bluuebunny/crossref_metadata_2025 huggingface dataset:
TLR4 expression on monocyte subsets in myocardial infarction
Authors: Tapp L. D. , Shantsila E. , Wrigley B. J. , Montoro‐Garcia S. , Lip G. Y. H.
Published: April 2013

Background

Monocyte toll‐like receptor 4 (TLR4) has been implicated in the pathogenesis of atherosclerosis with increased levels in myocardial infarction. The aim of this study was to assess the numbers of TLR4+ monocytes in each monocyte subset in MI, the expression of TLR4 and association with markers of monocyte activation, inflammation, myocardial damage and postmyocardial infarction (MI) cardiac contractility.

Methods

Surface expression of TLR4 and numbers of TLR4‐expressing monocytes were quantified by flow cytometry of venous blood in 50 patients with ST‐elevation MI (STEMI), 48 with non‐STEMI (NSTEMI) and 40 with stable coronary artery disease (CAD). These parameters were measured on days 1, 3, 7 and 30 post‐MI in STEMI patients. Three monocyte subsets were defined as CD14++ CD16− CCR2+ (Mon1), CD14++ CD16+ CCR2+ (Mon2) and CD14+ CD16++ CCR2− (Mon3). Plasma inflammatory cytokines were assessed using cytometric bead arrays.

Results

There was a significant increase in counts of TLR4+ Mon1 and Mon2 in STEMI patients and TLR4+ Mon2 in NSTEMI patients compared with controls with CAD. Monocyte TLR4+ expression was similar between the groups, and was not changed during follow‐up in STEMI patients. Plasma interleukin‐6 (IL6) levels correlated positively with TLR4+ Mon2 count (r = 0.54, P < 0.001), but negatively with TLR4 expression on Mon2 (r = −0.33, P = 0.021).

Conclusion

Following treatment of acute MI, TLR4 expression by individual monocyte subsets is unchanged. An increase in TLR4+ Mon1 and Mon2 count in patients with STEMI and TLR+ Mon2 count in those with NSTEMI is due to an increase in monocyte subset count and not to changes in TLR4 expression. Monocyte counts but not TLR4 expression correlate positively with plasma IL6 levels. We suggest that TLR4 expression may not be a reliable marker of monocyte activation in MI.
Endothelial cell metabolism and tumour angiogenesis: glucose and glutamine as essential fuels and lactate as the driving force
Authors: Polet F. , Feron O.
Published: April 2013

Angiogenic endothelial cells and tumour cells can survive under hypoxic conditions and even proliferate and migrate in a low‐oxygen environment. In both cell types, high rates of glycolysis (i.e. conversion of glucose to lactate) and glutaminolysis provide most of the required biosynthetic intermediates and energy to support sprouting and cell division without coupling to oxidative phosphorylation. This metabolic preference is observed under hypoxic conditions, but also in situations in which oxygen is present. In the case of tumour cells, this is known as the Warburg effect and is largely governed by oncogenes. In endothelial cells lining tumour blood vessels, the option of respiration‐independent metabolism allows the neovasculature to resist the hostile environment of fluctuating oxygen tension (ranging from severe hypoxia to quasi‐normal levels of oxygen). In addition, accumulation in tumours of lactate, the end‐product of glycolysis, largely contributes to the angiogenic phenotype through inhibition of prolyl hydroxylase 2 and the activation of HIF1α and NFκB. Activation of the latter in a hypoxia‐independent manner leads to the increased production of interleukin‐8/CXCL8 which drives the autocrine stimulation of endothelial cell proliferation and maturation of neovessels. In conclusion, the addiction of proliferating endothelial cells for glucose and glutamine as fuels and the driving force of lactate to promote angiogenesis provide novel potential treatment options without the disadvantages of conventional anti‐angiogenic drugs.
VEGFA and tumour angiogenesis
Authors: Claesson‐Welsh L. , Welsh M.
Published: April 2013

In this review we summarize the current understanding of signal transduction downstream of vascular endothelial growth factor A (VEGFA) and its receptor VEGFR2, and the relationship between these signal transduction pathways and the hallmark responses of VEGFA, angiogenesis and vascular permeability. These physiological responses involve a number of effectors, including extracellular signal‐regulated kinases (ERKs), Src, phosphoinositide 3 kinase (PI3K)/Akt, focal adhesion kinase (FAK), Rho family GTPases, endothelial NO and p38 mitogen‐activated protein kinase (MAPK). Several of these factors are involved in the regulation of both angiogenesis and vascular permeability. Tumour angiogenesis primarily relies on VEGFA‐driven responses, which to a large extent result in a dysfunctional vasculature. The reason for this remains unclear, although it appears that certain aspects of the VEGFA‐stimulated angiogenic milieu (high level of microvascular density and permeability) promote tumour expansion. The high degree of redundancy and complexity of VEGFA‐driven tumour angiogenesis may explain why tumours commonly develop resistance to anti‐angiogenic therapy targeting VEGFA signal transduction.
Clinical characteristics of a novel subgroup of chronic fatigue syndrome patients with postural orthostatic tachycardia syndrome
Authors: Lewis I. , Pairman J. , Spickett G. , Newton J. L.
Published: April 2013

Objectives

A significant proportion of patients with chronic fatigue syndrome (CFS) also have postural orthostatic tachycardia syndrome (POTS). We aimed to characterize these patients and differentiate them from CFS patients without POTS in terms of clinical and autonomic features.

