bluuebunny/crossref_metadata_2025 huggingface dataset:
Regulatory Factors and Structure of a Component Population of the Spionid Polydora bioccipitalis Infesting the Surf Clam Mesodesma donacium
Authors: Riascos José M. , Cuturrufo Miguel , Pacheco Aldo S. , Oliva Marcelo E.
Published: December 2011

Spionidae, particularly polydorids, are common polychaete parasites of edible mollusks around the world. However, our understanding of the regulatory factors and population structure of these parasites is scant. In this study involving Polydora bioccipitalis and the surf clam Mesodesma donacium we evaluated (1) the environmental correlates of the prevalence and mean intensity of the infestation, (2) the relationship between the number of egg capsules and juvenile and adult parasites and the time elapsed since infestation, and (3) the spatial patterns of juveniles and adults within the host. Environmental factors showed no significant correlations with prevalence and mean intensity, suggesting that these factors do not act directly as regulators. Rather, storm surges seemingly induced clam stranding, which in turn affected both the prevalence and intensity of the infestation. The numbers of juveniles and egg capsules in blisters were significantly related to the time since infestation, suggesting mechanisms of use and expansion of the space within the host. Juvenile worms showed an aggregated distribution that was probably related to the episodic nature of infestation events, whereas adults exhibited uniform distributions that probably reflect territorial behavior and reproductive strategies.

Received June 7, 2010; accepted April 7, 2011
Altered nuclear tRNA metabolism in La-deletedSchizosaccharomyces pombeis accompanied by a nutritional stress response involving Atf1p and Pcr1p that is suppressible by Xpo-t/Los1p
Authors: Cherkasova Vera , Lopez Maury Luis , Bacikova Dagmar , Pridham Kevin , Bähler Jürg , Maraia Richard J.
Published: December 2011

Deletion of the sla1+gene, which encodes a homologue of the human RNA-binding protein La in Schizosaccharomyces pombe, causes irregularities in tRNA processing, with altered distribution of pre-tRNA intermediates. We show, using mRNA profiling, that cells lacking sla1+have increased mRNAs from amino acid metabolism (AAM) genes and, furthermore, exhibit slow growth in Edinburgh minimal medium. A subset of these AAM genes is under control of the AP-1–like, stress-responsive transcription factors Atf1p and Pcr1p. Although S. pombe growth is resistant to rapamycin, sla1-Δ cells are sensitive, consistent with deficiency of leucine uptake, hypersensitivity to NH4, and genetic links to the target of rapamycin (TOR) pathway. Considering that perturbed intranuclear pre-tRNA metabolism and apparent deficiency in tRNA nuclear export in sla1-Δ cells may trigger the AAM response, we show that modest overexpression of S. pombe los1+(also known as Xpo-t), encoding the nuclear exportin for tRNA, suppresses the reduction in pre-tRNA levels, AAM gene up-regulation, and slow growth of sla1-Δ cells. The conclusion that emerges is that sla1+regulates AAM mRNA production in S. pombe through its effects on nuclear tRNA processing and probably nuclear export. Finally, the results are discussed in the context of stress response programs in Saccharomyces cerevisiae.
B-SOLANA: an approach for the analysis of two-base encoding bisulfite sequencing data
Authors: Kreck Benjamin , Marnellos George , Richter Julia , Krueger Felix , Siebert Reiner , Franke Andre
Published: December 2011

Summary: Bisulfite sequencing, a combination of bisulfite treatment and high-throughput sequencing, has proved to be a valuable method for measuring DNA methylation at single base resolution. Here, we present B-SOLANA, an approach for the analysis of two-base encoding (colorspace) bisulfite sequencing data on the SOLiD platform of Life Technologies. It includes the alignment of bisulfite sequences and the determination of methylation levels in CpG as well as non-CpG sequence contexts. B-SOLANA enables a fast and accurate analysis of large raw sequence datasets.

Availability and implementation: The source code, released under the GNU GPLv3 licence, is freely available at http://code.google.com/p/bsolana/.

Contact:  b.kreck@ikmb.uni-kiel.de

Supplementary information:  Supplementary data are available at Bioinformatics online.
The COACH risk engine: a multistate model for predicting survival and hospitalization in patients with heart failure
Authors: Postmus Douwe , van Veldhuisen Dirk J. , Jaarsma Tiny , Luttik Marie Louise , Lassus Johan , Mebazaa Alexandre , Nieminen Markku S. , Harjola Veli‐Pekka , Lewsey James , Buskens Erik , Hillege Hans L.
Published: December 2011

Aims

Several models for predicting the prognosis of heart failure (HF) patients have been developed, but all of them focus on a single outcome variable, such as all‐cause mortality. The purpose of this study was to develop a multistate model for simultaneously predicting survival and HF‐related hospitalization in patients discharged alive from hospital after recovery from acute HF.

Methods and results

The model was derived in the COACH (Coordinating Study Evaluating Outcomes of Advising and Counseling in Heart Failure) cohort, a multicentre, randomized controlled trial in which 1023 patients were enrolled after hospitalization because of HF. External validation was attained with the FINN‐AKVA (Finish Acute Heart Failure Study) cohort, a prospective, multicentre study with 620 patients hospitalized due to acute HF. The observed vs. predicted 18‐month survival was 72.1% vs. 72.3% in the derivation cohort and 71.4% vs. 71.2% in the validation cohort. The corresponding values of the c statistic were 0.733 [95% confidence interval (CI) 0.705–0.761] and 0.702 (95% CI 0.663–0.744), respectively. The model's accuracy in predicting HF hospitalization was excellent, with predicted values that closely resembled the values observed in the derivation cohort.

