bluuebunny/crossref_metadata_2025 huggingface dataset:
Resilience, Fragility, and Adaptation: New Evidence on the Performance of UK High Streets during Global Economic Crisis and its Policy Implications
Authors: Wrigley Neil , Dolega Les
Published: October 2011

At a time of increasing government concern with the economic health of UK town centres and high streets, and with an independent inquiry (led by Mary Portas) on Revitalising the High Street to report by the end of 2011, this paper seeks to make four contributions. First, to inject into an available evidence base, currently notable for its sparseness, new descriptive evidence on the differential performance of a sample of over 250 town centres/high streets in four regions of the UK as those centres adjusted to the shock wave of global economic crisis. Second, to address the task of theorising the nature of the complex adjustments underway by positioning the policy-significant findings provided in the paper within conceptualisations of ‘resilience’ in economic systems—particularly those which stress the anticipatory or reactive capacity of systems to minimise the impacts of a destabilising shock and which focus on resilience as a dynamic and evolutionary process. Third, to offer findings from theory-driven statistical modelling of the determinants of the differential resilience or fragility exhibited by that sample of centres. Fourth, to assess what the implications of those findings and a focus on ‘adaptive resilience’ might mean for the design of policy proposals and instruments aimed at revitalising UK town centres and high streets. Although some of the paper's empirical findings parallel those suggested by specialist commercial research companies which have emerged to fill the need to chart the posteconomic crisis malaise of UK retail centres, they also significantly extend available knowledge. In particular, they offer novel insight into the impact of two factors—‘diversity’ of a centre's preexisting retail structure and ‘town-centres-first’ policy-compliant ‘in-centre’ or ‘edge-of-centre’ corporate-foodstore entry. Although conventionally portrayed as polar opposites within popular debate in terms of attempts to protect and/or enhance the vitality and viability of town centres and high streets, our analysis suggests that this may not be the case. Indeed, the retail centres in our sample which proved most resilient to the shock wave of global economic crisis were characterised by both diversity and corporate-food-store entry.
Tunable synthetic phenotypic diversification on Waddington’s landscape through autonomous signaling
Authors: Sekine Ryoji , Yamamura Masayuki , Ayukawa Shotaro , Ishimatsu Kana , Akama Satoru , Takinoue Masahiro , Hagiya Masami , Kiga Daisuke
Published: October 2011

Phenotypic diversification of cells is crucial for developmental and regenerative processes in multicellular organisms. The diversification concept is described as the motion of marbles rolling down Waddington’s landscape, in which the number of stable states changes as development proceeds. In contrast to this simple concept, the complexity of natural biomolecular processes prevents comprehension of their design principles. We have constructed, in
Escherichia coli
, a synthetic circuit with just four genes, which programs cells to autonomously diversify as the motion on the landscape through cell–cell communication. The circuit design was based on the combination of a bistable toggle switch with an intercellular signaling system. The cells with the circuit diversified into two distinct cell states, “high” and “low,” in vivo and in silico, when all of the cells started from the low state. The synthetic diversification was affected by not only the shape of the landscape determined by the circuit design, which includes the synthesis rate of the signaling molecule, but also the number of cells in the experiments. This cell-number dependency is reminiscent of the “community effect”: The fates of developing cells are determined by their number. Our synthetic circuit could be a model system for studying diversification and differentiation in higher organisms. Prospectively, further integrations of our circuit with different cellular functions will provide unique tools for directing cell fates on the population level in tissue engineering.
Regulable neural progenitor-specific
Tsc1
loss yields giant cells with organellar dysfunction in a model of tuberous sclerosis complex
Authors: Goto June , Talos Delia M. , Klein Peter , Qin Wei , Chekaluk Yvonne I. , Anderl Stefanie , Malinowska Izabela A. , Di Nardo Alessia , Bronson Roderick T. , Chan Jennifer A. , Vinters Harry V. , Kernie Steven G. , Jensen Frances E. , Sahin Mustafa , Kwiatkowski David J.
Published: October 2011

Tuberous sclerosis complex (TSC) is a multiorgan genetic disease in which brain involvement causes epilepsy, intellectual disability, and autism. The hallmark pathological finding in TSC is the cerebral cortical tuber and its unique constituent, giant cells. However, an animal model that replicates giant cells has not yet been described. Here, we report that mosaic induction of
Tsc1
loss in neural progenitor cells in

Tsc1
cc
Nestin-rtTA

+
TetOp-cre
+
embryos by doxycycline leads to multiple neurological symptoms, including severe epilepsy and premature death. Strikingly,
Tsc1
-null neural progenitor cells develop into highly enlarged giant cells with enlarged vacuoles. We found that the vacuolated giant cells had multiple signs of organelle dysfunction, including markedly increased mitochondria, aberrant lysosomes, and elevated cellular stress. We found similar vacuolated giant cells in human tuber specimens. Postnatal rapamycin treatment completely reversed these phenotypes and rescued the mutants from epilepsy and premature death, despite prenatal onset of
Tsc1
loss and mTOR complex 1 activation in the developing brain. This TSC brain model provides insights into the pathogenesis and organelle dysfunction of giant cells, as well as epilepsy control in patients with TSC.
Structure–function analysis of varicella-zoster virus glycoprotein H identifies domain-specific roles for fusion and skin tropism
Authors: Vleck Susan E. , Oliver Stefan L. , Brady Jennifer J. , Blau Helen M. , Rajamani Jaya , Sommer Marvin H. , Arvin Ann M.
Published: October 2011

