bluuebunny/crossref_metadata_2025 huggingface dataset:
Symptom burden, loss of dignity, and demoralization in patients with cancer: a mediation model
Authors: Vehling Sigrun , Mehnert Anja
Published: October 2013

Background

Demoralization is a syndrome of existential distress that occurs in a substantial minority of cancer patients and is associated with a higher number of physical problems. Loss of dignity refers to a range of specific existential concerns. This study examines whether the association between number of physical problems and demoralization is mediated by loss of dignity.

Methods

This cross‐sectional study examined N = 112 inpatients with mixed tumor sites at early and advanced disease stages using the following standardized self‐report questionnaires: Physical problems list of the National Comprehensive Cancer Network (NCCN) Distress Thermometer (DT), Patient Dignity Inventory (PDI), Demoralization Scale (DS), Patient Health Questionnaire‐9 (PHQ‐9) and Illness‐Specific Social Support Scale Short Version‐8 (ISSS‐8). The mediation hypothesis was tested by multiple regression analyses controlling for age, gender, curative versus palliative treatment phase, and social support.

Results

Patients reported M = 4.7 (SD = 6.0) dignity‐related problems; 20% showed moderate to severe demoralization. Loss of dignity significantly mediated 81% of the effect of the number of physical problems on demoralization (Sobel zs = 4.4, p < .001). Testing the reverse direction, we found that demoralization mediated only 53% of the association between physical problems and loss of dignity (zs = 3.7, p < .001).

Conclusions

By supporting the mediation hypothesis, our results indicate that loss of dignity partially explains the association between physical problems and demoralization. Early recognition of dignity‐related existential concerns and interventions to enhance the sense of dignity may prevent demoralization in patients with cancer. Results provide a conceptual link between existential concerns (loss of dignity) and existential distress (demoralization) as two approaches to existential suffering in patients with cancer. Copyright © 2013 John Wiley & Sons, Ltd.
Mediators of physical exercise for improvement in cancer survivors' quality of life
Authors: Buffart L. M. , Ros W. J. G. , Chinapaw M. J. M. , Brug J. , Knol D. L. , Korstjens I. , van Weert E. , Mesters I. , van den Borne B. , Hoekstra‐Weebers J. E. H. M. , May A. M.
Published: October 2013

Objective

Mediating mechanisms of a 12‐week group‐based exercise intervention on cancer survivors' quality of life (QoL) were examined to inform future exercise intervention development.

Methods

Two hundred nine cancer survivors ≥3 months posttreatment (57% breast cancer) aged 49.5 (±10.4) years were assigned to physical exercise (n = 147) or wait‐list control (n = 62). QoL, fatigue, emotional distress, physical activity, general self‐efficacy and mastery were assessed at baseline and post‐intervention using questionnaires. Path analysis was conducted using Mplus to explore whether improved physical activity, general self‐efficacy and mastery mediated the effects of exercise on fatigue and distress and consequently QoL.

Results

The intervention was associated with increased physical activity (β = 0.46, 95% confidence interval (CI) = 0.14;0.59), general self‐efficacy (β = 2.41, 95%CI = 0.35;4.73), and mastery (β = 1.75, 95%CI = 0.36;2.78). Further, the intervention had both a direct effect on fatigue (β = −1.09, 95%CI = −2.12;0.01), and an indirect effect (β = −0.54, 95%CI = −1.00;−0.21) via physical activity (β = −0.29, 95%CI = −0.64;−0.07) and general self‐efficacy (β = −0.25, 95%CI = −0.61;−0.05). The intervention had a borderline significant direct effect on reduced distress (β =−1.32, 95%CI =−2.68;0.11), and a significant indirect effect via increased general self‐efficacy and mastery (β =−1.06, 95%CI =−1.89;−0.38). Reductions in fatigue (β =−1.33, 95%CI =−1.85;−0.83) and distress (β =−0.86, 95%CI =−1.25;−0.52) were associated with improved QoL. Further, increased physical activity was directly associated with improved QoL (β = 3.37, 95%CI = 1.01;5.54).

Conclusion

The beneficial effect of group‐based physical exercise on QoL was mediated by increased physical activity, general self‐efficacy and mastery, and subsequent reductions in fatigue and distress. In addition to physical activity, future interventions should target self‐efficacy and mastery. This may lead to reduced distress and fatigue, and consequently improved QoL of cancer survivors. Copyright © 2013 John Wiley & Sons, Ltd.
Emotions and social relationships for breast and gynecologic patients: a qualitative study of coping with recurrence
Authors: Thornton Lisa M. , Levin Anna O. , Dorfman Caroline S. , Godiwala Neha , Heitzmann Carolyn , Andersen Barbara L.
Published: October 2013

Background

In contrast to the large literature on patients' coping with an initial diagnosis of cancer, there have been few quantitative or qualitative studies of patients coping with recurrence. A qualitative study was undertaken to aid in the development of a tailored intervention for these patients.

Methods

Individuals (N=35) receiving follow‐up care for recurrent breast or gynecologic cancer at a university‐affiliated cancer center participated in an individual or a group interview. Transcripts of interviews were analyzed using a coding format with two areas of emphasis. First, we focused on patients' emotions, as there is specificity between emotions and the corresponding ways in which individuals choose to manage them. Secondly, we considered the patients' social environments and relationships, as they too appear key in the adjustment to, and survival from, cancer.

