bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular footprints of a germinal center derivation of human IgM+(IgD+)CD27+ B cells and the dynamics of memory B cell generation
Authors: Seifert Marc , Küppers Ralf
Published: November 2009

The origin of IgM+CD27+ B lymphocytes with mutated IgV genes, which account for ∼20% of human peripheral blood (PB) B cells, is controversially discussed. A generation in a primary diversification pathway, in T cell–independent immune responses, or in T cell–dependent germinal center (GC) reactions has been proposed. We show here that IgM+IgD+CD27+ and IgM+IgD−/lowCD27+ B cell subsets carry, like class-switched memory B cells, mutations in the Bcl6 gene as a genetic trait of a GC experience. Moreover, the identification of PB IgM+IgD+CD27+ B cells clonally related to GC-derived IgG+ memory B cells with shared and distinct IgV gene mutations demonstrates the GC origin also of the former subset. These findings provide genetic evidence for a GC derivation of somatically mutated IgM+ B cells and indicate that adult humans harbor a large population of IgM+IgD+ post-GC memory B cells. Furthermore, the analysis revealed that a highly diverse and often very large population of memory B cells is generated from a given GC B cell clone, and that (preferentially IgM) memory B cells are generated already early in the GC reaction. This provides novel insights into the dynamics of GC reactions and the generation of a memory B cell repertoire.
Differential requirement of MALT1 for BAFF-induced outcomes in B cell subsets
Authors: Tusche Michael W. , Ward Lesley A. , Vu Frances , McCarthy Doug , Quintela-Fandino Miguel , Ruland Jurgen , Gommerman Jennifer L. , Mak Tak W.
Published: November 2009

B cell activation factor of the TNF family (BAFF) activates noncanonical nuclear factor κB (NF-κB) heterodimers that promote B cell survival. We show that although MALT1 is largely dispensable for canonical NF-κB signaling downstream of the B cell receptor, the absence of MALT1 results in impaired BAFF-induced phosphorylation of NF-κB2 (p100), p100 degradation, and RelB nuclear translocation in B220+ B cells. This corresponds with impaired survival of MALT1−/− marginal zone (MZ) but not follicular B cells in response to BAFF stimulation in vitro. MALT1−/− MZ B cells also express higher amounts of TRAF3, a known negative regulator of BAFF receptor–mediated signaling, and TRAF3 was found to interact with MALT1. Furthermore, phenotypes associated with overexpression of BAFF, including increased MZ B cell numbers, elevated serum immunoglobulin titers, and spontaneous germinal center formation, were found to be dependent on B cell–intrinsic MALT1 expression. Our results demonstrate a novel role for MALT1 in biological outcomes induced by BAFF-mediated signal transduction.
Topological Hochschild homology of twisted group algebras
Authors: Vera Daniel
Published: November 2009

We show that the topological Hochschild homology spectrum of a twisted group algebra

THH
⁡
(

A

τ

[
G
]
)

\operatorname {THH}(A^{\tau }[G])

is the Thom spectrum associated with a parametrized orthogonal spectrum

E
(
A
,
G
)

E(A,G)

. We then analyze the structure of the parametrized orthogonal spectrum

E
(
A
,
G
)

E(A,G)

and show that it is locally trivial.
Snowballs are quasiballs
Authors: Meyer Daniel
Published: November 2009

We introduce snowballs, which are compact sets in

R

3

\mathbb {R}^3

homeomorphic to the unit ball. They are

3
3

-dimensional analogs of domains in the plane bounded by snowflake curves. For each snowball

B

\mathcal {B}

a quasiconformal map

f
:

R

3

→

R

3

f\colon \mathbb {R}^3\to \mathbb {R}^3

is constructed that maps

B

\mathcal {B}

to the unit ball.
The Leech lattice Λ and the Conway group ⋅𝑂 revisited
Authors: Bray John , Curtis Robert
Published: November 2009

We give a new, concise definition of the Conway group

⋅

O

\cdot \mathrm {O}

as follows. The Mathieu group

M

24

\mathrm {M}_{24}

acts quintuply transitively on 24 letters and so acts transitively (but imprimitively) on the set of

(

24

4

)

\left ({24}\atop {4} \right )

tetrads. We use this action to define a progenitor

P
P

of shape

2

⋆

(

24
4

)

:

M

24

2^{\star \left ( 24 \atop 4 \right )}:\mathrm {M}_{24}

; that is, a free product of cyclic groups of order 2 extended by a group of permutations of the involutory generators. A simple lemma leads us directly to an easily described, short relator, and factoring