Enveloped viruses require membrane fusion for cell entry and replication. For herpesviruses, this event is governed by the multiprotein core complex of conserved glycoproteins (g)B and gH/gL. The recent crystal structures of gH/gL from herpes simplex virus 2, pseudorabies virus, and Epstein–Barr virus revealed distinct domains that, surprisingly, do not resemble known viral fusogens. Varicella-zoster virus (VZV) causes chicken pox and shingles. VZV is an α-herpesvirus closely related to herpes simplex virus 2, enabling prediction of the VZV gH structure by homology modeling. We have defined specific roles for each gH domain in VZV replication and pathogenesis using structure-based site-directed mutagenesis of gH. The distal tip of domain (D)I was important for skin tropism, entry, and fusion. DII helices and a conserved disulfide bond were essential for gH structure and VZV replication. An essential
724
CXXC
727
motif was critical for DIII structural stability and membrane fusion. This assignment of domain-dependent mechanisms to VZV gH links elements of the glycoprotein structure to function in herpesvirus replication and virulence.
Early identification of antigen-specific immune responses in vivo by [
18
F]-labeled 3′-fluoro-3′-deoxy-thymidine ([
18
F]FLT) PET imaging
Authors: Aarntzen Erik H. J. G. , Srinivas Mangala , De Wilt Johannes H. W. , Jacobs Joannes F. M. , Lesterhuis W. Joost , Windhorst Albert D. , Troost Esther G. , Bonenkamp Johannes J. , van Rossum Michelle M. , Blokx Willeke A. M. , Mus Roel D. , Boerman Otto C. , Punt Cornelis J. A. , Figdor Carl G. , Oyen Wim J. G. , de Vries I. Jolanda M.
Published: October 2011

Current biomarkers are unable to adequately predict vaccine-induced immune protection in humans with infectious disease or cancer. However, timely and adequate assessment of antigen-specific immune responses is critical for successful vaccine development. Therefore, we have developed a method for the direct assessment of immune responses in vivo in a clinical setting. Melanoma patients with lymph node (LN) metastases received dendritic cell (DC) vaccine therapy, injected intranodally, followed by [
18
F]-labeled 3′-fluoro-3′-deoxy-thymidine ([
18
F]FLT) PET at varying time points after vaccination. Control LNs received saline or DCs without antigen. De novo immune responses were readily visualized in treated LNs early after the prime vaccination, and these signals persisted for up to 3 wk. This selective [
18
F]FLT uptake was markedly absent in control LNs, although tracer uptake in treated LNs increased profoundly with as little as 4.5 × 10
5
DCs. Immunohistochemical staining confirmed injected DC dispersion to T-cell areas and resultant activation of CD4
+
and CD8
+
T cells. The level of LN tracer uptake significantly correlates to the level of circulating antigen-specific IgG antibodies and antigen-specific proliferation of T cells in peripheral blood. Furthermore, this correlation was not observed with [
18
F]-labeled fluoro-2-deoxy-2-
d
-glucose. Therefore, [
18
F]FLT PET offers a sensitive tool to study the kinetics, localization, and involvement of lymphocyte subsets in response to vaccination. This technique allows for early discrimination of responding from nonresponding patients in anti-cancer vaccination and aid physicians in individualized decisionmaking.
Properties of the thalamic projection from the posterior medial nucleus to primary and secondary somatosensory cortices in the mouse
Authors: Viaene Angela N. , Petrof Iraklis , Sherman S. Murray
Published: October 2011

Primary somatosensory cortex (S1) receives two distinct classes of thalamocortical input via the lemniscal and paralemniscal pathways, the former via ventral posterior medial nucleus (VPM), and the latter, from the posterior medial nucleus (POm). These projections have been described as parallel thalamocortical pathways. Although the VPM thalamocortical projection has been studied in depth, several details of the POm projection to S1 are unknown. We studied the synaptic properties and anatomical features in the mouse of the projection from POm to all layers of S1 and to layer 4 of secondary somatosensory cortex (S2). Neurons in S1 responded to stimulation of POm with what has been termed Class 2 properties (paired-pulse facilitation, small initial excitatory postsynaptic potentials (EPSPs), a graded activation profile, and a metabotropic receptor component; thought to be modulatory), whereas neurons in layer 4 of S2 responded with Class 1A properties (paired-pulse depression, large initial EPSPs, an all-or-none activation profile, and no metabotropic receptor component, thought to be a main information input). Also, labeling from POm produced small boutons in S1, whereas both small and large boutons were found in S2. Our data suggest that the lemniscal and paralemniscal projections should not be thought of as parallel information pathways to S1 and that the paralemniscal projection may instead provide modulatory inputs to S1.
Hypothalamic mitochondrial dysfunction associated with anorexia in the
anx/anx
mouse
Authors: Lindfors Charlotte , Nilsson Ida A. K. , Garcia-Roves Pablo M. , Zuberi Aamir R. , Karimi Mohsen , Donahue Leah Rae , Roopenian Derry C. , Mulder Jan , Uhlén Mathias , Ekström Tomas J. , Davisson Muriel T. , Hökfelt Tomas G. M. , Schalling Martin , Johansen Jeanette E.
Published: October 2011