Results

Patients identified notable differences in their responses to an initial diagnosis of cancer and their current ones to recurrence, including the following: (i) depressive symptoms being problematic; (ii) with the passing years and the women's own aging, there is shrinkage in the size of social networks; and (iii) additional losses come from social support erosion, arising from a) intentional distancing by social contacts, b) friends and family not understanding that cancer recurrence is a chronic illness, and/or c) patients stemming their support requests across time.

Conclusion

The contribution of these findings to the selection of intervention strategies is discussed. Copyright © 2013 John Wiley & Sons, Ltd.
Which factors predict proposal and uptake of psychological counselling after BRCA1/2 test result disclosure?
Authors: Maheu Christine , Bouhnik Anne‐Deborah , Nogues Catherine , Mouret‐Fourme Emmanuelle , Stoppa‐Lyonnet Dominique , Lasset Christine , Berthet Pascaline , Fricker Jean‐Pierre , Caron Olivier , Luporsi Elizabeth , Gladieff Laurence , Julian‐Reynier Claire
Published: October 2013

Objective

The aim of this study is to prospectively determine the factors contributing to whether unaffected women from BRCA1/2 families reported that clinicians proposed psychological consultations and that they had attended these consultations during the genetic testing process.

Methods

A prospective study was performed on a national cohort, using self‐administered questionnaires to determine the rates of proposal and use of psychological services at the time of BRCA1/2 test result disclosure (N = 533) and during the first year after disclosure (N = 478) among unaffected French women from BRCA1/2 families who had undergone genetic testing for BRCA1/2. Multivariate adjustment was carried out using logistic regression models fitted using generalized estimation equations, with the genetic testing centre as the clustering variable.

Results

At the time of BRCA1/2 test result disclosure, a psychological consultation was proposed by cancer geneticists to 72% and 32% of the carriers (N = 232) and noncarriers (N = 301), respectively (p < 0.001). One year after disclosure, 21% of the carriers had consulted a psychologist, versus 9% of the noncarriers (p < 0.001). Both the proposal and the uptake depended on the women's BRCA1/2 mutation carrier status (proposal adjusted odds ratio (AOR): 4.9; 95% confidence interval (CI) 3.4–7.2; uptake AOR: 2.2; 95% CI 1.2–4.0), their level of education (proposal AOR: 1.7; 95% CI 1.1–2.7; uptake AOR: 4.5; 95% CI 1.7–12.1) and the distress they experienced about their genetic test results (proposal AOR: 1.02; 95% CI 1.01–1.03; uptake AOR: 1.04; 95% CI 1.02–1.06)

Conclusions

Determinants of the proposal/uptake of psychological consultations in the BRCA1/2 testing process highlight the need for inventive strategies to reach the different types of women's profiles. Copyright © 2013 John Wiley & Sons, Ltd.
Revisiting toric SU(3) structures
Authors: Larfors M.
Published: October 2013

Three‐dimensional smooth compact toric varieties (SCTV) admit SU(3) structures, and may thus be relevant for string compactifications, if they have even first Chern class (c1). This condition can be fulfilled by infinitely many SCTVs, including ℂℙ3 and ℂℙ1 bundles over all two‐dimensional SCTVs. We show that as long as c1 is even, toric SU(3) structures can be constructed using a method proposed in [1]. We perform a systematic study of the parametric freedom of the resulting SU(3) structures, with a particular focus on the metric and the torsion classes. Although metric positivity constrains the SU(3) parameters, we find that every SCTV admits several toric SU( 3) structures and that parametric choices can sometimes be made to match requirements of string vacua. We also provide a short review on the constraints that an SU(3) structure must meet to be relevant for four‐dimensional, maximally symmetric �� = 1 or �� = 0 string vacua.
Function‐based assessment of structural similarity measurements using metal co‐factor orientation
Authors: Senn Stefan , Nanda Vikas , Falkowski Paul , Bromberg Yana
Published: October 2013

Structure comparison is widely used to quantify protein relationships. Although there are several approaches to calculate structural similarity, specifying significance thresholds for similarity metrics is difficult due to the inherent likeness of common secondary structure elements. In this study, metal co‐factor location is used to assess the biological relevance of structural alignments. The distance between the centroids of bound co‐factors adds a chemical and function‐relevant constraint to the structural superimposition of two proteins. This additional dimension can be used to define cut‐off values for discriminating valid and spurious alignments in large alignment sets. The hypothesis underlying our approach is that metal coordination sites constrain structural evolution, thus revealing functional relationships between distantly related proteins. A comparison of three related nitrogenases shows the sequence and fold constraints imposed on the protein structures up to 18 Å away from the centers of their bound metal clusters. Proteins 2014; 82:648–656. © 2013 Wiley Periodicals, Inc.
Optimal controller location in wireless networked control systems
Authors: Xin Kefei , Cao Xianghui , Chen Jiming , Cheng Peng , Xie Lihua
Published: October 2013

