bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential impacts of age of acquisition on letter and semantic fluency in Alzheimer's disease patients and healthy older adults
Authors: Sailor Kevin M. , Zimmerman Molly E. , Sanders Amy E.
Published: June 2011

The degree to which the typical age of acquisition (AoA) of words and word frequency have separable influences on verbal production tasks has been strongly debated. To examine the overlap between these factors in verbal fluency tasks, the performance of Alzheimer's disease (AD) patients ( N = 34) and normal elderly controls ( N = 36) was compared on semantic (e.g., vegetables) and letter (e.g., words that begin with F) fluency tasks. These comparisons revealed that words generated for the semantic fluency task had an earlier AoA while words generated for the letter fluency task had a higher word frequency. Differences in AoA between AD patients and controls were larger for semantic than letter fluency. These results suggest that AoA has an effect on verbal production that is independent of word frequency and that AoA has a semantic locus.
Variation in working memory capacity and cognitive control: Goal maintenance and microadjustments of control
Authors: Unsworth Nash , Redick Thomas S. , Spillers Gregory J. , Brewer Gene A.
Published: June 2011

Variation in working memory capacity (WMC) and cognitive control was examined in four experiments. In the experiments high- and low-WMC individuals performed a choice reaction time task (Experiment 1), a version of the antisaccade task (Experiment 2), a version of the Stroop task (Experiment 3), and an arrow version of the flanker task (Experiment 4). An examination of response time distributions suggested that high- and low-WMC individuals primarily differed in the slowest responses in each experiment, consistent with the notion that WMC is related to active maintenance abilities. Examination of two indicators of microadjustments of control (posterror slowing and conflict adaptation effects) suggested no differences between high- and low-WMC individuals. Collectively these results suggest that variation in WMC is related to some, but not all, cognitive control operations. The results are interpreted within the executive attention theory of WMC.
String theory: a perspective over the last 25 years
Authors: Mukhi Sunil
Published: June 2011

This review provides some historical background and then reviews developments in string theory over the last 25 years or so. Both perturbative and non-perturbative approaches to string theory are surveyed and their impact on how we view quantum gravity is analysed.
A microcavity based on a porous silicon multilayer
Authors: Do Thuy Chi , Bui Huy , Nguyen Thuy Van , Nguyen The Anh , Nguyen Thanh Hai , Pham Van Hoi
Published: June 2011

We present a new result for the wavelength-selective characteristics of a 1D photonic microcavity based on porous silicon. These properties are studied in both experimentation and simulation. The 1D Fabry–Perot cavity is fabricated by the electrochemical etching of a low-resistivity silicon wafer with modulation of applied current densities. The simulation relies on the transfer matrix method (TMM) to design and predict the optical properties of a 1D photonic microcavity as well as the relation between anodization parameters with reflection spectra. The experimental results show that the elaborated porous silicon photonic microcavities have the wavelength-selective property in a controllable range of 550–775 nm. We have grown cavity structures of 20 stacked layers and the line width at full-width half-maximum (FWHM) of the transmission band of cavity is 20 nm, centered at 643.27 nm. Measured spectral characteristics of photonic microcavity agree with the simulation results.
Steffensen’s inequality and 𝐿¹-𝐿^{∞} estimates of weighted integrals
Authors: Rabier Patrick
Published: June 2011

Let

Φ
:
[
0
,
∞
)
→

R

\Phi :[0,\infty )\rightarrow \mathbb {R}

be a continuous convex function with

Φ
(
0
)
=
0.

\Phi (0)=0.

We prove that
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="normal upper Phi left-parenthesis StartFraction StartAbsoluteValue EndAbsoluteValue f StartAbsoluteValue EndAbsoluteValue Subscript 1 Baseline Over omega Subscript upper N Baseline StartAbsoluteValue EndAbsoluteValue f StartAbsoluteValue EndAbsoluteValue Subscript normal infinity Baseline EndFraction right-parenthesis less-than-or-equal-to StartFraction 1 Over omega Subscript upper N Baseline StartAbsoluteValue EndAbsoluteValue f StartAbsoluteValue EndAbsoluteValue Subscript normal infinity Baseline EndFraction integral Underscript double-struck upper R Superscript upper N Baseline Endscripts StartAbsoluteValue f left-parenthesis x right-parenthesis EndAbsoluteValue normal upper Phi prime left-parenthesis StartAbsoluteValue x EndAbsoluteValue Superscript upper N Baseline right-parenthesis d x">

Φ

(

|

|

f

|

|

1

ω

N

|

|

f

|

|

∞

)

≤

1

ω

N

|

|

f

|

|

∞

∫

R

N

|

f
(
x
)

|

Φ

′

(

|

x

|

N

)
d
x

\Phi \left ( \frac {||f||_{1}}{\omega _{N}||f||_{\infty }}\right ) \leq \frac {1}{\omega _{N}||f||_{\infty }}\int _{ \mathbb {R}^{N}}|f(x)|\Phi ^{\prime }(|x|^{N})dx

for every
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="f element-of upper L Superscript 1 Baseline left-parenthesis double-struck upper R Superscript upper N Baseline right-parenthesis intersection upper L Superscript normal infinity Baseline left-parenthesis double-struck upper R Superscript upper N Baseline right-parenthesis comma f not-equals 0 comma">

f
∈

L

1

(

R

N

)
∩

L

∞

(

R

N

)
,
f
≠
0
,

f\in L^{1}(\mathbb {R}^{N})\cap L^{\infty }(\mathbb {R}^{N}),f\neq 0,

where

ω

N

\omega _{N}

is the measure of the unit ball of

R

N

.

