differences in SSI rates were explained mainly by case mix.

Conclusion

When comparing SSI rates in all operations, differences between hospitals were explained by case mix. For individual types of surgery, case mix varied less between hospitals, and differences were explained largely by random variation. Although SSI rates may be used for monitoring quality improvement within hospitals, they should not be used for ranking hospitals.
National risk prediction model for elective abdominal aortic aneurysm repair
Authors: Grant S W , Hickey G L , Grayson A D , Mitchell D C , McCollum C N
Published: January 2013

Background

Mortality results for elective abdominal aortic aneurysm (AAA) repair are published by the Vascular Society of Great Britain and Ireland. These mortality results are not currently risk-adjusted. The objective of this study was to develop a national risk prediction model for elective AAA repair.

Methods

Data for consecutive patients undergoing elective AAA repair from the National Vascular Database between April 2008 and March 2011 were analysed. Multiple logistic regression and backwards model selection were used for model development. The study outcome measure was in-hospital mortality. Model calibration and discrimination were assessed for all AAA repairs, and separately for open repair and endovascular aneurysm repair (EVAR) subgroups.

Results

There were 312 in-hospital deaths among 11 423 AAA repairs (2·7 (95 per cent confidence interval (c.i.) 2·4 to 3·0) per cent): 230 after 4940 open AAA repairs (4·7 (4·1 to 5·3) per cent) and 82 after 6483 EVARs (1·3 (1·0 to 1·6) per cent). Variables associated with in-hospital death included in the final model were: open repair, increasing age, female sex, serum creatinine level over 120 µmol/l, cardiac disease, abnormal electrocardiogram, previous aortic surgery or stent, abnormal white cell count, abnormal serum sodium level, AAA diameter and American Society of Anesthesiologists fitness grade. The area under the receiver operating characteristic (ROC) curve was 0·781 (95 per cent c.i. 0·756 to 0·806) with a bias-corrected value of 0·774. Model calibration was good (P = 0·963) based on the Hosmer–Lemeshow goodness-of-fit test, (bias-corrected) calibration curves, risk group assessment and recalibration regression.

Conclusion

This multivariable model for elective AAA repair can be used to risk-adjust outcome analyses and provide patient-specific estimates of in-hospital mortality risk for open AAA repair or EVAR.
Rhodium‐Catalyzed Homogeneous and Aqueous Biphasic Hydroformylation of the Acrolein Acetal 2‐Vinyl‐5‐Methyl‐1,3‐Dioxane
Authors: Ternel Jérémy , Dubois Jean‐Luc , Couturier Jean‐Luc , Monflier Eric , Carpentier Jean‐François
Published: January 2013

The rhodium‐catalyzed hydroformylation of 2‐vinyl‐5‐methyl‐1,3‐dioxane (VMD), the acetal derived from acrolein and 2‐methyl‐1,3‐propanediol, has been investigated. Under homogeneous conditions, phosphane‐based catalysts afforded perfect chemoselectivity for the aldehydes. Catalysts based on diphosphine ligands with a narrow bite angle of approximately 85°, such as 1,2‐bis(phenylphosphino)ethane, were found to favor the branched aldehyde 2, with selectivities of up to 78 %, whereas diphosphine ligands with a large bite angle of approximately 110°, such as xantphos, produce the linear aldehyde 1 with up to 91 % selectivity. Control of the 1/2 regioselectivity by means of the PRhP bite angle was ascertained with a variety of ethylene‐, hydrazino‐ and CNC‐bridged diphosphines, irrespective of electronic factors induced by these ligands. Under aqueous biphasic conditions, chemoselective hydroformylation of VMD proved feasible only with disulfonated xantphos; in this case, remarkable activities (turnover frequencies of up to 1075 molaldehyde molRh−1 h−1 at 120 °C) were observed, with up to 82 % yield for the linear aldehyde. On the other hand, the catalyst based on tetrasulfonated dppe systematically induced the formation of very large amounts of the hydrogenated product.
Chlorine and Caesium Promotion of Silver Ethylene Epoxidation Catalysts
Authors: Özbek M. Oluş , Önal Işik , van Santen Rutger A.
Published: January 2013

