bluuebunny/crossref_metadata_2025 huggingface dataset:
Paracatenula
, an ancient symbiosis between thiotrophic
Alphaproteobacteria
and catenulid flatworms
Authors: Gruber-Vodicka Harald Ronald , Dirks Ulrich , Leisch Nikolaus , Baranyi Christian , Stoecker Kilian , Bulgheresi Silvia , Heindl Niels Robert , Horn Matthias , Lott Christian , Loy Alexander , Wagner Michael , Ott Jörg
Published: June 2011

Harnessing chemosynthetic symbionts is a recurring evolutionary strategy. Eukaryotes from six phyla as well as one archaeon have acquired chemoautotrophic sulfur-oxidizing bacteria. In contrast to this broad host diversity, known bacterial partners apparently belong to two classes of bacteria—the
Gamma
- and
Epsilonproteobacteria
. Here, we characterize the intracellular endosymbionts of the mouthless catenulid flatworm genus
Paracatenula
as chemoautotrophic sulfur-oxidizing
Alphaproteobacteria
. The symbionts of
Paracatenula galateia
are provisionally classified as “
Candidatus
Riegeria galateiae” based on 16S ribosomal RNA sequencing confirmed by fluorescence in situ hybridization together with functional gene and sulfur metabolite evidence. 16S rRNA gene phylogenetic analysis shows that all 16
Paracatenula
species examined harbor host species-specific intracellular
Candidatus
Riegeria bacteria that form a monophyletic group within the order
Rhodospirillales
. Comparing host and symbiont phylogenies reveals strict cocladogenesis and points to vertical transmission of the symbionts. Between 33% and 50% of the body volume of the various worm species is composed of bacterial symbionts, by far the highest proportion among all known endosymbiotic associations between bacteria and metazoans. This symbiosis, which likely originated more than 500 Mya during the early evolution of flatworms, is the oldest known animal–chemoautotrophic bacteria association. The distant phylogenetic position of the symbionts compared with other mutualistic or parasitic
Alphaproteobacteria
promises to illuminate the common genetic predispositions that have allowed several members of this class to successfully colonize eukaryote cells.
Comparative transcriptome and metabolite analysis of oil palm and date palm mesocarp that differ dramatically in carbon partitioning
Authors: Bourgis Fabienne , Kilaru Aruna , Cao Xia , Ngando-Ebongue Georges-Frank , Drira Noureddine , Ohlrogge John B. , Arondel Vincent
Published: June 2011

Oil palm can accumulate up to 90% oil in its mesocarp, the highest level observed in the plant kingdom. In contrast, the closely related date palm accumulates almost exclusively sugars. To gain insight into the mechanisms that lead to such an extreme difference in carbon partitioning, the transcriptome and metabolite content of oil palm and date palm were compared during mesocarp development. Compared with date palm, the high oil content in oil palm was associated with much higher transcript levels for all fatty acid synthesis enzymes, specific plastid transporters, and key enzymes of plastidial carbon metabolism, including phosphofructokinase, pyruvate kinase, and pyruvate dehydrogenase. Transcripts representing an ortholog of the WRI1 transcription factor were 57-fold higher in oil palm relative to date palm and displayed a temporal pattern similar to its target genes. Unexpectedly, despite more than a 100-fold difference in flux to lipids, most enzymes of triacylglycerol assembly were expressed at similar levels in oil palm and date palm. Similarly, transcript levels for all but one cytosolic enzyme of glycolysis were comparable in both species. Together, these data point to synthesis of fatty acids and supply of pyruvate in the plastid, rather than acyl assembly into triacylglycerol, as a major control over the storage of oil in the mesocarp of oil palm. In addition to greatly increasing molecular resources devoted to oil palm and date palm, the combination of temporal and comparative studies illustrates how deep sequencing can provide insights into gene expression patterns of two species that lack genome sequence information.
Disruption of adult expression of sexually selected traits by developmental exposure to bisphenol A
Authors: Jašarević Eldin , Sieli Paizlee T. , Twellman Erin E. , Welsh Thomas H. , Schachtman Todd R. , Roberts R. Michael , Geary David C. , Rosenfeld Cheryl S.
Published: June 2011

Exposure to endocrine disrupting compounds (EDCs), such as bisphenol A (BPA), may cause adverse health effects in wildlife and humans, but controversy remains as to what traits are most sensitive to EDCs and might serve as barometers of exposure. Expression of sexually selected traits that have evolved through intrasexual competition for mates and intersexual choice of mating partner are more dependent on developmental and physical condition of an animal than naturally selected traits and thus might be particularly vulnerable to disruption by developmental exposure to EDCs. We have used the deer mouse (
Peromyscus maniculatus
) as a model to test this hypothesis. Adult male–male competition for mates in this species is supported by enhanced spatial navigational and exploratory abilities, which enable males to search for prospective, widely dispersed females. Male deer mice exposed to BPA or ethinyl estradiol (EE) through maternal diet showed no changes in external phenotype, sensory development, or adult circulating concentrations of testosterone and corticosterone, but spatial learning abilities and exploratory behaviors were severely compromised compared with control males. Because these traits are not sexually selected in females, BPA exposure predictably had no effect, although EE-exposed females demonstrated enhanced spatial navigational abilities. Both BPA-exposed and control females preferred control males to BPA-exposed males. Our demonstration that developmental exposure to BPA compromises cognitive abilities and behaviors essential for males to reproduce successfully has broad implications for other species, including our own. Thus, sexually selected traits might provide useful biomarkers to assess risk of environmental contamination in animal and human populations.
Neural and computational mechanisms of postponed decisions
Authors: Martínez-García Marina , Rolls Edmund T. , Deco Gustavo , Romo Ranulfo
Published: June 2011