\mathbb {R}^{N}.

This can be used to obtain lower or upper bounds for weighted integrals

∫

R

N

|

f
(
x
)

|

η
(

|

x

|

)
d
x

\int _{\mathbb {R}^{N}}|f(x)|\eta (|x|)dx

in terms of the

L

1

L^{1}

and

L

∞

L^{\infty }

norms of

f
,

f,

which are often much sharper than crude estimates that may be obtained, if at all, by a visual inspection of the integrand. The basic inequality is essentially independent of Jensen’s inequality, but it is closely related to Steffensen’s inequality.
Impact of changes in blood pressure during the treatment of acute decompensated heart failure on renal and clinical outcomes†
Authors: Testani Jeffrey M. , Coca Steven G. , McCauley Brian D. , Shannon Richard P. , Kimmel Stephen E.
Published: June 2011

Aims

One of the primary determinants of blood flow in regional vascular beds is perfusion pressure. Our aim was to investigate if reduction in blood pressure during the treatment of decompensated heart failure would be associated with worsening renal function (WRF). Our secondary aim was to evaluate the prognostic significance of this potentially treatment‐induced form of WRF.

Methods and results

Subjects included in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial limited data were studied (386 patients). Reduction in systolic blood pressure (SBP) was greater in patients experiencing WRF (−10.3 ± 18.5 vs. −2.8 ± 16.0 mmHg, P < 0.001) with larger reductions associated with greater odds for WRF (odds ratio = 1.3 per 10 mmHg reduction, P < 0.001). Systolic blood pressure reduction (relative change > median) was associated with greater doses of in‐hospital oral vasodilators (P ≤ 0.017), thiazide diuretic use (P = 0.035), and greater weight reduction (P = 0.023). In patients with SBP‐reduction, WRF was not associated with worsened survival [adjusted hazard ratio (HR) = 0.76, P = 0.58]. However, in patients without SBP‐reduction, WRF was strongly associated with increased mortality (adjusted HR = 5.3, P < 0.001, P interaction = 0.001).

Conclusion

During the treatment of decompensated heart failure, significant blood pressure reduction is strongly associated with WRF. However, WRF that occurs in the setting of SBP‐reduction is not associated with an adverse prognosis, whereas WRF in the absence of this provocation is strongly associated with increased mortality. These data suggest that WRF may represent the final common pathway of several mechanistically distinct processes, each with potentially different prognostic implications.
Genome-wide Association Study Using Pooled DNA to Identify Candidate Markers Mediating Susceptibility to Postoperative Nausea and Vomiting
Authors: Janicki Piotr K. , Vealey Ryan , Liu Jiabin , Escajeda Jeremiah , Postula Marek , Welker Kelli
Published: June 2011

Background

A family history has been established as a risk factor for postoperative nausea and vomiting (PONV), but the identities of susceptibility genes remain unknown. The goal of this study was to identify the genetic loci that may contribute to PONV susceptibility in an adult population.

Methods

The authors performed a genome-wide association study involving pooling of DNA obtained from 122 patients with severe PONV and 129 matched controls. Each pool was hybridized to a single nucleotide polymorphism (SNP) microarray, and probe intensity was used to predict allele frequency. Differences in allele frequency between SNP in the PONV and control groups were ranked after accounting for the pooling error. The highest ranking SNPs were selected for individual genotyping in the subjects from whom the DNA pool was comprised and in the new verification cohort consisting of 208 subjects (104 PONV patients and 104 controls).

Results

The authors identified 41 SNP targets showing substantial difference in allelic frequency between pools. These markers were first genotyped in the individual DNA samples from which the pools were comprised. The authors observed evidence for an association between PONV and 19 different loci in the genome. In the separate verification cohort, the association with PONV was observed for four SNPs. This association remained significant after correcting for multiple testing (P < 0.0023) for one SNP (rs2165870), which is located upstream of the promoter for the muscarinic acetylcholine receptor 3 subtype (CHRM3) gene.

Conclusions

The authors performed the genome-wide association study for PONV using pooled DNA samples. Through individual genotyping, they confirmed association of at least one SNP that is predictive of PONV susceptibility.
Pediatric Surgery and Parental Smoking Behavior
Authors: Shi Yu , Warner David O.
Published: June 2011

Background

Secondhand smoke exposure poses health risks to children, including increased risks for anesthesia. In adult smokers, surgery serves as a teachable moment to motivate quitting. For parents who smoke, having a child undergo surgery may also serve as a teachable moment for smoking behavioral change. This study determined if there is an association between children undergoing a surgical procedure and changes in their parents' smoking behavior.

Methods

Secondary analyses were performed using logistic regression analysis of 2005 survey data from the National Health Interview Survey. Analyses included 9,289 parent respondents who provided information on both themselves and their children.

Results

Of the sampled children, 1,112 (12.6%, 95% CI:11.7, 13.4) lived in a home with at least one person who smoked inside in a usual week. In multivariate analysis of the relationship between parent and child surgical history in the past 12 months and smoking behavior, surgery in either the parent (odds ratio 2.19, 95% CI: 1.55, 3.08) or child (odds ratio 2.61, 95% CI: 1.56, 4.35) was associated with an increased likelihood of a quit attempt by the parent. However, these attempts were more likely to be successful if the parents (odds ratio 2.35, 95% CI: 1.35, 4.07), not their child (odds ratio 0.51, 95% CI: 0.20, 1.28), had surgery within the past 12 months.