The effect of co‐adsorbed Cs and Cl on the selectivity of ethylene epoxidation was studied computationally on an Ag2O(0 0 1) surface model. Cl blocks the oxygen vacant sites and prevents oxometallacycle (OMC) formation, which is responsible for aldehyde formation on the oxide surface. Cl also prevents unfavorable surface reconstruction induced by co‐adsorption of ethylene. It also has a positive effect on the stability of selective oxygen species when Cs co‐exists. Introduction of Cs on the Ag2O(0 0 1) surface results in the formation of CsOx‐type of complexes in the absence of Cl. Whereas oxygen atom adsorption energies are increased, Cs also introduces surface oxygen vacancies that reduce catalyst selectivity. Cs and Cl co‐exist on the surface in the form of CsClxOy complexes. Under reaction conditions, these complexes stabilize the oxide surface and reduce oxygen surface vacancy formation, which results in higher ethylene oxide (EO) selectivity.
A fault‐tolerant group key agreement protocol exploiting dynamic setting
Authors: Cheng Zi‐Yao , Liu Yun , Chang Chin‐Chen , Guo Cheng
Published: January 2013

A fault‐tolerant group key agreement is an essential infrastructure for Internet communication among all involved participants; it can establish a secure session key no matter how many malicious participants exit simultaneously in an effort to disrupt the key agreement process. Recently, Zhao et al. proposed an efficient fault‐tolerant group key agreement protocol named efficient group key agreement that can resist denial‐of‐service attacks, reply attacks, man‐in‐middle attacks, and common modulus attacks; it can also preserve forward secrecy with lower computational cost than previous protocols. We show that it is still vulnerable to active attacks by malicious participants and modify the corresponding security weakness adaptively. Furthermore, we propose an efficient fault‐tolerant group key agreement based on a binary tree structure and enhance it to a dynamic setting where participants can leave or join the group arbitrarily according to their preferences with instant session key refreshment. Additionally, our session key refreshment is based on secure key updating to protect forward/backward confidentiality and is resistant to active/passive attacks. The performance analysis shows that our proposed protocol has lower computational cost and little additional communication cost exploiting dynamic setting. Copyright © 2013 John Wiley & Sons, Ltd.
Metabolic studies of formestane in horses
Authors: Leung Gary N. W. , Kwok W. H. , Wan Terence S. M. , Lam Kenneth K. H. , Schiff Peter J.
Published: January 2013

Formestane (4‐hydroxyandrost‐4‐ene‐3,17‐dione) is an irreversible steroidal aromatase inhibitor with reported abuse in human sports. In 2011, our laboratory identified the presence of formestane in a horse urine sample from an overseas jurisdiction. This was the first reported case of formestane in a racehorse. The metabolism of formestane in humans has been reported previously; however, little is known about its metabolic fate in horses. This paper describes the in vitro and in vivo metabolic studies of formestane in horses, with the objective of identifying the target metabolite with the longest detection time for controlling formestane abuse. In vitro metabolic studies of formestane were performed using homogenized horse liver. Seven in vitro metabolites, namely 4‐hydroxytestosterone (M1), 3β,4α‐dihydroxy‐5β‐androstan‐17‐one (M2a), 3β,4β‐dihydroxy‐5β‐androstan‐17‐one (M2b), 3β,4α‐dihydroxy‐5α‐androstan‐17‐one (M2c), androst‐4‐ene‐3α,4,17β‐triol (M3a), androst‐4‐ene‐3β,4,17β‐triol (M3b), and 5β‐androstane‐3β,4β,17β‐triol (M4) were identified. For the in vivo studies, two thoroughbred geldings were each administered with 800 mg of formestane (32 capsules of Formadex) by stomach tubing. The results revealed that the parent drug and seven metabolites were detected in post‐administration urine. The six in vitro metabolites (M1, M2a, M2b, M2c, M3a, and M3b) identified earlier were all detected in post‐administration urine samples. In addition, 3α,4α‐dihydroxy‐5α‐androstan‐17‐one (M2d), a stereoisomer of M2a/M2b/M2c, was also identified. This study has shown that the detection of formestane administration would be best achieved by monitoring 4‐hydroxytestosterone (M1) in the glucuronide‐conjugated fraction. M1 could be detected for up to 34 h post‐administration. In blood samples, the parent drug could be detected for up to 34 h post administration. Copyright © 2013 John Wiley & Sons, Ltd.
NHC PdII Complex Bearing 1,6‐Hexylene Linker: Synthesis and Catalytic Activity in the Suzuki–Miyaura and Heck–Mizoroki Reactions
Authors: Liu Qing‐Xiang , Zhang Wei , Zhao Xiao‐Jun , Zhao Zhi‐Xiang , Shi Meng‐Chao , Wang Xiu‐Guang
Published: January 2013

