bluuebunny/crossref_metadata_2025 huggingface dataset:
Adaptive capacity of the Adjusted Clinical Groups Case-Mix System to the cost of primary healthcare in Catalonia (Spain): a observational study
Authors: Sicras-Mainar Antoni , Velasco-Velasco Soledad , Navarro-Artieda Ruth , Prados-Torres Alexandra , Bolibar-Ribas Buenaventura , Violan-Fors Concepción ,   for the ACG Study Group
Published: June 2012

Objectives

To describe the adaptive capacity of the Adjusted Clinical Groups (ACG) system to the cost of care in primary healthcare centres in Catalonia (Spain).

Design

Retrospective study (multicentres) conducted using computerised medical records.

Setting

13 primary care teams in 2008 were included.

Participants

All patients registered in the study centres who required care between 1 January and 31 December 2008 were finally studied. Patients not registered in the study centres during the study period were excluded.

Outcome measures

Demographic (age and sex), dependent (cost of care) and case-mix variables were studied. The cost model for each patient was established by differentiating the fixed and variable costs. To evaluate the adaptive capacity of the ACG system, Pearson's coefficient of variation and the percentage of outliers were calculated. To evaluate the explanatory power of the ACG system, the authors used the coefficient of determination (R2).

Results

The number of patients studied was 227 235 (frequency: 5.9 visits per person per year), with a mean of 4.5 (3.2) episodes and 8.1 (8.2) visits per patient per year. The mean total cost was €654.2. The explanatory power of the ACG system was 36.9% for costs (56.5% without outliers). 10 ACG categories accounted for 60.1% of all cases and 19 for 80.9%. 5 categories represented 71% of poor performance (N=78 887, 34.7%), particularly category 0300-Acute Minor, Age 6+ (N=26 909, 11.8%), which had a coefficient of variation =139% and 6.6% of outliers.

Conclusions

The ACG system is an appropriate manner of classifying patients in routine clinical practice in primary healthcare centres in Catalonia, although improvements to the adaptive capacity through disaggregation of some categories according to age groups and, especially, the number of acute episodes in paediatric patients would be necessary to reduce intra-group variation.
Barriers and facilitators to change in the organisation and delivery of endoscopy services in England and Wales: a focus group study
Authors: Rapport Frances , Seagrove Anne C , Hutchings Hayley A , Russell Ian T , Cheung Ivy , Williams John G , Cohen David
Published: June 2012

Objective

Explore professional views of changes to gastroenterology service organisation and delivery and barriers and facilitators impacting on change. The work was undertaken as part of an evaluation in endoscopy service provision catalysed by the Modernising Endoscopy Services Programme of the Modernisation Agency.

Design

Focus groups followed by analysis and group-working activities identifying key themes.

Setting

English and Welshsecondary care gastroenterology units.

Participants

20 professionals working in gastroenterology in England and Wales. Medical, surgical and nursing specialists including endoscopy nurses. Opportunistic sampling to include senior people in leadership and management roles who were directly involved in service modernisation, excluding those involved in the Modernisation Endoscopy Services Programme.

Results

Four 1.5 h focus groups took place in 2007. Summative and thematic analyses captured essential aspects of text and achieved consensus on key themes. 4 themes were revealed: ‘loss of personal autonomy and erosion of professionalism’, ‘lack of senior management understanding’, ‘barriers and facilitators to change’ and ‘differences between English and Welsh units’. Themes indicated that low staff morale, lack of funding and senior management support were barriers to effective change. Limitations to the study include the disproportionately low number of focus group attendees from English units and the time delay in reporting these findings.

Conclusions

Despite ambitions to implement change, ineffective management support continued to hamper modernisation of service organisation and delivery. While the National Health Service Modernisation Agency Modernising Endoscopy Services Programme acted as a catalyst for change, affecting the way staff work, communicate and think, it was not effective in heralding change itself. However, gastroenterologists were keen to consider the potential for change and future service modernisation. The methodological framework of innovative qualitative enquiry offers comprehensive and rigorous enhancement of quantitative studies, including randomised trials, when a mixed methods approach is needed.
Comparing the effectiveness of using generic and specific search terms in electronic databases to identify health outcomes for a systematic review: a prospective comparative study of literature search methods
Authors: Egan Matt , MacLean Alice , Sweeting Helen , Hunt Kate
Published: June 2012

Objective

To compare the effectiveness of systematic review literature searches that use either generic or specific terms for health outcomes.

Design

Prospective comparative study of two electronic literature search strategies. The ‘generic’ search included general terms for health such as ‘adolescent health’, ‘health status’, ‘morbidity’, etc. The ‘specific’ search focused on terms for a range of specific illnesses, such as ‘headache’, ‘epilepsy’, ‘diabetes mellitus’, etc.

Data sources

The authors searched Medline, Embase, the Cumulative Index to Nursing and Allied Health Literature, PsycINFO and the Education Resources Information Center for studies published in English between 1992 and April 2010.

Main outcome measures

Number and proportion of studies included in the systematic review that were identified from each search.

Results

The two searches tended to identify different studies. Of 41 studies included in the final review, only three (7%) were identified by both search strategies, 21 (51%) were identified by the generic search only and 17 (41%) were identified by the specific search only. 5 of the 41 studies were also identified through manual searching methods. Studies identified by the two ELS differed in terms of reported health outcomes, while each ELS uniquely identified some of the review's higher quality studies.