We consider the mechanisms that enable decisions to be postponed for a period after the evidence has been provided. Using an information theoretic approach, we show that information about the forthcoming action becomes available from the activity of neurons in the medial premotor cortex in a sequential decision-making task after the second stimulus is applied, providing the information for a decision about whether the first or second stimulus is higher in vibrotactile frequency. The information then decays in a 3-s delay period in which the neuronal activity declines before the behavioral response can be made. The information then increases again when the behavioral response is required. We model this neuronal activity using an attractor decision-making network in which information reflecting the decision is maintained at a low level during the delay period, and is then selectively restored by a nonspecific input when the response is required. One mechanism for the short-term memory is synaptic facilitation, which can implement a mechanism for postponed decisions that can be correct even when there is little neuronal firing during the delay period before the postponed decision. Another mechanism is graded firing rates by different neurons in the delay period, with restoration by the nonspecific input of the low-rate activity from the higher-rate neurons still firing in the delay period. These mechanisms can account for the decision making and for the memory of the decision before a response can be made, which are evident in the activity of neurons in the medial premotor cortex.
Attachment figures activate a safety signal-related neural region and reduce pain experience
Authors: Eisenberger Naomi I. , Master Sarah L. , Inagaki Tristen K. , Taylor Shelley E. , Shirinyan David , Lieberman Matthew D. , Naliboff Bruce D.
Published: June 2011

Although it has long been hypothesized that attachment figures provide individuals with a sense of safety and security, the neural mechanisms underlying attachment-induced safety have not been explored. Here, we investigated whether an attachment figure acts as a safety signal by exploring whether viewing an attachment figure during a threatening experience (physical pain) led to increased activity in a neural region associated with safety signaling, the ventromedial prefrontal cortex (VMPFC), and corresponding reductions in pain. Female participants in long-term romantic relationships were scanned as they received painful stimuli while viewing pictures of their partner and control images (stranger, object). Consistent with the idea that the attachment figure may signal safety, results revealed that viewing partner pictures while receiving painful stimulation led to reductions in self-reported pain ratings, reductions in pain-related neural activity (dorsal anterior cingulate cortex, anterior insula), and increased activity in the VMPFC. Moreover, greater VMPFC activity in response to partner pictures was associated with longer relationship lengths and greater perceived partner support, further highlighting a role for the VMPFC in responding to the safety value of the partner. Last, greater VMPFC activity while viewing partner pictures was associated with reduced pain ratings and reduced pain-related neural activity. An implication of these findings is that, in the same way that stimuli that historically have threatened survival (e.g., snakes, spiders) are considered to be prepared fear stimuli, attachment figures, who have historically benefited survival, may serve as prepared safety stimuli, reducing threat- or distress-related responding in their presence.
Premotor functional connectivity predicts impulsivity in juvenile offenders
Authors: Shannon Benjamin J. , Raichle Marcus E. , Snyder Abraham Z. , Fair Damien A. , Mills Kathryn L. , Zhang Dongyang , Bache Kevin , Calhoun Vince D. , Nigg Joel T. , Nagel Bonnie J. , Stevens Alexander A. , Kiehl Kent A.
Published: June 2011

Teenagers are often impulsive. In some cases this is a phase of normal development; in other cases impulsivity contributes to criminal behavior. Using functional magnetic resonance imaging, we examined resting-state functional connectivity among brain systems and behavioral measures of impulsivity in 107 juveniles incarcerated in a high-security facility. In less-impulsive juveniles and normal controls, motor planning regions were correlated with brain networks associated with spatial attention and executive control. In more-impulsive juveniles, these same regions correlated with the default-mode network, a constellation of brain areas associated with spontaneous, unconstrained, self-referential cognition. The strength of these brain–behavior relationships was sufficient to predict impulsivity scores at the individual level. Our data suggest that increased functional connectivity of motor-planning regions with networks subserving unconstrained, self-referential cognition, rather than those subserving executive control, heightens the predisposition to impulsive behavior in juvenile offenders. To further explore the relationship between impulsivity and neural development, we studied functional connectivity in the same motor-planning regions in 95 typically developing individuals across a wide age span. The change in functional connectivity with age mirrored that of impulsivity: younger subjects tended to exhibit functional connectivity similar to the more-impulsive incarcerated juveniles, whereas older subjects exhibited a less-impulsive pattern. This observation suggests that impulsivity in the offender population is a consequence of a delay in typical development, rather than a distinct abnormality.
Expression of a functional VEGFR-1 in tumor cells is a major determinant of anti-PlGF antibodies efficacy
Authors: Yao Jenny , Wu Xiumin , Zhuang Guanglei , Kasman Ian M. , Vogt Tobias , Phan Vernon , Shibuya Masabumi , Ferrara Napoleone , Bais Carlos
Published: June 2011