A new functionalized N‐heterocyclic carbene PdII complex, [1,1′‐(hexylene‐1,6‐diyl)bis(3‐n‐butylbenzimidazol‐2‐ylidene)][PdCl2(CH3CN)]2 (2) has been synthesized by reaction of NHC‐Ag transmetalation reagent with PdCl2(CH3CN)2. The molecular structure of 2 adopts an open conformation. Complex 2 was tested as a catalyst for Suzuki–Miyaura couplings of aryl halides with arylboronic acids in water and air. The results of these efforts show that 2 is an efficient precatalyst for such reactions. In addition, 2 is a good catalyst in Heck–Mizoroki reactions of aryl bromides with styrene.
Complementary and Stereodivergent Approaches to the Synthesis of 5‐Hydroxy‐ and 4,5‐Dihydroxypipecolic Acids from Enantiopure Hydroxylated Lactams
Authors: Scarpi Dina , Bartali Laura , Casini Andrea , Occhiato Ernesto G.
Published: January 2013

We describe two complementary and stereodivergent routes, from commercially available and inexpensive starting materials, for the synthesis of 4,5‐dihydroxy‐ and 5‐hydroxypipecolic acids based on the chemistry of lactam‐derived enol phosphates. The synthesis of the 4,5‐cis‐4,5‐dihydroxypipecolic acids required the preparation from 2‐deoxy‐D‐ and ‐L‐ribose of the enantiopure cis‐(4S,5R)‐ and ‐(4R,5S)‐4,5‐dihydroxy‐δ‐valerolactam, respectively. These new chiral synthons are potentially useful for the synthesis of other natural products. The key step is the Pd‐catalyzed methoxycarbonylation reaction of the enol phosphates generated from these lactams. This reaction provided enecarbamate esters that were easily converted by stereoselective reduction to the target compounds. The synthesis of the 4,5‐trans‐4,5‐dihydroxypipecolic acid, as well as of 5‐hydroxypipecolic acids, was realized from a known (S)‐5‐hydroxy‐δ‐valerolactam derivative and, for the dihydroxylated compound, required a highly stereoselective allylic bromination reaction of the enecarbamate ester obtained by methoxycarbonylation of the enol phosphate. The preparation of the (4R,5S) enantiomer of the cis‐4,5‐dihydroxy‐δ‐valerolactam from 2‐deoxy‐L‐ribose, alongside the fact that (R)‐5‐hydroxy‐δ‐valerolactam can be prepared from (R)‐(–)‐γ‐hydroxymethyl‐γ‐butyrolactone, means our approach allows for the synthesis of all stereoisomers of these compounds, which can be employed as conformationally constrained scaffolds in drug discovery.
Expression and clinical relevance of MET and ALK in Ewing sarcomas
Authors: Fleuren Emmy D.G. , Roeffen Melissa H.S. , Leenders William P. , Flucke Uta E. , Vlenterie Myrella , Schreuder Hendrik W. , Boerman Otto C. , van der Graaf Winette T.A. , Versleijen‐Jonkers Yvonne M.H.
Published: January 2013