The control performance of wireless networked control systems (WNCS) has been shown to heavily depend on the packet delivery quality of both the sensor‐to‐controller and controller‐to‐actuator communications. Such quality relies on the relative distance between the wireless transmitter and receiver, which naturally raises the challenging problem of controller placement in WNCS for optimal control performance. In this paper, we investigate the optimal controller location (OCL) problem in WNCS based on linear‐quadratic‐Gaussian control strategy. For the one‐hop network case where the controller can only be placed at either the sensor side or the actuator side, we derive a simple yet effective criterion to determine the OCL. For the more general multi‐hop case where the controller can be located at either one of the sensors, relays, or actuators, we obtain the necessary and sufficient condition under which the closed‐loop system is guaranteed to be stable. On the basis of these results, we further transform the OCL problem into an optimization problem that can be solved efficiently. Numerical results are provided to verify our analysis. Copyright © 2013 John Wiley & Sons, Ltd.
Robust H ∞  filtering for singular time‐delayed systems with uncertain Markovian switching probabilities
Authors: Wang Guoliang , Xu Shengyuan
Published: October 2013

This paper is concerned with the robust H ∞  filter design for a class of uncertain singular time‐delayed Markovian jump systems, whose transition rate matrix has elementwise bounded uncertainties. By the LMI approach, a novel bounded real lemma is proposed such that the singular Markovian jump system is robustly exponentially mean‐square admissible with a prescribed H ∞  performance index. Based on this, a sufficient condition for the existence of a robust H ∞  filter is developed in terms of LMIs. Finally, a numerical example is provided to show the effectiveness of the theoretical results. Copyright © 2013 John Wiley & Sons, Ltd.
Opportunities and challenges of combined effect measures based on prioritized outcomes
Authors: Rauch Geraldine , Jahn‐Eimermacher Antje , Brannath Werner , Kieser Meinhard
Published: October 2013

Many authors have proposed different approaches to combine multiple endpoints in a univariate outcome measure in the literature. In case of binary or time‐to‐event variables, composite endpoints, which combine several event types within a single event or time‐to‐first‐event analysis are often used to assess the overall treatment effect. A main drawback of this approach is that the interpretation of the composite effect can be difficult as a negative effect in one component can be masked by a positive effect in another. Recently, some authors proposed more general approaches based on a priority ranking of outcomes, which moreover allow to combine outcome variables of different scale levels. These new combined effect measures assign a higher impact to more important endpoints, which is meant to simplify the interpretation of results. Whereas statistical tests and models for binary and time‐to‐event variables are well understood, the latter methods have not been investigated in detail so far. In this paper, we will investigate the statistical properties of prioritized combined outcome measures. We will perform a systematical comparison to standard composite measures, such as the all‐cause hazard ratio in case of time‐to‐event variables or the absolute rate difference in case of binary variables, to derive recommendations for different clinical trial scenarios. We will discuss extensions and modifications of the new effect measures, which simplify the clinical interpretation. Moreover, we propose a new method on how to combine the classical composite approach with a priority ranking of outcomes using a multiple testing strategy based on the closed test procedure. Copyright © 2013 John Wiley & Sons, Ltd.
On the accuracy of classifying hospitals on their performance measures
Authors: He Yulei , Selck Frederic , Normand Sharon‐Lise T.
Published: October 2013

The evaluation, comparison, and public report of health care provider performance is essential to improving the quality of health care. Hospitals, as one type of provider, are often classified into quality tiers (e.g., top or suboptimal) based on their performance data for various purposes. However, potential misclassification might lead to detrimental effects for both consumers and payers. Although such risk has been highlighted by applied health services researchers, a systematic investigation of statistical approaches has been lacking. We assess and compare the expected accuracy of several commonly used classification methods: unadjusted hospital‐level averages, shrinkage estimators under a random‐effects model accommodating between‐hospital variation, and two others based on posterior probabilities. Assuming that performance data follow a classic one‐way random‐effects model with unequal sample size per hospital, we derive accuracy formulae for these classification approaches and gain insight into how the misclassification might be affected by various factors such as reliability of the data, hospital‐level sample size distribution, and cutoff values between quality tiers. The case of binary performance data is also explored using Monte Carlo simulation strategies. We apply the methods to real data and discuss the practical implications. Copyright © 2013 John Wiley & Sons, Ltd.
Controlling Mechanical Properties of Cell‐Laden Hydrogels by Covalent Incorporation of Graphene Oxide
Authors: Cha Chaenyung , Shin Su Ryon , Gao Xiguang , Annabi Nasim , Dokmeci Mehmet R. , Tang Xiaowu (Shirley) , Khademhosseini Ali
Published: October 2013