Conclusion

The COACH risk engine accurately predicted survival and various measures of recurrent hospitalization in (acute) HF patients. It may therefore become a valuable tool in improving and personalizing patient care and optimizing the use of scarce healthcare resources.
Interferon treatment suppresses enteric adenovirus infection in a model gastrointestinal cell-culture system
Authors: Sherwood Victoria , King Elizabeth , Tötemeyer Sabine , Connerton Ian , Mellits Kenneth H.
Published: December 2011

Exposure to interferon results in the rapid transcriptional induction of genes, many of which function to create an antiviral environment in potential host cells. For the majority of adenoviruses, replication is unaffected by the actions of interferon. It has previously been shown, using non-gastrointestinal cells, that the species F human adenoviruses are sensitive to the action of interferon. Here, we have developed an enterocyte-like cell-culture model to re-evaluate this question, and determined the effects of interferon on species F adenovirus during infection of gastrointestinal cells. We show that species F adenovirus type 40 is sensitive to the effects of interferon in gastrointestinal-like cells, which may help to explain its fastidious growth in culture.
The chromatin-tethering domain of human cytomegalovirus immediate-early (IE) 1 mediates associations of IE1, PML and STAT2 with mitotic chromosomes, but is not essential for viral replication
Authors: Shin Hye Jin , Kim Young-Eui , Kim Eui Tae , Ahn Jin-Hyun
Published: December 2011

Human cytomegalovirus (HCMV) immediate-early (IE) 1 protein associates with chromosomes in mitotic cells using its carboxyl-terminal 16 aa region. However, the role of this IE1 activity in viral growth has not been evaluated in the context of mutant virus infection. We produced a recombinant HCMV encoding mutant IE1 with the carboxyl-terminal chromosome-tethering domain (CTD) deleted. This IE1(ΔCTD) virus grew like the wild-type virus in fibroblasts, indicating that the CTD is not essential for viral replication in permissive cells. Unlike wild-type virus infections, PML and STAT2, which interact with IE1, did not accumulate at mitotic chromosomes in IE1(ΔCTD) virus-infected fibroblasts, demonstrating that their associations with chromosomes are IE1 CTD-dependent. IE1 SUMOylation did not affect IE1 association with chromosomes. Our results provide genetic evidence that the CTD is required for the associations of IE1, PML and STAT2 with mitotic chromosomes, but that these IE1-related activities are not essential for viral replication in fibroblasts.
Decaaquabis(μ3-4-hydroxypyridine-2,6-dicarboxylato)bis(4-hydroxypyridine-2,6-dicarboxylato)tetramanganese(II) 3.34-hydrate: a new three-dimensional open metal–organic framework based on a tetranuclear MnIIcomplex of chelidamic acid and undecameric stitching water clusters
Authors: Mirzaei M. , Lippolis V. , Eshtiagh-Hosseini H. , Mahjoobizadeh M.
Published: December 2011

4-Hydroxypyridine-2,6-dicarboxylic acid (chelidamic acid, cdaH3) reacts with MnCl2·2H2O in the presence of 2-amino-4-methylpyrimidine in water to afford the tetranuclear title complex, [Mn4(C8H3NO5)4(H2O)10]·3.34H2O, built through carboxylate bridging. The tetranuclear complex sits on a centre of inversion at (1 \over 2, 1 \over 2, 1 \over 2). In the crystal, discrete undecameric (H2O)10.34water clusters (involving both coordinated and uncoordinated water molecules, with one site of an uncoordinated water molecule not fully occupied) assemble these tetranuclear MnIIcomplex unitsviaan intricate array of hydrogen bonding into an overall three-dimensional network. The degree of structuring of the (H2O)10.34supramolecular association of water molecules observed in the present compound, imposed by its environment andvice versa, will be discussed in comparison to that observed for the (H2O)14supramolecular clusters in the case of the dinuclear complex [Mn2(cdaH)2(H2O)4]·4H2O [Ghoshet al.(2005).Inorg. Chem.44, 3856–3862].
HIF‐1α and HSP90: Target molecules selected from a tumorigenic papillary thyroid carcinoma cell line
Authors: Mo Ji‐Hun , Choi Ik J. , Jeong Woo‐Jin , Jeon Eun‐Hui , Ahn Soon‐Hyun
Published: December 2011