Conclusions

Electronic literature searches (ELS) are a vital stage in conducting systematic reviews and therefore have an important role in attempts to inform and improve policy and practice with the best available evidence. While the use of both generic and specific health terms is conventional for many reviewers and information scientists, there are also reviews that rely solely on either generic or specific terms. Based on the findings, reliance on only the generic or specific approach could increase the risk of systematic reviews missing important evidence and, consequently, misinforming decision makers. However, future research should test the generalisability of these findings.
Socioeconomic position and the risk of spontaneous abortion: a study within the Danish National Birth Cohort
Authors: Norsker Filippa Nyboe , Espenhain Laura , á Rogvi Sofie , Morgen Camilla Schmidt , Andersen Per Kragh , Nybo Andersen Anne-Marie
Published: June 2012

Objectives

To investigate the relationship between different indicators of socioeconomic position and the risk of spontaneous abortion.

Design

Cohort study.

Setting

1996–2002, Denmark.

Participants

All first time participants, a total of 89 829 pregnant women, enrolled in the Danish National Birth Cohort were included in the present study. Overall, 4062 pregnancies ended in spontaneous abortion. Information on education, income and labour market attachment in the year before pregnancy was drawn from national registers.

Main outcome measure

Spontaneous abortion, that is, fetal death within the first 22 weeks of pregnancy, was the outcome of interest. The authors estimated HRs of spontaneous abortion using Cox regression analysis with gestational age as the underlying time scale.

Results

Women with <10 years of education had an elevated risk of spontaneous abortion when compared with women with >12 years of education (HR 1.19 (95% CI 1.05 to 1.34)). The HR estimates for the four lowest income quintiles were all increased (HRs between 1.09 and 1.15) as compared with the upper quintile but did not differ considerably from each other. In general, no statistically significant association was found between labour market attachment and the risk of spontaneous abortion; however, the group of women on disability pension had an increased HR of spontaneous abortion when compared with women who were employed (HR 1.32 (95% CI 0.82 to 2.13)).

Conclusions

Educational level and income were inversely associated with the risk of spontaneous abortion. As these factors most likely are non-causally related to spontaneous abortion, the findings indicate that factors related to social position, probably of the environmental and behavioural type, may affect spontaneous abortion risk. The study highlights the need for studies addressing such exposures in order to prevent spontaneous abortions.
Acupuncture for acute non-specific low back pain: a protocol for a randomised, controlled multicentre intervention study in general practice—the Acuback Study: Figure 1
Authors: Skonnord Trygve , Skjeie Holgeir , Brekke Mette , Grotle Margreth , Lund Iréne , Fetveit Arne
Published: June 2012

Introduction

Some general practitioners (GPs) treat acute low back pain (LBP) with acupuncture, despite lacking evidence of its effectiveness for this condition. The aim of this study was to evaluate whether a single treatment session with acupuncture can reduce time to recovery when applied in addition to standard LBP treatment according to the Norwegian national guidelines. Analyses of prognostic factors for recovery and cost-effectiveness will also be carried out.

Methods and analysis

In this randomised, controlled multicentre study in general practice in Southern Norway, 270 patients will be allocated into one of two treatment groups, using a web-based application based on block randomisation. Outcome assessor will be blinded for group allocation of the patients. The control group will receive standard treatment, while the intervention group will receive standard treatment plus acupuncture treatment. There will be different GPs treating the two groups, and both groups will just have one consultation. Adults who consult their GP because of acute LBP will be included. Patients with nerve root affection, ‘red flags’, pregnancy, previous sick leave more than 14 days and disability pension will be excluded. The primary outcome of the study is the median time to recovery (in days). The secondary outcomes are rated global improvement, back-specific functional status, sick leave, medication, GP visits and side effects. A pilot study will be conducted.

Ethics and dissemination

Participation is based on informed written consent. The authors will apply for an ethical approval from the Regional Committee for Medical and Health Research Ethics when the study protocol is published. Results from this study, positive or negative, will be disseminated in scientific medical journals.

Trial Registration Number

ClinicalTrials.gov Identifier:NCT01439412.
Protocol for an observation and implementation study investigating optimisation of the management of stroke and transient ischaemic attack (TIA)
Authors: Sheppard James Peter , Mellor Ruth Mary , Bailey Sheila Marie , Barton Pelham , Boyal Amunpreet , Greenfield Sheila , Jowett Sue , Mant Jonathan , Quinn Tom , Singh Satinder , McManus Richard J ,   on behalf of the BBC CLAHRC Investigators
Published: June 2012

Introduction

Patients benefit from early and intensive treatment in both acute ischaemic stroke and transient ischaemic attack. Recent audits of acute stroke/transient ischaemic attack care suggest that although standards have improved, current services still fall short of optimal care. The aim of this study is to establish a database of patients accessing stroke services. Data will be collected and analysed to provide individualised feedback to healthcare professionals who can then use these findings to develop strategies for service improvement.

Methods and analysis

This longitudinal observational study will evolve with the ongoing findings from the research output. The project will consist of three phases: assessment of current practice, feedback of findings and evaluation of service change. Consecutive patients will be recruited from participating hospitals, and identifiable data will be collected to link records from the Primary Care, Secondary Care and Emergency Services. As this study focuses on observation of current practice, a sample size calculation is not deemed appropriate. Patients will be sent follow-up questionnaires examining quality of life at 3 and 12 months post-event. Qualitative interviews will examine the care pathway through the experiences of patients, their carers, healthcare personnel and commissioners. Collected data will be used in economic analyses, which will evaluate the impact of current care and service redesign on the NHS costs and patient outcomes (death and quality of life).