Conclusions

Parents who smoke were more likely to make a quit attempt within the past 12 months if their children had surgery within this time, but they were not more likely to succeed in maintaining abstinence and thus could benefit from assistance.
The cost of a bodyguard
Authors: Maure Fanny , Brodeur Jacques , Ponlet Nicolas , Doyon Josée , Firlej Annabelle , Elguero Éric , Thomas Frédéric
Published: June 2011

Host manipulation by parasites not only captures the imagination but has important epidemiological implications. The conventional view is that parasites face a trade-off between the benefits of host manipulation and their costs to fitness-related traits, such as longevity and fecundity. However, this trade-off hypothesis remains to be tested.
Dinocampus coccinellae
is a common parasitic wasp of the spotted lady beetle
Coleomegilla maculata
. Females deposit a single egg in the haemocoel of the host, and during larval development the parasitoid feeds on host tissues. At the prepupal stage, the parasitoid egresses from its host by forcing its way through the coccinellid's abdominal segments and begins spinning a cocoon between the ladybird's legs. Remarkably,
D. coccinellae
does not kill its host during its development, an atypical feature for parasitoids. We first showed under laboratory conditions that parasitoid cocoons that were attended by a living and manipulated ladybird suffered less predation than did cocoons alone or cocoons under dead ladybirds. We then demonstrated that the length of the manipulation period is negatively correlated with parasitoid fecundity but not with longevity. In addition to documenting an original case of bodyguard manipulation, our study provides the first evidence of a cost required for manipulating host behaviour.
William Whewell, Galileo, and reconceptualizing the history of science and religion
Authors: Wilson David B.
Published: June 2011

This paper advocates a reconceptualization of the history of science and religion. It is an approach to the subject that would aid research by historians of science as well as their message to others, both academic and non-academic. The approach is perfectly illustrated by the life and ideas of William Whewell and Galileo.
Extensions of Noether's Second Theorem: from continuous to discrete systems
Authors: Hydon Peter E. , Mansfield Elizabeth L.
Published: June 2011

A simple local proof of Noether's Second Theorem is given. This proof immediately leads to a generalization of the theorem, yielding conservation laws and/or explicit relationships between the Euler–Lagrange equations of any variational problem whose symmetries depend on a set of free or partly constrained functions. Our approach extends further to deal with finite-difference systems. The results are easy to apply; several well-known continuous and discrete systems are used as illustrations.
Stochastic modelling of phytoremediation
Authors: Manzoni Stefano , Molini Annalisa , Porporato Amilcare
Published: June 2011

Leaching of heavy metals and other contaminants from soils poses a significant environmental threat as it affects the quality of downstream water bodies. Quantifying these losses is particularly important when employing phytoremediation approaches to reduce soil contamination, as contaminant escaping the system through leaching cannot be taken up by vegetation. Despite its undoubted importance, the role of such hydrologic forcing has seldom been fully considered in models describing the long-term contaminant mass balance during phytoremediation. The partitioning of contaminants between leaching and vegetation uptake is controlled by a number of biophysical processes as well as rainfall variability. Here, we develop a novel stochastic framework that provides analytical expressions to quantify the partitioning of contaminants between leaching and plant uptake and the probability of phytoremediation duration as a function of rainfall statistics and soil and vegetation characteristics. Simple expressions for the mean phytoremediation duration and effectiveness (defined as the fraction of contaminant that is recovered in plant biomass) are derived. The proposed framework can be employed to estimate under which conditions phytoremediation is more efficient, as well as to design phytoremediation projects that maximize contaminant recovery and minimize the duration of the remediation process.
Mate choice for major histocompatibility complex genetic divergence as a bet-hedging strategy in the Atlantic salmon (
Salmo salar
)
Authors: Evans Melissa L. , Dionne Mélanie , Miller Kristina M. , Bernatchez Louis
Published: June 2011

Major histocompatibility complex (MHC)-dependent mating preferences have been observed across vertebrate taxa and these preferences are expected to promote offspring disease resistance and ultimately, viability. However, little empirical evidence linking MHC-dependent mate choice and fitness is available, particularly in wild populations. Here, we explore the adaptive potential of previously observed patterns of MHC-dependent mate choice in a wild population of Atlantic salmon (
Salmo salar
) in Québec, Canada, by examining the relationship between MHC genetic variation and adult reproductive success and offspring survival over 3 years of study. While Atlantic salmon choose their mates in order to increase MHC diversity in offspring, adult reproductive success was in fact maximized between pairs exhibiting an intermediate level of MHC dissimilarity. Moreover, patterns of offspring survival between years 0+ and 1+, and 1+ and 2+ and population genetic structure at the MHC locus relative to microsatellite loci indicate that strong temporal variation in selection is likely to be operating on the MHC. We interpret MHC-dependent mate choice for diversity as a likely bet-hedging strategy that maximizes parental fitness in the face of temporally variable and unpredictable natural selection pressures.
Jasmonate Controls Polypeptide Patterning in Undamaged Tissue in Wounded Arabidopsis Leaves
Authors: Gfeller Aurélie , Baerenfaller Katja , Loscos Jorge , Chételat Aurore , Baginsky Sacha , Farmer Edward E.
Published: June 2011