P
P

by this relator results in

⋅

O

\cdot \mathrm {O}

. Consideration of the lowest dimension in which

⋅

O

\cdot \mathrm {O}

can act faithfully produces Conway’s elements

ξ
T

\xi _T

and the 24–dimensional real, orthogonal representation. The Leech lattice is obtained as the set of images under

⋅

O

\cdot \mathrm {O}

of the integral vectors in

R

24

{\mathbb R}_{24}

.
Mixed boundary value problems for the Stokes system
Authors: Brown R. , Mitrea I. , Mitrea M. , Wright M.
Published: November 2009

We prove the well-posedness of the mixed problem for the Stokes system in a class of Lipschitz domains inRn{\mathbb {R}}^n,n≥3n\geq 3. The strategy is to reduce the original problem to a boundary integral equation, and we establish certain new Rellich-type estimates which imply that the intervening boundary integral operator is semi-Fredholm. We then prove that its index is zero by performing a homotopic deformation of it onto an operator related to the Lamé system, which has recently been shown to be invertible.
A new approach to classification of integral quadratic forms over dyadic local fields
Authors: Beli Constantin
Published: November 2009

In 1963, O’Meara solved the classification problem for lattices over dyadic local fields in terms of Jordan decompositions. In this paper we translate his result in terms of good BONGs. BONGs (bases of norm generators) were introduced in 2003 as a new way of describing lattices over dyadic local fields. This result and the notions we introduce here are a first step towards a solution of the more difficult problem of representations of lattices over dyadic fields.
Siegel metric and curvature of the moduli space of curves
Authors: Colombo Elisabetta , Frediani Paola
Published: November 2009

We study the curvature of the moduli space

M
g

{M_g}

of curves of genus

g
g

with the Siegel metric induced by the period map

j
:

M
g

→

A
g

j:{ M_g}\rightarrow {A_g}

. We give an explicit formula for the holomorphic sectional curvature of

M
g

{M_g}

along a Schiffer variation

ξ
P

\xi _P

, for

P
P

a point on the curve

X
X

, in terms of the holomorphic sectional curvature of

A
g

{A_g}

and the second Gaussian map. Finally we extend the Kähler form of the Siegel metric as a closed current on

M
¯

g

\overline {M}_g

and we determine its cohomology class as a multiple of

λ
\lambda

.
Varieties with few subalgebras of powers
Authors: Berman Joel , Idziak Paweł , Marković Petar , McKenzie Ralph , Valeriote Matthew , Willard Ross
Published: November 2009

The Constraint Satisfaction Problem Dichotomy Conjecture of Feder and Vardi (1999) has in the last 10 years been profitably reformulated as a conjecture about the set

S
P

fin

(

A

)

\sf {SP}_\textsf {fin}(\mathbf {A})

of subalgebras of finite Cartesian powers of a finite universal algebra

A

\mathbf {A}

. One particular strategy, advanced by Dalmau in his doctoral thesis (2000), has confirmed the conjecture for a certain class of finite algebras

A

\mathbf {A}

which, among other things, have the property that the number of subalgebras of

A

n

\mathbf {A}^n

is bounded by an exponential polynomial. In this paper we characterize the finite algebras

A

\mathbf {A}

with this property, which we call having few subpowers, and develop a representation theory for the subpowers of algebras having few subpowers. Our characterization shows that algebras having few subpowers are the finite members of a newly discovered and surprisingly robust Maltsev class defined by the existence of a special term we call an edge term. We also prove some tight connections between the asymptotic behavior of the number of subalgebras of

A

n

\mathbf {A}^n

and some related functions on the one hand, and some standard algebraic properties of

A

\mathbf {A}

on the other hand. The theory developed here was applied to the Constraint Satisfaction Problem Dichotomy Conjecture, completing Dalmau’s strategy.
Write to Learn: Reflective Practice Writing
Authors: Bolton Gillie
Published: November 2009

Reflection is an attitude which makes the difference between 20 years of experience or only 1 year of experience repeated 20 times. Reflection is a state of mind, an ongoing constituent of practice, not a technique or curriculum element. It is a way of learning from one's own experience to inform practice, widen perspectives and challenge assumptions, taken-for-granteds and damaging social and cultural biases and a way of learning from the experience of others.
A Case of Faulty Machinery?
Authors: Simon Chantal
Published: November 2009