The anorectic
anx/anx
mouse exhibits disturbed feeding behavior and aberrances, including neurodegeneration, in peptidergic neurons in the appetite regulating hypothalamic arcuate nucleus. Poor feeding in infants, as well as neurodegeneration, are common phenotypes in human disorders caused by dysfunction of the mitochondrial oxidative phosphorylation system (OXPHOS). We therefore hypothesized that the anorexia and degenerative phenotypes in the
anx/anx
mouse could be related to defects in the OXPHOS. In this study, we found reduced efficiency of hypothalamic OXPHOS complex I assembly and activity in the
anx/anx
mouse. We also recorded signs of increased oxidative stress in
anx/anx
hypothalamus, possibly as an effect of the decreased hypothalamic levels of fully assembled complex I, that were demonstrated by native Western blots. Furthermore, the
Ndufaf1
gene, encoding a complex I assembly factor, was genetically mapped to the
anx
interval and found to be down-regulated in
anx/anx
mice. These results suggest that the anorexia and hypothalamic neurodegeneration of the
anx/anx
mouse are associated with dysfunction of mitochondrial complex I.
Imaging β amyloid's pore performance
Authors: Short Ben
Published: October 2011

Study visualizes Alzheimer's disease–related peptides forming toxic calcium channels in the plasma membrane.
Multiple pathways can bypass the essential role of fission yeast Hsk1 kinase in DNA replication initiation
Authors: Matsumoto Seiji , Hayano Motoshi , Kanoh Yutaka , Masai Hisao
Published: October 2011

Cdc7/Hsk1 is a conserved kinase required for initiation of DNA replication that potentially regulates timing and locations of replication origin firing. Here, we show that viability of fission yeast hsk1Δ cells can be restored by loss of mrc1, which is required for maintenance of replication fork integrity, by cds1Δ, or by a checkpoint-deficient mutant of mrc1. In these mutants, normally inactive origins are activated in the presence of hydroxyurea and binding of Cdc45 to MCM is stimulated. mrc1Δ bypasses hsk1Δ more efficiently because of its checkpoint-independent inhibitory functions. Unexpectedly, hsk1Δ is viable at 37°C. More DNA is synthesized, and some dormant origins fire in the presence of hydroxyurea at 37°C. Furthermore, hsk1Δ bypass strains grow poorly at 25°C compared with higher temperatures. Our results show that Hsk1 functions for DNA replication can be bypassed by different genetic backgrounds as well as under varied physiological conditions, providing additional evidence for plasticity of the replication program in eukaryotes.
Estimating Constituency Preferences from Sparse Survey Data Using Auxiliary Geographic Information
Authors: Selb Peter , Munzert Simon
Published: October 2011

Measures of constituency preferences are of vital importance for the study of political representation and other research areas. Yet, such measures are often difficult to obtain. Previous survey-based estimates frequently lack precision and coverage due to small samples, rely on questionable assumptions or require detailed auxiliary information about the constituencies' population characteristics. We propose an alternative Bayesian hierarchical approach that exploits minimal geographic information readily available from digitalized constituency maps. If at hand, social background data are easily integrated. To validate the method, we use national polls and district-level results from the 2009 GermanBundestagelection, an empirical case for which detailed structural information is missing.
Ancient origin and recent divergence of a haplochromine cichlid lineage from isolated water bodies in the East African Rift system
Authors: Hermann C. M. , Sefc K. M. , Koblmüller S.
Published: October 2011

Phylogenetic analysis identified haplochromine cichlids from isolated water bodies in the eastern branch of the East African Rift system as an ancient lineage separated from their western sister group in the course of the South Kenyan–North Tanzanian rift system formation. Within this lineage, the close phylogenetic relatedness among taxa indicates a recent common ancestry and historical connections between now separated water bodies. In connection with a total lack of local genetic diversity attributable to population bottlenecks, the data suggest cycles of extinction and colonization in the unstable habitat provided by the small lakes and rivers in this geologically highly active area.
Novel mutations in MEN1, CDKN1B and AIP genes in patients with multiple endocrine neoplasia type 1 syndrome in Spain
Authors: Belar Oihana , Hoz Carmen De La , Pérez‐Nanclares Gustavo , Castaño Luis , Gaztambide Sonia ,   Spanish MEN1 Group
Published: October 2011

Context  Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal dominant disorder mostly owing to a genetic defect in MEN1 gene. Not all patients with MEN1 phenotype present a defect in this gene. Thus, other genes like CDKN and AIP have been showed to be involved in MEN1‐like patients.

Objective  The aim of this study was to perform a genetic screening in our cohort or patients with suspected MEN1 syndrome by direct sequencing analysis of MEN1, CDKN1B and AIP, and dosage analysis of MEN1 and AIP.

Results  A total of 79 different sporadic and familial cases with the MEN1 phenotype have been studied, in which 34 of them (48%) present a mutation in MEN1 gene. In two patients without a detectable mutation in MEN1 gene, we have identified a novel missense mutation (c.163G>A/p.Ala55Thr) in CDKN1B gene and a novel frameshift mutation (c.825_845delCGCGGCCGTGTGGAATGCCCA/p. His275GlnfsX49) in AIP gene, respectively.