Because novel therapeutic options are limited in Ewing sarcomas (ES), we investigated the expression, genetic aberrations and clinical relevance of MET and anaplastic lymphoma kinase (ALK) in ES and determined the relevance of targeting these receptors. MET and ALK protein expression was determined immunohistochemically in 31 (50 samples) and 36 (59 samples) ES patients, respectively. Samples included primary tumors, postchemotherapy resections, metastases and relapses. MET and ALK RTK domains were sequenced in respectively 33 and 32 tumors. Five ES cell lines were treated in vitro with the MET/ALK‐inhibitor crizotinib, the ALK‐inhibitor NVP‐TAE684 or the MET‐inhibitor cabozantinib and analyzed by MTT assays. Modest to high MET and ALK expression was detected in the majority of ES (86 and 69%, respectively). ALK expression was significantly lower in postchemotherapy resections compared to paired untreated primary tumors (p = 0.031, z = −2.310, n = 11). In primary tumors (n = 20), membranous MET expression significantly correlated with a poor overall survival (OS) (60 vs. 197 months, p = 0.014). There was a trend toward a poor event‐free survival (67 vs. 111 months, p = 0.078) and OS (88 vs. 128 months, p = 0.074) in patients with highest ALK levels (n = 29). ALK or MET RTK domain aberrations were demonstrated in 5/32 (16%) and 3/33 (9%) tumors, respectively. Crizotinib (IC50 1.22–3.59 μmol/L), NVP‐TAE684 (IC50 0.15–0.79 μmol/L) and cabozantinib (IC50 2.69–8.27 μmol/L) affected ES cell viability in vitro. Altogether, our data suggest that MET and ALK are potential novel therapeutic targets in ES and targeting these receptors may be of great interest to rationally design future studies in ES.
Allostery mediates ligand binding to Grb2 adaptor in a mutually exclusive manner
Authors: McDonald Caleb B. , El Hokayem Jimmy , Zafar Nawal , Balke Jordan E. , Bhat Vikas , Mikles David C. , Deegan Brian J. , Seldeen Kenneth L. , Farooq Amjad
Published: January 2013

Allostery plays a key role in dictating the stoichiometry and thermodynamics of multi‐protein complexes driving a plethora of cellular processes central to health and disease. Herein, using various biophysical tools, we demonstrate that although Sos1 nucleotide exchange factor and Gab1 docking protein recognize two non‐overlapping sites within the Grb2 adaptor, allostery promotes the formation of two distinct pools of Grb2–Sos1 and Grb2–Gab1 binary signaling complexes in concert in lieu of a composite Sos1–Grb2–Gab1 ternary complex. Of particular interest is the observation that the binding of Sos1 to the nSH3 domain within Grb2 sterically blocks the binding of Gab1 to the cSH3 domain and vice versa in a mutually exclusive manner. Importantly, the formation of both the Grb2–Sos1 and Grb2–Gab1 binary complexes is governed by a stoichiometry of 2:1, whereby the respective SH3 domains within Grb2 homodimer bind to Sos1 and Gab1 via multivalent interactions. Collectively, our study sheds new light on the role of allostery in mediating cellular signaling machinery. Copyright © 2013 John Wiley & Sons, Ltd.
Regional and local scale atmospheric forcing upon sea level along the coast of SW Europe
Authors: Rasilla Álvarez Domingo F. , García‐Codrón Juan C.
Published: January 2013