Mr B is a 56-year-old Caucasian businessman who is usually very fit and well. He has long-standing hypertension and takes atenolol 50 mg daily, ramipril 10 mg daily and simvastatin 40 mg nocte. He has no other past medical history of note.
Endocarditis
Authors: Bhat Nanda
Published: November 2009

Endocarditis is the inflammation of the endocardium (the inner lining) of the myocardium and the heart valves. Endocarditis is a rare condition and is most commonly infective, resulting in significant mortality and morbidity from both intracardiac and systemic effects. Endocarditis occasionally presents as an acute and fulminating disease, but more often, it presents insidiously. The term ‘infective endocarditis’ (IE) is now preferred to the previously used ‘bacterial endocarditis’ as not all the infecting organisms are bacterial.
Hypercalcaemia
Authors: Waters Marie
Published: November 2009

Hypercalcaemia has an incidence of approximately 1 in 500 in the community. It is most commonly caused by malignancy or hyperparathyroidism (90% of cases). Severe hypercalcaemia can be a medical emergency requiring hospital admission. This article covers the management of the common causes, gives a brief overview of the rare causes and provides a strategy with which to investigate hypercalcaemia of unknown aetiology.
Management of Hypertension
Authors: Bond Ruth
Published: November 2009

High blood pressure (BP) is associated with an increased risk of stroke, coronary heart disease (CHD), heart failure and also an accelerated decline in both cognitive and renal function. As BP increases, so does the likelihood of these complications. In the UK, hypertension still remains undiagnosed and under treated with less than half of treated hypertensives having optimally controlled BP. A reduction of BP by an average of 12 mmHg systolic and 6 mmHg diastolic can be expected to reduce stroke by 40% and CHD by 20% (relative risk reduction).
Treatment of Type 2 Diabetes
Authors: Gadsby Roger
Published: November 2009

The prevalence of type 2 diabetes is rising rapidly in the UK, and most practices will now have around 4% of their registered population living with diabetes. The care of people with diabetes has in the last 20 years moved from being a largely hospital-based activity to one largely carried out in primary care ( Gadsby, 2009 ). The Quality and Outcomes Framework of the new GP contract introduced in 2004 has provided encouragement and incentive for primary care to take on this work. All GPs and doctors training to become GPs therefore need to have an understanding of up to date diabetes management.
Hydroxyurea upregulates NKG2D ligand expression in myeloid leukemia cells synergistically with valproic acid and potentially enhances susceptibility of leukemic cells to natural killer cell‐mediated cytolysis
Authors: Lu Xuzhang , Ohata Kinya , Kondo Yukio , Luis Espinoza J. , Qi Zhirong , Nakao Shinji
Published: November 2009

(Cancer Sci 2010; 101: 609–615)

Valproic acid (VPA), a histone deacetylase inhibitor, upregulates NKG2D ligands (NKG2DLs) on some monocytic and lymphoid leukemic cells. However, its effect on myeloid leukemia cells and synergistic agents that can augment the effect of VPA remains unknown. Of the various myeloid cell lines examined, OUN‐1, a chronic myelogenous leukemia cell line, showed the most prominent upregulation of MICA/B and ULBP2 in response to VPA. The NKG2DL upregulation was observed only in leukemic cells without apoptosis and the effect was abrogated by pretreatment of cells with caffeine, an inhibitor of ATM/ATR. Several activators of ATM/ATR were screened for their effect on NKG2DL expression, but only hydroxyurea (HU) efficiently upregulated both MICA/B and ULPB2 expression on the cell line. VPA and HU synergistically upregulated the NKG2DLs on OUN‐1 cells as well as primary leukemic cells from some patients with acute myeloid leukemia. The upregulation of NKG2DLs by VPA and/or HU was associated with increased transcription of each NKG2DL gene. OUN‐1 cells treated with VPA + HU were more susceptible to killing by natural killer (NK) cells than untreated cells and the enhanced cytotoxicity of NK cells was blocked by the treatment of NK cells with anti‐NKG2D monoclonal antibodies. The same concentrations of VPA and HU did not affect the cytotoxicity of NK cells against OUN‐1 cells. These data suggest that VPA and HU might enhance the NK cell‐mediated antileukemia effect by increasing the susceptibility of myeloid leukemic cells to NK cells.
Cellular context‐dependent “colors” of transforming growth factor‐β signaling
Authors: Ikushima Hiroaki , Miyazono Kohei
Published: November 2009