Wounding initiates a strong and largely jasmonate-dependent remodelling of the transcriptome in the leaf blades of Arabidopsis (Arabidopsis thaliana). How much control do jasmonates exert on wound-induced protein repatterning in leaves? Replicated shotgun proteomic analyses of 2.5-mm-wide leaf strips adjacent to wounds revealed 106 differentially regulated proteins. Many of these gene products have not emerged as being wound regulated in transcriptomic studies. From experiments using the jasmonic acid (JA)-deficient allene oxide synthase mutant we estimated that approximately 95% of wound-stimulated changes in protein levels were deregulated in the absence of JA. The levels of two tonoplast proteins already implicated in defense response regulation, TWO-PORE CHANNEL1 and the calcium-V-ATPase ACA4 increased on wounding, but their transcripts were not wound inducible. The data suggest new roles for jasmonate in controlling the levels of calcium-regulated pumps and transporters, proteins involved in targeted proteolysis, a putative bacterial virulence factor target, a light-dependent catalyst, and a key redox-controlled enzyme in glutathione synthesis. Extending the latter observation we found that wounding increased the proportion of oxidized glutathione in leaves, but only in plants able to synthesize JA. The oxidizing conditions generated through JA signaling near wounds help to define the cellular environment in which proteome remodelling occurs.
Developmental Analysis of aMedicago truncatula smooth leaf margin1Mutant Reveals Context-Dependent Effects on Compound Leaf Development
Authors: Zhou Chuanen , Han Lu , Hou Chunyan , Metelli Alessandra , Qi Liying , Tadege Million , Mysore Kirankumar S. , Wang Zeng-Yu
Published: June 2011

Compound leaf development requires highly regulated cell proliferation, differentiation, and expansion patterns. We identified loss-of-function alleles at the SMOOTH LEAF MARGIN1 (SLM1) locus in Medicago truncatula, a model legume species with trifoliate adult leaves. SLM1 encodes an auxin efflux carrier protein and is the ortholog of Arabidopsis thaliana PIN-FORMED1 (PIN1). Auxin distribution is impaired in the slm1 mutant, resulting in pleiotropic phenotypes in different organs. The most striking change in slm1 is the increase in the number of terminal leaflets and a simultaneous reduction in the number of lateral leaflets, accompanied by reduced expression of SINGLE LEAFLET1 (SGL1), an ortholog of LEAFY. Characterization of the mutant indicates that distinct developmental domains exist in the formation of terminal and lateral leaflets. In contrast with the pinnate compound leaves in the wild type, the slm1 sgl1 double mutant shows nonpeltately palmate leaves, suggesting that the terminal leaflet primordium in M. truncatula has a unique developmental mechanism. Further investigations on the development of leaf serrations reveal different ontogenies between distal serration and marginal serration formation as well as between serration and leaflet formation. These data suggest that regulation of the elaboration of compound leaves and serrations is context dependent and tightly correlated with the auxin/SLM1 module in M. truncatula.
Interface between normal and transformed epithelial cells: A road to a novel type of cancer prevention and treatment
Authors: Fujita Yasuyuki
Published: June 2011

Cell transformation arises from activation of oncoproteins and/or inactivation of tumor suppressor proteins. During the initial stage of carcinogenesis, transformation occurs in a single cell within an epithelial monolayer. However, it is not known what happens at the interface between normal and transformed cells once the initial transformation has occurred. Using elaborate cell culture systems, recent reports have shown that interactions between normal and transformed epithelial cells can induce various phenomena. For example, when Ras‐ or Src‐transformed cells are surrounded by normal epithelial cells, multiple signaling pathways are activated and the transformed cells are apically extruded from the epithelium. In addition, normal and certain types of transformed cells compete with each other for cell survival, and the transformed cells undergo apoptosis. Importantly, when transformed cells alone are present, neither apoptosis nor elimination from epithelia occurs, indicating that the presence of surrounding normal cells influences the signaling pathways and fate of transformed cells. Comparable phenomena are also observed in zebrafish and mice in vivo model systems. In this review, I will introduce this newly emerging research field and discuss how these studies can potentially lead to establishment of novel types of cancer prevention and treatment. (Cancer Sci 2011; 102: 1749–1755)
Structure and evolution of mass transport deposits in the South Caspian Basin, Azerbaijan
Authors: Richardson Steve E. J. , Davies Richard J. , Allen Mark B. , Grant Simon F.
Published: June 2011

The Quaternary to late Pliocene sedimentary succession along the margin of the South Caspian Basin contains numerous kilometre‐scale submarine slope failures, which were sourced along the basin slope and from the inclined flanks of contemporaneous anticlines. This study uses three‐dimensional (3D) seismic reflection data to visualise the internal structure of 27 mass transport deposits and catalogues the syndepositional structures contained within them. These are used to interpret emplacement processes occurring during submarine slope failure. The deposits consist of three linked structural domains: extensional, translational and compressive, each containing characteristic structures. Novel features are present within the mass transport deposits: (1) a diverging retrogression of the headwall scarp; (2) the absence of a conventional headwall scarp around growth stratal pinch outs; (3) restraining bends in the lateral margin; (4) a downslope increase in the throw of thrust faults. The results of this study shed light on the deformation that occurred during submarine slope failure, and highlight an important geological process in the evolution of the South Caspian Basin margin.
Influence of methotrexate on infliximab pharmacokinetics and pharmacodynamics in ankylosing spondylitis
Authors: Ternant David , Mulleman Denis , Lauféron Francine , Vignault Céline , Ducourau Emilie , Wendling Daniel , Goupille Philippe , Paintaud Gilles
Published: June 2011

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Infliximab pharmacokinetics in ankylosing spondylitis has been described but using sparce data.