Sea level height variability along the coast of southwestern Europe is analyzed in relation with local and regional scale atmospheric forcing mechanisms. A circulation type (CP) catalogue, derived from a combination of principal component analysis and cluster analysis was used to characterize the regional scale atmospheric circulation, whereas the local scale was highlighted through the analysis of hourly wind records during extreme events. A large portion of common anomalous sea level variability at 6‐hourly time frame can be explained by the effect of one CP, depicting a deep extra‐tropical disturbance, close to the Iberian Peninsula, which represents the dominance of the inverse barometer mechanism. Other CPs can induce occasionally similar effects, but showing a spatially restricted scope, in relationship with the location of the main centres of action. Embedded into this synoptic framework, a local forcing, related to both meteorological processes (wind set up) and coastal oceanographic features (depth of the continental shelf) usually control the timing and less frequently, the magnitude of the surges. The decreasing trend observed in the magnitude of the sea level residuals derived from a hindcast model as well as some spatial differences (more intense trend in the upper percentiles along the northern Spain and Mediterranean coasts) can also be explained by long‐term changes in the frequency, and specially, in the internal variability of the CPs, which might be linked to the recent positive phase and eastward displacement of the southern node of the North Atlantic Oscillation. An overall increase in sea level pressure, detected in all CPs, has been accompanied by significant increases in types characterized by anticyclones over the Iberian Peninsula and decreases of northerly flows, related to a reduction of the number of cyclones passing through the Gulf of Biscay and the Western Mediterranean Basin.
Scenario development for estimating potential climate change impacts on crop production in the North China Plain
Authors: Chen Chao , Greene Arthur M. , Robertson Andrew W. , Baethgen Walter E. , Eamus Derek
Published: January 2013

It is important to investigate potential changes in temperature, precipitation and solar radiation for assessing the impacts of future climate change on agricultural production for specific regions. In this study, climate scenarios of precipitation, temperature and solar radiation for the North China Plain (NCP) were constructed in terms of stochastic daily weather sequences. A nonhomogeneous hidden Markov model (NHMM) was used to downscale daily precipitation projections at 32 stations during winter wheat and summer maize growing seasons for a baseline (1966–2005) and a 21st century (2080–2099) A1B scenario, using selected general circulation models (GCMs). A climatological seasonal cycle of regional‐averaged daily reanalysis precipitation was used as input to the down‐scaling for the baseline simulation; this input was then scaled by the precipitation changes from GCM projections to generate down‐scaled stochastic simulations of precipitation in the 21st century. Temperature was generated using a weakly stationary generating process, conditional on precipitation occurrence, with 21st century additive changes taken from the GCMs at the regional scale. Three hypotheses about changes in solar radiation (−20%, 0% and 20%) were made considering the large uncertainty in its future change. The down‐scaled simulations exhibit station increases in the mean daily rainfall of 13.9–69.7% in the scenarios driven by the GCM with the projected largest and multi‐model mean precipitation increase for the wheat season, with changes of 0.4–29.9% for the maize season. In the scenario driven by the GCM with the largest projected precipitation decrease, the simulated rainfall decreases at all stations, with changes ranging from −24.6 to −0.1% for the wheat and maize seasons, respectively. Temperature increases by about 3.7 °C for the wheat season and 3.6 °C for the maize season.
Development and validation studies for determination of phenylpropanoid‐substituted flavan‐3‐ols in semipurified extract of Trichilia catigua by high‐performance liquid chromatography with photodiode array detection
Authors: Longhini Renata , Klein Traudi , Luciano Bruschi Marcos , da Silva Waldir Veríssimo , Rodrigues Juliana , Lopes Norberto Peporine , de Mello João Carlos Palazzo
Published: January 2013