Conclusions  Our data support that MEN1 gene is the main target for genetic analysis in clinical MEN1 syndrome. We confirm that in those patients without MEN1 gene mutation, other genes such as CDKN1B/p27Kip, or AIP in those including pituitary tumours should also be tested.
Lithology and fluid prediction from prestack seismic data using a Bayesian model with Markov process prior
Authors: Hammer Hugo , Kolbjørnsen Odd , Tjelmeland Håkon , Buland Arild
Published: October 2011

We invert prestack seismic amplitude data to find rock properties of a vertical profile of the earth. In particular we focus on lithology, porosity and fluid. Our model includes vertical dependencies of the rock properties. This allows us to compute quantities valid for the full profile such as the probability that the vertical profile contains hydrocarbons and volume distributions of hydrocarbons. In a standard point wise approach, these quantities can not be assessed. We formulate the problem in a Bayesian framework, and model the vertical dependency using spatial statistics. The relation between rock properties and elastic parameters is established through a stochastic rock model, and a convolutional model links the reflectivity to the seismic. A Markov chain Monte Carlo (MCMC) algorithm is used to generate multiple realizations that honours both the seismic data and the prior beliefs and respects the additional constraints imposed by the vertical dependencies. Convergence plots are used to provide quality check of the algorithm and to compare it with a similar method. The implementation has been tested on three different data sets offshore Norway, among these one profile has well control. For all test cases the MCMC algorithm provides reliable estimates with uncertainty quantification within three hours. The inversion result is consistent with the observed well data. In the case example we show that the seismic amplitudes make a significant impact on the inversion result even if the data have a moderate well tie, and that this is due to the vertical dependency imposed on the lithology fluid classes in our model. The vertical correlation in elastic parameters mainly influences the upside potential of the volume distribution.

The approach is best suited to evaluate a few selected vertical profiles since the MCMC algorithm is computer demanding.
Fatigue and physical activity levels in patients with liver cirrhosis
Authors: Wu Li‐Jan , Wu Ming‐Shun , Lien GI‐Shih , Chen Feng‐Chia , Tsai Jen‐Chen
Published: October 2011

Aims and objectives.  This study aimed to explore the correlation between fatigue and physical activity in patients with liver cirrhosis.

Background.  Many patients with liver cirrhosis perceive lower physical functioning and more fatigue than non‐cirrhotic individuals. To date, however, few studies have examined the relationship between fatigue and physical activity in this patient population.

Design.  This study used a correlation design. Participants were patients with liver cirrhosis recruited from the gastroenterology clinic of a teaching medical centre in Taiwan.

Methods.  Data were collected using a structured questionnaire, consisting of a fatigue scale and a seven‐day Physical Activity Recall scale. spss version 13.0 software was used to analyse the data through statistical methods, including one‐way analysis of variance, independent t‐test and Pearson’s correlations.

Results.  Patients participating in this study suffered from moderate‐to‐severe fatigue, and their engagement in physical activity of moderate or higher intensity was decreased. On average, fatigue had a moderate level of influence on physical activity. A significant negative correlation was found between the fatigue level and average seven‐day physical activity level.

Conclusions.  Patients with liver cirrhosis can experience severe fatigue, which may reduce their level of physical activity.

Relevance to clinical practice.  Early evaluation of the fatigue level and physical activity constraints in patients with liver cirrhosis should be conducted in the clinic or community. Individualised instructions for patient’s physical activity should be provided.
Equine Pre‐Implantation Conceptuses Express Neuraminidase 2 – A Potential Mechanism for Desialylation of the Equine Capsule
Authors: Klein C , Troedsson MHT
Published: October 2011

Contents

During the second and third week of pregnancy, the equine conceptus is covered by an acellular glycoprotein capsule. This capsule contains glycoproteins resembling those of the mucin family with sialic acid making up a high proportion of the carbohydrate. Coinciding with conceptus fixation, a marked decline in sialic acid content of the capsule occurs, which has been proposed to contribute to cessation of conceptus mobility. Herein, we describe the expression of neuraminidase 2 (NEU2) by pre‐implantation stages of equine conceptus development. NEU2 transcript abundance was examined in conceptuses obtained 8, 10, 12, 14 and 16 days after ovulation; highest levels were observed 16 days after ovulation. Transcript abundance observed in endometrial tissue was on average 474‐fold lower than in conceptus tissue. Protein expression was localized to trophoblast cells and capsular material. Functionality of NEU2 was shown using an Amplex Red reagent‐based assay. NEU2, formerly known as sialidase 2, belongs to a family of enzymes that cleave sialic acid from polysaccharide chains. The expression of NEU2 described herein provides a mechanism by which the conceptus can regulate the sialic acid content of its own capsule. The timely desialylation coinciding with conceptus fixation has been suggested integral for establishment of normal pregnancy.
Communication experience of individuals treated with home mechanical ventilation
Authors: Laakso Katja , Markström Agneta , Idvall Markus , Havstam Christina , Hartelius Lena
Published: October 2011

Background: Mechanical ventilatory support seriously affects speaking and communication, and earlier studies show that many ventilator‐supported patients experience difficulties and frustration with their speech and voice production. Since there is a growing number of individuals who require mechanical ventilatory support and there is a paucity of studies that examine ventilator‐supported communication, this research area needs to be developed to ensure adequate health services for this population. The present study focused on ventilator‐supported communication from the point of view of individuals receiving home mechanical ventilation (HMV).