Methods

A total of 179 patients with CFS (1994 Centers for Disease Control and Prevention criteria) attending one of the largest Department of Health‐funded CFS clinical services were included in this study. Outcome measures were as follows: (i) symptom assessment tools including the fatigue impact scale, Chalder fatigue scale, Epworth sleepiness scale (ESS), orthostatic grading scale (OGS) and hospital anxiety and depression scale (HADS‐A and ‐D, respectively), (ii) autonomic function analysis including heart rate variability and (iii) haemodynamic responses including left ventricular ejection time and systolic blood pressure drop upon standing.

Results

CFS patients with POTS (13%, n = 24) were younger (29 ± 12 vs. 42 ± 13 years, P < 0.0001), less fatigued (Chalder fatigue scale, 8 ± 4 vs. 10 ± 2, P = 0.002), less depressed (HADS‐D, 6 ± 4 vs. 9 ± 4, P = 0.01) and had reduced daytime hypersomnolence (ESS, 7 ± 6 vs. 10 ± 5, P = 0.02), compared with patients without POTS. In addition, they exhibited greater orthostatic intolerance (OGS, 11 ± 5; P < 0.0001) and autonomic dysfunction. A combined clinical assessment tool of ESS ≤9 and OGS ≥9 identifies accurately CFS patients with POTS with 100% positive and negative predictive values.

Conclusions

The presence of POTS marks a distinct clinical group of CFS patents, with phenotypic features differentiating them from those without POTS. A combination of validated clinical assessment tools can determine which CFS patients have POTS with a high degree of accuracy, and thus potentially identify those who require further investigation and consideration for therapy to control heart rate.
At the heart of the arterial baroreflex: a physiological basis for a new classification of carotid sinus hypersensitivity
Authors: Wieling W. , Krediet C. T. P. , Solari D. , de Lange F. J. , van Dijk N. , Thijs R. D. , van Dijk J. G. , Brignole M. , Jardine D. L.
Published: April 2013

The aim of this review is to provide an update of the current knowledge of the physiological mechanisms underlying reflex syncope. Carotid sinus syncope will be used as the classical example of an autonomic reflex with relatively well‐established afferent, central and efferent pathways. These pathways, as well as the pathophysiology of carotid sinus hypersensitivity (CSH) and the haemodynamic effects of cardiac standstill and vasodilatation will be discussed. We will demonstrate that continuous recordings of arterial pressure provide a better understanding of the cardiovascular mechanisms mediating arterial hypotension and cerebral hypoperfusion in patients with reflex syncope. Finally we will demonstrate that the current criteria to diagnoseCSHare too lenient and that the conventional classification of carotid sinus syncope as cardioinhibitory, mixed and vasodepressor subtypes should be revised because isolated cardioinhibitoryCSH(asystole without a fall in arterial pressure) does not occur. Instead, we suggest that all patients withCSHshould be thought of as being ‘mixed’, between cardioinhibition and vasodepression. The proposed stricter set of criteria forCSHshould be evaluated in future studies.
The role of mitochondrial DNA mutations and free radicals in disease and ageing
Authors: Lagouge M. , Larsson N.‐G.
Published: April 2013

Considerable efforts have been made to understand the role of oxidative stress in age‐related diseases and ageing. The mitochondrial free radical theory of ageing, which proposes that damage to mitochondrial DNA (mtDNA) and other macromolecules caused by the production of reactive oxygen species (ROS) during cellular respiration drives ageing, has for a long time been the central hypothesis in the field. However, in contrast with this theory, evidence from an increasing number of experimental studies has suggested that mtDNA mutations may be generated by replication errors rather than by accumulated oxidative damage. Furthermore, interventions to modulate ROS levels in humans and animal models have not produced consistent results in terms of delaying disease progression and extending lifespan. A number of recent experimental findings strongly question the mitochondrial free radical theory of ageing, leading to the emergence of new theories of how age‐associated mitochondrial dysfunction may lead to ageing. These new hypotheses are mainly based on the underlying notion that, despite their deleterious role, ROS are essential signalling molecules that mediate stress responses in general and the stress response to age‐dependent damage in particular. This novel view of ROS roles has a clear impact on the interpretation of studies in which antioxidants have been used to treat human age‐related diseases commonly linked to oxidative stress.
Cutaneous lupus erythematosus: clinical aspects and molecular pathogenesis
Authors: Oke V. , Wahren‐Herlenius M.
Published: April 2013

Lupus erythematosus (LE) is an autoimmune disease with diverse clinical manifestations ranging from limited cutaneous (CLE) to potentially life‐threatening systemic disease (SLE). Susceptibility to LE arises from genetic variation in multiple loci, and disease activity is provoked by exogenous or endogenous trigger(s), the best characterized of which is exposure to ultraviolet radiation (UVR). Amongst patients with LE, a cluster of photosensitive subjects with cutaneous lesions and positivity for anti‐Ro/SSA autoantibodies have been described. The Ro52 antigen belongs to the tripartite motif protein family and has E3 ligase activity. New data reveal that Ro52 ubiquitinates interferon regulatory factors and modulates their transcriptional activity, indicating an important role for Ro52 in inflammation as a negative feedback regulator. Our findings indicate that UVR exposure induces upregulation of Ro52 in the CLE target cell, the keratinocyte, and that Ro52 is upregulated in spontaneous and UVR‐induced CLE lesions. Recently described functional analysis of Ro52‐deficient mice revealed that loss of Ro52 results in uncontrolled inflammation in response to minor skin injury leading to an LE‐like condition. In summary, emerging data suggest that abnormal function or regulation of Ro52 contributes to the pathogenesis of UVR‐induced CLE in genetically susceptible individuals. Ro52 may thus be an interesting therapeutic target, as its activation could contribute to downregulation of the chronic inflammatory process in LE. Here, we review the available data on the pathogenesis of CLE and, in particular, the role of the Ro52 autoantigen.
Effects of individual and combined dietary weight loss and exercise interventions in postmenopausal women on adiponectin and leptin levels
Authors: Abbenhardt C. , McTiernan A. , Alfano C. M. , Wener M. H. , Campbell K. L. , Duggan C. , Foster‐Schubert K. E. , Kong A. , Toriola A. T. , Potter J. D. , Mason C. , Xiao L. , Blackburn G. L. , Bain C. , Ulrich C. M.
Published: April 2013