Graphene‐based materials are useful reinforcing agents to modify the mechanical properties of hydrogels. Here, an approach is presented to covalently incorporate graphene oxide (GO) into hydrogels via radical copolymerization to enhance the dispersion and conjugation of GO sheets within the hydrogels. GO is chemically modified to present surface‐grafted methacrylate groups (MeGO). In comparison to GO, higher concentrations of MeGO can be stably dispersed in a pre‐gel solution containing methacrylated gelatin (GelMA) without aggregation or significant increase in viscosity. In addition, the resulting MeGO‐GelMA hydrogels demonstrate a significant increase in fracture strength with increasing MeGO concentration. Interestingly, the rigidity of the hydrogels is not significantly affected by the covalently incorporated GO. Therefore, this approach can be used to enhance the structural integrity and resistance to fracture of the hydrogels without inadvertently affecting their rigidity, which is known to affect the behavior of encapsulated cells. The biocompatibility of MeGO‐GelMA hydrogels is confirmed by measuring the viability and proliferation of the encapsulated fibroblasts. Overall, this study highlights the advantage of covalently incorporating GO into a hydrogel system, and improves the quality of cell‐laden hydrogels.
Studying the laws of software evolution in a long‐lived FLOSS project
Authors: Gonzalez‐Barahona Jesus M. , Robles Gregorio , Herraiz Israel , Ortega Felipe
Published: October 2013

Some free, open‐source software projects have been around for quite a long time, the longest living ones dating from the early 1980s. For some of them, detailed information about their evolution is available in source code management systems tracking all their code changes for periods of more than 15 years. This paper examines in detail the evolution of one of such projects, glibc, with the main aim of understanding how it evolved and how it matched Lehman's laws of software evolution. As a result, we have developed a methodology for studying the evolution of such long‐lived projects based on the information in their source code management repository, described in detail several aspects of the history of glibc, including some activity and size metrics, and found how some of the laws of software evolution may not hold in this case. © 2013 The Authors. Journal of Software: Evolution and Process published by John Wiley & Sons Ltd.
Detecting asynchrony and dephase change patterns by mining software repositories
Authors: Jaafar Fehmi , Guéhéneuc Yann‐Gaël , Hamel Sylvie , Antoniol Giuliano
Published: October 2013

Software maintenance accounts for the largest part of the costs of any program. During maintenance activities, developers implement changes (sometimes simultaneously) on artifacts in order to fix bugs and to implement new requirements. To reduce this part of the costs, previous work proposed approaches to identify the artifacts of programs that change together. These approaches analyze historical data, mined from version control systems, and report change patterns, which lead at the causes, consequences, and actors of the changes to source code files. They also introduce so‐called change patterns that describe some typical change dependencies among files. In this paper, we introduce two novel change patterns: the asynchrony change pattern, corresponding to macro co‐changes (MC), that is, of files that co‐change within a large time interval (change periods) and the dephase change pattern, corresponding to dephase macro co‐changes (DC), that is, MC that always happens with the same shifts in time. We present our approach, that we named Macocha, to identify these two change patterns in large programs. We use the k‐nearest neighbor algorithm to group changes into change periods. We also use the Hamming distance to detect approximate occurrences of MC and DC. We apply Macocha and compare its performance in terms of precision and recall with UMLDiff (file stability) and association rules (co‐changing files) on seven systems: ArgoUML, FreeBSD, JFreeChart, Openser, SIP, XalanC, and XercesC developed with three different languages (C, C++, and Java). These systems have a size ranging from 532 to 1693 files, and during the study period, they have undergone 1555 to 23,944 change commits. We use external information and static analysis to validate (approximate) MC and DC found by Macocha. Through our case study, we show the existence and usefulness of these novel change patterns to ease software maintenance and, potentially, reduce related costs. Copyright © 2013 John Wiley & Sons, Ltd.
Channel assignment schemes for cooperative spectrum sensing in multi‐channel cognitive radio networks
Authors: Wang Weiwei , Kasiri Behzad , Cai Jun , Alfa Attahiru S.
Published: October 2013

In this paper, channel assignment for spectrum sensing is studied in multi‐channel cognitive radio (CR) networks to maximize the number of channels satisfying sensing performance (called available channels). Beginning with a nonlinear integer programming problem, we derive the upper bound of optimal value through many‐to‐many assignment problem and then propose three algorithms for both centralized and distributed scenarios. In centralized case, a heuristic scheme is proposed based on the signal‐to‐noise ratios (SNRs) over all primary channels (PCs). Then, a greedy scheme is proposed to reduce the reported information from the CRs. In distributed case, a novel scheme with multi‐round operation is designed following the coalitional game theory. In each round, each CR selects some PCs based on SNRs. Then, the CRs selecting the same channel play coalitional game, and thereby, multiple games are played concurrently over multiple channels. Finally, the best coalition for each channel is chosen among the formed coalitions to perform the cooperative spectrum sensing. The simulation results show that the proposed schemes can significantly increase the number of available channels. Copyright © 2013 John Wiley & Sons, Ltd.
Northern bobwhite response to habitat restoration in eastern oklahoma
Authors: Crosby Andrew D. , Elmore R. Dwayne , Leslie David M.
Published: October 2013

In response to the decline of northern bobwhite (Colinus virginianus; hereafter, bobwhite) in eastern Oklahoma, USA, a cost‐share incentive program for private landowners was initiated to restore early successional habitat. Our objectives were to determine whether the program had an effect on bobwhite occupancy in the restoration areas and evaluate how local‐ and landscape‐level habitat characteristics affect occupancy in both restoration and control areas. We surveyed 14 sample units that received treatment between 2009 and 2011, and 17 sample units that were controls. We used single‐season occupancy models, with year as a dummy variable, to test for an effect of restoration treatment and habitat variables on occupancy. We found no significant treatment effect. Model selection showed that occupancy was best explained by the combination of overstory canopy cover and habitat area at both the local and landscape scales. Moran's I revealed positive spatial autocorrelation in the 1,000–3,000‐m distance band, indicating that the likelihood of bobwhite occupancy increased with proximity to other populations. We show that creating ≥20 ha of habitat within 1–3 km of existing bobwhite populations increases the chance of restoration being successful. © 2013 The Wildlife Society. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.
Trauma‐induced malformed antler development in male white‐tailed deer
Authors: Karns Gabriel R. , Ditchkoff Stephen S.
Published: October 2013