Transforming growth factor (TGF)‐β signaling has interesting characteristics in the context of cancer. Although perturbations of TGF‐β signaling are strongly implicated in cancer progression, TGF‐β signaling has both tumor‐suppressive and tumor‐promoting effects. For example, TGF‐β inhibits cancer cell proliferation in some cellular contexts, but promotes it in others. Although several approaches to treating cancer have been considered using TGF‐β‐based therapeutic strategies, the contradictory behaviors of TGF‐β have made these approaches complex. To put them to practical use, either the tumor‐suppressive or tumor‐promoting arm needs to be specifically manipulated. However, there is virtually no method to specifically regulate a certain cell response induced by TGF‐β. In this review, we first consider the basic machinery of TGF‐β signaling, and describe several cell responses induced by TGF‐β stimulation in specific contexts. Mechanisms by which TGF‐β can induce several responses in a cellular context‐dependent fashion are discussed with established paradigms and models. We also address perspectives on the specific control of only a subset of numerous cell responses induced by TGF‐β stimulation. Such methods will aid specific regulation of either the tumor‐suppressive or tumor‐promoting arm of the TGF‐β pathway and in realization of TGF‐β‐based treatment of malignant tumors. (Cancer Sci 2010; 101: 306–312)
Pattern recognition receptors of innate immunity and their application to tumor immunotherapy
Authors: Seya Tsukasa , Shime Hiroaki , Ebihara Takashi , Oshiumi Hiroyuki , Matsumoto Misako
Published: November 2009

Dendritic cells (DC) begin maturation in response to complex stimuli consisting of antigens and pattern molecules (PAMP) for the activation of the immune system. Immune adjuvant usually contains PAMP. Infection represents one event that is capable of inducing such a complex set of stimuli. Recently, DC were subdivided into a number of subsets with distinct cell‐surface markers, with each subset displaying unique differential maturation in response to pattern molecules to induce various types of effector cells. In the present study, we review how pattern recognition molecules and adaptors in each DC subset drive immune effector cells and their effect in the stimulated DC. Although tumor cells harbor tumor‐associated antigens, they usually lack PAMP. Hence, we outline the properties of exogenously‐added PAMP in the modulation of raising tumor immunity. In addition, we describe the mechanism by which DC‐dependent natural killer activation is triggered for the induction of antitumor immunity. (Cancer Sci 2010; 101: 313–320)
Ethnic differences in drinking outcomes following a brief alcohol intervention in the trauma care setting
Authors: Field Craig A. , Caetano Raul , Harris T. R. , Frankowski Ralph , Roudsari Bahman
Published: November 2009

Background  Evidence suggests that brief interventions in the trauma care setting reduce drinking, subsequent injury and driving under the influence (DUI) arrest. However, evidence on the effectiveness of these interventions in ethnic minority groups is lacking. The current study evaluates the efficacy of brief intervention among whites, blacks and Hispanics in the United States.

Methods  We conducted a two‐group parallel randomized trial comparing brief motivational intervention (BMI) and treatment as usual with assessment (TAU+) to evaluate treatment differences in drinking patterns by ethnicity. Patients were recruited from a level 1 urban trauma center over a 2‐year period. The study included 1493 trauma patients, including 668 whites, 288 blacks and 537 Hispanics. Hierarchical linear modeling was used to evaluate ethnic differences in drinking outcomes including volume per week, maximum amount consumed in 1 day, percentage days abstinent and percentage days heavy drinking at 6‐ and 12‐month follow‐up. Analyses controlled for age, gender, employment status, marital status, prior alcohol treatment, type of injury and injury severity. Special emphasis was given to potential ethnic differences by testing the interaction between ethnicity and BMI.

Results  At 6‐ and 12‐month follow‐up, BMI significantly reduced maximum amount consumed in 1 day (P < 0.001; P < 0.001, respectively) and percentage days heavy drinking (P < 0.05; P < 0.05, respectively) among Hispanics. Hispanics in the BMI group also reduced average volume per week at 12‐month follow‐up (χ2 = 6.8, df = 1, P < 0.01). In addition, Hispanics in TAU+ reduced maximum amount consumed at 6‐ and 12‐month follow‐up (P < 0.001; P < 0.001) and volume per week at 12‐month follow‐up (P < 0.001). Whites and blacks in both BMI and TAU+ reduced volume per week and percentage days heavy drinking at 12‐month follow‐up (P < 0.001; P < 0.01, respectively) and decreased maximum amount at 6‐ (P < 0.001) and 12‐month follow‐up (P < 0.001). All three ethnic groups In both BMI and TAU+ reduced volume per week at 6‐month follow‐up (P < 0.001) and percentage days abstinent at 6‐ (P < 0.001) and 12‐month follow‐up (P < 0.001).