Background

Excess body weight and a sedentary lifestyle are associated with the development of several diseases, including cardiovascular disease, diabetes and cancer in women. One proposed mechanism linking obesity to chronic diseases is an alteration in adipose‐derived adiponectin and leptin levels. We investigated the effects of 12‐month reduced calorie, weight loss and exercise interventions on adiponectin and leptin concentrations.

Methods

Overweight/obese postmenopausal women (n = 439) were randomized as follows: (i) a reduced calorie, weight‐loss diet (diet; N = 118), (ii) moderate‐to‐vigorous intensity aerobic exercise (exercise; N = 117), (iii) a combination of a reduced calorie, weight‐loss diet and moderate‐to‐vigorous intensity aerobic exercise (diet + exercise; N = 117), and (iv) control (N = 87). The reduced calorie diet had a 10% weight‐loss goal. The exercise intervention consisted of 45 min of moderate‐to‐vigorous aerobic activity 5 days per week. Adiponectin and leptin levels were measured at baseline and after 12 months of intervention using a radioimmunoassay.

Results

Adiponectin increased by 9.5% in the diet group and 6.6% in the diet + exercise group (both P ≤ 0.0001 vs. control). Compared with controls, leptin decreased with all interventions (diet + exercise, −40.1%, P < 0.0001; diet, −27.1%, P < 0.0001; exercise, −12.7%, P = 0.005). The results were not influenced by the baseline body mass index (BMI). The degree of weight loss was inversely associated with concentrations of adiponectin (diet, P‐trend = 0.0002; diet + exercise, P‐trend = 0.0005) and directly associated with leptin (diet, P‐trend < 0.0001; diet + exercise, P‐trend < 0.0001).

Conclusion

Weight loss through diet or diet + exercise increased adiponectin concentrations. Leptin concentrations decreased in all of the intervention groups, but the greatest reduction occurred with diet + exercise. Weight loss and exercise exerted some beneficial effects on chronic diseases via effects on adiponectin and leptin.
Out‐of‐hospital cardiac arrest: 10 years of progress in research and treatment
Authors: Hollenberg J. , Svensson L. , Rosenqvist M.
Published: April 2013

Cardiac disease is the most common cause of mortality in Western countries, with most deaths due to out‐of‐hospital cardiac arrest (OHCA). In Sweden, 5000–10 000 OHCAs occur annually. During the last decade, the time from cardiac arrest to start of cardiopulmonary resuscitation (CPR) and defibrillation has increased, whereas survival has remained unchanged or even increased. Resuscitation of OHCA patients is based on the ‘chain‐of‐survival’ concept, including early (i) access, (ii) CPR, (iii) defibrillation, (iv) advanced cardiac life support and (v) post‐resuscitation care. Regarding early access, agonal breathing, telephone‐guided CPR and the use of ‘track and trigger systems’ to detect deterioration in patients' condition prior to an arrest are all important. The use of compression‐only CPR by bystanders as an alternative to standard CPR in OHCA has been debated. Based on recent findings, guidelines recommend telephone‐guided chest compression‐only CPR for untrained rescuers, but trained personnel are still advised to give standard CPR with both compressions and ventilation, and the method of choice for this large group remains unclear and demands for a randomized study. Data have shown the benefit of public access defibrillation for dispatched rescuers (e.g. police and fire fighters) but data are not as strong for the use of automated defibrillators (AEDs) by trained or untrained rescuers. Postresuscitation, use of therapeutic hypothermia, the importance of specific prognostic survival factors in the intensive care unit and the widespread use of percutaneous coronary intervention have all been considered. Despite progress in research and improved treatment regimens, most patients do not survive OHCA. Particular areas of interest for improving survival include (i) identification of high‐risk patients prior to their arrest (e.g. early warning symptoms and genes); (ii) increased use of bystander CPR training (e.g. in schools) and simplified CPR techniques; (iii) better identification of high‐incidence sites and better recruitment of AEDs (via mobile phone solutions?); (iv) improved understanding of the use of therapeutic hypothermia; (v) determining which patients should undergo immediate coronary angiography on hospital admission; and (vi) clarifying the importance of extracorporeal membrane oxygenation during CPR.
Auditors and Corporate Governance: Evidence from the Public Sector
Authors: Schelker Mark
Published: April 2013

Corporate auditors review and evaluate financial statements. Audit quality depends on auditor expertise and independence. To enhance auditor independence the selection process and auditor rotation requirements have been debated intensively. The available empirical evidence is not conclusive and suffers from serious endogeneity problems. I propose learning from the public sector where auditors play a similar role and present empirical evidence on the impact of auditor expertise, term length and rotation requirements on government performance at the US state level. I find evidence indicating that greater auditor expertise and rotation requirements have a positive effect on state credit ratings.
Do Consumer Tastes Evolve with Competition? The Case of the Slovenian Beer Market
Authors: Šušteršič Janez , Šušteršič Snežana
Published: April 2013