• A previous work suggests that infliximab concentrations influence clinical response in ankylosing spondylitis, but the infliximab concentration–effect relationship is not known in this disease.

• Methotrexate was shown to influence infliximab pharmacokinetics in rheumatoid arthritis.

WHAT THIS STUDY ADDS

• This study is the first to describe infliximab pharmacokinetics in ankylosing arthritis using rich data.

• The infliximab concentration explains only a small part of interindividual variability in the response of ankylosing arthritis patients.

• Contrary to what is observed in rheumatoid arthritis, methotrexate influences neither infliximab pharmacokinetics nor concentration–response relationship in ankylosing spondylitis.

AIMS

Infliximab, an anti‐tumour necrosis factor α monoclonal antibody, has profoundly modified the treatment of several inflammatory diseases. The objective was to assess the influence of methotrexate on the variability of infliximab pharmacokinetics and concentration–effect relationship in axial ankylosing spondylitis (AAS) patients.

METHODS

Twenty‐six patients with AAS were included in a prospective study. They were treated by infliximab 5 mg kg−1 infusions at weeks 0, 2, 6, 12 and 18. Infliximab concentrations were measured before, and 2 and 4 h after each infusion, and at each intermediate visit (weeks 1, 3, 4, 5, 8, 10 and 14). Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was measured at each visit. Infliximab pharmacokinetics was described using a two‐compartment model with first‐order distribution and elimination constants. A population approach was used. Infliximab pharmacodynamics was described using the area under the BASDAI curve.

RESULTS

A total of 507 blood samples and 329 BASDAI measurements were collected. The following pharmacokinetic parameters were obtained (interindividual coefficient of variation): volumes of distribution for the central compartment = 2.4 l (9.6%) and peripheral compartment = 1.8 l (26%), systemic clearance = 0.23 l day−1 (22%) and intercompartment clearance = 2.3 l day−1. Methotrexate influenced neither pharmacokinetic nor BASDAI variability.

CONCLUSIONS

Using the present dosage, the clinical efficacy of infliximab is only weakly influenced by its serum concentrations. The results do not support the combination of methotrexate with infliximab in ankylosing spondylitis.
Surveillance of female patients with inherited bleeding disorders in United States Haemophilia Treatment Centres
Authors: BYAMS V. R. , KOUIDES P. A. , KULKARNI R. , BAKER J. R. , BROWN D. L. , GILL J. C. , GRANT A. M. , JAMES A. H. , KONKLE B. A. , MAAHS J. , DUMAS M. M. , McALISTER S. , NANCE D. , NUGENT D. , PHILIPP C. S. , SOUCIE J. M. , STANG E. ,   and the Haemophilia Treatment Centres Network Investigators
Published: June 2011

Summary.  Inherited bleeding disorders are especially problematic for affected girls and women due to the monthly occurrence of menstrual periods and the effects on reproductive health. Although heavy menstrual bleeding (HMB) is the most common manifestation, females with inherited bleeding disorders (FBD) experience other bleeding symptoms throughout the lifespan that can lead to increased morbidity and impairment of daily activities. The purpose of this article is to describe the utility of a female‐focused surveillance effort [female Universal Data Collection (UDC) project] in the United States Haemophilia Treatment Centres (HTCs) and to describe the baseline frequency and spectrum of diagnoses and outcomes. All FBD aged 2 years and older receiving care at selected HTCs were eligible for enrolment. Demographic data, diagnoses and historical data regarding bleeding symptoms, treatments, gynaecological abnormalities and obstetrical outcomes were analysed. Analyses represent data collected from 2009 to 2010. The most frequent diagnoses were type 1 von Willebrand’s disease (VWD) (195/319; 61.1%), VWD type unknown (49/319; 15.4%) and factor VIII deficiency (40/319; 12.5%). HMB was the most common bleeding symptom (198/253; 78.3%); however, 157 (49.2%) participants reported greater than four symptoms. Oral contraceptives were used most frequently to treat HMB (90/165; 54.5%), followed by desmopressin [1‐8 deamino‐D‐arginine vasopressin (DDAVP)] (56/165; 33.9%). Various pregnancy and childbirth complications were reported, including bleeding during miscarriage (33/43; 76.7%) and postpartum haemorrhage (PPH) (41/109; 37.6%). FBD experience multiple bleeding symptoms and obstetrical‐gynaecological morbidity. The female UDC is the first prospective, longitudinal surveillance in the US focusing on FBD and has the potential to further identify complications and reduce adverse outcomes in this population.
Prenatal diagnosis and preimplantation genetic diagnosis: novel technologies and state of the art of PGD in different regions of the world
Authors: PEYVANDI F. , GARAGIOLA I. , MORTARINO M.
Published: June 2011