Aims: The specific aim was to examine the communication experience of individuals receiving HMV.

Methods & Procedures: A qualitative approach was adopted for this study, and data were collected by means of semi‐structured interviews. Qualitative content analysis was used to structure, condense and interpret the data. The participants were recruited from the National Respiratory Centre (NRC) in Sweden, and included 19 individuals receiving HMV.

Outcomes & Results: The main theme A long and lonely struggle to find a voice and six subthemes detailing different facets of it emerged from data analysis: Managing changed speech conditions, Prioritising voice, A third party supporting communication, Using communication to get things done, Depending on technology, and Facing ignorance. Important aspects influencing the ventilator‐supported individuals’ communicative performance (speech, support from others and technological solutions) are discussed.

Conclusions & Implications: The study revealed that healthcare practitioners involved in the care of individuals receiving HMV need to improve their understanding and knowledge of issues related to ventilator‐supported communication. Individuals receiving HMV encounter a needlessly long and lonely struggle to achieve effective communication. They face numerous challenges regarding their communication, and they need to be heard in both literal and figurative senses. To overcome these challenges they need support from competent healthcare practitioners and personal assistants, and continuous follow‐up by speech and language therapists tailoring communicative solutions to fit individual needs.
MECHANISMS AND PUBLIC ADMINISTRATION REFORM: ITALIAN CASES OF BETTER REGULATION AND DIGITALIZATION
Authors: NATALINI ALESSANDRO , STOLFI FRANCESCO
Published: October 2011

This article applies a processual approach to the explanation of administrative reform in Italy over fifteen years. By carrying out a comparison between better regulation and digitalization policies it shows that the oscillation in the level of implementation over time and across policies can be explained by the intensity and direction of spillover and certification mechanisms and that in turn these mechanisms are activated by design features and contextual factors at different levels of analysis.
WHY PUBLIC EMPLOYMENT SERVICES ALWAYS FAIL. DOUBLE‐SIDED ASYMMETRIC INFORMATION AND THE PLACEMENT OF LOW‐SKILL WORKERS IN SIX EUROPEAN COUNTRIES
Authors: LARSEN CHRISTIAN ALBREKT , VESAN PATRIK
Published: October 2011

It has been a general finding across Europe that very few job matches are facilitated by public employment services (PES).The article explains this failure by highlighting the existence of a double‐sided asymmetric information problem on the labour market. It is argued that although a PES potentially reduces search costs, both employers and employees have strong incentives not to use PES. The reason is that employers try to avoid the ‘worst’ employees, and employees try to avoid the ‘worst’ employers. Therefore these services get caught in a low‐end equilibrium that is almost impossible to escape. The mechanisms leading to this low‐end equilibrium are illustrated by means of qualitative interviews with 40 private employers in six European countries.
A child‐centred exploration of the relevance of family and friends to theory of mind development
Authors: WRIGHT BARLOW C. , MAHFOUD JANINA
Published: October 2011

Wright, B. C. & Mahfoud, J. (2012). A child‐centred exploration of the relevance of family and friends to theory of mind development. Scandinavian Journal of Psychology 53, 32–40.

Theory of Mind (ToM) is said to develop at around 4 years old. But some studies suggest it develops considerably earlier than this, with others suggesting it develops much later. Although several recent studies have found that social factors (like gender, family size, number of siblings, and number of friends) can impact on ToM, other studies contradict those findings. We wondered whether addressing several procedural issues and ensuring the task concerns real protagonists in real time, would bear on the above issues. Here, 114 children of 3–6 years completed four ToM tasks incorporating controls from experimental psychology, including randomly varying the order of ToM and non‐ToM questions across participants. Now, children passed ToM tasks from around 5 years old, rather than 4 years or earlier. Girls did not develop ToM any earlier than boys. There was clear correlational evidence for the older‐sibling effect and effects of friends but no reliable effects of nuclear or extended family. However, when these factors were set in the context of one another, the sibling effect was driven by a negative influence from younger siblings (as opposed to older siblings) and the friends effect was driven by friends at school (as opposed to friends at home). Finally, “friends” was a stronger predictor than siblings but memory (a cognitive factor) and age (a maturational factor) were the strongest predictors of all.
Parents of deaf children with cochlear implants: a study of technology and community
Authors: Mauldin Laura
Published: October 2011

The cochlear implant (CI) is increasingly used to treat deafness, despite arguments from the deaf community. Deaf children born to hearing parents are the fastest growing group of CI recipients, making parents the primary consumers. Instead of focusing on the controversy over implants, this article examines the clinical structures shaping parental decision‐making and how parents integrate clinical practices into family and community. Observations and in‐depth interviews were conducted in a CI clinic and at various community sites. The data reveal strong inter‐institutional co‐operations between the clinic, the state and local school districts. Working together, these institutions anticipate parental needs, foster a CI community and thus increase compliance. I conclude that implantation is an ongoing practice enculturating parents into a new community characterised by the adoption of long‐term rehabilitative duties. However, the long‐term nature of rehabilitation creates disparities in outcomes, which would be better understood through further research on the social relations in families and across parent networks in the CI community.
Citizens' Response Patterns to Warning Messages
Authors: Vihalemm T. , Kiisel M. , Harro‐Loit H.
Published: October 2011