Conclusions  All three ethnic groups evidenced reductions in drinking at 6‐ and 12‐month follow‐up independent of treatment assignment. Among Hispanics, BMI reduced alcohol intake significantly as measured by average volume per week, percentage days heavy drinking and maximum amount consumed in 1 day.
What neurobiology cannot tell us about addiction
Authors: Kalant Harold
Published: November 2009

Molecular neurobiological studies have yielded enormous amounts of valuable information about neuronal response mechanisms and their adaptive changes. However, in relation to addiction this information is of limited value because almost every cell function appears to be involved. Thus it tells us only that neurons adapt to ‘addictive drugs’ as they do to all sorts of other functional disturbances. This information may be of limited help in the development of potential auxiliary agents for treatment of addiction. However, a reductionist approach which attempts to analyse addiction at ever finer levels of structure and function, is inherently incapable of explaining what causes these mechanisms to be brought into play in some cases and not in others, or by self‐administration of a drug but not by passive exposure. There is abundant evidence that psychological, social, economic and specific situational factors play important roles in initiating addiction, in addition to genetic and other biological factors. Therefore, if we hope to be able to make predictions at any but a statistical level, or to develop effective means of prevention, it is necessary to devise appropriate integrative approaches to the study of addiction, rather than pursue an ever‐finer reductive approach which leads steadily farther away from the complex interaction of drug, user, environment and specific situations that characterizes the problem in humans.
Randomized controlled trial of cognitive–behavioural therapy for coexisting depression and alcohol problems: short‐term outcome
Authors: Baker Amanda L. , Kavanagh David J. , Kay‐Lambkin Frances J. , Hunt Sally A. , Lewin Terry J. , Carr Vaughan J. , Connolly Jennifer
Published: November 2009

Aims  Alcohol use disorders and depression co‐occur frequently and are associated with poorer outcomes than when either condition occurs alone. The present study (Depression and Alcohol Integrated and Single‐focused Interventions; DAISI) aimed to compare the effectiveness of brief intervention, single‐focused and integrated psychological interventions for treatment of coexisting depression and alcohol use problems.

Methods  Participants (n = 284) with current depressive symptoms and hazardous alcohol use were assessed and randomly allocated to one of four individually delivered interventions: (i) a brief intervention only (single 90‐minute session) with an integrated focus on depression and alcohol, or followed by a further nine 1‐hour sessions with (ii) an alcohol focus; (iii) a depression focus; or (iv) an integrated focus. Follow‐up assessments occurred 18 weeks after baseline.

Results  Compared with the brief intervention, 10 sessions were associated with greater reductions in average drinks per week, average drinking days per week and maximum consumption on 1 day. No difference in duration of treatment was found for depression outcomes. Compared with single‐focused interventions, integrated treatment was associated with a greater reduction in drinking days and level of depression. For men, the alcohol‐focused rather than depression‐focused intervention was associated with a greater reduction in average drinks per day and drinks per week and an increased level of general functioning. Women showed greater improvements on each of these variables when they received depression‐focused rather than alcohol‐focused treatment.

Conclusions  Integrated treatment may be superior to single‐focused treatment for coexisting depression and alcohol problems, at least in the short term. Gender differences between single‐focused depression and alcohol treatments warrant further study.
Can hepatitis C virus prevalence be used as a measure of injection‐related human immunodeficiency virus risk in populations of injecting drug users? An ecological analysis
Authors: Vickerman Peter , Hickman Matthew , May Margaret , Kretzschmar Mirjam , Wiessing Lucas
Published: November 2009

Background Human immunodeficiency virus (HIV) outbreaks occur among injecting drug users (IDUs), but where HIV is low insight is required into the future risk of increased transmission. The relationship between hepatitis C virus (HCV) and HIV prevalence among IDUs is explored to determine whether HCV prevalence could indicate HIV risk.

Methods Systematic review of IDU HIV/HCV prevalence data and regression analysis using weighted prevalence estimates and time–series data.