Ethics and dissemination

Ethical approval for this study has been obtained from the National Research Ethics Committee (reference; 09/H0716/71), and site-specific R&D approval has been acquired from the relevant NHS trusts. All findings will be presented at relevant healthcare/academic conferences and written up for publication in peer-reviewed journals. Results will be fed back to patients and participating trusts through a series of reports and presentations. These will be used to facilitate discussions about service redesign and implementation.
Network structure and the role of key players in a translational cancer research network: a study protocol
Authors: Long Janet C , Cunningham Frances C , Braithwaite Jeffrey
Published: June 2012

Introduction

Translational research networks are a deliberate strategy to bridge the gulf between biomedical research and clinical practice through interdisciplinary collaboration, supportive funding and infrastructure. The social network approach examines how the structure of the network and players who hold important positions within it constrain or enable function. This information can be used to guide network management and optimise its operations. The aim of this study was to describe the structure of a translational cancer research network (TCRN) in Australia over its first year, identify the key players within the network and explore these players' opportunities and constraints in maximising important network collaborations.

Methods and analysis

This study deploys a mixed-method longitudinal design using social network analysis augmented by interviews and review of TCRN documents. The study will use network documents and interviews with governing body members to explore the broader context into which the network is embedded as well as the perceptions and expectations of members. Of particular interest are the attitudes and perceptions of clinicians compared with those of researchers. A co-authorship network will be constructed of TCRN members using journal and citation databases to assess the success of past pre-network collaborations. Two whole network social network surveys will be administered 12 months apart and parameters such as density, clustering, centrality and betweenness centrality computed and compared using UCINET and Netdraw. Key players will be identified and interviewed to understand the specific activities, barriers and enablers they face in that role.

Ethics and dissemination

Ethics approvals were obtained from the University of New South Wales, South Eastern Sydney Northern Sector Local Health Network and Calvary Health Care Sydney. Results will be discussed with members of the TCRN, submitted to relevant journals and presented as oral presentations to clinicians, researchers and policymakers.
EDAX SPECTRA AS A TOOL TO EVALUATE STRUCTURAL, COMPOSITIONAL AND ELECTRICAL PARAMETERS
Authors: KAVITHA B. , DHANAM M.
Published: July 2012

Near-stoichiometric and stoichiometric Cu(InAl)Se2 (CIAS) thin films have been prepared by successive ionic layer adsorption and reaction (SILAR) onto well-cleaned substrates. energy dispersive X-ray analysis (EDAX) spectra of the prepared thin films enabled to determine the film composition, stoichiometry nature, type of conductivity, lattice constants, volume of the unit cell and density of CIAS thin films. The estimated compositional, structural and electrical parameters are presented and discussed in this paper in detail.
APPROACHES TO LENIENCY REDUCTION IN MULTI-CRITERIA DECISION MAKING WITH INTERVAL-VALUED FUZZY SETS AND AN EXPERIMENTAL ANALYSIS
Authors: CHEN TING-YU
Published: July 2012

The purpose of this paper is to present a useful method for estimating the importance of criteria and reducing the leniency bias in multiple criteria decision analysis based on interval-valued fuzzy sets. Several types of net predispositions are defined to represent an aggregated effect of interval-valued fuzzy evaluations. The suitability function for measuring the overall evaluation of each alternative is then determined based on simple additive weighting (SAW) methods. Because positive or negative leniency may exist when most criteria are assigned unduly high or low ratings, respectively, deviation variables are introduced to mitigate the effects of overestimated and underestimated ratings of criterion importance. Considering the two objectives of maximal weighted suitability and minimal deviation values, an integrated programming model is proposed to compute optimal weights for the criteria and corresponding suitability degrees for alternative rankings. A flexible algorithm using interval-valued fuzzy SAW methods is established by considering both objective and subjective information to compute optimal multiple criteria decisions. The feasibility and effectiveness of the proposed methods are illustrated by a numerical example. Finally, an experimental analysis of interval-valued fuzzy rankings given different conditions for the criterion weights is conducted with discussions on average Spearman correlation coefficients and contradiction rates.
A METHOD BASED ON MEAN DEVIATION FOR WEIGHT DETERMINATION FROM FUZZY PREFERENCE RELATIONS AND MULTIPLICATIVE PREFERENCE RELATIONS
Authors: XU YEJUN , PATNAYAKUNI RAVI , WANG HUIMIN
Published: July 2012

The group decision-making problem is studied, in which the experts provide their preference information by different formats, i.e., multiplicative preference relations and fuzzy preference relations. The net flow scores of fuzzy preference relations and multiplicative preference relations are introduced. The mean deviation method is developed to determine the relative weights of individual different preference relations objectively and then select the most desirable alternative(s) according to the aggregated net flow scores. The method does not need to transform the experts' preference relations into the same format and also does not produce any loss of information. Finally, the proposed method is tested and examined with three examples and proved to be simple, effective and practical.
Contemporary Anthropologies of Indigenous Australia
Authors: Lea Tess
Published: July 2012