We use the natural experiment of EU entry to test the hypothesis that the lack of consumer tastes for diversity in beer may be responsible for slow development of small breweries in a highly concentrated beer market. Our contribution is to propose that lagged imports diversity, which increased after joining the common market, may be used as a proxy for consumer tastes development. Our reasoning is that after the EU entry, when imports soared, consumers became increasingly exposed to a much wider variety of beer styles. This might have led at least some of them to develop a taste for diversity in beer. In turn, this increased appreciation of diversity may have led them also to appreciate more the products of domestic microbreweries. Using monthly sales data, we are able to find some empirical confirmation that variety of imports indeed helps domestic small producers to cope with increasing competition. This suggest that the »taste for beer diversity« may develop as consumers are faced by a larger variety of beers. However, higher significance of domestic supply diversity compared to imported diversity may indicate that apart from actual beer tasting, there are additional channels of “taste development”, such as the general international fad for microbreweries which is developing in recent years.
Measuring Job Satisfaction withCUBModels
Authors: Gambacorta Romina , Iannario Maria
Published: April 2013

In this paper we present two statistical approaches for discussing and modelling job satisfaction based on data collected in theSurvey onHouseholdIncome andWealth (SHIW) conducted by theBank ofItaly. In particular, we analyse these data by means of a mixture model introduced for ordinal data and compare results with theOrdinalProbit model. The aim is to establish common outcomes and differences in the estimated patterns of global job satisfaction, but also to stress the potential for curbing the effects of measurement errors on estimates by usingCUBmodels [aCombination of discreteUniform and (shifted)Binomial distributions], allowing control for the effect of uncertainty and shelter choices in the response process.
Majority Party Power and Procedural Motions in the U.S. Senate
Authors: Smith Steven S. , Ostrander Ian , Pope Christopher M.
Published: April 2013

While the metaphor of House parties as cartels is widely accepted, its application to the Senate is difficult as the majority party lacks the power to unilaterally manipulate rules and pass legislation. Nevertheless, several scholars have argued that the Senate majority party is able to employ nondebatable motions to table to exclude unwanted amendments with procedural rather than substantive votes. Does the motion to table yield negative agenda control or special party influence? Using an analysis of individual Senators' behavior on thousands of votes and an assessment of interest group scores, we find that motions to table do not elicit higher party influence or provide much political cover. A desire to speed up the legislative process, rather than to insulate members from electoral scrutiny, seems to motivate the use of motions to table.
Pathology of SSLOW, a transmissible and fatal synthetic prion protein disorder, and comparison with naturally occurring classical transmissible spongiform encephalopathies
Authors: Jeffrey M. , McGovern G. , Makarava N. , González L. , Kim Y.‐S. , Rohwer R. G. , Baskakov I. V.
Published: April 2013

Aims

Naturally occurring transmissible spongiform encephalopathies (TSEs) accumulate disease‐specific forms of prion protein on cell membranes in association with pathognomonic lesions. We wished to determine whether synthetic prion protein disorders recapitulated these and other subcellular TSE‐specific changes.

Methods

SSLOW is a TSE initiated with refolded synthetic prion protein. Five terminally sick hamsters previously intracerebrally inoculated with third passage SSLOW were examined using light and immunogold electron microscopy.

Results

SSLOW‐affected hamsters showed widespread abnormal prion protein (PrPSSLOW) and amyloid plaques. PrPSSLOW accumulated on plasma lemmas of neurites and glia without pathological changes. PrPSSLOW also colocalized with increased coated vesicles and pits, coated spiral membrane invaginations and membrane microfolding. PrPSSLOW was additionally observed in lysosomes of microglial cells but not of neurones or astrocytes.

Conclusions

PrPSSLOW is propagated by cell membrane conversion of normal PrP and lethal disease may be linked to the progressive growth of amyloid plaques. Cell membrane changes present in SSLOW are indistinguishable from those of naturally occurring TSEs. However, some lesions found in SSLOW are absent in natural animal TSEs and vice versa. SSLOW may not entirely recapitulate neuropathological features previously described for natural disease. End‐stage neuropathology in SSLOW, particularly the nature and distribution of amyloid plaques may be significantly influenced by the early redistribution of seeds within the inoculum and its recirculation following interstitial, perivascular and other drainage pathways. The way in which seeds are distributed and aggregate into plaques in SSLOW has significant overlap with murine APP overexpressing mice challenged with Aβ.
Adult stem cells for acute lung injury: Remaining questions and concerns
Authors: Zhu Ying‐Gang , Hao Qi , Monsel Antoine , Feng Xiao‐Mei , Lee Jae‐Woo
Published: April 2013

Acute lung injury (ALI) or acute respiratory distress syndrome remains a major cause of morbidity and mortality in hospitalized patients. The pathophysiology of ALI involves complex interactions between the inciting event, such as pneumonia, sepsis or aspiration, and the host immune response resulting in lung protein permeability, impaired resolution of pulmonary oedema, an intense inflammatory response in the injured alveolus and hypoxemia. In multiple preclinical studies, adult stem cells have been shown to be therapeutic due to both the ability to mitigate injury and inflammation through paracrine mechanisms and perhaps to regenerate tissue by virtue of their multi‐potency. These characteristics have stimulated intensive research efforts to explore the possibility of using stem or progenitor cells for the treatment of lung injury. A variety of stem or progenitor cells have been isolated, characterized and tested experimentally in preclinical animal models of ALI. However, questions remain concerning the optimal dose, route and the adult stem or progenitor cell to use. Here, the current mechanisms underlying the therapeutic effect of stem cells in ALI as well as the questions that will arise as clinical trials for ALI are planned are reviewed.
Family caregivers’ experiences of relinquishing the care of a person with dementia to a nursing home: insights from a meta‐ethnographic study
Authors: Graneheim Ulla H. , Johansson Anneli , Lindgren Britt‐Marie
Published: April 2013