It is important to properly identify aggressive tumors among differentiated thyroid cancers that are most often indolent. By comparison of a tumorigenic clone with an originally less tumorigenic papillary thyroid carcinoma (PTC) cell line, we looked for markers involved in the aggressive biology of thyroid cancer. Human PTC cell lines BHP10‐3 and its tumorigenic subclone BHP10‐3SCmice were compared using microarray analysis. Upregulated genes in the tumorigenic clone were selected for RT‐PCR, immunoblot analysis and immunohistochemistry in human tissue. Hypoxia‐inducible factor (HIF)‐1α and its chaperone protein heat shock protein (HSP)90 showed significantly increased expression in BHP10‐3SCmice and human PTC tissue. These two genes, HIF‐1α and HSP90, were further validated using siRNA gene knockdown, pharmacological inhibition using 17‐N‐allylamino‐17‐demethoxygeldanamycin (17‐AAG), an inhibitor of both HSP90 and HIF‐1α and in vivo orthotopic animal model. Invasiveness of BHP10‐3SCmice was abrogated by blockade of HIF‐1αin vitro by both siRNA and 17‐AAG. The same finding was demonstrated in the orthotopic animal model. These findings support that HIF‐1α is important in tumorigenesis of PTC and that it may serve to be an important target for identification and treatment of aggressive tumors. (Cancer Sci 2012; 103: 464–471)
Behind the scenes of non‐nodal MCL: downmodulation of genes involved in actin cytoskeleton organization, cell projection, cell adhesion, tumour invasion, TP53 pathway and mutated status of immunoglobulin heavy chain genes
Authors: Del Giudice Ilaria , Messina Monica , Chiaretti Sabina , Santangelo Simona , Tavolaro Simona , De Propris Maria Stefania , Nanni Mauro , Pescarmona Edoardo , Mancini Francesca , Pulsoni Alessandro , Martelli Maurizio , Di Rocco Alice , Finolezzi Erica , Paoloni Francesca , Mauro Francesca R. , Cuneo Antonio , Guarini Anna , Foà Robin
Published: December 2011

Mantle cell lymphoma (MCL) is an aggressive neoplasm with a short survival. Cases with leukaemic MCL and splenomegaly without adenopathies (non‐nodal MCL) may have a more indolent course. To gain insights into the biological features underlying this presentation, we investigated the gene expression profile (GEP) and the IGHV mutational status in a cohort of leukaemic MCL cases. Comparison of MCL with other lymphoproliferative disorders (i.e. splenic marginal zone lymphoma, follicular lymphoma, chronic lymphocytic leukaemia) revealed a MCL signature enriched for the following gene categories: mitochondrion, oxidoreductase activity, response to stress, to DNA damage and TP53‐pathway. Furthermore, GEP analysis revealed that non‐nodal MCL cases were characterized by the down‐modulation of the following gene categories: cell projection, actin cytoskeleton organization, cell adhesion (ITGAE, CELSR1, PCDH9) and tumour invasion/progression (PGF, ST14, ETS1, OCIAD1, EZR). Many down‐modulated genes were related to the TP53‐pathway and to DNA damage response. IGHV status proved unmutated in all nodal and mutated in all non‐nodal MCL. Non‐nodal leukaemic MCLs display a peculiar clinical presentation, with distinctive biological features, such as mutated IGHV and a transcriptional profile lacking tumour invasion properties, that might contribute to the absence of nodal involvement and to the less aggressive clinical course.
Asymmetric and differential gene introgression at a contact zone between two highly divergent lineages of field voles (Microtus agrestis)
Authors: BEYSARD M. , PERRIN N. , JAAROLA M. , HECKEL G. , VOGEL P.
Published: December 2011

Secondary contact zones have the potential to shed light on the mode and rate at which reproductive isolation accumulates during allopatric speciation. We investigated the population genetics of a contact zone between two highly divergent lineages of field voles (Microtus agrestis) in the Swiss Jura mountains. To shed light on the processes underlying introgression, we used maternally, paternally, and bi‐parentally inherited markers. Though the two lineages maintained a strong genetic structure, we found some hybrids and evidence of gene flow. The extent of introgression varied with the mode of inheritance, being highest for mtDNA and absent for the Y chromosome. In addition, introgression was asymmetric, occurring only from the Northern to the Southern lineage. Both patterns seem parsimoniously explained by neutral processes linked to differences in effective sizes and sex‐biased dispersal rates. The lineage with lower effective population size was also the more introgressed, and the mode‐of‐inheritance effect correlated with the male‐biased dispersal rate of microtine rodents. We cannot exclude, however, that Haldane’s effect contributed to the latter, as we found a marginally significant deficit in males (the heterogametic sex) among hybrids. We propose a possible demographic scenario to account for the patterns documented, and empirical extensions to further investigate this contact zone.
Fracture risk after thiazide‐associated hyponatraemia
Authors: Chow K. M. , Szeto C. C. , Kwan B. C.‐H. , Ma T. K.‐W. , Leung C. B. , Li P. K.‐T.
Published: December 2011

Background/Aim:  Although thiazide‐type diuretics can promote a positive calcium balance, thiazide can be associated with hyponatraemia, which is recently linked with heightened fracture risk. We examine the chance of developing fracture in patients with and without hyponatraemia after taking thiazide diuretics.

Methods:  In this single‐centre retrospective study, we followed up a previously published cohort of patients with (n= 223) and without (n= 216) thiazide‐induced hyponatraemia.

Results:  A total of 61 osteoporotic fractures was recorded during a mean follow‐up period of 82 months. Using univariate regression analysis, the hazard ratio of thiazide‐induced hyponatraemia was 1.78 (95% confidence interval (CI), 1.05–3.03; P= 0.033). Cox proportional hazards regression analysis, however, showed that age, body mass index and diabetes mellitus were the only independent predictors of osteoporotic fractures. No association of a history of thiazide‐induced hyponatraemia and risk of fracture was evident in the final model.

Conclusion:  Since a history of thiazide‐induced hyponatraemia is associated with osteoporotic fracture in univariate but not multivariate analyses, an alternative explanation is that confounding factors of older age and low body mass index accounted for the apparently increased risk of osteoporotic fracture in patients with thiazide‐induced hyponatraemia.
Arterial stiffness as a cause of cognitive decline and dementia: a systematic review and meta‐analysis
Authors: Pase M. P. , Herbert A. , Grima N. A. , Pipingas A. , O'Rourke M. F.
Published: December 2011

Background:  Although arterial stiffness has recently been confirmed as a predictor of cardiovascular disease, the association between arterial stiffness and cognitive decline is less clear.