PlGF, one of the ligands for VEGFR-1, has been implicated in tumor angiogenesis. However, more recent studies indicate that genetic or pharmacological inhibition of PlGF signaling does not result in reduction of microvascular density in a variety of tumor models. Here we screened 12 human tumor cell lines and identified 3 that are growth inhibited by anti-PlGF antibodies in vivo. We found that efficacy of anti-PlGF treatment strongly correlates with VEGFR-1 expression in tumor cells, but not with antiangiogenesis. In addition, PlGF induced VEGFR-1 signaling and biological responses in tumor cell lines sensitive to anti-PlGF, but not in refractory tumor cell lines or in endothelial cells. Also, genetic ablation of VEGFR-1 signaling in the host did not affect the efficacy of PlGF blockade. Collectively, these findings suggest that the role of PlGF in tumorigenesis largely consists of promoting autocrine/paracrine growth of tumor cells expressing a functional VEGFR-1 rather than stimulation of angiogenesis.
Multiple mating and clutch size in invertebrate brooders versus pregnant vertebrates
Authors: Avise John C. , Tatarenkov Andrey , Liu Jin-Xian
Published: June 2011

We summarize the genetic literature on polygamy rates and sire numbers per clutch in invertebrate animals that brood their offspring and then compare findings with analogous data previously compiled for vertebrate species displaying viviparity or other pregnancy-like syndromes. As deduced from molecular parentage analyses of several thousand broods from more than 100 “pregnant” species, invertebrate brooders had significantly higher mean incidences of multiple mating than pregnant vertebrates, a finding generally consistent with the postulate that clutch size constrains successful mate numbers in species with extended parental care. However, we uncovered no significant correlation in invertebrates between brood size and genetically deduced rates of multiple mating by the incubating sex. Instead, in embryo-gestating animals otherwise as different as mammals and mollusks, polygamy rates and histograms of successful mates per brooder proved to be strikingly similar. Most previous studies have sought to understand why gestating parents have so many mates and such high incidences of successful multiple mating; an alternative perspective based on logistical constraints turns the issue on its head by asking why mate numbers and polygamy rates are much lower than they theoretically could be, given the parentage-resolving power of molecular markers and the huge sizes of many invertebrate broods.
B cell priming for extrafollicular antibody responses requires Bcl-6 expression by T cells
Authors: Lee Sau K. , Rigby Robert J. , Zotos Dimitra , Tsai Louis M. , Kawamoto Shimpei , Marshall Jennifer L. , Ramiscal Roybel R. , Chan Tyani D. , Gatto Dominique , Brink Robert , Yu Di , Fagarasan Sidonia , Tarlinton David M. , Cunningham Adam F. , Vinuesa Carola G.
Published: June 2011

T follicular helper cells (Tfh cells) localize to follicles where they provide growth and selection signals to mutated germinal center (GC) B cells, thus promoting their differentiation into high affinity long-lived plasma cells and memory B cells. T-dependent B cell differentiation also occurs extrafollicularly, giving rise to unmutated plasma cells that are important for early protection against microbial infections. Bcl-6 expression in T cells has been shown to be essential for the formation of Tfh cells and GC B cells, but little is known about its requirement in physiological extrafollicular antibody responses. We use several mouse models in which extrafollicular plasma cells can be unequivocally distinguished from those of GC origin, combined with antigen-specific T and B cells, to show that the absence of T cell–expressed Bcl-6 significantly reduces T-dependent extrafollicular antibody responses. Bcl-6+ T cells appear at the T–B border soon after T cell priming and before GC formation, and these cells express low amounts of PD-1. Their appearance precedes that of Bcl-6+ PD-1hi T cells, which are found within the GC. IL-21 acts early to promote both follicular and extrafollicular antibody responses. In conclusion, Bcl-6+ T cells are necessary at B cell priming to form extrafollicular antibody responses, and these pre-GC Tfh cells can be distinguished phenotypically from GC Tfh cells.
CIN85 drives B cell responses by linking BCR signals to the canonical NF-κB pathway
Authors: Kometani Kohei , Yamada Takayuki , Sasaki Yoshiteru , Yokosuka Tadashi , Saito Takashi , Rajewsky Klaus , Ishiai Masamichi , Hikida Masaki , Kurosaki Tomohiro
Published: June 2011

CIN85, an adaptor protein which binds the C-terminal domain of tyrosine phosphorylated Cbl and Cbl-b, has been thought to be involved in the internalization and subsequent degradation of receptors. However, its physiological function remains unclear. To determine its role in B cells, we used Mb1-cre to generate mice with a B cell–specific deletion of CIN85. These mice had impaired T cell–independent type II antibody responses in vivo and diminished IKK-β activation and cellular responses to B cell receptor (BCR) cross-linking in vitro. Introduction of a constitutively active IKK-β construct corrected the defective antibody responses as well as cellular responses in the mutant mice. Together, our results suggest that CIN85 links the BCR to IKK-β activation, thereby contributing to T cell–independent immune responses.
Ionic mechanisms and Ca2+ dynamics underlying the glucose response of pancreatic β cells: a simulation study
Authors: Cha Chae Young , Nakamura Yasuhiko , Himeno Yukiko , Wang JianWu , Fujimoto Shinpei , Inagaki Nobuya , Earm Yung E , Noma Akinori
Published: June 2011