Many people with dementia are cared for in their homes by family caregivers. As the dementia progresses, admission of the family member to a nursing home becomes inevitable. The aim of this meta‐ethnographic study was to describe caregivers’ experiences of relinquishing the care of a family member with dementia to a nursing home. A systematic literature search of PubMed, Cinahl and PsychInfo, between the years 1992 and 2012, was performed, and 10 qualitative articles, based on 180 family caregivers’ experiences, were included. The family caregivers’ described their experiences as a process that went from being responsible for the decision, through living with the decision, adjusting to a new caring role and having changed relationships. They felt unprepared and lonely with these changes. They experienced loss, guilt and shame, but also feelings of relief. Their roles in the nursing home environment were to make sure that the individual needs of the person with dementia were respected and to monitor the quality of care. They wished to maintain their relationship with the person with dementia and to establish meaningful relationships with caring staff. The process of relinquishing care is similar to a crisis process, which starts with a turning point, followed by a coping face and finally the outcome of the process. The adaption to the new situation can be facilitated if the family caregivers are recognised as partners in the care of the person with dementia. The family caregivers’ unique knowledge of their relatives’ previous life story should be acknowledged in both care planning and daily care. Welcoming family caregivers to regular meetings with staff can contribute to increase the feeling of partnership. Offering staff clinical supervision could be one way of preparing them to deal with the emotional strain reported by family caregivers.
Sedimentology and depositional architecture of tufas deposited in stepped fluvial systems of changing slope: Lessons from the Quaternary Añamaza valley (Iberian Range, Spain)
Authors: Arenas Concha , Vázquez‐Urbez Marta , Pardo Gonzalo , Sancho Carlos
Published: April 2013

The Pleistocene and Holocene tufas of the Añamaza valley (stepped build‐ups, up to 70 m thick, along the valley) consist of several depositional stages separated by erosional surfaces. Eight associations of tufa and related carbonate facies, plus minor polygenic detrital facies, represent the processes that occurred in different fluvial and related environments. The bedrock lithology and structure controlled the location of the knickpoints along the valley and allowed separation of two stepped stretches with distinct conceptual facies models. The moderate‐slope model includes extensive standing‐water areas dammed by barrage‐cascades. In the lakes, bioclastic silts, sands and limestones along with phytoclastic and marly, at places peaty, sediments formed. Abundant stem phytoherms account for extensive palustrine areas. The high‐slope model consists of smaller dammed areas between close‐up cascades and barrage‐cascades, which were composed primarily of moss phytoherms and phytoclastic tufas. An outstanding feature is the extensive steep reach with phytoclastic and polygenic detrital sediments, and stepped cascades consisting of stromatolitic and moss phytoherms. There, the steep slope limited the preservation of stem phytoherms and favoured erosion. The geometry and thickness of the sedimentary fill (wedge‐shaped units composed of cascade and barrage‐cascade deposits downstream, and dammed and gentle‐sloped channel deposits upstream) are therefore different for each model. Multi‐storey wedges are a distinctive feature of the high‐slope model. The initial knickpoint geometry and the tufa aggradation/progradation ratio on such steep surfaces (for example, related to changes in discharge) controlled the growth style of the cascades or barrage‐cascades and, hence, the extent, thickness and vertical evolution of the upstream deposits. The sedimentological attributes and stable‐isotope composition of the carbonate facies suggest a higher and more variable precipitation/evaporation ratio during the Pleistocene than during the Holocene, consistent with an overall decrease in the river discharge. This evolution was coupled with warm conditions, which prevailed during the stages of tufa formation. These results may help to assess architectural patterns in interpreting other basins, and underscore the significance of tufas as records of past hydrology and climate.
Foxp3 Expression and Nitric Oxide Production in Peripheral Blood Mononuclear Cells of Communicants with Pulmonary Tuberculosis
Authors: Cavalcanti Y. V. N. , de Almeida T. M. , de Almeida A. F. , Reis L. C. , Lucena‐Silva N. , Pereira V. R. A.
Published: April 2013

The understanding of the mechanisms involved in the immune response is of significant relevance to the control of tuberculosis (TB), especially in individuals living with patients with TB. To characterize the nitric oxide (NO) production and the Foxp3 marker expression in this population, peripheral blood mononuclear cells of intradomiciliary contacts of individuals with pulmonary tuberculosis with (CTb, susceptible) and without (STb, resistant) previous history of active infection were stimulated in vitro with Mycobacterium tuberculosis antigen (TbAg) and with the mitogen Concanavalin A for 24 and 48 h. The groups analysed did not present significant difference in the Foxp3 mRNA expression nor in the NO production. Negative correlation (P = 0.09) between NO and Foxp3 after a 48‐h stimulation with TbAg was observed in the STb group. In this group, after a 24‐h culture stimulated with TbAg (P = 0.03), this same correlation was observed. In comparison with the cytokines previously studied by our group (Cavalcanti et al., 2009), a positive correlation was observed between IL‐10 and Foxp3 after a 48‐h culture of cells from communicants susceptible to tuberculosis (STb) stimulated with TbAg (P = 0.04). Evaluating the entire population, a positive correlation was observed between the cytokine TNF‐α and the Foxp3 marker in the cultures stimulated for 24 (P = 0.03) and 48 (P = 0.02) hours with TbAg. Therefore, considering the similarity in the exposure and the individual capacity of responding to the contact with M. tuberculosis, the present study contributes to the comprehension of the immune regulation in individuals living with patients with TB.
Pharmacokinetics of micafungin in patients undergoing allogeneic hematopoietic stem cell transplantation
Authors: Oshima K. , Kanda Y. , Kako S. , Ohno K. , Kishino S. , Kurokawa M.
Published: April 2013