The phenolic compounds are the main phytochemical constituents of the bark of Trichilia catigua and are commonly used for medicinal purposes. An HPLC method for the simultaneous quantification of phenolic compounds (procyanidin B2 (PB2), epicatechin (EPC), chinchonains Ia, Ib, IIa, IIb, catechin, and chrologenic acid) in T. catigua extract was developed and validated. A suitable chromatographic system was selected, which uses a gradient elution with methanol/ACN (75:25), and water both with 0.05% TFA, as mobile phase, column Luna, 280 nm, and flow 0.4 mL/min. Validation of the analytical method was based on the parameters: linearity, precision, LODs and LOQs, accuracy, robustness, and stability. The method showed linearity for PB2 and EPC, in the range 10–120 μg/mL with good correlation coefficients (>0.996). For precision, the repeatability ranged from 1.89 to 3.23%, and the values for accuracy for PB2 and EPC were 95 and 89%, respectively. The LODs and LOQs for PB2 were 1.36 and 4.12 μg/mL, and for EPC were 2.18 and 6.61 μg/mL, respectively. The method was robust under the conditions employed. The proposed method could be employed for quality assessment of T. catigua, as well as pharmaceutical products.
Molecularly imprinted polymer‐based solid phase clean‐up for analysis of ochratoxin A in beer, red wine, and grape juice
Authors: Cao Jiliang , Kong Weijun , Zhou Shujun , Yin Lihui , Wan Li , Yang Meihua
Published: January 2013

A simple, reliable, and low‐cost method based on molecularly imprinted polymer as a selective sorbent of SPE was proposed for the determination of ochratoxin A (OTA) in beer, red wine, and grape juice by HPLC coupled with fluorescence detection (HPLC‐FLD). Samples were diluted with water and cleaned up with an AFFINIMIP® SPE OTA column. After washing and eluting, the analyte was analyzed by HPLC‐FLD. Under the optimized conditions, LOD and LOQ for OTA were 0.025 and 0.08 ng/mL, respectively. The recoveries of OTA from beer, red wine, and grape spiked at 0.1, 2, and 5 ng/mL ranged from 91.6 to 101.7%. Furthermore, after a simple regenerated procedure, the molecularly imprinted polymer based SPE column could be reused at least 14 times to achieve more than 80% recoveries of OTA in real samples. The developed method was applied to the detection of 30 beer, red wine, and grape juice samples and only four samples were contaminated by OTA with levels below the legal limits.
Ultra‐performance LC‐ESI/quadrupole‐TOF MS for rapid analysis of chemical constituents of Shaoyao‐Gancao decoction
Authors: Yin Quanwei , Wang Ping , Zhang Aihua , Sun Hui , Wu Xiuhong , Wang Xijun
Published: January 2013

Shaoyao–Gancao decoction (SGD), a traditional Chinese formulae containing Paeoniae Radix and Glycyrrhizae Radix, is commonly used to relieve abdominal pain. It has attracted increasingly much attention as one of the most popular and valuable herbal medicine in clinic. However, the systematic analysis of chemical constituents of SGD are difficult to determine and thus remain unclear. In this paper, a rapid, sensitive, and reliable ultra‐performance LC‐ESI/quadrupole‐TOF high‐definition MS (UPLC‐ESI‐Q‐TOF‐MS) with automated MetaboLynx analysis in negative ion mode were established to characterize the chemical constituents of SGD. The analysis was performed on a Waters UPLCTM HSS T3 (2.1 × 100 mm, 1.8 μm) using gradient elution system. MS/MS fragmentation behavior was proposed for aiding the structural identification of the components. With the optimized conditions, a total of 58 peaks were tentatively characterized by comparing the retention time and mass spectrometry data and retrieving the reference literatures. Of note, 44 ingredients were identified from Glycyrrhizae Radix, and 14 were from Paeoniae Radix. It is concluded that a rapid and robust platform based on UPLC‐ESI‐Q‐TOF‐MS was successfully developed for globally identifying multiple‐constituent of traditional Chinese medicine prescriptions. This is the first report on systematic analysis of chemical constituents and in vivo metabolites of SGD.
Global attractivity of a discrete SIRS epidemic model with standard incidence rate
Authors: Wang Lei , Teng Zhidong , Jiang Haijun
Published: January 2013