To clarify the mechanisms underlying the pancreatic β-cell response to varying glucose concentrations ([G]), electrophysiological findings were integrated into a mathematical cell model. The Ca2+ dynamics of the endoplasmic reticulum (ER) were also improved. The model was validated by demonstrating quiescent potential, burst–interburst electrical events accompanied by Ca2+ transients, and continuous firing of action potentials over [G] ranges of 0–6, 7–18, and >19 mM, respectively. These responses to glucose were completely reversible. The action potential, input impedance, and Ca2+ transients were in good agreement with experimental measurements. The ionic mechanisms underlying the burst–interburst rhythm were investigated by lead potential analysis, which quantified the contributions of individual current components. This analysis demonstrated that slow potential changes during the interburst period were attributable to modifications of ion channels or transporters by intracellular ions and/or metabolites to different degrees depending on [G]. The predominant role of adenosine triphosphate–sensitive K+ current in switching on and off the repetitive firing of action potentials at 8 mM [G] was taken over at a higher [G] by Ca2+- or Na+-dependent currents, which were generated by the plasma membrane Ca2+ pump, Na+/K+ pump, Na+/Ca2+ exchanger, and TRPM channel. Accumulation and release of Ca2+ by the ER also had a strong influence on the slow electrical rhythm. We conclude that the present mathematical model is useful for quantifying the role of individual functional components in the whole cell responses based on experimental findings.
Spatially resolved simulation of a radio-frequency driven micro-atmospheric pressure plasma jet and its effluent
Authors: Hemke Torben , Wollny Alexander , Gebhardt Markus , Brinkmann Ralf Peter , Mussenbrock Thomas
Published: June 2011

Radio-frequency driven plasma jets are frequently employed as efficient plasma sources for surface modification and other processes at atmospheric pressure. The radio-frequency driven micro-atmospheric pressure plasma jet (μAPPJ) is a particular variant of that concept whose geometry allows direct optical access. In this work, the characteristics of the μAPPJ operated with a helium–oxygen mixture and its interaction with a helium environment are studied by numerical simulation. The density and temperature of the electrons, as well as the concentration of all reactive species are studied both in the jet itself and in its effluent. It is found that the effluent is essentially free of charge carriers but contains a substantial amount of activated oxygen (O, O3 and O2(1Δ)).

The simulation results are verified by comparison with experimental data.
A note on discreteness of 𝐹-jumping numbers
Authors: Schwede Karl
Published: June 2011

Suppose that

R
R

is a ring essentially of finite type over a perfect field of characteristic

p
>
0

p > 0

and that

a

⊆
R

\mathfrak {a} \subseteq R

is an ideal. We prove that the set of

F
F

-jumping numbers of

τ
b

(
R
;

a

t

)

\tau _b(R; \mathfrak {a}^t)

has no limit points under the assumption that

R
R

is normal and

Q

\mathbb {Q}

-Gorenstein – we make no assumption as to whether the

Q

\mathbb {Q}

-Gorenstein index is divisible by

p
p

. Furthermore, we also show that the

F
F

-jumping numbers of

τ
b

(
R
;
Δ
,

a

t

)

\tau _b(R; \Delta , \mathfrak {a}^t)

are discrete under the more general assumption that

K
R

+
Δ

K_R + \Delta

is

R

\mathbb {R}

-Cartier.
A uniform contraction principle for bounded Apollonian embeddings
Authors: Dubois Loïc , Rugh Hans
Published: June 2011

Let

H
^

=
H
∪
{
∞
}

\widehat {H}=H \cup \{\infty \}

denote the standard one-point completion of a real Hilbert space

H
H

. Given any non-trivial proper subset

U
⊂

H
^

U\subset \widehat {H}

one may define the so-called “Apollonian” metric

d
U

d_U

on

U
U

. When

U
⊂
V
⊂

H
^

U\subset V \subset \widehat {H}

are nested proper subsets we show that their associated Apollonian metrics satisfy the following uniform contraction principle: Let

Δ
=

d
i
a
m

V

(
U
)
∈
[
0
,
+
∞
]

\Delta =\mathrm {diam}_{V}(U) \in [0,+\infty ]

be the diameter of the smaller subsets with respect to the large. Then for every

x
,
y
∈
U

x,y\in U

we have
\[
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="d Subscript upper V Baseline left-parenthesis x comma y right-parenthesis less-than-or-equal-to hyperbolic tangent StartFraction normal upper Delta Over 4 EndFraction d Subscript upper U Baseline left-parenthesis x comma y right-parenthesis period">

d
V

(
x
,
y
)
≤
tanh
⁡

Δ
4

 
 

d
U

(
x
,
y
)
.

d_V(x,y) \leq \tanh \frac {\Delta }{4} \ \ d_U(x,y) .

\]
In dimension one, this contraction principle was established by Birkhoff [Bir57] for the Hilbert metric of finite segments on

R

P

1

{{\mathbb R}\textrm {P}}^1

. In dimension two it was shown by Dubois in [Dub09] for subsets of the Riemann sphere

C

^

∼

R

2

^

\widehat {\mathbb {C}}\sim \widehat {\mathbb {R}^2}

. It is new in the generality stated here.
Characterization of human invariant natural killer T cells expressing FoxP3
Authors: Engelmann Péter , Farkas Klára , Kis János , Richman Geoffrey , Zhang Zhaoyun , Liew Chong Wee , Borowiec Maciej , Niewczas Monika A. , Jalahej Heyam , Orbán Tihamér
Published: June 2011