Aim:  We performed a systematic review and meta‐analysis to examine the evidence for large artery stiffness as a cause of cognitive decline and dementia.

Method:  Electronic databases were systematically searched until September 2011 for studies reporting on the longitudinal relationship between any validated measure of large artery stiffness and cognitive decline or dementia. Meta‐analysis was performed on four studies investigating the association between aortic pulse wave velocity and a decline in Mini‐Mental State Examination scores.

Results:  Six relevant longitudinal studies were located, conducted over an average of 5 years follow up. Arterial stiffness was predictive of cognitive decline in five/six studies. In meta‐analysis, higher aortic stiffness predicted lower Mini‐Mental State Examination scores within the sample (β=−0.03, 95% confidence interval (CI): −0.06 to 0.01, n= 3947), although studies were not all homogeneous, and statistical heterogeneity was present (I2= 71.9%, P= 0.01). Removal of one study with a relatively younger cohort and lower median aortic stiffness found higher aortic stiffness to significantly predict cognitive decline (β=−0.04, 95% CI: −0.07 to −0.01, n= 3687) without evidence of heterogeneity (I2= 9.5%, P= 0.33). There was little research investigating the effects of aortic stiffness on the development of dementia.

Conclusion:  Aortic stiffness was found to predict cognitive decline in both qualitative review and quantitative analysis.
An evolutionary mechanism for diversity in siderophore‐producing bacteria
Authors: Lee William , van Baalen Minus , Jansen Vincent A. A.
Published: December 2011

Ecology Letters (2011)

Bacteria produce a great diversity of siderophores to scavenge for iron in their environment. We suggest that this diversity results from the interplay between siderophore producers (cooperators) and non‐producers (cheaters): when there are many cheaters exploiting a siderophore type it is beneficial for a mutant to produce a siderophore unusable by the dominant population. We formulated and analysed a mathematical model for tagged public goods to investigate the potential for the emergence of diversity. We found that, although they are rare most of the time, cheaters play a key role in maintaining diversity by regulating the different populations of cooperators. This threshold‐triggered feedback prevents any stain of cooperators from dominating the others. Our study provides a novel general mechanism for the evolution of diversity that may apply to many forms of social behaviour.
Effects of mealtime insulin aspart and bedtime neutral protamine Hagedorn insulin on postprandial coagulation and fibrinolysis in patients with type 2 diabetes
Authors: Bladbjerg E. M. , Henriksen J. E. , Akram S. , Gram J.
Published: December 2011

Aim: Acute hyperglycaemia induces coagulation activation in diabetes patients. We hypothesized that rapid‐acting insulin has a beneficial postprandial effect on coagulation and fibrinolysis compared with intermediate‐acting insulin because of its ability to lower postprandial hyperglycaemia.

Methods: This was tested in a parallel controlled study in well‐controlled patients with type 2 diabetes assigned to bedtime neutral protamine Hagedorn (NPH) insulin (n = 41) or mealtime insulin aspart (n = 37). They were served standard diabetic meals for breakfast (8:00 hours) and lunch (12:00 hours). Blood samples were collected at 7:40 hours (fasting), 9:30, 11:30, 13:30 and 15:30 hours and analysed for glucose, activated factor VII (FVIIa), D‐dimer, prothrombin fragment 1+2 (F1+2), tissue plasminogen activator antigen (t‐PA) and plasminogen activator inhibitor activity (PAI).

Results: The postprandial glucose response differed significantly between insulin regimens with a postprandial increase on NPH insulin and a decrease on insulin aspart. There was a significant postprandial decrease in F1+2, PAI and t‐PA, and no changes in FVIIa and D‐dimer, on both insulin regimens, but with no differences between insulin treatment groups.

Conclusions: The rapid‐acting insulin analogue aspart and the intermediate‐acting insulin NPH had similar postprandial effects on markers of coagulation activation and fibrinolysis despite different effects on postprandial glucose response.
Bridging the theory practice gap: a review of Graduate Nurse Program (GNP) in Dubai, United Arab Emirates
Authors: Nematollahi R. , Isaac J.P.
Published: December 2011

NEMATOLLAHI R. & ISAAC J.P. (2012) Bridging the theory practice gap: a review of Graduate Nurse Program (GNP) in Dubai, United Arab Emirates. International Nursing Review59, 194–199

Background:  One of the prime concerns of government is the investment in people and resources for the education and health care of its nation. The United Arab Emirates has invested in improving Arab nurse education to reflect the latest emerging standards in international nurse education as part of this ongoing investment: a need to bridge the theory practice divide was identified.

Introduction:  The Dubai Health Authority (DHA), which is the main government healthcare provider in Dubai, granted full scholarship for Arab nationals to enrol in the first baccalaureate nursing degree program offered by a local university in the country.

Problem:  Since its conception, 56 students have graduated from the program, of which eight graduates have resigned or did not join the nursing workforce. Current new graduates expressed lack of confidence and not feeling work ready to join the workforce; in addition, the nurses in service also voiced the opinion that the new Arab nursing graduates were inadequately prepared for service provision at the time of graduation.

Conclusion:  A graduate nurse program to bridge the gap between theory and practice and to ease the transition of new graduate nurses into the nursing workforce was developed by the DHA.