This review covers sociocultural ethnographies of indigenous Australia from the 1970s to the present. It explores three trends: ethnographic reckonings with indigenous encapsulation within a liberal-settler state; the influence of international theoretical emphases; and movements toward an anthropology of the otherwise. The advent of land repossession, and the ethnographic and employment opportunities this created, indelibly shaped the discipline. With their immersion in land rights and native title, anthropologists were also embroiled in the state adjudication of indigeneity. Beyond the courts, the discipline struggled to shake the strictures of area studies and its ongoing, if unrecognized, imbrication in statist cultural logics. Consequently, indigenist anthropologies have not shifted, but perhaps helped affirm, the West's sense of being the apex of modernity. Emergent approaches, which refuse the ossifications of statist logics using forms of immersion and multimedia ethnography, show signs of ways forward.
Phenomenological Approaches in Landscape Archaeology
Authors: Johnson Matthew H.
Published: July 2012

This review explores why phenomenology has been such a popular theme in landscape archaeology in the last two decades—and why it has also provoked anger and controversy. The article concentrates less on the philosophical essence of phenomenological traditions than on their practical applications and context, particularly within British landscape archaeology. Criticisms of phenomenological approaches are reviewed and suggestions for future research made. The review concludes that research into landscape and human subjectivity will continue to be a strong research theme, whether or not such work explicitly derives its theoretical approach from phenomenology.
RNA Interference Pathways in Fungi: Mechanisms and Functions
Authors: Chang Shwu-Shin , Zhang Zhenyu , Liu Yi
Published: July 2012

RNA interference (RNAi) is a conserved eukaryotic gene regulatory mechanism that uses small noncoding RNAs to mediate posttranscriptional/transcriptional gene silencing. The fission yeast Schizosaccharomyces pombe and the filamentous fungus Neurospora crassa have served as important model systems for RNAi research. Studies on these two organisms and other fungi have contributed significantly to our understanding of the mechanisms and functions of RNAi in eukaryotes. In addition, surprisingly diverse RNAi-mediated processes and small RNA biogenesis pathways have been discovered in fungi. In this review, we give an overview of different fungal RNAi pathways with a focus on their mechanisms and functions.
Independent and Confluent Middle Mesial Root Canals in Mandibular First Molars: A Report of Four Cases
Authors: Deepalakshmi Mohanavelu , Karumaran Chellasamy Savarimala , Miglani Revathi , Indira Rajamani
Published: June 2012

Mandibular molars demonstrate considerable variations with respect to number of roots and root canals. The possibility of additional root canals should be considered even in teeth with a low frequency of abnormal root canal anatomy. This paper discusses the endodontic management of the rare anatomical complexity middle mesial canals in mandibular first molar and also serves to remind the clinicians that such anatomical variations should be taken into account during the endodontic treatment of the mandibular molars.
On Decomposable Measures Induced by Metrics
Authors: Qiu Dong , Zhang Weiquan
Published: July 2012

We prove that for a given normalized compact metric space it can induce a σ‐max‐superdecomposable measure, by constructing a Hausdorff pseudometric on its power set. We also prove that the restriction of this set function to the algebra of all measurable sets is a σ‐max‐decomposable measure. Finally we conclude this paper with two open problems.
Advanced Presentation of BETHSY 6.2TC Test Results Calculated by RELAP5 and TRACE
Authors: Prošek Andrej , Berar Ovidiu-Adrian
Published: June 2012

Today most software applications come with a graphical user interface, including U.S. Nuclear Regulatory Commission TRAC/RELAP Advanced Computational Engine (TRACE) best-estimate reactor system code. The graphical user interface is called Symbolic Nuclear Analysis Package (SNAP). The purpose of the present study was to assess the TRACE computer code and to assess the SNAP capabilities for input deck preparation and advanced presentation of the results. BETHSY 6.2 TC test was selected, which is 15.24 cm equivalent diameter horizontal cold leg break. For calculations the TRACE V5.0 Patch 1 and RELAP5/MOD3.3 Patch 4 were used. The RELAP5 legacy input deck was converted to TRACE input deck using SNAP. The RELAP5 and TRACE comparison to experimental data showed that TRACE results are as good as or better than the RELAP5 calculated results. The developed animation masks were of great help in comparison of results and investigating the calculated physical phenomena and processes.
Improved Low-Profile Helical Antenna Design for INMARSAT Applications
Authors: Fu Shiqiang , Cao Yuan , Zhou Yue , Fang Shaojun
Published: June 2012

A new low-profile variable pitch angle cylindrical helical antenna employing a copper strip as impedance transformer is proposed in this paper. Under the circumstance of a limited antenna height, the circular polarization performance of the antenna has been enhanced by changing the pitch angle and the input impedance matching has been improved by adjusting the copper strip match stub. The design method of the proposed antenna is given. The optimal antenna structure for INMARSAT application has been fabricated and measured. The measured results show that in the whole maritime satellite communication work band the VSWR is less than 1.2, its antenna gain is higher than 9 dBi, and the axial ratio is lower than 2.5 dB. The experimental results have a good agreement with the simulations. The proposed antenna is compact and easy tuning. It provides a promising antenna element for maritime satellite communication applications.
Finding Transcription Factor Binding Motifs for Coregulated Genes by Combining Sequence Overrepresentation with Cross-Species Conservation
Authors: Jia Hui , Li Jinming
Published: June 2012