Objectives

Micafungin (MCFG) is an antifungal agent that is widely used for the treatment of invasive fungal infection. Although the pharmacokinetics of MCFG is considered to depend on the hepatic metabolism, the impact of hepatic function on the pharmacokinetics of MCFG has been inconsistent among previous studies. The object of this study was to evaluate the relationship between plasma MCFG concentration and clinical and laboratory data.

Patients and methods

We examined the plasma concentration of MCFG in 10 patients who underwent allogeneic hematopoietic stem cell transplantation (HSCT). MCFG at 150 mg/day was administered intravenously a median of 58.5 days after HSCT. Trough and peak concentrations of MCFG (Cmin and Cmax) were measured at a median of 5.5 days after the first administration of MCFG.

Results

The presence of graft‐versus‐host disease involving the liver at blood sampling was associated with significantly higher Cmin and Cmax of MCFG. Among the laboratory data, Cmin and Cmax were significantly higher in patients with severely impaired hepatic function defined as serum total bilirubin (TBi) level >5 mg/dL and/or serum gamma‐glutamyltransferase (γ‐GTP) level >500 IU/L, but the presence of mildly impaired hepatic function defined as serum TBi level >2 mg/dL and/or serum γ‐GTP level >200 IU/L did not affect Cmin and Cmax. Renal function did not show significant impact on Cmin and Cmax.

Conclusion

These findings suggest that the pharmacokinetics of MCFG is affected only by severely impaired liver function.
IMAGING DIAGNOSIS: FIBRODYSPLASIA OSSIFICANS PROGRESSIVA IN A CAT
Authors: Klang Andrea , Kneissl Sibylle , Glänzel Romana , Fuchs‐Baumgartinger Andrea
Published: April 2013

A 1‐year‐old female cat was presented for progressive alopecia, gait abnormalities, and stiffness. Radiography demonstrated multiple calcified lesions within the soft tissues of the cervical and thoracic spine, shoulder, and limbs. Postmortem computed tomography provided more detailed information on the distribution, pattern, and extension of lesions. In addition, computed tomography helped guide sample selection for histopathology. The final diagnosis was fibrodysplasia ossificans progressiva. This is a rare disorder of unknown etiology, characterized by fibrosis and heterotopic bone formation in connective tissues. To the authors’ knowledge, this is the first report describing this disease in a European cat.
Review of Applications of Nonlinear Normal Modes for Vibrating Mechanical Systems
Authors: Avramov Konstantin V. , Mikhlin Yuri V.
Published: April 2013

This paper is an extension of the previous review, done by the same authors (Mikhlin, Y., and Avramov, K. V., 2010, “Nonlinear Normal Modes for Vibrating Mechanical Systems. Review of Theoretical Developments,” ASME Appl. Mech. Rev., 63(6), p. 060802), and it is devoted to applications of nonlinear normal modes (NNMs) theory. NNMs are typical regimes of motions in wide classes of nonlinear mechanical systems. The significance of NNMs for mechanical engineering is determined by several important properties of these motions. Forced resonances motions of nonlinear systems occur close to NNMs. Nonlinear phenomena, such as nonlinear localization and transfer of energy, can be analyzed using NNMs. The NNMs analysis is an important step to study more complicated behavior of nonlinear mechanical systems.This review focuses on applications of Kauderer–Rosenberg and Shaw–Pierre concepts of nonlinear normal modes. The Kauderer–Rosenberg NNMs are applied for analysis of large amplitude dynamics of finite-degree-of-freedom nonlinear mechanical systems. Systems with cyclic symmetry, impact systems, mechanical systems with essentially nonlinear absorbers, and systems with nonlinear vibration isolation are studied using this concept. Applications of the Kauderer–Rosenberg NNMs for discretized structures are also discussed. The Shaw–Pierre NNMs are applied to analyze dynamics of finite-degree-of-freedom mechanical systems, such as floating offshore platforms, rotors, piece-wise linear systems. Studies of the Shaw–Pierre NNMs of beams, plates, and shallow shells are reviewed, too. Applications of Shaw–Pierre and King–Vakakis continuous nonlinear modes for beam structures are considered. Target energy transfer and localization of structures motions in light of NNMs theory are treated. Application of different asymptotic methods for NNMs analysis and NNMs based model reduction are reviewed.
Activation of the Yeast Hippo Pathway by Phosphorylation-Dependent Assembly of Signaling Complexes
Authors: Rock Jeremy M. , Lim Daniel , Stach Lasse , Ogrodowicz Roksana W. , Keck Jamie M. , Jones Michele H. , Wong Catherine C. L. , Yates John R. , Winey Mark , Smerdon Stephen J. , Yaffe Michael B. , Amon Angelika
Published: April 2013

Signal Scaffolds

Scaffolds in cellular signaling pathways are turning out to do way more than just hold proteins together in a complex.

Kim
et al.