Discussion:  This paper offers a positional discussion on the development of this program in Dubai, its findings, action planning and works in progress to resolve identified issues.
Blind spots and adverse conditions of care: screening migrants for tuberculosis in France and Germany
Authors: Kehr Janina
Published: December 2011

Tuberculosis (TB) is an infectious disease that declined significantly throughout the 20th century. Large‐scale TB screening of entire populations in France and Germany has thus been replaced by active screening of risk‐groups, particularly migrants. The article engages with its problems and practices on three levels: by looking at the way information on migrants as an at‐risk group is produced through disease surveillance data; by analysing how such at‐risk group data influence local screening practices; and by showing which political and medical problems arise in the field. I overturn the discussion about screening and surveillance of migrants as a risk‐group by showing that it is not the stigmatisation of migrants through disease risk that is most at stake, but the invisibility of the most vulnerable among them in disease surveillance data and the way restrictive national immigration policies interfere with and subvert local screening and treatment practices targeting them. The aim of my article is to promote a pragmatic sociology of screening, while paying attention to the practical complexities, political conditions and medical ambivalences of screening and follow‐up care, especially when the migrant groups concerned are socially, politically and medically vulnerable.
“WHAT COULD POSSIBLY BE GIVEN?”: TOWARDS AN EXPLORATION OF KENOSIS AS FORGIVENESS—CONTINUING THE CONVERSATION BETWEEN COAKLEY, HAMPSON, AND PAPANIKOLAOU1
Authors: CHAU CAROLYN A.
Published: December 2011

This article engages the conversation between Sarah Coakley, Daphne Hampson, and Aristotle Papanikolaou (Modern Theology, Vol. 19 no. 1, January 2003) on the appropriateness of kenosis as a theological trope for women and deeply oppressed and vulnerable others. It affirms Coakley's and Papanikolaou's stance, which maintains that kenosis is a necessary or at least distinctively valuable category in Christian theology for understanding the transformation and redemption of all persons. The paper expands on Papanikolaou's analysis of the kenosis involved in the healing and recovery of personhood, arguing that the “emptying of fear” reaches the fullness of self‐giving love in the scandalous act of forgiveness.
RECENT DEVELOPMENTS IN THE THEOLOGY OF INTERRELIGIOUS DIALOGUE: FROM SOTERIOLOGICAL OPENNESS TO HERMENEUTICAL OPENNESS
Authors: MOYAERT MARIANNE
Published: December 2011

In this article I will reflect on interreligious dialogue and the tensive relation between openness and identity from a theological perspective. First, I consider the so‐called theology of religions and the threefold soteriological typology of exclusivism, inclusivism and pluralism. Second, I address one of the main criticisms of this approach, namely that the soteriological approach amounts to a perversion of the virtue of openness. This critique is articulated especially within particularism, a model which sets out to move beyond the soteriological fixation of the classical theology of religions. Because this relatively new model has not yet been analyzed systematically in the relevant literature, I will analyze some of its main tenets. I focus especially on the way this model sets out to alter the terms of the discussion on the dialogical tension between openness and commitment by claiming that hermeneutical openness should precede soteriological appreciation. Third, I turn to comparative theology as a fertile expression of particularism. Comparative theology presents itself as a genuinely adequate way to understand and appreciate the otherness of the religious other without losing sight of one's own identity. Moreover, comparative theology gives a new twist to the discussion on the dialogical tension between openness and commitment. Whereas the classical theology of religions seems to be actuated by the conviction that it is both possible and necessary to come to a final and definite soteriological appreciation of the religions, comparative theology sees interreligious encounter first and foremost as an ongoing conversational process, which can yield preliminary results only. It is my contention that this marks the nature of real and authentic dialogue.
CCAAT‐enhancer‐binding protein‐beta expression in vivo is associated with muscle strength
Authors: Harries Lorna W. , Pilling Luke C. , Hernandez L. Dena G. , Bradley‐Smith Rachel , Henley William , Singleton Andrew B. , Guralnik Jack M. , Bandinelli Stefania , Ferrucci Luigi , Melzer David
Published: December 2011

Declining muscle strength is a core feature of aging. Several mechanisms have been postulated, including CCAAT/enhancer‐binding protein‐beta (C/EBP‐β)‐triggered macrophage‐mediated muscle fiber regeneration after micro‐injury, evidenced in a mouse model. We aimed to identify in vivo circulating leukocyte gene expression changes associated with muscle strength in the human adult population. We undertook a genome‐wide expression microarray screen, using peripheral blood RNA samples from InCHIANTI study participants (aged 30 and 104). Logged expression intensities were regressed with muscle strength using models adjusted for multiple confounders. Key results were validated by real‐time PCR. The Short Physical Performance Battery (SPPB) score tested walk speed, chair stand, and balance. CEBPB expression levels were associated with muscle strength (β coefficient = 0.20560, P = 1.03*10−6, false discovery rate q = 0.014). The estimated handgrip strength in 70‐year‐old men in the lowest CEBPB expression tertile was 35.2 kg compared with 41.2 kg in the top tertile. CEBPB expression was also associated with hip, knee, ankle, and shoulder strength and the SPPB score (P = 0.018). Near‐study‐wide associations were also noted for TGF‐β3 (P = 3.4*10−5, q = 0.12) and CEBPD expression (P = 9.7*10−5, q = 0.18) but not for CEBPA expression. We report here a novel finding that raised CEBPB expression in circulating leukocyte‐derived RNA samples in vivo is associated with greater muscle strength and better physical performance in humans. This association may be consistent with mouse model evidence of CEBPB‐triggered muscle repair: if this mechanism is confirmed, it may provide a target for intervention to protect and enhance aging muscle.
Value‐Based Insurance Design: More Health at Any Price
Authors: Fendrick A. Mark , Martin Jenifer J. , Weiss Alison E.
Published: December 2011