Novel computational methods for finding transcription factor binding motifs have long been sought due to tedious work of experimentally identifying them. However, the current prevailing methods yield a large number of false positive predictions due to the short, variable nature of transcriptional factor binding sites (TFBSs). We proposed here a method that combines sequence overrepresentation and cross-species sequence conservation to detect TFBSs in upstream regions of a given set of coregulated genes. We applied the method to 35S. cerevisiaetranscriptional factors with known DNA binding motifs (with the support of orthologous sequences from genomes ofS. mikatae,S. bayanus, andS. paradoxus), and the proposed method outperformed the single-genome-based motif finding methodsMEMEandAlignACEas well as the multiple-genome-based methodsPHYMEandFootprinterfor the majority of these transcriptional factors. Compared with the prevailing motif finding software, our method has some advantages in finding transcriptional factor binding motifs for potential coregulated genes if the gene upstream sequences of multiple closely related species are available. Although we used yeast genomes to assess our method in this study, it might also be applied to other organisms if suitable related species are available and the upstream sequences of coregulated genes can be obtained for the multiple closely related species.
Modeling and Analysis of Epidemic Diffusion within Small‐World Network
Authors: Liu Ming , Xiao Yihong
Published: June 2012

To depict the rule of epidemic diffusion, two different models, the Susceptible‐Exposure‐Infected‐Recovered‐Susceptible (SEIRS) model and the Susceptible‐Exposure‐Infected‐Quarantine‐Recovered‐Susceptible (SEIQRS) model, are proposed and analyzed within small‐world network in this paper. Firstly, the epidemic diffusion models are constructed with mean‐filed theory, and condition for the occurrence of disease diffusion is explored. Then, the existence and global stability of the disease‐free equilibrium and the endemic equilibrium for these two complex epidemic systems are proved by differential equations knowledge and Routh‐Hurwiz theory. At last, a numerical example which includes key parameters analysis and critical topic discussion is presented to test how well the proposed two models may be applied in practice. These works may provide some guidelines for decision makers when coping with epidemic diffusion controlling problems.
Treatment of Dentine Hypersensitivity by Diode Laser: A Clinical Study
Authors: Umberto Romeo , Claudia Russo , Gaspare Palaia , Gianluca Tenore , Alessandro Del Vecchio
Published: June 2012

Introduction. Dentine hypersensitivity (DH) is characterized by pain after stimuli that usually provoke no symptoms. This study compared the effectiveness of GaAlAs diode laser alone and with topical sodium fluoride gel (NaF).Materials and Methods. The study was conducted on 10 patients (8 F/2 M, age 25–60) and 115 teeth with DH assessed by air and tactile stimuli measured by Numeric Rating Scale (NRS). Teeth were randomly divided into G1 (34 teeth) treated by 1.25% NaF; G2 (33 teeth) lased at 0.5 W PW (T on 100 m and T off 100 ms), fluence 62.2 J/cm2in defocused mode with a 320 μfiber. Each tooth received three 1′ applications; G3 (48 teeth) received NaF gel plus laser at same G2 parameters. NRS was checked at each control.Results. Significant pain reduction was showed. The NRS reduction percentages were calculated, and there was a concrete decrease of DH above all in G3 than G2 and G1.Conclusion. Diode laser is a useful device for DH treatment if used alone and mainly if used with NaF gel.
On Almost Orthogonal Frames
Authors: Virender  , Zothansanga A. , Kaushik S. K.
Published: June 2012

Almost orthogonal frames have been introduced and studied. It has been proved that a bounded almost orthogonal frame satisfies Feichtinger conjecture. Also, we prove that a bounded almost orthogonal frame contains a Riesz basis.
On the Solvability of Discrete Nonlinear Two-Point Boundary Value Problems
Authors: Kone Blaise , Ouaro Stanislas
Published: June 2012

We prove the existence and uniqueness of solutions for a family of discrete boundary value problems by using discrete's Wirtinger inequality. The boundary condition is a combination of Dirichlet and Neumann boundary conditions.
Investment Trait, Activity Engagement, and Age: Independent Effects on Cognitive Ability
Authors: von Stumm Sophie
Published: June 2012

In cognitive aging research, the “engagement hypothesis” suggests that the participation in cognitively demanding activities helps maintain better cognitive performance in later life. In differential psychology, the “investment” theory proclaims that age differences in cognition are influenced by personality traits that determine when, where, and how people invest their ability. Although both models follow similar theoretical rationales, they differ in their emphasis of behavior (i.e., activity engagement) versus predisposition (i.e., investment trait). The current study compared a cognitive activity engagement scale (i.e., frequency of participation) with an investment trait scale (i.e., need for cognition) and tested their relationship with age differences in cognition in 200 British adults. Age was negatively associated with fluid and positively with crystallized ability but had no relationship with need for cognition and activity engagement. Need for cognition was positively related to activity engagement and cognitive performance; activity engagement, however, was not associated with cognitive ability. Thus, age differences in cognitive ability were largely independent of engagement and investment.
Association of Intrarenal B-Cell Infiltrates with Clinical Outcome in Lupus Nephritis: A Study of 192 Cases
Authors: Shen Yan , Sun Chuan-Yin , Wu Feng-Xia , Chen Yi , Dai Min , Yan Yu-Cheng , Yang Cheng-De
Published: June 2012