Though normal antlers are branched and bilaterally symmetrical, male white‐tailed deer (Odocoileus virginianus) sometimes develop malformed antlers because of various reasons. As management for antler quality has grown more popular in recent years, there has been concern that spike‐on‐one‐side (SOOS) antler configuration has a genetic cause. We hypothesized that the majority of SOOS antlers are the artifact of injuries to the antlerogenic periosteum region. We collected 71 SOOS specimens over 2 hunting seasons (2010–2011 and 2011–2012) in Alabama, USA, and identified probable cause for malformed antler development. We confidently assigned cause to 62% of specimens, and frequency of skull and/or pedicle trauma increased with age classes (yearling, 2.5‐yr‐old, and ≥3.5‐yr‐old M). It was difficult to determine the reason that yearling males developed SOOS antler traits (30%), but ease of prescription increased with male age (76% for ≥3.5‐yr‐old M). Based on the physiology of skull and/or pedicle versus skeletal injuries, we recommended different culling strategies for yearling versus adult male white‐tailed deer according to management objectives. © 2013 The Wildlife Society. © The Wildlife Society, 2013
The same-sign top signature of R-parity violation
Authors: Durieux Gauthier , Smith Christopher
Published: October 2013

Abstract

Baryonic R-parity violation could explain why low-scale supersymmetry has not yet been discovered at colliders: sparticles would be hidden in the intense hadronic activity. However, if the known flavor structures are any guide, the largest baryon number violating couplings are those involving the top/stop, so a copious production of same-sign top-quark pairs is in principle possible. Such a signal, with its low irreducible background and efficient identification through same-sign dileptons, provides us with tell-tale signs of baryon number violating supersymmetry. Interestingly, this statement is mostly independent of the details of the supersymmetric mass spectrum. So, in this paper, after analyzing the sparticle decay chains and lifetimes, we formulate a simplified benchmark strategy that covers most supersymmetric scenarios. We then use this information to interpret the samesign dilepton searches of CMS, draw approximate bounds on the gluino and squark masses, and extrapolate the reach of the future 14 TeV runs.
Emergence of sandflies (Phlebotominae) in Austria, a Central European country
Authors: Poeppl Wolfgang , Obwaller Adelheid G. , Weiler Martin , Burgmann Heinz , Mooseder Gerhard , Lorentz Susanne , Rauchenwald Friedrich , Aspöck Horst , Walochnik Julia , Naucke Torsten J.
Published: October 2013

The possible existence of autochthonous sandfly populations in Central Europe north of the Alps has long been excluded. However, in the past years, sandflies have been documented in Germany, Belgium, and recently, also in Austria, close to the Slovenian border. Moreover, autochthonous human Leishmania and Phlebovirus infections have been reported in Central Europe, particularly in Germany. From 2010 to 2012, sandfly trapping (740 trap nights) was performed at 53 different capture sites in Austria using battery-operated CDC miniature light traps. Sites were chosen on the basis of their climate profile in the federal states Styria, Burgenland, and Lower Austria. Sandfly specimens found were transferred to 70 % ethanol for conservation. Identification was based on morphological characters of the male genitalia and the female spermathecae, respectively. Altogether, 24 specimens, 22 females and 2 males, all identified as Phlebotomus (Transphlebotomus) mascittii Grassi, 1908, were found at six different sampling sites in all three federal states investigated. The highest number of catches was made on a farm in Lower Austria. Altogether, the period of sandfly activity in Austria was shown to be much longer than presumed, the earliest capture was made on July 3rd and the latest on August 28th. Sandflies have been autochthonous in Austria in small foci probably for long, but in the course of global warming, further spreading may be expected. Although P. mascittii is only an assumed vector of Leishmania spp.—data on its experimental transmission capacity are still lacking—the wide distribution of sandflies in Austria, a country thought to be free of sandflies, further supports a potential emergence of sandflies in Central Europe. This is of medical relevance, not only with respect to the transmission of Leishmania spp. for which a reservoir is given in dogs, but also with respect to the phleboviruses.
Activating the expression of bacterial cryptic genes by rpoB mutations in RNA polymerase or by rare earth elements
Authors: Ochi Kozo , Tanaka Yukinori , Tojo Shigeo
Published: October 2013

Since bacteria were found to contain genes encoding enzymes that synthesize a plethora of potential secondary metabolites, interest has grown in the activation of these cryptic pathways. Homologous and heterologous expression of these cryptic secondary metabolite-biosynthetic genes, often “silent” under ordinary laboratory fermentation conditions, may lead to the discovery of novel secondary metabolites. We review current progress on this topic, describing concepts for activating silent genes. We especially focus on genetic manipulation of transcription and translation, as well as the utilization of rare earth elements as a novel method to activate the silent genes. The possible roles of silent genes in bacterial physiology are also discussed.
Actinomycetes biosynthetic potential: how to bridge in silico and in vivo?
Authors: Rebets Yuriy , Brötz Elke , Tokovenko Bogdan , Luzhetskyy Andriy
Published: October 2013