When everyone is required to pay the same out‐of‐pocket amount for health care services regardless of clinical indication, there is evidence of underuse of high‐value services and overuse of interventions of no or marginal clinical benefit. Unlike most current health plan designs, value‐based insurance design (V‐BID) acknowledges heterogeneity of clinical interventions and patient characteristics. It encourages the use of services with strong evidence of clinical benefit and likewise discourages the use of low‐value services. Implementing this concept into the national policy debate required a strategy that included conceptual framework development, program implementation, rigorous evaluation, media outreach, and an advocacy plan. Upon completion of this strategy involving several colleagues from multiple disciplines, Congress included language specifically authorizing V‐BID in the Patient Protection and Affordable Care Act. A wide‐ranging approach, planned as early as possible, can lead to the successful translation of health services research to policy.
Combined effect of 25‐OH vitamin D plasma levels and genetic Vitamin DReceptor (NR 1I1) variants on fibrosis progression rate in HCV patients
Authors: Baur Katharina , Mertens Joachim C. , Schmitt Johannes , Iwata Rika , Stieger Bruno , Eloranta Jyrki J. , Frei Pascal , Stickel Felix , Dill Michael T. , Seifert Burkhardt , Bischoff Ferrari Heike A. , von Eckardstein Arnold , Bochud Pierre‐Yves , Müllhaupt Beat , Geier Andreas ,   the Swiss Hepatitis C Cohort Study Group
Published: December 2011

Background

Decreased vitamin D levels have been described in various forms of chronic liver disease and associated with advanced fibrosis. Whether this association is a cause or consequence of advanced fibrosis remains unclear to date.

Aims

To analyse combined effects of 25‐OH vitamin D plasma levels and vitamin D receptor gene (VDR; NR1I1) polymorphisms on fibrosis progression rate in HCV patients.

Methods

251 HCV patients underwent VDR genotyping (bat‐haplotype: BsmI rs1544410 C, ApaI rs7975232 A and TaqI rs731236 A). Plasma 25‐OH vitamin D levels were quantified in a subgroup of 97 patients without advanced fibrosis. The VDR haplotype and genotypes as well as plasma 25‐OH vitamin D levels were associated with fibrosis progression.

Results

The bAt[CCA]‐haplotype was significantly associated with fibrosis progression >0.101 U/year (P = 0.007; OR = 2.02) and with cirrhosis (P = 0.022; OR = 1.84). Forty‐five percent of bAt[CCA]‐haplotype patients were rapid fibrosers, 21.1% were cirrhotic. Likewise, ApaI rs7975232 CC genotype was significantly associated with fibrosis progression and cirrhosis. Lower plasma 25‐OH vitamin D levels were significantly associated with fibrosis progression >0.101 U/year in F0–2 patients (P = 0.013). Combined analysis of both variables revealed a highly significant additive effect on fibrosis progression with 45.5% rapid fibrosers for bAt[CCA]‐haplotype and 25‐OH vitamin D < 20 μg/L compared with only 9.1% for the most favourable combination (P = 0.006). In multivariate analysis, the bAt‐haplotype was an independent risk factor for fibrosis progression (P = 0.001; OR = 2.83).

Conclusion

Low 25‐OH vitamin D plasma levels and the unfavourable VDR bAt[CCA]‐haplotype are associated with rapid fibrosis progression in chronic HCV patients. In combination, both variables exert significant additive effects on fibrosis progression.
Identification of Cytokines and Signaling Proteins Differentially Regulated by Sumatriptan/Naproxen
Authors: Vause Carrie V. , Durham Paul L.
Published: December 2011

Objectives.— The goal of this study was to use protein array analysis to investigate temporal regulation of stimulated cytokine expression in trigeminal ganglia and the spinal trigeminal nucleus in response to co‐treatment of sumatriptan and naproxen sodium or individual drug.

Background.— Activation of neurons and glia in trigeminal ganglia and the spinal trigeminal nucleus leads to increased levels of cytokines that promote peripheral and central sensitization, which are key events in migraine pathology. While recent clinical studies have provided evidence that a combination of sumatriptan and naproxen sodium is more efficacious in treating migraine than either drug alone, it is not well understood why the combination therapy is superior to monotherapy.

Methods.— Male Sprague–Dawley rats were left untreated (control), injected with capsaicin, or pretreated with sumatriptan/naproxen, sumatriptan, or naproxen for 1 hour prior to capsaicin. Trigeminal ganglia and the spinal trigeminal nucleus were isolated 2 and 24 hours after capsaicin or drug treatment, and levels of 90 proteins were determined using a RayBio® Label‐Based Rat Antibody Array (RayBiotech, Norcross, GA, USA).

Results.— Capsaicin stimulated a >3‐fold increase in expression of the majority of cytokines in trigeminal ganglia at 2 hours that was sustained at 24 hours. Significantly, treatment with sumatriptan/naproxen almost completely abolished the stimulatory effects of capsaicin at 2 and 24 hours. Capsaicin stimulated >3‐fold expression of more proteins in the spinal trigeminal nucleus at 24 hours when compared to 2 hours. Similarly, sumatriptan/naproxen abolished capsaicin stimulation of proteins in the spinal trigeminal nucleus at 2 hours and greatly suppressed protein expression 24 hours post‐capsaicin injection. Interestingly, treatment with sumatriptan alone suppressed expression of different cytokines in trigeminal ganglia and the spinal trigeminal nucleus than repressed by naproxen sodium.