Background. Lupus nephritis (LN) remains a major cause of morbidity and end-stage renal disease. Dysfunction of B lymphocytes is thought to be important in the pathogenesis of SLE/LN. Intrarenal B cells have been found in several forms of inflammatory kidney diseases although their role in LN renal is not well defined.Methods. Intrarenal B cells were analyzed in 192 renal biopsies from patients diagnosed with lupus nephritis. Immunohistochemical staining of serial sections was performed for each LN patient using CD20, CD3, and CD21 antibodies.Results. Intrarenal B cells were more likely to be associated with class IV LN and were mainly distributed in the renal interstitium, with very few in the glomerulus. The systemic lupus erythematosus disease activity index (SLEDAI), blood urea nitrogen, and serum creatinine levels were all significantly greater in the LN-B cell groups (allP<0.05). LN renal activity and chronicity indices correlated with B-cells infiltrates (allP<0.0001). Renal biopsies were classified into four distinct categories according to the organizational grade of inflammatory cell infiltrates. Germinal center- (GC-) like structures were not identified in any LN biopsies.Conclusion. It is hypothesized that intrarenal B cells enhance immunological responses and exaggerate the local immune response to persisting autoimmune damage in the tubulointerstitium.
Surface-Enhanced Raman Scattering as an Emerging Characterization and Detection Technique
Authors: Culha Mustafa , Cullum Brian , Lavrik Nickolay , Klutse Charles K.
Published: June 2012

While surface-enhanced Raman spectroscopy (SERS) has been attracting a continuously increasing interest of scientific community since its discovery, it has enjoyed a particularly rapid growth in the last decade. Most notable recent advances in SERS include novel technological approaches to SERS substrates and innovative applications of SERS in medicine and molecular biology. While a number of excellent reviews devoted to SERS appeared in the literature over the last two decades, we will focus this paper more specifically on several promising trends that have been highlighted less frequently. In particular, we will briefly overview strategies in designing and fabricating SERS substrates using deterministic patterning and then cover most recent biological applications of SERS.
Regional Blockade of the Shoulder: Approaches and Outcomes
Authors: Bowens Clifford , Sripada Ramprasad
Published: June 2012

The article reviews the current literature regarding shoulder anesthesia and analgesia. Techniques and outcomes are presented that summarize our present understanding of regional anesthesia for the shoulder. Shoulder procedures producing mild to moderate pain may be managed with a single-injection interscalene block. However, studies support that moderate to severe pain, lasting for several days is best managed with a continuous interscalene block. This may cause increased extremity numbness, but will provide greater analgesia, reduce supplemental opioid consumption, improve sleep quality and patient satisfaction. In comparison to the nerve stimulation technique, ultrasound can reduce the volume of local anesthetic needed to produce an effective interscalene block. However, it has not been shown that ultrasound offers a definitive benefit in preventing major complications. The evidence indicates that the suprascapular and/or axillary nerve blocks are not as effective as an interscalene block. However in patients who are not candidates for the interscalene block, these blocks may provide a useful alternative for short-term pain relief. There is substantial evidence showing that subacromial and intra-articular injections provide little clinical benefit for postoperative analgesia. Given that these injections may be associated with irreversible chondrotoxicity, the injections are not presently recommended.
SDSim: A Novel Simulator for Solar Drying Processes
Authors: Bolea Yolanda , Grau Antoni , Miranda Alexandre
Published: June 2012

SDSim is a novel solar dryer simulator based in a multicrop, inclined multipass solar air heather with in‐built thermal storage mathematical model. This model has been developed as a designing and developing tool used to study and forecast the behavior of the system model in order to improve its drying efficiency and achieving a return on the dryer investment. The main feature of this simulator is that most of the parameters are permitted to be changed during the simulation process allowing finding the more suitable system for any specific situation with a user‐friendly environment. The model has been evaluated in a real solar dryer system by comparing model estimates to collected data.
Decreased Apoptotic Rate of Alveolar Macrophages of Patients with Idiopathic Pulmonary Fibrosis
Authors: Drakopanagiotakis Fotios , Xifteri Areti , Tsiambas Evaggelos , Karameris Andreas , Tsakanika Konstantina , Karagiannidis Napoleon , Mermigkis Demetrios , Polychronopoulos Vlasis , Bouros Demosthenes
Published: June 2012

Introduction. Increased apoptosis of epithelial cells and decreased apoptosis of myofibroblasts are involved in the pathogenesis of IPF. The apoptotic profile of alveolar macrophages (AMs) in IPF is unclear.Aim. To investigate whether AMs of patients with IPF exhibit a different apoptotic profile compared to normal subjects.Methods. We analyzed, by immunohistochemistry, the expression of the apoptotic markers fas, fas ligand , bcl-2, and bax in AM obtained from bronchoalveolar lavage fluid (BALF) of 20 newly diagnosed, treatment-naive IPF patients and of 16 controls. Apoptosis of AM was evaluated by Apoptag immunohistochemistry. IPF patients received either interferon-g and corticosteroids or azathioprine and corticosteroids for six months.Results. BALF AMs undergoing apoptosis were significantly less in IPF patients. No difference was found in the expression of fas or fas ligand, bcl-2 and bax between IPF and control group. No difference was found between the respiratory function parameters of the two treatment groups after six months. A positive correlation was found between the number of bcl-2 positive stained macrophages and DLCO after treatment.Conclusions. The decreased apoptotic rate of AM of patients with IPF is not associated with decreased expression of apoptosis mediators involved in the external or internal apoptotic pathway.
Combination Small Molecule MEK and PI3K Inhibition Enhances Uveal Melanoma Cell Death in a Mutant GNAQ- and GNA11-Dependent Manner
Authors: Khalili Jahan S. , Yu Xiaoxing , Wang Ji , Hayes Brendan C. , Davies Michael A. , Lizee Gregory , Esmaeli Bita , Woodman Scott E.
Published: June 2012