In this paper, a discrete Susceptible‐Infected‐Recovered‐Susceptible (SIRS) epidemic model with standard incidence rate is studied. By means of the iteration technique and the comparison principle of difference equations, the sufficient conditions are obtained for the global attractivity of the endemic equilibrium when the basic reproduction numberis greater than unity. Two examples are given to illustrate the main theoretical results. Copyright © 2013 John Wiley & Sons, Ltd.
Convergence analysis of a linearized Crank–Nicolson scheme for the two‐dimensional complex Ginzburg–Landau equation
Authors: Zhang Ya‐nan , Sun Zhi‐zhong , Wang Ting‐chun
Published: January 2013

A linearized Crank–Nicolson‐type scheme is proposed for the two‐dimensional complex Ginzburg–Landau equation. The scheme is proved to be unconditionally convergent in the L2 ‐norm by the discrete energy method. The convergence order is
\documentclass{article}\usepackage{mathrsfs}\usepackage{amsmath}\pagestyle{empty} \begin{document} \begin{align*}\mathcal{O}(\tau^2+h_1^2+h^2_2)\end{align*} \end{document}, where τ is the temporal grid size and h1,h2 are spatial grid sizes in the x ‐ and y ‐directions, respectively. A numerical example is presented to support the theoretical result. © 2013 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq, 2013
Learning from an epidemiological, population‐based study on prescribed medicine use in adults
Authors: Eckert Kerena A. , Shi Zumin , Taylor Anne W. , Wittert Gary , Price Kay , Goldney Robert D.
Published: January 2013

Objective

The aim of this study was to examine changes in the prevalence of use of prescribed medicines in Australian community samples.

Study design and setting

In this study, face‐to‐face interviews were carried out with random, representative samples of South Australian adults, aged ≥15 years. Data on self‐reported use of prescribed medicines, most commonly reported categories of prescribed medicines and use of multiple medicines for common body systems were collected. It was not possible to distinguish between medicines prescribed for acute and chronic use.

Results

A total of 3015 respondents were interviewed in 2004 and 3034 in 2008, representing participation rates of 76% and 73%. There was no significant increase in the prevalence of use of ≥1 (46.8% vs 47.3%, p = 0.6) or ≥6 medicines (5.7% vs 5.5%, p = 0.7). In both years, the use of medicines was higher in women (56.7% vs 57.5%). On subgroup analyses, a significant reduction in the use of medicines was observed in respondents aged 15–24 (25.0% vs 18.5%, p = 0.01) and ≥65 years (87.7% vs 82.5%, p = 0.01), whereas use in those aged 35–44 years increased significantly (26.4% vs 33.6%, p = 0.01). The number of cardiovascular system agents (23.1% vs 24.6%, p = 0.20) and psychotropic medicines (9.8% vs 10.6%, p = 0.35) used by respondents remained unchanged while use of respiratory (7.2% vs 5.7%, p = 0.01) and musculoskeletal system medicines (8.7% vs 5.6% p= < 0.001) decreased significantly.

Conclusions

In presenting what we believe is the first Australian population‐based study to compare changes in prescribed medicines across the adult age spectrum, we highlight some key questions to ensure the quality use of medicines. Our findings identify a need to discuss de‐prescribing, monitor practices to minimise adverse events and challenge if consumers and prescribers need to consider the costs to governments of medicines. Copyright © 2013 John Wiley & Sons, Ltd.
Validation of an algorithm to estimate gestational age in electronic health plan databases
Authors: Li Qian , Andrade Susan E. , Cooper William O. , Davis Robert L. , Dublin Sascha , Hammad Tarek A. , Pawloski Pamala A. , Pinheiro Simone P. , Raebel Marsha A. , Scott Pamela E. , Smith David H. , Dashevsky Inna , Haffenreffer Katherine , Johnson Karin E. , Toh Sengwee
Published: January 2013

Purpose

To validate an algorithm that uses delivery date and diagnosis codes to define gestational age at birth in electronic health plan databases.