Conclusion.— We found that the combination of sumatriptan/naproxen was effective in blocking capsaicin stimulation of pro‐inflammatory proteins implicated in the development of peripheral and central sensitization in response to capsaicin activation of trigeminal neurons. Based on our findings that sumatriptan and naproxen regulate expression of different proteins in trigeminal ganglia and the spinal trigeminal nucleus, we propose that these drugs function on therapeutically distinct cellular targets to suppress inflammation and pain associated with migraine.
Extended Practice and Aerobic Exercise Interventions Benefit Untrained Cognitive Outcomes in Older Adults: A Meta‐Analysis
Authors: Hindin Shoshana B. , Zelinski Elizabeth M.
Published: December 2011

Objectives

To examine whether therapeutic interventions of extended practice of cognitive tasks or aerobic exercise have led to significant improvement in untrained cognitive tasks.

Design

The PSYCINFO, MEDLINE, and Abstracts in Social Gerontology databases were searched for English‐language studies of cognitive interventions of exercise or extended cognitive practice between 1966 and 2010. The final search was in January 2011. Studies included were experimental interventions hypothesizing improvement on untrained cognitive outcomes with pre‐ and posttests. Studies of varying quality were included and compared.

Setting

Interventions generally took place in laboratories, in gymnasium facilities, in the home, and outdoors. Experimenters administered testing.

Participants

Forty‐two studies with 3,781 healthy older adults aged 55 and older were analyzed.

Measurements

Between‐group effect sizes (ESs), which account for practice effects on outcome measures, and within‐experimental group ESs were computed from untrained cognitive outcome domains, including choice reaction time, memory, and executive function, and compared. ESs were also coded for training type and study quality. Multilevel mixed‐effect analyses accommodated multiple outcomes from individual studies.

Results

Extended practice (estimated ES = 0.33, 95% confidence interval (CI) = 0.13–0.52) and aerobic fitness (estimated ES = 0.33, 95% CI = 0.10–0.55) training produced significant between‐group ESs, but they did not differ in magnitude. Better study quality was associated with larger ESs.

Conclusion

Findings indicate that aerobic and extended cognitive practice training interventions for healthy older adults improve performance on untrained cognitive tasks.
Why do Infants Look at and Use Positive Information from Some Informants Rather Than Others in Ambiguous Situations?
Authors: Stenberg Gunilla
Published: December 2011

Three laboratory experiments on social referencing examined whether infants’ tendencies to look at and use positive information from the experimenter could be interpreted from a perspective of novelty or expertise. In Study 1, novelty was manipulated. Forty‐eight 12‐month‐old infants participated. In a between‐subject design, a more novel or a less novel experimenter presented an ambiguous object and provided positive information. The infants looked more at and regulated their behavior more in accordance with information coming from the less novel experimenter. In Study 2, expertise was manipulated. Forty‐eight 12‐month‐old infants were exposed to one experimenter who showed expertise about the laboratory situation and one experimenter who did not show such competence. The infants looked more at and regulated their behavior more in accordance with information coming from the expert. In Study 3, 40 12‐month‐old infants participated. The infants were exposed to a toy‐expert who was either novel or familiar. The infants, in both groups, looked as much at the toy‐experts and used the information regardless of whether the novel or familiar toy‐expert had provided information. The findings suggest that novelty does not increase looking in ambiguous situations. Instead, the results support the expertise perspective of infant looking preferences.
The Relationship of the Canine Femoral Head to the Femoral Neck: An Anatomic Study with Relevance for Hip Arthroplasty Implant Design and Implantation
Authors: Franklin Samuel P. , Franklin Ashley L. , Wilson Howard , Schultz Loren , Sonny Bal B. , Cook James L.
Published: December 2011

Objectives

(1) To evaluate a novel method for characterizing the relationship of the canine femoral head to the femoral neck and (2) to determine whether the femoral head is symmetrically positioned upon the femoral neck.

Study Design

Cadaveric study.

Sample Population

Cadaveric dog femurs (16 dogs, 32 femurs)

Methods

Femurs were photographed in frontal and sagittal planes simultaneously using 2 cameras positioned orthogonally. Ten measurements were made by 2 independent observers and agreement assessed by calculating intraclass correlation coefficients (ICC). Repeatability in specimen positioning was assessed by repositioning and imaging a single femur10 times.

Results

ICC values exceeded 0.6 for 8 of the 10 different measurements made. Mean ± SD femoral head offset ratios in the frontal and sagittal planes were 0.14 ± 0.08 and 2.66 ± 1.16. The mean specimen positioning error (±SD) for the single specimen that was repositioned 10 times was 0.93° ± 1.92° and 2.39° ± 1.13° in the frontal and sagittal planes, respectively.