Purpose: Activating Q209L/P mutations in GNAQ or GNA11 (GNAQ/11) are present in approximately 80% of uveal melanomas. Mutant GNAQ/11 are not currently therapeutically targetable. Inhibiting key down-stream effectors of GNAQ/11 represents a rational therapeutic approach for uveal melanomas that harbor these mutations. The mitogen-activated protein/extracellular signal–regulated kinase/mitogen-activated protein kinase (MEK/MAPK) and PI3K/AKT pathways are activated in uveal melanoma. In this study, we test the effect of the clinically relevant small molecule inhibitors GSK1120212 (MEK inhibitor) and GSK2126458 (pan class I PI3K inhibitor) on uveal melanoma cells with different GNAQ/11 mutation backgrounds.

Experimental Design: We use the largest set of genetically annotated uveal melanoma cell lines to date to carry out in vitro cellular signaling, cell-cycle regulation, growth, and apoptosis analyses. RNA interference and small molecule MEK and/or PI3K inhibitor treatment were used to determine the dependency of uveal melanoma cells with different GNAQ/11 mutation backgrounds on MEK/MAPK and/or PI3K/AKT signaling. Proteomic network analysis was done to unveil signaling alterations in response to MEK and/or PI3K small molecule inhibition.

Results: GNAQ/11 mutation status was not a determinant of whether cells would undergo cell-cycle arrest or growth inhibition to MEK and/or phosphoinositide 3-kinase (PI3K) inhibition. A reverse correlation was observed between MAPK and AKT phosphorylation after MEK or PI3K inhibition, respectively. Neither MEK nor PI3K inhibition alone was sufficient to induce apoptosis in the majority of cell lines; however, the combination of MEK + PI3K inhibitor treatment resulted in the marked induction of apoptosis in a GNAQ/11 mutant–dependent manner.

Conclusions: MEK + PI3K inhibition may be an effective combination therapy in uveal melanoma, given the inherent reciprocal activation of these pathways within these cells. Clin Cancer Res; 18(16); 4345–55. ©2012 AACR.
The Zinc Finger Gene ZIC2 Has Features of an Oncogene and Its Overexpression Correlates Strongly with the Clinical Course of Epithelial Ovarian Cancer
Authors: Marchini Sergio , Poynor Elizabeth , Barakat Richard R. , Clivio Luca , Cinquini Michela , Fruscio Robert , Porcu Luca , Bussani Cecilia , D’Incalci Maurizio , Erba Eugenio , Romano Michela , Cattoretti Giorgio , Katsaros Dionyssios , Koff Andrew , Luzzatto Lucio
Published: June 2012

Purpose: Epithelial ovarian tumors (EOT) are among the most lethal of malignancies in women. We have previously identified ZIC2 as expressed at a higher level in samples of a malignant form (MAL) of EOT than in samples of a form with low malignant potential (LMP). We have now investigated the role of ZIC2 in driving tumor growth and its association with clinical outcomes.

Experimental Design: ZIC2 expression levels were analyzed in two independent tumor tissue collections of LMP and MAL. In vitro experiments aimed to test the role of ZIC2 as a transforming gene. Cox models were used to correlate ZIC2 expression with clinical endpoints.

Results: ZIC2 expression was about 40-fold in terms of mRNA and about 17-fold in terms of protein in MAL (n = 193) versus LMP (n = 39) tumors. ZIC2 mRNA levels were high in MAL cell lines but undetectable in LMP cell lines. Overexpression of ZIC2 was localized to the nucleus. ZIC2 overexpression increases the growth rate and foci formation of NIH3T3 cells and stimulates anchorage-independent colony formation; downregulation of ZIC2 decreases the growth rate of MAL cell lines. Zinc finger domains 1 and 2 are required for transforming activity. In stage I MAL, ZIC2 expression was significantly associated with overall survival in both univariate (P = 0.046) and multivariate model (P = 0.049).

Conclusions: ZIC2, a transcription factor related to the sonic hedgehog pathway, is a strong discriminant between MAL and LMP tumors: it may be a major determinant of outcome of EOTs. Clin Cancer Res; 18(16); 4313–24. ©2012 AACR.
The Impact of Initial Gefitinib or Erlotinib versus Chemotherapy on Central Nervous System Progression in Advanced Non–Small Cell Lung Cancer with EGFR Mutations
Authors: Heon Stephanie , Yeap Beow Y. , Lindeman Neal I. , Joshi Victoria A. , Butaney Mohit , Britt Gregory J. , Costa Daniel B. , Rabin Michael S. , Jackman David M. , Johnson Bruce E.
Published: June 2012

Purpose: This retrospective study was undertaken to investigate the impact of initial gefitinib or erlotinib (EGFR tyrosine kinase inhibitor, EGFR-TKI) versus chemotherapy on the risk of central nervous system (CNS) progression in advanced non–small cell lung cancer (NSCLC) with EGFR mutations.