Recently described forkhead box protein 3 (FoxP3) transcription factor is a key molecule in CD4+ CD25hi+ T-cell characterization. Invariant NK T (iNKT) cells are also characterized as regulatory cells modulating the immune response by rapidly producing Th1 and Th2 cytokines. We aimed to analyze cellular markers important in regulatory features of human iNKT cells and to study their role in functional assays. iNKT cells were single cell sorted from peripheral mononuclear cells of healthy individuals after immunostaining of invariant TCR α-chain. We found FoxP3 expression in human iNKT clones. Randomly selected iNKT cell clones (CD4+, double negative, CD8+) expressed FoxP3 mRNA and protein at different levels upon stimulation as supported by various approaches. FoxP3 mRNA and protein expression was detected in unstimulated iNKT cells as well. Furthermore, different stimulations changed the FoxP3 expression in iNKT cells over time and the most dramatic changes were observed upon anti-CD3 stimulation. Both the supernatant of iNKT cells and iNKT cells themselves exerted similar stimulation effects on PBMC proliferation in functional assays and these stimulations showed a negative correlation with FoxP3 expression. Our data indicate that the FoxP3 expression in iNKT cells may be a key transcriptional factor in controlling the regulatory function of the iNKT cells.
Research design
Authors: Peacock Janet L. , Peacock Philip J.
Published: June 2011

Introduction 2

Introduction to research 3

Research questions 4

Interventional studies 6

Randomized controlled trials 8

Randomization in RCTs 10

Patient consent in research studies 12

Blinding in RCTs 14

RCTs: parallel groups and crossover designs 16

Zelen randomized consent design 18

Superiority and equivalence trials ...
Collecting data
Authors: Peacock Janet L. , Peacock Philip J.
Published: June 2011

Data collection forms 76

Form filling and coding 78

Examples of questions with possible coding 80

Data quality 81

Questions and questionnaires 82

Designing good questions 84

Sensitive topics 86

Designing questionnaires 88

Example of a validated questionnaire 90

Designing a new measurement tool: psychometrics ...
Handling data: what steps are important
Authors: Peacock Janet L. , Peacock Philip J.
Published: June 2011

Data entry 102

Forms which can be automatically scanned for data entry 106

Variable names and labels 108

Joining datasets 110

Joining datasets: examples 112

Storing and transporting data 114

Data checking and errors 116

Data checking: examples 118

Formal data monitoring 122

Statistical issues in data monitoring ...
Choosing and using statistical software for analysing data
Authors: Peacock Janet L. , Peacock Philip J.
Published: June 2011

Statistical software packages 156

Choosing a package 158

Using a package 160

Examples of using statistical packages 162

Using spreadsheets for analysis 166

Transferring data between packages 168

Common packages 170

In this chapter we will describe the main features of statistics packages, what they do, and what they do not do. We will describe how we as users interact with packages, how we transfer data between packages, and how to decide which package to use. There are many statistical analysis computer packages and programs on the market and this chapter will not provide a review of what is available. Instead we will discuss the main issues that drive the choice of package to use. To illustrate, we will briefly describe a few packages that we know well....
Summarizing data
Authors: Peacock Janet L. , Peacock Philip J.
Published: June 2011

Why summarize data? 174

Types of data 176

Quantitative data 178

Categorical data 180

Summarizing quantitative data 182

Calculation of mean, SD 184

Calculation of median, interquartile range 186

Geometric mean, harmonic mean, mode 188

Choosing a summary measure for quantitative data 190

Summarizing categorical data ...
Statistical tests
Authors: Peacock Janet L. , Peacock Philip J.
Published: June 2011

Introduction 238

Samples and populations 240

Confidence interval for a mean 242

95% confidence interval for a proportion 244

Tests of statistical significance 246

P values 248

Statistical significance and clinical significance 250

t test for two independent means 252

t test for two independent means: example ...
Diagnostic studies
Authors: Peacock Janet L. , Peacock Philip J.
Published: June 2011

Sensitivity and specificity 340

Calculations for sensitivity and specificity 342

Effect of prevalence 344

Likelihood ratio, pre-test odds, post-test odds 346

Receiver operating characteristic (ROC) curves 348

Links to other statistics 350

In this chapter we describe how statistical methods are used in diagnostic testing to obtain different measures of a test’s performance. We describe how to calculate sensitivity, specificity, and positive and negative predictive values, and show the relevance of pre- and post-test odds and likelihood ratio in evaluating a test in a clinical situation. We also describe the receiver operating characteristic curve and show how this links with logistic regression analysis. All methods are illustrated with examples....
Other statistical methods
Authors: Peacock Janet L. , Peacock Philip J.
Published: June 2011

Kappa for inter-rater agreement 354

Extensions to kappa 358

Bland–Altman method to measure agreement 360

Chi-squared goodness of fit test 364

Number needed to treat 366

Life tables 370

Direct standardization 372

Indirect standardization 374

In this chapter we describe several individual statistical methods that do not fit neatly in the other chapters but which are commonly used in medical research. These include methods used to assess agreement in measurement and reliability studies, the number needed to treat as a measure of efficacy in a trial, and life tables. All methods are illustrated with examples....
Bayesian statistics
Authors: Peacock Janet L. , Peacock Philip J.
Published: June 2011