(p.
867
, published online 11 April) showed the importance of the scaffold protein Axin as an active participant controlling the kinetics of activation of signaling through the pathways. Axin is part of two protein complexes that have opposing actions that may regulate the timing of signaling—either activating Wnt signaling, thus protecting β-catenin from destruction, or causing proteolytic destruction of β-catenin.

Rock
et al.

(p.
871
, published online 11 April) characterized the role of the scaffold protein Nud1 in the mitotic exit network and found that the kinase that produces the output from the signaling complex only interacts with a scaffold that is primed by its activator protein kinase, already bound to the scaffold and creating a docking site.
Draft Genome Sequence for Desulfovibrio africanus Strain PCS
Authors: Brown Steven D. , Utturkar Sagar M. , Arkin Adam P. , Deutschbauer Adam M. , Elias Dwayne A. , Hazen Terry C. , Chakraborty Romy
Published: April 2013

Desulfovibrio africanus
strain PCS is an anaerobic sulfate-reducing bacterium (SRB) isolated from sediment from Paleta Creek, San Diego, CA. Strain PCS is capable of reducing metals such as Fe(III) and Cr(VI), has a cell cycle, and is predicted to produce methylmercury. We present the
D. africanus
PCS genome sequence.
Genome Sequence of a Novel Reassortant H3N6 Avian Influenza Virus from Domestic Mallard Ducks in Eastern China
Authors: Li Qunhui , Zhong Lei , Zhao Qingqing , He Liang , Duan Zhiqiang , Chen Chaoyang , Chen Yuxin , Gu Min , Wang Xiaoquan , Liu Xiaowen , Liu Xiufan
Published: April 2013

Here, we report the complete genome sequence of an H3N6 avian influenza virus (AIV) isolated from domestic ducks in Jiangsu province of eastern China in 2010. Phylogenetic analysis showed that the H3N6 virus is a natural recombinant virus whose genes were derived from H3N8, H4N6, H6N6, H7N7, and H11N2 AIVs. This analysis will help to understand the molecular characteristics and evolution of the H3N6 influenza virus in eastern China.
Use of simulation to assess electronic health record safety in the intensive care unit: a pilot study
Authors: March Christopher A , Steiger David , Scholl Gretchen , Mohan Vishnu , Hersh William R , Gold Jeffrey A
Published: April 2013

Objective

To establish the role of high-fidelity simulation training to test the efficacy and safety of the electronic health record (EHR)–user interface within the intensive care unit (ICU) environment.

Design

Prospective pilot study.

Setting

Medical ICU in an academic medical centre.

Participants

Postgraduate medical trainees.

Interventions

A 5-day-simulated ICU patient was developed in the EHR including labs, hourly vitals, medication administration, ventilator settings, nursing and notes. Fourteen medical issues requiring recognition and subsequent changes in management were included. Issues were chosen based on their frequency of occurrence within the ICU and their ability to test different aspects of the EHR–user interface. ICU residents, blinded to the presence of medical errors within the case, were provided a sign-out and given 10 min to review the case in the EHR. They then presented the case with their management suggestions to an attending physician. Participants were graded on the number of issues identified. All participants were provided with immediate feedback upon completion of the simulation.

Primary and secondary outcomes

To determine the frequency of error recognition in an EHR simulation. To determine factors associated with improved performance in the simulation.

Results

38 participants including 9 interns, 10 residents and 19 fellows were tested. The average error recognition rate was 41% (range 6–73%), which increased slightly with the level of training (35%, 41% and 50% for interns, residents, and fellows, respectively). Over-sedation was the least-recognised error (16%); poor glycemic control was most often recognised (68%). Only 32% of the participants recognised inappropriate antibiotic dosing. Performance correlated with the total number of screens used (p=0.03).

Conclusions

Despite development of comprehensive EHRs, there remain significant gaps in identifying dangerous medical management issues. This gap remains despite high levels of medical training, suggesting that EHR-specific training may be beneficial. Simulation provides a novel tool in order to both identify these gaps as well as foster EHR-specific training.
Functional foods and nutraceuticals as therapeutic tools for the treatment of diet-related diseases
Authors: Magrone Thea , Perez de Heredia Fatima , Jirillo Emilio , Morabito Giuseppa , Marcos Ascension , Serafini Mauro
Published: April 2013

In Western societies, the incidence of diet-related diseases is progressively increasing due to greater availability of hypercaloric food and a sedentary lifestyle. Obesity, diabetes, atherosclerosis, and neurodegeneration are major diet-related pathologies that share a common pathogenic denominator of low-grade inflammation. Functional foods and nutraceuticals may represent a novel therapeutic approach to prevent or attenuate diet-related disease in view of their ability to exert anti-inflammatory responses. In particular, activation of intestinal T regulatory cells and homeostatic regulation of the gut microbiota have the potential to reduce low-grade inflammation in diet-related diseases. In this review, clinical applications of polyphenol-rich functional foods and nutraceuticals in postprandial inflammation, obesity, and ageing will be discussed. We have placed special emphasis on polyphenols since they are broadly distributed in plants.
The effects of lead agency, nongovernmental organizations, and recovery team membership on the identification of critical habitat for species at risk: insights from the Canadian experience
Authors: Taylor Eric B. , Pinkus Susan
Published: April 2013