Summary.  Prenatal diagnosis (PND) aims to provide accurate, rapid results as early in pregnancy as possible. Conventional PND involves sampling cells of foetal origin by chorionic villus sampling at 11–14th weeks of pregnancy or amniocentesis after 15th week. These are invasive procedures and have a small but significant rate of 0.5% to 1% for loss of pregnancy. An alternative to existing methods for conventional PND for couples at risk of transmitting a genetic disease to their child is preimplantation genetic diagnosis (PGD). PGD is a newly emerging form of a very early prenatal diagnosis. The technique combines assisted reproductive technology with molecular genetics and cytogenetics to allow the identification of abnormality in embryos prior to implantation. The diagnosis of genetic disease in human preimplantation embryos was pioneered in the late 1980s for testing of aneuploidy, single gene and X‐linked disease, such as cystic fibrosis, haemophilia and chromosomal abnormalities. The PGD‐related legal and ethical issues have been debated at many levels both nationally and internationally. The attitude towards PGD varies substantially not only in different parts of the world but also within the Europe, owing to scientific, cultural and religious differences. PGD has become widely practised throughout the world for various indications and can substantially decrease the eventual risks of passing a genetic undesired condition of the offspring. Nevertheless, its extension to some new and non‐medical indications has raised ethical concerns, in particular its potential eugenic dimension.
Management of pregnancy, labour and delivery in women with inherited bleeding disorders
Authors: HUQ F. Y. , KADIR R. A.
Published: June 2011

Summary. Pregnancy, labour and delivery present intrinsic haemostatic challenges to women with and carriers of bleeding disorders and their offspring. Deficiency of fibrinogen and factor XIII are associated with miscarriage, placental abruption and foetal loss. The risk of antenatal complications including antepartum haemorrhage is unknown in women with other bleeding disorders. There is a significant risk of postpartum haemorrhage (primary and secondary) in women with all types of bleeding disorders. This can be serious and life threatening in those with severe defects such as Bernard Soulier syndrome and Glanzmann’s thrombasthenia. Three to four percent of infants with haemophilia experience cranial bleeding that occurs during labour and delivery. The safest method of delivery for affected babies remains controversial. However, the rate of planned Caesarean section is increasing among known carriers of haemophilia. If vaginal delivery is planned, prolonged labour and difficult delivery especially vacuum extraction are associated with the highest risk of cranial bleeding and should be avoided. The optimal management of pregnancy in women with inherited bleeding disorders requires a multidisciplinary approach and advanced individualized management plan taking into consideration obstetric and bleeding risk factors. Women with mild or moderate bleeding disorders can be managed at their local maternity unit in close collaboration with a tertiary centre. However, those with severe or rare disorders or carrying an affected infant should be managed in a tertiary centre with an onsite Haemophilia centre.
Quality of life in women with bleeding disorders
Authors: Von MACKENSEN S.
Published: June 2011

Summary. ; The assessment of health‐related quality of life (HRQOL) has been increasingly used over the last years, is regarded one of the most relevant health outcome measures and is included as secondary and primary endpoint in clinical and observational trials. Bleeding disorders and their treatment impact on patients’ HRQOL, especially in women with bleeding disorders and can affect the everyday life of patients and their families. In women with inherited bleeding disorders, menorrhagia is the most common symptom, manifest by significant bleeding and pain leading to limitation in conducting daily activities and changes in social functioning with an adverse effect on women’s HRQOL. Only few studies used validated questionnaires for the assessment of HRQOL in women with bleeding disorders, mainly generic instruments. Few disease‐specific instruments are available for the adequate assessment of the impact of menorrhagia on HRQOL, namely the Ruta Menorrhagia Severity Scale, the menorrhagia multi‐attribute utility scale and the Menorrhagia Impact Questionnaire. The von Willebrand disease (VWD)‐QOL questionnaire, a disease‐specific questionnaire for patients with VWD contains a specific dimension ‘menstruation’ for women. These studies revealed that menorrhagia has a larger impact on HRQOL in women with inherited bleeding disorders compared with women with normal haemostasis. Moreover, age, type of VWD and gender have an influence on the HRQOL of patients with VWD. The need of disease‐specific instruments for an adequate assessment of HRQOL in women with bleeding disorders could be demonstrated in these studies.
The long‐term psychological management of women and girls with inherited bleeding disorders
Authors: DUNN N. F.
Published: June 2011

Summary.  A woman with an inherited bleeding disorder faces two main challenges: managing her symptoms medically and integrating her condition into her daily life. Health professionals have an obligation to support young girls and women affected with these disorders as they negotiate the life‐cycle transition of their condition. This support should include helping women to integrate their diagnosis into a new sense of self. The psychological effects of menorrhagia can also be addressed by working with key family members such as a young patient’s mother or a woman’s partner to prevent the experience of body shame. Couples require support to sustain their sexual relationship and to develop communal coping strategies as they face the challenges that menorrhagia brings to their relationship. These may include both fertility and pregnancy issues. Maintaining contact with the medical team can benefit women approaching the menopause by preparing them psychologically for the change and its associated symptoms.
How to deal with medical and social aspects of bleeding disorders – preparing women and the family in developing countries
Authors: KARIMI M. , RAVANBOD S. , COHAN N. , ALA F.
Published: June 2011