Bayesian statistics 478

How Bayesian methods work 480

Prior distributions 482

Likelihood; posterior distributions 484

Summarizing and presenting results 486

Using Bayesian analyses in medicine 488

Software for Bayesian statistics 492

Reading Bayesian analyses in papers 494

Bayesian methods: a summary 496

In this chapter we describe the Bayesian approach to statistical analysis in contrast to the frequentist approach. We describe how Bayesian methods work including a description of prior and posterior distributions. We outline the role and choice of prior distributions and how they are combined with the data collected to provide an updated estimate of the unknown quantity being studied. We include examples of the use of Bayesian methods in medicine, and discuss the pros and cons of the Bayesian approach compared with the frequentist approach Finally, we give guidance on how to read and interpret Bayesian analyses in the medical literature....
Glossary of terms
Authors: Peacock Janet L. , Peacock Philip J.
Published: June 2011

Analysis of variance See One-way analysis of variance (p. 280) and Two-way analysis of variance (p. 412)

Bayes’s theorem A formula that allows the reversal of conditional probabilities (see Bayes’ theorem, p. 234)

Bayesian statistics A statistical approach based on Bayes’ theorem, where prior information or beliefs are combined with new data to provide estimates of unknown parameters (see ...
Charles Gavan Duffy's Ministerial Tour: Oratory, Electioneering and the Meaning of Colonial Democracy*
Authors: Scalmer Sean
Published: June 2011

During 1871 and 1872 the Victorian Premier, Charles Gavan Duffy, led his minsters on a banqueting tour of the colony during which he made a series of speeches in defence of his Government. Little noticed since but controversial at the time, Duffy's tour called into question the centrality of parliament and the meaning of colonial democracy. Earlier interpretations, derived from the study of colonial New South Wales, paint Australian politics in this period as ideologically somnolent and unprincipled. Yet Duffy's tour and the associated hullabaloo reveal the intellectual vitality and vigour of democracy's brash antipodean form. Its significance has been overlooked by historians. However Duffy's oratory tour was undertaken almost a decade before Gladstone's 1879 apparently pioneering Midlothian campaign, and the electioneering practices he initiated in the early 1870s shaped elections in the years that followed.
Protestantism and Social Liberalism in Imperial Germany: Gustav Adolf Deissmann (1866–1937) and Friedrich Naumann (1860–1919)*
Authors: Gerber Albrecht
Published: June 2011

Adolf Deissmann was an internationally prominent German theologian, celebrated primarily for his groundbreaking contributions in the widely divergent fields of post‐classical Greek philology, lexicography, the archaeological excavations of Ephesus, international conciliation and leading role in the nascent ecumenical movement. Less known — yet of considerable consequence — is his involvement with social liberal politics, especially his friendship with, and staunch backing of, Friedrich Naumann, a onetime Protestant pastor turned liberal career politician, pioneer of European integration and, ultimately, the first president of the German Democratic Party. This paper investigates to what degree these two men were intellectually indebted to each other in their mutual search to find a way forward to reconcile Germany's sharply divided class‐society through Protestant‐based social politics — and that in an era deeply troubled with seemingly insoluble conflicts over the form of the future German Reich.
Discredited Fascism: the New Guard after 1932*
Authors: Moore Andrew
Published: June 2011

In large part Australian interwar fascism has been studied in isolation. The present article compares and contrasts the New Guard with kindred movements in Europe during the 1930s. Using the conceptual model of “generic fascism” developed by Roger Griffin, its principal concern is to explain why, in the “era of fascism”, with many factors encouraging the growth of authoritarian movements to replace parliamentary democracy, the New Guard proved to be so manifestly unsuccessful.
Fault, Gender Politics and Family Law Reform
Authors: Swain Shurlee , Thornton Danielle
Published: June 2011

Recent public debates about family law reform have revealed both support for and criticism of legislative policies that seek to shape social norms. Amidst this debate was a suggestion from some quarters that the Whitlam Government's removal of fault‐based divorce is responsible for the gendered tensions that characterise modern reform debates. This article draws on archival records and interviews conducted with family law professionals who worked in the system in the 1970s and experienced the transition to the no‐fault system, to explore the principles underlying the introduction of the Family Law Act of 1975 and to identify the sources of continuing dissension about its impact.
Legitimacy, Democracy and Rights: the Conservatism of Janet Albrechtsen
Authors: Porter Eric
Published: June 2011

In recent years, media columnists have been instrumental in redefining Australian conservatism. One of the most prominent is Janet Albrechtsen. Using her critique of a bill of rights, this article examines how this new Australian conservatism rejects or reverses core elements of traditional conservatism. Utilitarianism exchanges the transcendent for the social. Equality and democracy replace elitism. Elites were minorities, albeit ones with leadership virtue. Now minorities of any sort threaten equality and undermine democracy. These changes reflect broader changes in society itself. In this sense, conservatism has made peace with modernity, hostility to which originally prompted its birth. Now the enemy is internationalism or postmodernity, the two often interchangeable. Albrechtsen's hostility to a bill of rights matches her rejection of international law and institutions that threaten the nation‐state and its guarantee of democracy and the rule of law.
Integrating Agriculture and Biodiversity Management: Between Green Legitimisation and Knowledge Production
Authors: Granjou Céline
Published: June 2011