Experimental Design: Patients with stage IV or relapsed NSCLC with a sensitizing EGFR mutation initially treated with gefitinib, erlotinib, or chemotherapy were identified. The cumulative risk of CNS progression was calculated using death as a competing risk.

Results: One hundred and fifty-five patients were eligible (EGFR-TKI: 101, chemotherapy: 54). Twenty-four patients (24%) in the EGFR-TKI group and 12 patients (22%) in the chemotherapy group had brain metastases at the time of diagnosis of advanced NSCLC (P = 1.000); 32 of the 36 received CNS therapy before initiating systemic treatment. Thirty-three patients (33%) in the EGFR-TKI group and 26 patients (48%) in the chemotherapy group developed CNS progression after a median follow-up of 25 months. The 6-, 12-, and 24-month cumulative risk of CNS progression was 1%, 6%, and 21% in the EGFR-TKI group compared with corresponding rates of 7%, 19%, and 32% in the chemotherapy group (P = 0.026). The HR of CNS progression for upfront EGFR-TKI versus chemotherapy was 0.56 [95% confidence interval (CI), 0.34–0.94].

Conclusions: Our data show lower rates of CNS progression in EGFR-mutant advanced NSCLC patients initially treated with an EGFR-TKI compared with upfront chemotherapy. If validated, our results suggest that gefitinib and erlotinib may have a role in the chemoprevention of CNS metastases from NSCLC. Clin Cancer Res; 18(16); 4406–14. ©2012 AACR.
Role of Hedgehog Signaling in Malignant Pleural Mesothelioma
Authors: Shi Yandong , Moura Ubiratan , Opitz Isabelle , Soltermann Alex , Rehrauer Hubert , Thies Svenja , Weder Walter , Stahel Rolf A. , Felley-Bosco Emanuela
Published: June 2012

Purpose: The aim of this study was to assess the activity of hedgehog signaling pathway in malignant pleural mesothelioma (MPM).

Experimental Design: The expression of hedgehog signaling components was assessed by quantitative PCR and in situ hybridization in 45 clinical samples. Primary MPM cultures were developed in serum-free condition in 3% oxygen and were used to investigate the effects of smoothened (SMO) inhibitors or GLI1 silencing on cell growth and hedgehog signaling. In vivo effects of SMO antagonists were determined in an MPM xenograft growing in nude mice.

Results: A significant increase in GLI1, sonic hedgehog, and human hedgehog interacting protein gene expression was observed in MPM tumors compared with nontumoral pleural tissue. SMO antagonists inhibited GLI1 expression and cell growth in sensitive primary cultures. This effect was mimicked by GLI1 silencing. Reduced survivin and YAP protein levels were also observed. Survivin protein levels were rescued by overexpression of GLI1 or constitutively active YAP1. Treatment of tumor-bearing mice with the SMO inhibitor HhAntag led to a significant inhibition of tumor growth in vivo accompanied by decreased Ki-67 and nuclear YAP immunostaining and a significant difference in selected gene expression profile in tumors.

Conclusions: An aberrant hedgehog signaling is present in MPM, and inhibition of hedgehog signaling decreases tumor growth indicating potential new therapeutic approach. Clin Cancer Res; 18(17); 4646–56. ©2012 AACR.
Vascular Endothelial Growth Factor Pathway Polymorphisms as Prognostic and Pharmacogenetic Factors in Cancer: A Systematic Review and Meta-analysis
Authors: Eng Lawson , Azad Abul Kalam , Habbous Steven , Pang Vincent , Xu Wei , Maitland-van der Zee Anke H. , Savas Sevtap , Mackay Helen J. , Amir Eitan , Liu Geoffrey
Published: June 2012

Angiogenesis is an important host process that interacts with cancer cells to promote growth, invasion, and metastasis. Numerous therapeutic agents targeting the VEGF pathway have been developed. Host variability in VEGF pathway can influence angiogenesis-dependent signaling, altering sensitivity to antiangiogenic drugs and prognosis. A systematic review and meta-analysis was conducted (May 1990–July 2011). Eligible studies involved cancer patients and compared polymorphisms in the VEGF pathway [VEGF and molecules directly interacting with VEGF: KDR, FLT1, FGF, FGF2, FGFR, NRP1, endostatin (encoded by COL18A1)], and reported one of the following outcomes: overall survival, progression-free survival, time to recurrence, disease-free survival, response rate, or drug toxicity. We identified 48 cancer studies assessing prognosis and 12 cancer studies exploring pharmacogenetics of anti-VEGF therapy across various VEGF pathway polymorphisms. There was marked inter- and intradisease site heterogeneity in the effect of polymorphisms on both outcome and response to therapy. Meta-analyses of 5 VEGF polymorphisms (+936C>T, −460T>C, +405G>C, −1154G>A, and −2578C>A) identified a significant prognostic relationship: VEGF +405G>C variants showed a highly statistically significant improvement in overall survival [HR, 0.74; 95% confidence interval, 0.60–0.91; P = 0.004]. Variants (heterozygotes and/or homozygotes) of VEGF +405G>C were significantly associated with improved survival in a meta-analysis of multiple cancer sites. Clin Cancer Res; 18(17); 4526–37. ©2012 AACR.