Methods

Using data from 225 384 live born deliveries to women aged 15–45 years in 2001–2007 within eight of the 11 health plans participating in the Medication Exposure in Pregnancy Risk Evaluation Program, we compared (1) the algorithm‐derived gestational age versus the “gold‐standard” gestational age obtained from the infant birth certificate file and (2) the prenatal exposure status of two antidepressants (fluoxetine and sertraline) and two antibiotics (amoxicillin and azithromycin) as determined by the algorithm‐derived versus the gold‐standard gestational age.

Results

The mean algorithm‐derived gestational age at birth was lower than the mean obtained from the birth certificate file among singleton deliveries (267.9 vs 273.5 days) but not among multiple‐gestation deliveries (253.9 vs 252.6 days). The algorithm‐derived prenatal exposure to the antidepressants had a sensitivity and a positive predictive value of ≥95%, and a specificity and a negative predictive value of almost 100%. Sensitivity and positive predictive value were both ≥90%, and specificity and negative predictive value were both >99% for the antibiotics.

Conclusions

A gestational age algorithm based upon electronic health plan data correctly classified medication exposure status in most live born deliveries, but trimester‐specific misclassification may be higher for drugs typically used for short durations. Copyright © 2013 John Wiley & Sons, Ltd.
Reducing the psychological distress of family caregivers of home‐based palliative care patients: short‐term effects from a randomised controlled trial
Authors: Hudson Peter , Trauer Tom , Kelly Brian , O'Connor Moira , Thomas Kristina , Summers Michael , Zordan Rachel , White Vicki
Published: January 2013

Background

Palliative care is expected to incorporate comprehensive support for family caregivers given that many caregivers suffer psychological morbidity. However, systematically implemented evidence‐based psychological support initiatives are lacking.

Aim

The objective of this study was to prepare caregivers for the role of supporting a patient with advanced cancer receiving home‐based palliative care by offering a one‐to‐one psycho‐educational intervention. We hypothesised that primary family caregivers who participated in the intervention would report decreased psychological distress (primary outcome), fewer unmet needs and increased levels of perceived preparedness, competence and positive emotions.

Methods

A three‐arm randomised controlled trial was conducted comparing two versions of the intervention (one face‐to‐face visit versus two visits) plus standard care to a control group (standard care) across four sites in Australia.

Results

A total of 298 participants were recruited; 148 were in the Control condition, 57 in Intervention 1 (one visit) and 93 in Intervention 2 (two visits). Relative to participants in the control group; the psychological well‐being of participants in the intervention condition was improved by a small amount but non‐significantly. No significant reduction in unmet needs or improvements in positive aspects of caregiving amongst the intervention group were identified. However, the intervention demonstrated significant improvements in participants' levels of preparedness and competence for Intervention 2.

Conclusion/implications

This research adds to accumulating body of evidence demonstrating that relatively short psycho‐educational interventions can enable family caregivers to feel more prepared and competent in the role of supporting a dying relative. Further investigation is required to determine the longer term outcomes of such interventions. Copyright © 2013 John Wiley & Sons, Ltd.
Job Characteristics, Recovery Experiences and Occupational Well‐being: Testing Cross‐lagged Relationships across 1 Year
Authors: Kinnunen Ulla , Feldt Taru
Published: January 2013

The aim of the present study conducted among 274 Finnish employees was to examine the relationships between job characteristics, recovery experiences and occupational well‐being across 1 year. We hypothesized that these relationships would follow normal causation, that is, job characteristics at T1 predict recovery experiences (detachment, relaxation, mastery and control at off‐job time) and well‐being (fatigue at work and work engagement) at T2, and recovery experiences at T1 predict well‐being at T2. The structural equation modelling analyses lent support to the hypothesized normal causation model compared with the reversed causation and reciprocal models. However, only the longitudinal relationships between job characteristics and recovery experiences were significant. More specifically, high job demands at T1 predicted poor detachment, relaxation and control during off‐job time at T2; and high job resources at T1 predicted high mastery experiences in off‐job time at T2. Thus, our study showed that job demands in particular inhibited recovery experiences in the long term, but this was not reflected in employee well‐being across 1 year. Copyright © 2013 John Wiley & Sons, Ltd.