This article analyses the impact of a local breed restoration project on biodiversity management policy within an alpine area (Les Bauges, France). At the present time, this region is witnessing the rebranding of breeding practices as an activity that is an environmental problem in terms of objectives to restore for wildlife to that of a solution permitting the open management of these alpine areas. The success of this ‘greening’ re‐legitimisation process can be linked to the specific local agricultural development context. However, this text seeks to go beyond an interpretation that focuses solely on the strength of the agricultural lobby to show that the involvement of both agricultural and environmental actors in the restoration of pastoral farming in scrublands creates both knowledge and knowledge practice, specifically with respect to the emerging relationship between stock animals and grassland biodiversity.
Serum homocysteine and physical exercise in patients with Parkinson's disease
Authors: NASCIMENTO Carla Manuela Crispim , STELLA Florindo , GARLIPP Célia Regina , SANTOS Ruth Ferreira , GOBBI Sebastião , GOBBI Lilian Teresa Bucken
Published: June 2011

Background:  Hyperhomocysteinemia is a major risk factor for cerebral and peripheral vascular diseases, as well as cortical and hippocampal injury, including an increased risk of dementia and cognitive impairment. Elevated serum homocysteine (Hcy) concentrations are common in patients with Parkinson's disease (PD) who have been treated with levodopa; however, physical exercises can help reduce Hcy concentrations. The aim of the present study was to compare serum Hcy levels in patients with PD who partook in regular physical exercises, sedentary PD patients, and healthy controls.

Methods:  Sixty individuals were enrolled in the present study across three groups: (i) 17 patients who did not partake of any type of exercise; (ii) 24 PD patients who exercised regularly; and (iii) 19 healthy individuals who did not exercise regularly. All participants were evaluated by Hoehn and Yahr scale, the Unified Parkinson’s Disease Rating Scale (UPDRS) and Schwab and England scale (measure daily functionality). The serum levels of Hcy were analyzed by blood samples collected of each participant. An analysis of variance and a Tukey’s post hoc test were applied to compare and to verify differences between groups. Pearson’s correlation and stepwise multiple regression analyses were used to consider the association between several variables.

Results:  Mean plasma Hcy concentrations in individuals who exercised regularly were similar to those in the healthy controls and significantly lower than those in the group that did not exercise at all (P= 0.000). In addition, patients who did not exercise were receiving significantly higher doses of levodopa than those patients who exercised regularly (P= 0.001). A positive relationship between levodopa dose and Hcy concentrations (R2= 0.27; P= 0.03) was observed in patients who did not exercise, but not in those patients who exercised regularly (R2= 0.023; P= 0.15).

Conclusions:  The results of the present study suggest that, even with regular levodopa therapy, Hcy concentrations in PD patients who exercise regularly are significantly lower than in patients who do not exercise and are similar Hcy concentrations in healthy controls.
Creutzfeldt–Jakob disease
Authors: GENÇER Ali Görkem , PELIN Zerrin , KÜÇÜKALI Cem İsmail , TOPÇUOĞLU Özgür Bilgin , YILMAZ Nuriye
Published: June 2011

Creutzfeldt–Jakob disease (CJD) is a progressive, degenerative, and fatal disease of the central nervous system. It is caused by abnormal accumulation of prion proteins and is characterized mainly by progressive dementia, myoclonus, and cerebellar, pyramidal, and extrapyramidal findings. Psychiatric symptoms may also accompany CJD and are often the first signs of the disease. The incidence of CJD is approximately 1 in 1 000 000. In certain cases, a diagnosis can be made by demonstrating the accumulation of pathological prion proteins. However, in many cultures brain biopsies or post‐mortem evaluations are not welcomed by either the patients or their relatives. In these cases, the importance of additional diagnostic tools increases. Herein, we report on a CJD patient who first consulted a psychiatrist with early psychiatric symptoms. The patient developed neurological symptoms later and was subsequently diagnosed as sporadic CJD based on clinical and laboratory findings rather than brain biopsy. Repeated electroencephalograms (EEG) played a pivotal role in our evaluation of the patient. This case is an interesting presentation of CJD both because of the timing of the symptoms and because of the typical EEG findings that led to the diagnosis.
A CTSA Agenda to Advance Methods for Comparative Effectiveness Research
Authors: Helfand Mark , Tunis Sean , Whitlock Evelyn P. , Pauker Stephen G. , Basu Anirban , Chilingerian Jon , Harrell Jr. Frank E. , Meltzer David O. , Montori Victor M. , Shepard Donald S. , Kent David M. ,   The Methods Work Group of the National CTSA Strategic Goal Committee on Comparative Effectiveness Research
Published: June 2011

Clinical research needs to be more useful to patients, clinicians, and other decision makers. To meet this need, more research should focus on patient‐centered outcomes, compare viable alternatives, and be responsive to individual patients’ preferences, needs, pathobiology, settings, and values. These features, which make comparative effectiveness research (CER) fundamentally patient‐centered, challenge researchers to adopt or develop methods that improve the timeliness, relevance, and practical application of clinical studies.