This paper elaborates the concept of citizens' crisis‐coping strategies, using data from a qualitative study of people who have experienced a real crisis plus discussions of simulated warning messages. The analysis results suggest that, to emotionally cope with a crisis, citizens may need more than institutionally framed warnings. They may either seek information from informal information networks or simply take their own response action. The paper concludes that the use of alternative sources and channels of warning messages would help people to cope, emotionally and cognitively, with crises. These alternatives would increase the efficacy of institutional crisis communication plans and consequently the public's response to crisis messages.
Cultural Experience as a (Critical) Factor in Crisis Communication Planning
Authors: Harro‐Loit Halliki , Vihalemm Triin , Ugur Kadri
Published: October 2011

A key issue in crisis communication is the way people process crisis‐relevant information to minimize danger. This paper discusses the impact of previously experienced crises on the public's interpretation of warning messages. People may not have direct experience of a crisis, but they still have acquired mediated experiences of a variety of crises. The present study introduces the term cultural experience of crisis to label the synthesis of mediated crisis experiences, media and fictional narratives, collective memories of societal disasters, conversations, and immediate crisis experiences of witnesses and victims. The proposed model of cultural experience of crisis is elaborated on the basis of a qualitative text analysis derived from four qualitative interviews 16 focus groups interviews carried out in Estonia from 2008 to 2009.
Social Support and Hopelessness in Women Undergoing Infertility Treatment in Eastern Turkey
Authors: Yağmur Yurdagül , Oltuluoğlu Hatice
Published: October 2011

Objectives

The aim of this study was to determine the social support and hopelessness in women undergoing infertility treatment in eastern Turkey.

Design and Sample

For this descriptive design study, the sample was composed of 456 women.

Measures

Beck's Hopelessness Scale (BHS) and the Multidimensional Scale of Perceived Social Support (MSPSS) were used. Percentile, correlation, unpaired t test, and one‐way analysis of variance test were used for statistical analysis.

Results

The mean BHS score was 6.97 ± 3.64, with a range of 0–19 while the mean MSPSS score was 61.98 ± 16.05 with a range of 12–84. A negative correlation (r = −.336, p = .000) was noted between MSPSS scores and BHS scores.

Conclusions

Hopelessness levels in women negatively correlate with reported level of social support. Informing health professionals about these issues will be an important step toward improving the quality and levels of social support given to women undergoing infertility treatment.
Carbonic anhydrase isozymes II, IX, and XII in uterine tumors
Authors: HYNNINEN PIRITTA , PARKKILA SEPPO , HUHTALA HEINI , PASTOREKOVA SILVIA , PASTOREK JAROMIR , WAHEED ABDUL , SLY WILLIAM S. , TOMAS EIJA
Published: October 2011

Hynninen P, Parkkila S, Huhtala H, Pastorekova S, Pastorek J, Waheed A, Sly WS, Tomas E. Carbonic anhydrase isozymes II, IX, and XII in uterine tumors. APMIS 2011.

Histopathological diagnostics of gynecological malignancies continues to be challenging despite the well established criteria. For example, the morphological distinction of uterine leiomyosarcoma from certain variants of benign leiomyoma can be difficult. Herein, we investigated the expression of Carbonic anhydrase (CA) II, IX, and XII in the normal endometrium, leiomyomas, uterine sarcomas, and endometrial adenocarcinomas using immunohistochemistry. These isozymes are considered promising diagnostic markers and therapeutic targets. The normal endometrium showed high CA XII expression, whereas the signals were lower in endometrial adenocarcinoma (p < 0.004). Only sporadic CA IX staining was found in the normal endometrium, whereas the enzyme was overexpressed in most cases of endometrial adenocarcinoma (p < 0.005). CA II expression was slightly weaker in the normal endometrium than that in the adenocarcinomas (p < 0.008). Positive immunostaining reactions for CAs were observed in the uterine sarcomas, whereas all leiomyomas were negative for CA II and XII. A comparison between leiomyomas and sarcomas showed statistically significant differences for all studied isozymes (p < 0.001). Our study shows that CA isozymes could together serve as histopathological biomarkers for differential diagnosis between uterine leiomyosarcoma and leiomyoma. In addition to being found in leiomyosarcomas, CA II and IX were overexpressed in endometrial adenocarcinoma, where they might regulate the pH of the tumor microenvironment.
Low‐dose vs. high‐dose thalidomide for advanced multiple myeloma: a prospective trial from the Intergroupe Francophone du Myélome
Authors: Yakoub‐Agha Ibrahim , Mary Jean‐Yves , Hulin Cyrille , Doyen Chantal , Marit Gérald , Benboubker Lotfi , Voillat Laurent , Moreau Philippe , Berthou Christian , Stoppa Anne‐Marie , Maloisel Frédéric , Rodon Philippe , Dib Mamoun , Pegourie Brigitte , Casassus Philippe , Slama Borhane , Damaj Ghandi , Zerbib Robert , Harousseau Jean‐Luc , Mohty Mohamad , Facon Thierry ,   for the Intergroupe Francophone du Myélome (IFM)
Published: October 2011