Actinomycetes genome sequencing and bioinformatic analyses revealed a large number of “cryptic” gene clusters coding for secondary metabolism. These gene clusters have the potential to increase the chemical diversity of natural products. Indeed, reexamination of well-characterized actinomycetes strains revealed a variety of hidden treasures. Growing information about this metabolic diversity has promoted further development of strategies to discover novel biologically active compounds produced by actinomycetes. This new task for actinomycetes genetics requires the development and use of new approaches and tools. Application of synthetic biology approaches led to the development of a set of strategies and tools to satisfy these new requirements. In this review, we discuss strategies and methods to discover small molecules produced by these fascinating bacteria and also discuss a variety of genetic instruments and regulatory elements used to activate secondary metabolism cryptic genes for the overproduction of these metabolites.
DNA assembly techniques for next-generation combinatorial biosynthesis of natural products
Authors: Cobb Ryan E , Ning Jonathan C , Zhao Huimin
Published: October 2013

Natural product scaffolds remain important leads for pharmaceutical development. However, transforming a natural product into a drug entity often requires derivatization to enhance the compound’s therapeutic properties. A powerful method by which to perform this derivatization is combinatorial biosynthesis, the manipulation of the genes in the corresponding pathway to divert synthesis towards novel derivatives. While these manipulations have traditionally been carried out via restriction digestion/ligation-based cloning, the shortcomings of such techniques limit their throughput and thus the scope of corresponding combinatorial biosynthesis experiments. In the burgeoning field of synthetic biology, the demand for facile DNA assembly techniques has promoted the development of a host of novel DNA assembly strategies. Here we describe the advantages of these recently developed tools for rapid, efficient synthesis of large DNA constructs. We also discuss their potential to facilitate the simultaneous assembly of complete libraries of natural product biosynthetic pathways, ushering in the next generation of combinatorial biosynthesis.
Antioxidant Property, Thymoquinone Content and Chemical Characteristics of Different Extracts from Nigella sativa L. Seeds
Authors: Solati Zeinab , Baharin Badlishah Sham , Bagheri Hossein
Published: October 2013

In this study, Nigella sativa L. seeds were extracted using supercritical carbon dioxide (SC‐CO2) and Soxhlet. Chemical characteristics, fatty acid composition, antioxidant activity and thymoquinone content of N. sativa L. extracts obtained through different methods were investigated and compared. It was revealed that antioxidant activity and thymoquinone content could be significantly different for SC‐CO2 and Soxhlet extracts. The results for fatty acid composition indicated that linoleic acid, palmitic acid and oleic acid were the main fatty acids in both extracts. The SC‐CO2 extraction could provide an extract with higher quality and antioxidant activity compared to Soxhlet extraction method and can be considered a more appropriate method for attaining a high‐quality extract.
Prognostic value of age and Wassel classification in the reconstruction of thumb duplication
Authors: Cabrera González Marisa , Pérez López Laura M. , Martínez Soto Gino , Gutiérrez de la Iglesia Diego
Published: October 2013

Background

Various surgical techniques for thumb duplication have been described. The main goal in thumb reconstruction is to achieve optimal function, stability, and shape. Few publications have quantified the functional results of each surgical option and factors that may affect these outcomes.

Methods

We performed a retrospective review during the period from 1990 to 2011 of 115 surgery patients, 99 of whom had a mean postoperative follow-up of 44.1 months. They were classified according to the Wassel classification. We assessed the surgical technique, functional results, and complications, and evaluated the probable prognostic value of age and Wassel classification.

Results

This case series comprised mainly female patients (62 %) and the right hand (74 %), with a mean age at operation of 20 months. The most common group was Wassel type IV (54 %). On the basis of the Tada scoring system, we obtained 91 good results (91 %). Complications occurred in 27 patients (27 %), mainly instability and axis deformation. In a comparison of preoperative factors (age at the time of surgery and Wassel classification) with the final results (Tada score and complications), the association between older age at surgery and complications ( p = 0.0001) and Wassel types III and IV and complications ( p = 0.0210 and p = 0.0095) was statistically significant.

Conclusions

Following the basic concepts of anatomical reconstruction, we obtained good results in most patients. The main complications were instability and axial deformity. These were most common in patients who underwent operations at an age of more than 12 months, and patients with Wassel types III and IV deformities.
Why does the impact of multidisciplinary pain management on quality of life differ so much between chronic pain patients?
Authors: Vartiainen P. , Heiskanen T. , Roine R.P. , Kalso E.
Published: October 2013

Aims

To assess the change in quality of life and factors predicting this change in 1425 chronic pain patients treated in a multidisciplinary pain clinic.