Summary.  There is a considerable number of women with inherited bleeding disorders in Iran. von Willebrand disease, Glanzman thrombasthenia and factor XIII deficiency are the most common coagulation disorders. The main cause of this high rate of coagulation disorders is attributed to a high rate of consanguineous marriages in Iran. Medical care continues to improve for individuals affected with coagulation disorders in Iran. However, these disorders continue to have a significant impact on the affected Iranian women. As a result of the hereditary nature of these disorders, the impact extends to the psychosocial dimension of the lives of the women. Therefore it is recommended that women with coagulation disorders are provided with psychological and social support along with coagulation therapy.
A set of five microsatellite markers linked to F8 gene can detect haemophilia A carriers across India
Authors: SAHA A. , NAYAK S. , MANI K. R. , CHANDAK G. R. ,   INDIAN GENOME VARIATION CONSORTIUM, RAY K. , MUKHOPADHYAY A.
Published: June 2011

Summary.  Haemophilia A (HA) is an X‐linked recessive bleeding disorder, primarily because of defects in the 186‐kb long factor VIII gene (F8) affecting 1–2 men per 10 000 worldwide. Available markers for carrier detection are not effective in all populations, especially in India. In this study, we have chosen a set of five microsatellite markers, namely, DSX9897, DSX1073, intron 1 (GT)n, intron 22 (CA)n and intron 25 (CA)n, in and around the F8 gene to achieve better sensitivity for carrier detection. Each marker locus has been PCR amplified in the individual DNA samples using fluorescent markers followed by genotyping experiment in automated sequencer. Genotype calls have been made by GeneMapper Software (version 4). Allele frequency of each microsatellite marker was calculated manually. Heterozygosity was determined by counting the heterozygotes in the female subset. We have shown that in 253 normal individuals from 20 different ethnic groups of India, the heterozygosity for the markers ranged from 0.25 to 0.54; and for the entire subset of 102 female samples we could successfully discriminate between the two X‐chromosomes using these five markers. These markers could also discriminate between the two X‐chromosomes for each of 39 obligate carriers included in this study. In conclusion, this panel of five markers around the F8 locus can be used for carrier detection of HA with higher sensitivity across India for families affected with the disease.
Animal age, packaging and antioxidant treatment effects on sensory characteristics of beef Infraspinatus muscle
Authors: Wadhwani Ranjeeta , Cornforth Daren P. , Murdia Lalit K. , Whittier Dick
Published: June 2011

The objective was to determine effects of animal age, packaging and antioxidant treatment on colour and sensory characteristics of infraspinatus (IF) muscle of the beef shoulder (chuck). IF steaks from older animals (USDA commercial grade; >42 months age) had higher (P < 0.05) muscle pigment levels and redness than young select grade steaks. Steaks in 80% oxygen‐modified atmospheric packaging (O2‐MAP) had higher (P < 0.05) thiobarbituric acid values than steaks in 0.4% carbon monoxide‐modified atmospheric packaging (CO‐MAP) (1.30 and 0.41, respectively). Descriptive rancidity scores were lowest for select grade steaks in CO‐MAP (1.03). Beef flavour intensity was higher (P < 0.05) for steaks in CO‐MAP, even though steaks were held longer (21 days) before cooking. Sour/grassy scores were highest (P < 0.05) for steaks in polyvinyl‐chloride film (5 days storage), and lowest (P < 0.05) for steaks in CO‐MAP, indicating that sour/grassy flavour dissipated at longer storage times.
Preparation of biopolymer film from chitosan modified with lipid fraction
Authors: Souza Vanderlei C. , Monte Micheli L. , Pinto Luiz A. A.
Published: June 2011

Films formed from polysaccharides, as chitosan, present a high permeability in water vapour. In order to increase resistance to water vapour for chitosan‐based films, different lipid fractions were incorporated into a filmogenic matrix: fish and vegetable oils, stearic and oleic acids. The chitosan showed a molecular weight of 150 kDa and a deacetylation degree of 86 ± 1%. Results showed that incorporation of different lipid fractions decreased the water vapour permeability (WVP) (1.3–1.8 g mm m−2 day−1 kPa−1) as compared with pure chitosan film (3.8 g mm m−2 day−1 kPa−1). A higher reduction in WVP (65%) was found with the addition of refined fish oil to the continuous matrix of the films than with the addition of refined rice oil, oleic or stearic acid (50–60%). However, pure chitosan films showed better tensile strength (TS = 33 MPa) and elongation percentage (E = 18%) than lipids fraction–chitosan films (7–19 MPa and 7–13%, respectively).
Effect of solvent type on the extractability of bioactive compounds, antioxidant capacity and colour properties of natural annatto extracts
Authors: Chisté Renan C. , Benassi Marta T. , Mercadante Adriana Z.
Published: June 2011

This study was conducted to obtain annatto extracts with both high antioxidant capacity and colour potential using solvents of different polarities (water, ethanol/water, ethanol, ethanol/ethyl acetate and ethyl acetate). The highest levels of total phenolic compounds were found in the water, ethanol/water and ethanol extracts (0.5 mg GAE mL−1), and the highest level of bixin was found in the ethanol/ethyl acetate extract (5.2 mg mL−1), which was characterised as the reddest and the most vivid one (a* = 40.5, h° = 46.1, C* = 58.4). The ethanol/ethyl acetate extract also showed the highest antioxidant activity (4.7 μm TEAC mL−1) and the highest percentage of tryptophan protection against singlet oxygen (63.6%). On the other hand, ethyl acetate and ethanol/water were the least effective solvents for the extraction of phenolic compounds and bixin, respectively. According to the multivariate statistical analysis, ethanol/ethyl acetate and ethyl acetate were the most promising solvents to obtain annatto extracts with both antioxidant and colour properties.
Morphine‐Induced Changes in Opioid Sensitivity in Postpartum Females: A Unique Progesterone Response
Authors: Sukikara M. H. , Cruz A. M. , Felippe É. C. G. , Anselmo‐Franci J. A. , Canteras N. S. , de Oliveira C. A. , Felicio L. F.
Published: June 2011