Evaluation of legislation and procedures in place to help recover species at risk of extinction is an important component of conservation efforts. Despite its biological importance and key role in species protection and recovery legislation, identification of critical habitat is inconsistently applied. We analyzed data from 126 recovery strategies implemented under Canada’s nascent (2002) Species at Risk Act (SARA) to determine how lead agency, Federal Court rulings, and the proportion of independent team members influenced identification of critical habitat. Only 17% of strategies led by the Department of Fisheries and Oceans included critical habitat, compared with 63% of strategies led by Environment Canada, indicating that aquatic species at risk are much less likely to have critical habitat identified. A 50% increase in recovery strategies that identified critical habitat following precedent-setting court judgments suggests that legal action by nongovernmental organizations played a key role in the evolution of recovery policy for species at risk in Canada. The proportion of independent scientists on a recovery team was statistically unrelated to identification of critical habitat at a national scale, but case studies indicate that independent team members may play an important role in ensuring compliance and transparency during recovery planning.
A 3.03 μW 10-BIT 200 KS/s SAR ADC IN 0.18 μM CMOS
Authors: ZHU ZHANGMING , XIAO YU , LIANG LIANG , LIU LIANXI , YANG YINTANG
Published: April 2013

Based on TSMC 0.18 μm 1.8 V CMOS process, a low power 10-bit 200 KS/s successive approximation register (SAR) analog-to-digital (ADC) is realized. This paper mainly considers the improvement of linearity and the optimization of power consumption. And a novel switching sequence is proposed which allows both to achieve a better compromise. Moreover, the fully dynamic comparator, which consumes no static power, and the optimization of SAR control logic, further reduce power consumption. The simulation results show that at 1.0 V supply and 200 KS/s, the ADC achieves an signal-to-noise and distortion-ration (SNDR) of 59.78 dB and consumes 3.03 μW, resulting in a figure-of-merit (FOM) of 19.0 fJ/conversion-step. The ADC core occupies an active area of only 260 × 220 μm2.
A SHARP UPPER BOUND FOR REGION UNKNOTTING NUMBER OF TORUS KNOTS
Authors: VIKASH SIWACH , PRABHAKAR MADETI
Published: April 2013

Region crossing change for a knot or a proper link is an unknotting operation. In this paper, we provide a sharp upper bound on the region unknotting number for a large class of torus knots and proper links. Also, we discuss conditions on torus links to be proper.
SPIN POLARIZATION IN HIGH DENSITY QUARK MATTER
Authors: BOHR HENRIK , PANDA PRAFULLA K. , PROVIDÊNCIA CONSTANÇA , DA PROVIDÊNCIA JOÃO
Published: April 2013

We investigate the occurrence of a ferromagnetic phase transition in high density hadronic matter (e.g., in the interior of a neutron star). This could be induced by a four-fermion interaction analogous to the one which is responsible for chiral symmetry breaking in the Nambu–Jona-Lasinio model, to which it is related through a Fierz transformation. Flavor SU(2) and flavor SU(3) quark matter are considered. A second-order phase transition is predicted at densities about 5 times the normal nuclear matter density. It is also found that in flavor SU(3) quark matter, a first-order transition from the so-called 2 flavor super-conducting phase to the ferromagnetic phase arises. The color-flavor-locked phase may be completely hidden by the FP.
SOME OPERATIONS OVER ATANASSOV'S INTUITIONISTIC FUZZY SETS BASED ON EINSTEIN T-NORM AND T-CONORM
Authors: WANG WEIZE , LIU XINWANG
Published: April 2013

We define some operations over Atanassov's intuitionistic fuzzy sets (AIFSs), such as Einstein intersection, Einstein product, Einstein scalar multiplication and Einstein exponentiation, etc., and then define new concentration and dilation of AIFSs. These definitions will be useful while dealing with various linguistic hedges like “very”, “more or less”, “highly”, “very very” etc., involved in the problems under intuitionistic fuzzy environment. We also prove some propositions and present some examples in this context.
SOME NEW RESULTS ON WEIGHTED GEOMETRIC MEAN FOR COPULAS
Authors: ZHANG KONGSHENG , LIN JINGUAN , HUANG CHAO
Published: April 2013

Cuadras (Constructing copula functions with weighted geometric means, Journal of Statistical Planning and Inference139 (2009) 3766–3772) showed that geometric mean of the Cuadras–Augé copula and the Gumbel–Barnett copula is a copula by means of generalized function. In this paper, we adopt the method proposed by Durante et al. (2-Increasing binary aggregation operators, Information Sciences177 (2007) 111–129) to investigate weighted geometric mean of the Cuadras–Augé copula and the Gumbel–Barnett copula, as well as weighted geometric mean of the Gumbel–Barnett copula and the New copula. We also consider weighted geometric mean of Archimedean copulas.
SNAP-THROUGH AND BIFURCATION OF NANO-ARCHES ON ELASTIC FOUNDATION BY THE STRAIN GRADIENT AND NONLOCAL THEORIES
Authors: KAVIANI FAREED , MIRDAMADI HAMID REZA
Published: April 2013

This paper presents the snap-through and bifurcation elastic stability analysis of nano-arch type structures with the Winkler foundation under transverse loadings by the strain gradient and stress gradient (nonlocal) theories. The equations of equilibrium are derived by using the variational method and virtual displacement theorem of minimum total potential energy. In the elastic stability analysis, von Karman's nonlinear strain component is included, with the deformation represented by a series solution. It is concluded that in general, the strain gradient theory pushes the system away from instability as compared to the classical theory. However, the nonlocal theory does the reverse and causes the system to experience instability earlier than that of the classical theory. Moreover, theories with different small-size considerations change the mechanism of instability in different ways. For example, in similar conditions, the strain gradient theory causes the system to reach a snap-through point, while the nonlocal theory causes the system to stop at a bifurcation critical point.