Methods

This is an observational follow-up study using the 15D generic health-related quality of life (HRQoL) instrument. Patients filled in the HRQoL questionnaire at baseline, and 6 and 12 months after discharge. To assess if mental factors predicted treatment success, the changes in the overall 15D score were compared and related to the baseline variables of depression and distress. The group of patients, who scored 4 or 5 on the 1–5 scale for the depression and distress dimensions of the 15D instrument, were considered mentally distressed (N =199). They were compared with the non-distressed patients (i.e. those who scored 1; N = 401).

Results

Pain was associated to depression and distress: 85.4% of mentally distressed patients scored 4 or 5 also on the discomfort and symptoms dimension, vs. 51.4% of the non-distressed (p < 0.001). The mean 15D score of the mentally distressed patients improved statistically significantly more (from 0.572 to 0.636, N =141) during the first six months after treatment compared with the 15D of those who were not mentally distressed, who improved only marginally (0.790–0.803, N = 294; p < 0.001).

Conclusions

Patients with more severe depression or distress at baseline appear to gain more from the treatment than those who have less mental distress. In our ongoing study more baseline factors will be evaluated to assess their effect on the success of treatment.
Health care utilization in chronic pain—A population based study
Authors: Jonsdottir Thorbjörg , Jonsdottir Helga , Gunnarsdottir Sigridur , Lindal Eirikur
Published: October 2013

Aims

To investigate health care utilization in relation to chronic pain.

Methods

In this cross-sectional study postal questionnaires, measuring sociodemographic characteristics, pain, health related quality of life (HRQoL), attitudes to pain and health care utilization past six months, were sent to 4500 individuals aged 20–70 years, randomly drawn from the Icelandic National Registry.

Results

Total response rate was 36.9% (n = 1589) and was higher among older individuals and women. Nearly one half of respondents (47.5%, n = 754) reported chronic pain (≥3 months) with mean duration of 9.3 years (median = 6.0 years, SD = 10.0) and 57.5% of them had consulted health care service for their pain past six months. Use of pain related health care was significantly related to attitudes towards pain and individuals with pain in chest, upper extremities, hips and lower extremities consulted health care for their pain significantly more often than people with other pain locations. Pain related health care utilization was not significantly related to sociodemographic characteristics. There was a significant difference in both Physical (PCS) and Mental (MCS) component HRQoL scales as well as nature of pain (severity, interference, spread and pattern), between individuals who had consulted health care for their pain and those who had not. However, when these relationships were tested by using logistic regression models, only PCS and pain interference remained significant in this relationship.

Conclusions

Chronic pain related health care utilization is related to several pain characteristics and its influence on daily life, where interference and physical components of HRQoL are most important.
Pain treatment in rural Ghana—A qualitative study
Authors: Ayim-Aboagye Desmond , Gordh Torsten
Published: October 2013

Aims

We investigated how treatment of pain was functioning among a rural population in African context.

Methods

The investigation employed the observation approach and in-depth interview approach in a rural population of about 5000 inhabitants. However, at the zenith of the study 10 patients were selected for the in-depth interview, having serious conditions, which had rendered them immobile, received a major focus in the study. With qualitative methods, we were capable of procuring rich information through narratives.

Results

The patients employ both biomedical practitioners and traditional practitioners in the culture who have potent knowledge of culture specific disabilities. Even when patients had received satisfactory treatments leading to pain relief from the former practitioners, they still cherish some psychological pain, which demand that they consult other practitioners in the culture for further treatments. Those that only receive help from the mainstream hospitals or speciality clinics show improvement, but usually assailed by fear and excessive worry that their pains will not disappear entirely. While the younger generation patients are reluctant to reveal these consultations with traditional practitioners openly, the older group felt more positive about it and brag of having endured their ordeal because of these consultations with those who could offer them additional protection.

Conclusion

The employment of different practitioners’ treatments alleviated these patients’ pain disabilities and psychological symptoms, which were that of pain relief, psychological pain, and death fear. Traditional treatment of pain has a social function, and therefore must be given attention to and recognition by biomedical-trained doctors.
Pain psychology specialist training 2012–2014
Authors: Soini P. , Valjakka A. , Tuurinkoski S. , Elomaa M. , Väänänen T. , Hägg V.
Published: October 2013

Aims

The training includes learning the practical skills related to the psychological examination, treatment and rehabilitation of pain patients. The completion of the training prepares for work in multiprofessional teams as a specialist in pain psychology. A joint project of the Finnish Association of the Study of Pain and the Psychology Institute since 2008.

Participants

Psychologists working in public, private or occupational health care, in rehabilitation or psychiatric clinics. The fourth training group of 20 psychologists started in the spring of 2012. More than 40 psychologists have already been trained in 1998-2010.

The structure and content of the training: Seminars

Eight seminars include 12 days of training on the topics of pain as a psychosocial phenomenon, psychological assessment, treatment and rehabilitation of pain patients, interaction and multiprofessional teamwork.

Tutorial groups

Eight tutorial meetings of 5 students and one tutor in each group gather together in different parts of Finland to discuss selected scientific articles, work on their professional identity as pain psychologists and receive supervision of clinical and diploma work.

Literature

Getting acquainted with scientific research reports on pain psychology and with vocational literature.

Diploma work

Written article or a short research report on a development project, experiment or a phenomenon related to pain psychology.