In this paper, we describe 10 priority areas that address 3 critical needs for research on patient‐centered outcomes (PCOR): (1) developing and testing trustworthy methods to identify and prioritize important questions for research; (2) improving the design, conduct, and analysis of clinical research studies; and (3) linking the process and outcomes of actual practice to priorities for research on patient‐centered outcomes. We argue that the National Institutes of Health, through its clinical and translational research program, should accelerate the development and refinement of methods for CER by linking a program of methods research to the broader portfolio of large, prospective clinical and health system studies it supports. Insights generated by this work should be of enormous value to PCORI and to the broad range of organizations that will be funding and implementing CER. Clin Trans Sci 2011; Volume 4: 188–198
Association of TCF7L2 Allelic Variations with Gastric Function, Satiation, and GLP‐1 Levels
Authors: Vazquez‐Roque Maria I. , Camilleri Michael , Vella Adrian , Carlson Paula , Laugen Jeanette , Zinsmeister Alan R.
Published: June 2011

Objective: Genetic variation in transcription factor 7‐like 2 (TCF7L2), a regulator of proglucagon processing, is reproducibly associated with type 2 diabetes. GLP‐1 alters gastric function and increases satiation.

Hypothesis: Genetic variation in TCF7L2 is associated with satiation, gastric motor function, and GLP‐1 concentrations.

Methods: In 62 adults, a single nucleotide polymorphism (SNP) of TCF7L2 (rs7903146) was genotyped and associations with gastric emptying (GE) of solids and liquids, gastric volume (GV), and satiation (maximum tolerated volume and symptoms after nutrient drink test) were explored using a dominant genetic model, with gender and BMI as covariates. In 50 of the participants, we also measured plasma GLP‐1 during fasting and after ingestion of a nutrient drink.

Results: Presence of the T allele compared to CC genotype in rs7903146 SNP of the TCF7L2 gene was associated with reduced fasting GV (246.3 ± 11.4 mL for CC group, compared to 215.7 ± 11.4 mL for CT/TT group, p= 0.05) and accelerated GE t1/2 of liquids (26.3 ± 2.0 minutes for CC compared to 17.7 ± 1.4 for CT/TT, p < 0.005). There was no significant association of rs7903146 SNP with GE of solids, gastric accommodation, satiation, fasting, or postprandial GLP‐1.

Conclusion: Our data suggest TCF7L2 is associated with altered gastric functions that may predispose to obesity. Clin Trans Sci 2011; Volume 4: 183–187
Community Conceptualizations of Health: Implications for Transdisciplinary Team Science
Authors: Martinez Linda S. , Rubin Carolyn L. , Russell Beverley , Leslie Laurel K. , Brugge Doug
Published: June 2011

Objective: This exploratory study set out to identify how communities in the Tufts University Clinical Translational Science Institute (CTSI) catchment area define health‐related research priority areas.

Methods: Three focus groups comprising community stakeholders were conducted in three communities. Participants were representatives from community‐based organizations and health centers. A systematic content analysis was performed that involved the identification, labeling, and categorization of data followed by thematic analysis.

Results: Participant conceptualizations of health and health priorities were not formulated in the context of specific disease conditions, such as diabetes, obesity, cardiovascular disease, or asthma. Instead, participants described contextual factors including social, environmental, economic, and political conditions that influence health and health behavior.

Conclusions: Respondents in the Tufts University CTSI catchment area, like many diverse urban communities, described multiple interconnected social determinants of health and well‐being. As such, they were interested in research that focuses on “upstream” areas of intervention as opposed to disease prevention at the individual level. In addition, respondents were interested in research that would catalyze community change. Clin Trans Sci 2011; Volume 4: 163–167
Complement Proteins C3 and C4 Bind to Collagen and Elastin in the Vascular Wall: A Potential Role in Vascular Stiffness and Atherosclerosis
Authors: Shields Kelly J. , Stolz Donna , Watkins Simon C. , Ahearn Joseph M.
Published: June 2011

Circulating inflammatory mediators including complement activation products participate in the pathogenesis of cardiovascular diseases. As such, previous reports demonstrating the presence of complement proteins within atherosclerotic plaque and on the luminal surface would be anticipated. In contrast, we have recently made the unexpected observation that complement proteins also deposit along the external elastic lamina of mouse aortas in the absence of luminal deposition or plaque development. This suggests that complement activation may play a critical role in the pathogenesis of vascular stiffness and atherosclerosis through a mechanism initiated within the adventitia rather than on the endothelial surface. This hypothesis was tested in the current study by ultrastructural identification of the C3‐ and C4‐binding targets within the adventitia of the mouse aorta. The results demonstrate extensive binding of C3 and C4 to both collagen and elastin fibers within the adventitia in both ApoE(−/−) and C57Bl/6J control mice, as well as the presence of C3 and C4 within perivascular adipose tissue. These observations suggest a potential “outside‐in” mechanism of vascular stiffness during which perivascular adipose may produce C3 and C4 that bind to collagen and elastin fibers within the adventitia through covalent thiolester bonds, leading to increased vascular stiffness. Clin Trans Sci 2011; Volume 4: 146–152
The Tobin Tax: A Review of the Evidence
Authors: McCulloch Neil , Pacillo Grazia
Published: June 2011

The debate about the Tobin tax, and other financial transaction taxes (FTTs), gives rise to strong views both for and against. Unfortunately, little of the popular debate refers to the now considerable body of evidence about the impact of such taxes. This review attempts to synthesise what we know from the available theoretical and empirical literature about the impact of FTTs on volatility in financial markets. We also review the literature on how a Tobin tax might be implemented, the amount of revenue that it might realistically produce, and the likely incidence of the tax. We conclude that, contrary to what is often assumed, a Tobin tax is feasible and, if appropriately designed, could make a significant contribution to revenue without causing major distortions. However, it would be unlikely to reduce market volatility and could even increase it.