This multicentre prospective randomised trial compared the efficacy and safety of two doses of thalidomide in patients with relapsed or refractory myeloma. The study was designed to test the non‐inferior efficacy and to confirm the better tolerability of low‐dose thalidomide as compared to a higher dose. Four hundred patients were randomly assigned to receive either 100 or 400 mg/day of thalidomide. Dexamethasone treatment was added in both arms for patients with stable disease or treatment failure at 12 weeks. The primary endpoint was 1‐year overall survival (OS). Thalidomide 100 mg/day was better tolerated than 400 mg/day with less high‐grade somnolence, constipation, nausea/vomiting and peripheral neuropathy (P < 0.001, P = 0.007, P = 0.03 and P = 0.007, respectively). In the per‐protocol population (PP), the estimated 1‐year OS rates were of 74.5% (n = 149) and 67.3% (n = 156) in the 400 and 100 groups, respectively. The upper limit of the difference between these rates was of 15.6% higher than the non‐inferiority acceptable limit of 12.75%, and the hypothesis of non‐inferiority of 100 could not be established (P = 0.14). On the other hand, when intent‐to‐treat (ITT) population was analysed, the non‐inferiority was demonstrated because the 1‐year OS rates were of 72.8% (n = 195) and 68.8% (n = 205) in the same groups, leading to an upper limit of the difference of 11.49% lower than the non‐inferiority acceptable limit. In addition, in patients alive 12 weeks postrandomisation and those who received thalidomide plus dexamethasone, there were no significant differences in response rates, time to progression, progression‐free survival and OS between the two groups. Collectively, low‐dose thalidomide 100 mg/day has significant activity in advanced myeloma with an improved safety profile and can be a good salvage therapy in combination with dexamethasone.
Autoimmune bullous skin diseases. Part 2: diagnosis and therapy
Authors: Kneisel Andrea , Hertl Michael
Published: October 2011

Autoimmune bullous skin diseases represent a heterogenous group of disorders of skin and mucosa which are commonly associated with IgG or IgA autoantibodies against distinct adhesion molecules of the skin. The antibodyinduced loss of adhesion between epidermis and dermis results in blister formation and extensive erosions. There is a great need for rapidly establishing the diagnosis of these disorders since they may run a severe and potentially life‐threatening course. In addition, because of their rarity and heterogeneous symptoms, autoimmune bullous skin diseases often pose a major diagnostic challenge. While histopathological examinations provide evidence for the level of blister formation, immunofluorescence microscopy has been established to identify tissue‐bound and circulating autoantibodies. Direct immunofluorescence microscopy represents the gold standard for detecting tissue‐bound autoantibodies. Indirect immunofluorescence microscopy with defined tissue substrates is considered the first step in detecting circulating autoantibodies. Confirmatory tests such as ELISA, immunoblot or immunoprecipitation analyses are performed utilizing recombinant proteins or keratinocyte extracts. The later assays can be used for primary diagnosis as well as for immunoserological follow‐up. Systemic immunosuppressive drugs usually represent the main therapeutic regimen. Initially, systemic corticosteroids are commonly administered in combination with steroid‐sparing, immunosuppressive agents. Novel targeted treatments such as immunoadsorption, rituximab or high‐dose intravenous immunoglobulins have proven to be highly effective in severe and refractory pemphigus. This review presents a state‐of‐the‐art algorithm for making the diagnosis of autoimmune bullous disorders and provides an overview on currently available therapeutic options.
Restricted versus Unrestricted Choice in Labeled Choice Experiments: Exploring the Trade‐Offs of Expanding Choice Dimensions
Authors: Rolfe John , Windle Jill
Published: October 2011

A key methodological question in choice experiments is to identify whether there is a difference in choice behavior, and subsequent value estimates, when choices are constrained to mutually exclusive alternatives in labeled experiments compared to when combinations of alternatives are available. This issue is important when policy management options are represented in labeled experiments, as it is easier to represent management options as mutually exclusive choice alternatives, but combinations of management options may be more relevant in the policy world. This issue is tested with a case study application to the Great Barrier Reef in Australia. A split‐sample experiment is implemented where one survey includes four labeled alternatives: a status quo option and three specific policy management options (restricted choice). The other survey provides respondents with an unrestricted choice set by including a fifth alternative choice, labeled as “a combination of management options.” The results provide some evidence that adding a combination policy alternative does change the way that respondents view trade‐offs, but that choice behavior and subsequent value estimates are consistent across the two survey formats.