Optional studies

Giving a lecture or training on the topic of pain psychology to other professionals or patients, participating in a pain education organized by others, writing a report on a research, treatment or rehabilitation experiment or a book review to be published
Pain assessment, documentation, and management in a university hospital
Authors: Zoёga S. , Aspelund T. , Sigurdsson G. , Ward S.E. , Sveinsdóttir H. , Gunnarsdóttir S.
Published: October 2013

Aims

To determine if pain is assessed, documented, and treated in a university hospital according to recommended practice.

Methods

A cross-sectional descriptive study, conducted in 23 medical and surgical wards in a university hospital. Participants were patients hospitalized for at least 24hours, ≥18 years of age, and able to participate. Data were collected from patients with a questionnaire (APS-POQ-R), from their medical records, and from Therapy®, the hospital medication system.

Results

The response rate was 73%. Participants (N =308) mean age was 67.5 years (SD = 17.4), 50.5% were women. Pain prevalence in the past 24 h was 83.1% and severe pain was experienced by 34.5%. Descriptions of pain were documented for 60.7%. Standardized methods of assessment were used in 11.6% of patients, other forms of documentation included descriptions as “no pain-complaints”, and “patient received 2 Panodil”. The majority of patients (66.8%) were prescribed pain medications and 34.0% of patients used non-pharmacological methods to treat their pain. The pain management index (PMI = prescribed pain medication – worst pain severity) was negative for 38.6% indicating insufficient treatment. The PMI was more favorable in surgical compared to medical patients, x
2(6, N = 306) = 17.81, p = 0.007.

Conclusions

Pain was both prevalent and severe. Although some form of documentation of pain was recorded for the majority of patients, pain was rarely assessed with standardized methods. Many patients did not receive adequate treatment. There is a need to improve the pain management practices in the hospital, with an initial emphasis on pain assessment.
Promising effects of donepezil when added to patients treated with gabapentin for neuropathic pain
Authors: Basnet A. , Butler S. , Hartvig Honoré P. , Butler M. , Gordh T.E. , Kristensen K. , Bjerrum O.J.
Published: October 2013

Aims

The clinical relevance of adding the acetylcholinesterase inhibitor donepezil to existing gabapentin treatment in patients with post-traumatic neuropathic pain was explored in this open-label study. The two drugs have previously shown synergism following co-administration in nerve-injured rats [1,2].

Methods

The study comprised two consecutive periods of minimum six weeks: (1) titration of gabapentin until highest tolerable dose or maximum 24GG mg daily; and (2) addition of donepezil 5 mg once daily to the fixed gabapentin dose. Efficacy and tolerability were assessed by ratings of pain intensity, questionnaires for pain and health-related quality of life, and reporting of adverse events and analgesic rescue medication. Pain scores were also analyzed using mixed-effects analysis (i.e. incorporating inter-subject variability) with the software NONMEM.

Results

Eight patients commenced treatment with donepezil upon the gabapentin titration period, of which two withdrew due to adverse events. Addition of donepezil reduced pain by >35% in four of six patients compared to gabapentin monotherapy. Mixed-effects analysis revealed that pain scores were significantly lower during co-administration (p < 0.05 combination vs. monotherapy). Donepezil was well tolerated in combination with gabapentin. At the end of study, three patients wished to continue combination therapy with gabapentin and donepezil.

Conclusions

Donepezil may provide additional analgesia to neuropathic pain patients with insufficient pain relief from gabapentin as monotherapy. Further confirmation in controlled clinical trials is justified. Mixed-effects analysis was sensitive enough to detect statistically significant effects, showing its usefulness in small-scale trials and/or when data is associated with high variability.
Proteomic analysis of cerebrospinal fluid gives insight into the pain relief of spinal cord stimulation
Authors: Lind Anne-Li , Wetterhall Magnus , Sjödin Marcus , Gordh Torsten
Published: October 2013

Aims

Neuropathic pain is caused by a lesion or disease of the somatosensory nervous system affecting approximately 2% of the population. Current pharmacological treatments are ineffective for more than 50% of the patients and often give much adverse effects. Spinal cord stimulation (SCS) is an alternative cost-effective treatment with high efficacy, prolonged pain relief, few side effects. We have compared the cerebrospinal fluid (CSF) proteomes from neuropathic pain patients during pain relief induced by SCS and during pain sensation without SCS, to gain further insights into the mechanisms behind the obtained analgesia.

Methods

Paired CSF samples were taken from SCS-responsive neuropathic pain patients after the SCS had been turned off for 48 h and when the SCS had been used normally for three weeks. Thus, each patient acted as their own control. The corresponding proteomes for each patient were relatively quantified using a mass spectrometry based shotgun approach.

Results

In total, 419 unique proteins were simultaneously identified and relatively quantified. A panel consisting of seven proteins, 5 up-regulated and 2 down, were found to be significantly regulated by SCS in two complementary statistical tests (P ≤ 0.01). The most up-regulated protein in the SCS linked panel is a known modulator of nicotinic acetylcholine (ACh) receptor activity. Interestingly, it has a striking tertiary structural similarity and biological functionality as pain modulating prototoxins found in snake venoms.

Conclusions

Our findings reveal possible insights into the mechanism of spinal cord stimulation and the obtained pain relief.