Conclusions

Correlations between observers were moderately strong or strong for 8 of 10 measurements. Specimen positioning was repeatable. The offset ratios indicate that dogs have a substantial cranial and ventral offset of the femoral head from the femoral neck.
Political Liberalism and Political Embeddedness: Understanding Politics in the Work of Chinese Criminal Defense Lawyers
Authors: Liu Sida , Halliday Terence C.
Published: December 2011

This article examines the meanings of politics in everyday legal practice using the case of Chinese criminal defense lawyers. Based on 194 in-depth interviews with criminal defense lawyers and other informants in 22 cities across China, we argue that lawyers’ everyday politics have two faces: on the one hand, lawyers potentially can challenge state power, protect citizen rights, and pursue proceduralism in their daily work; on the other hand, they often have to rely on political connections with state agencies to protect themselves and to solve problems in their legal practice. The double meanings of politics—namely, political liberalism and political embeddedness—explain the complex motivations and coping tactics that are frequently found in Chinese lawyers’ everyday work. Our data show that the Chinese criminal defense bar is differentiated along these two meanings of politics into five clusters of lawyers: progressive elites, pragmatic brokers, notable activists, grassroots activists, and routine practitioners. They also suggest that a principal manifestation of political lawyering is not merely short-term mobilization or revolutionary struggle against arbitrary state power, but also an incremental everyday process that often involves sophisticated tactics to manage interests that often conflict.
Talking Law in Times of Reform: Paradoxes of Legal Entitlement in Cameroon
Authors: Muñoz José-María
Published: December 2011

Based on ethnographic fieldwork carried out between 2003 and 2005, this article examines how legality is constructed in present-day Adamaoua Province, Cameroon. Focusing on an instance of a process locally referred to as la concertation, I analyze how state officials and cattle traders gather to discuss the practical fate of law. As a heightened moment of suspended enforcement, la concertation is productive for both officials, who work out the limits of their respective spheres of authority and imagine a trade based on business norms and practices that severely limit the scope of regulatory action, and traders, who manage to stave off the increased scrutiny that income tax law presupposes, while asserting their concern for the integrity and consistency of the law.
What's So Private about Private Ordering?
Authors: Sagy Tehila
Published: December 2011

Private ordering—i.e., development of extralegal forums and forms of dispute processing by nonhierarchical groups—has preoccupied legal economists for nearly three decades. According to the prevailing analysis, private orders grow in socially-flat market communities without any intervention by the state. This article challenges the received view on two fronts: First, it establishes a causal connection between the development of private orders and a social hierarchy. Second, the article demonstrates that the state often intentionally assumes a proactive role in the creation of these orders. To illustrate this two-pronged theory of private ordering, this article offers a detailed analysis of three well-known cases that have been considered prototypes of private ordering by market communities: the Diamond Dealers Club of New York, the kibbutz in Israel, and ranch owners in Shasta County, California. Finally, the article argues for a need to re-evaluate the feasibility and desirability of private ordering and privatization of law.
Paying for the Past: Redressing the Legacy of Land Dispossession in South Africa
Authors: Atuahene Bernadette
Published: December 2011

The constitution of South Africa mandates equitable redress for individuals and communities evicted from their properties during colonialism and apartheid. The Commission on Restitution of Land Rights' institution-wide assumption is that the financial awards given as equitable redress had no long-term economic impact on recipients because the money is gone and they are still in poverty, whereas if people had received land, the economic impact would have been lasting. Consequently, in recent years, the commission has adopted a policy of using its soft power to force claimants to choose land restitution instead of financial awards. However, the interviews I conducted with financial award recipients show that in 30 percent of the cases, the award did produce a long-term economic benefit because respondents invested in their homes. This empirical evidence suggests that the commission should rethink its recent shift in policy and not totally discount the potential of financial awards to produce a lasting economic benefit.
Acute Clinical Evaluation of a Left Ventricular Automatic Threshold Determination Algorithm Based on Evoked Response Sensing
Authors: KALAHASTY GAUTHAM , GIUDICI MICHAEL , LOBBAN JOHN , DOSHI RAHUL , DELANEY COLLEEN , SHOME SHIBAJI , GOLD MICHAEL R. , ELLENBOGEN KENNETH
Published: December 2011

Introduction:

Automatic pacing threshold (AT) testing may simplify device follow‐up and improve device longevity. This study's objective was to evaluate the performance of a left ventricular (LV) evoked response sensing‐based AT algorithm, for cardiac resynchronization therapy (CRT) devices.

Methods:

Patients scheduled for CRT‐D/P implant were enrolled. A manual step‐down threshold test and a Left Ventricular Automatic Threshold (LVAT) test in each of four pacing vectors—LVTip→Can, LVTip→right ventricle (RV),
= LVRing→Can, and LVRing→RV—were conducted. Patients were randomized to either 0.4‐ms or 1.0‐ms pacing pulse width and in the manual and LVAT test order. A blinded core lab electrophysiologist (EP) determined the threshold using the surface electrocardiogram (gold standard).

Results:

Data from 70 patients were analyzed. Bipolar LV leads from three major manufacturers were used. A total of 273 AT tests were performed; 12 AT tests did not result in a threshold due to improper testing conditions. Of 261 eligible tests, 234 AT tests (89.6%) returned a threshold measurement. Of the 234 tests, in 233 tests (99.5%) the algorithm‐determined threshold matched the EP‐determined threshold for that test. A total of 16,689 capture and 526 noncapture beats were collected and the accuracy for detecting capture and noncapture were 98.5% and 99.7% with a two‐sided 95% confidence level of (98.4%, 98.7%) and (99.4%, 100%), respectively. No AT threshold measurement was lower than the EP‐determined threshold.

Conclusion:

In this study, the results suggest that the LVAT algorithm is accurate at determining pacing thresholds in multiple pacing configurations and a wide range of LV leads in CRT‐D/P patients. (PACE 2011;1–5)