Opioid peptides play an important role in maternal behaviour, as well as in physiological and pathological phenomena involving motivation. Daily 3.5 mg/kg doses of morphine from days 17–21 of pregnancy are able to change the expression of maternal behaviour patterns. However, the role of hormones on such opioid behavioural actions remains to be determined. The present study investigated the endocrine responses to this morphine treatment. Corticosterone, progesterone, oestradiol and prolactin serum concentrations were measured after each morphine injection. No significant differences were found in corticosterone, oestradiol or prolactin serum concentrations. The results suggest that the treatment was unable to promote different effects, other than those caused by saline injections. In morphine‐treated animals, however, progesterone concentrations were consistently and significantly increased from days 18–20 of treatment. Thus, because this behavioural meaningful opioidergic stimulation during late pregnancy affects progesterone levels, the findings of the present study raise the hypothesis that this hormone may play a role in morphine‐induced changes in opioid sensitivity during late pregnancy and early lactation.
Pharmacokinetics of the cytochrome P‐450 substrates phenytoin, theophylline, and diazepam in healthy Greyhound dogs
Authors: KuKANICH B. , NAUSS J. L.
Published: June 2011

KuKanich, B., Nauss, J. L. Pharmacokinetics of the cytochrome P‐450 substrates phenytoin, theophylline, and diazepam in healthy Greyhound dogs.J. vet. Pharmacol. Therap. 35, 275–281.

The purpose of this study was to determine the pharmacokinetics of phenytoin, theophylline, and diazepam in six healthy Greyhound dogs. Additionally, the pharmacokinetics of the diazepam metabolites, oxazepam and nordiazepam, after diazepam administration was determined. Phenytoin sodium (12 mg/kg), aminophylline (10 mg/kg), and diazepam (0.5 mg/kg) were administered IV on separate occasions, and blood was collected at predetermined time points for the quantification of plasma drug concentrations by florescence polarization immunoassay (phenytoin, theophylline) or mass spectrometry (diazepam, oxazepam, and nordiazepam). The terminal half‐life was 4.9, 9.2, and 1.0 h, respectively, for phenytoin, theophylline, and diazepam, and 6.2 and 2.4 h for oxazepam and nordiazepam after IV diazepam. The clearance was of 2.37, 0.935, and 27.9 mL·min/kg, respectively, for phenytoin, theophylline, and diazepam. TheCMAXwas 44.7 and 305.2 ng/mL for oxazepam and nordiazepam, respectively, after diazepam administration. Temazepam was not detected above 5 ng/mL in any sample after IV diazepam.
Transcriptional regulation of MG_149, an osmoinducible lipoprotein gene from Mycoplasma genitalium
Authors: Zhang Wenbo , Baseman Joel B.
Published: June 2011

Transcriptional regulation remains poorly understood in Mycoplasma genitalium, the smallest self‐replicating cell and the causative agent of a spectrum of urogenital diseases. Previously, we reported that MG_149, a lipoprotein‐encoding gene, was highly induced under physiological hyperosmolarity conditions. In this study we further analysed MG_149 transcription with a focus on the identification of promoter elements and regulatory mechanisms. We established MG_149 as a genuine osmoinducible gene that exhibited the highest transcript abundance compared with other lipoprotein genes. Using genetic approaches, we demonstrated that the −10 region of the MG_149 promoter was essential for osmoinduction. Moreover, we showed that MG_149 osmoinduction was regulated by DNA supercoiling, as the presence of novobiocin decreased MG_149 expression in a dose‐dependent manner. Taken together, these results indicate that DNA supercoiling participates in controlling MG_149 expression during in vivo‐like conditions.
Regulation of fructooligosaccharide metabolism in an extra‐intestinal pathogenic Escherichia coli strain
Authors: Porcheron Gaëlle , Kut Emmanuel , Canepa Sylvie , Maurel Marie‐Christine , Schouler Catherine
Published: June 2011

A gene cluster involved in the metabolism of prebiotic short‐chain fructooligosaccharides (scFOS) has recently been identified in the extra‐intestinal avian pathogenic Escherichia coli strain BEN2908. This gene cluster, called the fos locus, plays a major role in the initiation stage of chicken intestinal colonization. This locus is composed of six genes organized as an operon encoding a sugar transporter and enzymes involved in scFOS metabolism, and of a divergently transcribed gene encoding a transcriptional regulator, FosR, belonging to the LacI/GalR family. To decipher the regulation of scFOS metabolism, we monitored the fos operon promoter activity using a luciferase reporter gene assay. We demonstrated that the expression of fos genes is repressed by FosR, controlled by catabolite repression and induced in the presence of scFOS. Using electrophoretic mobility shift assays and surface plasmon resonance experiments, we showed that FosR binds to two operator sequences of the fos operon promoter region. This binding to DNA was inhibited in the presence of scFOS, especially by GF2. We then propose a model of scFOS metabolism regulation in a pathogenic bacterium, which will help to identify the environmental conditions required for fos gene expression and to understand the role of this locus in intestinal colonization.