Une question d’ordre méthodologique importante se pose dans le cas de la méthode des choix discrets expérimentaux : déterminer s’il existe ou non une différence dans les choix des répondants et dans les estimations subséquentes lorsque les alternatives proposées sont mutuellement exclusives et lorsque les alternatives proposées peuvent être des combinaisons d’alternatives mutuellement exclusives. Il s’agit d’un point important lorsque les options de gestion de politiques figurent dans des expériences avec des alternatives nongénériques étant donné qu’il est plus facile de présenter les stratégies de gestion comme des alternatives mutuellement exclusives, bien que les combinaisons de stratégies de gestion puissent être plus pertinentes pour les décideurs. Nous avons vérifié ce point à l’aide d’une étude de cas appliquée à la grande barrière de corail (Great Barrier Reef) de l’Australie. Nous avons utilisé la technique de l’échantillon fractionné : un premier sondage comprenait quatre choix distincts : conservation du statu quo et trois alternatives de gestion de politiques (choix contraint); un deuxième sondage comprenait un choix complet d’alternatives incluant une cinquième alternative intitulée « combinaison de stratégies de gestion ». Les résultats semblent indiquer que l’ajout d’une telle alternative influence la perception des répondants à l’égard de la valorisation des attributs, mais que les choix des répondants et les estimations subséquentes se ressemblent dans les deux formules de sondage.
‘Make No Little Plans’: Anatomy of Planning Ambition and Prospect
Authors: GLEESON BRENDAN
Published: October 2011

This review paper applies a critical geographic perspective to analysis of planning ambition and prospect. Its point of departure is that planning, an applied spatial science, has lacked consistent review from critical geography in recent decades. The consequences of this drift for planning conception and practice are considered, focusing on the influential construct, the compact city. The review finds evidence of serious epistemological and methodological flaws in planning thought and ambition; failings that were earlier identified and analysed in the break with positivism in geographical sciences. The consequences of these limitations for planning thought and practice are considered. Broadly they undermine the ability of the compact city ideal to address what is arguably the most critical threat facing humanity, climate change. Specifically, the proposition that urban density has straightforward influences on human behaviour, including resource use, is without scientific foundation. Planning has a critically important part to play in climate response: securing the resilience and well‐being of an increasingly urbanised human species. Urban compaction may not achieve these ends.
Antagonism of the TRPv1 receptor partially corrects muscle metaboreflex overactivity in spontaneously hypertensive rats
Authors: Mizuno Masaki , Murphy Megan N. , Mitchell Jere H. , Smith Scott A.
Published: October 2011

Non‐technical summary  The cardiovascular response to exercise is exaggerated in hypertension. This heightened circulatory responsiveness increases the risk of occurrence of an adverse cardiovascular event during and immediately following a bout of exercise. Accumulating evidence suggests the muscle metaboreflex, a chemically sensitive peripheral reflex originating in skeletal muscle, contributes significantly to this abnormal cardiovascular response to exercise. However, its role remains controversial. In addition, the receptor mechanisms underlying metaboreflex dysfunction in hypertension remain undetermined. To this end, the current investigation demonstrates that the metaboreflex is overactive in hypertensive rats eliciting exaggerated increases in sympathetic nerve activity and blood pressure. Importantly, the study shows, for the first time, that the metaboreflex dysfunction manifest in hypertension is mediated, in part, by activation of the skeletal muscle TRPv1 receptor. As such, the investigation identifies the muscle metaboreflex, specifically the TRPv1 receptor, as a potential target for the treatment of cardiovascular hyperexcitability during exercise in hypertension.
Biophysical properties of slow potassium channels in human embryonic stem cell derived cardiomyocytes implicate subunit stoichiometry
Authors: Wang Kai , Terrenoire Cecile , Sampson Kevin J. , Iyer Vivek , Osteen Jeremiah D. , Lu Jonathan , Keller Gordon , Kotton Darrell N. , Kass Robert S.
Published: October 2011

Non‐technical summary  The human heart is a pump that works only when its internal electrical system coordinates both its filling and its capacity to eject blood. This critical electrical timing is coordinated by many different ion channels, and this study looks at the one known as IKs. Mutations in its α subunit, KCNQ1, constitute the majority of cases of the disorder long QT syndrome (LQT‐1). Here we have examined properties of human cardiac cells during very early stages of development and found evidence for the manner in which the subunits of IKs assemble; our data suggest that this assembly may be flexible and may change during development and/or disease.
Customer-Driven Optimal Design for Convergence Products
Authors: Wang Z. , Kannan P. K. , Azarm S.
Published: October 2011

Convergence products are multifunctional designs which are changing the way consumers use existing functionalities. Manufacturers’ ventures in developing convergence products abound in the marketplace. Smartphones, tablet computers, and internet TV are just a few examples. The complexity of designing a convergence product can differ significantly from that of single function products which most research in “design for market systems” aims at. In this paper, a new customer-driven approach for designing convergence products is proposed to address the following issues: (i) a design representation scheme that considers information from design solutions used in existing products. The representation facilitates the coupling of and combining multiple functionalities; (ii) a hierarchical Bayes model that evaluates consumers’ heterogeneous choices while revealing how usage of multiple functionalities impacts consumers’ preferences; and (iii) design metrics which help to evaluate profitability of design alternatives and account for future market penetration given evolving consumer preferences. An example problem for designing a tablet computer is used to demonstrate the proposed approach. The data for the example are collected by conducting a choice-based conjoint survey which yielded 92 responses. The proposed approach is demonstrated with three scenarios differentiated by the consideration of consumer heterogeneity and future market penetration, while comparing how the resulting optimal design solutions for the convergence product differ.