Results HIV/HCV prevalence estimates were obtained for 343 regions. In regions other than South America/sub‐Saharan Africa (SAm/SSA), mean IDU HIV prevalence is likely to be negligible if HCV prevalence is <30% (95% confidence interval 22–38%) but increases progressively with HCV prevalence thereafter [linearly (β = 0.39 andR2 = 0.67) or in proportion to cubed HCV prevalence (β = 0.40 andR2 = 0.67)]. In SAm/SSA, limited data suggest that mean HIV prevalence is proportional to HCV prevalence (β = 0.84,R2 = 0.99), but will be much greater than in non‐SAm/SSA settings with no threshold HCV prevalence that corresponds to low HIV risk. At low HCV prevalences (<50%), time–series data suggest that any change in HIV prevalence over time is likely to be much smaller (<25%) than the change in HCV prevalence over the same time‐period, but that this difference diminishes at higher HCV prevalences.

Conclusions HCV prevalence could be an indicator of HIV risk among IDUs. In most settings, reducing HCV prevalence below a threshold (30%) would reduce substantially any HIV risk, and could provide a target for HIV prevention.
The impact of cigarette deprivation and cigarette availability on cue–reactivity in smokers
Authors: Bailey Steffani R. , Goedeker Katherine C. , Tiffany Stephen T.
Published: November 2009

Aims  This experiment was conducted to determine the impact of cigarette deprivation and cigarette availability on reactivity measures to cigarette cues.

Participants  Smokers were recruited who were 18 years of age or older, not attempting to quit or cut down on their smoking, smoked at least 20 cigarettes daily, had been smoking regularly for past year and had an expired carbon monoxide level of at least 10 parts per million.

Design  Smokers were assigned randomly to abstain from smoking for 24 hours (n = 51) or continue smoking their regular amount (n = 50). Twenty‐four hours later, they were exposed to trials of either a lit cigarette or a glass of water with a 0, 50 or 100% probability of being able to sample the cue on each trial. Craving, mood, heart rate, skin conductance, puff topography and latency to access door to sample the cue were measured.

Findings  Both exposure to cigarette cues and increasing availability of those cues produced higher levels of craving to smoke. Deprivation produced a generalized increase in craving. There was no consistent evidence, however, that even under conditions of high cigarette availability, deprived smokers were sensitized selectively to presentations of cigarette cues.

Conclusions  The data suggest that, even under conditions of immediate cigarette availability, deprivation and cue presentations have independent, additive effects on self‐reported craving levels in smokers.
Continuities and changes in self‐change research
Authors: Klingemann Harald , Sobell Mark B. , Sobell Linda C.
Published: November 2009

Aims  A substantial literature demonstrates that natural recoveries from substance use disorders not only occur but are a common pathway to recovery. This article reviews selectively and comments on the current state‐of‐the‐art in natural recovery research.

Methods  Basic concepts in natural recovery research are presented, and topical and methodological trends and changes in self‐change research over time are discussed.

Conclusions  Although considerable progress has occurred in natural recovery research, several topics deserving of further research are identified, and implications for policy practice are discussed.
Appropriate laryngeal mask airway size for overweight and underweight children
Authors: Kim H. J. , Park M. J. , Kim J. T. , Kim C. S. , Kim S. D. , Kim H. S.
Published: November 2009

The aim of this study was to compare conventional laryngeal mask airway sizing by weight with sizing by age in over‐ or underweight children. We studied 26 overweight (body mass index > 85th centile) and 26 underweight (body mass index < 15th centile) children. After general anaesthesia was induced, laryngeal mask airways sized by the patient’s weight and by an ideal weight (estimated from the patient’s age according to standardised tables) were inserted consecutively. In overweight children, oropharyngeal leak pressure was significantly greater when the laryngeal mask was sized by the patient’s actual weight. On the other hand in underweight children, it was significantly greater when sized by the ideal weight. In conclusion, laryngeal mask airway sizing according to the manufacturer’s weight‐based recommendation is to be preferred in overweight children, but laryngeal mask airway size by an ideal weight estimated from the patient’s age is a better choice in underweight children.
Radiation exposure to anaesthetists during interventional radiology*
Authors: Ismail S. , Khan F. , Sultan N. , Naqvi M.
Published: November 2009

This prospective study determined the level of radiation exposure of anaesthetists during interventional radiological procedures performed in the endoscopic retrograde cholangiopancreatography suite and cardiac catheterisation laboratory and compared it with the current safety guidelines. Anaesthetists wore area‐specific lithium fluoride thermo‐luminescent dosimeter badges at standardised positions. A total of 1344 procedures were performed over a 6‐month period. Anaesthetists were involved in 39/645 (6.0%) procedures associated with ionisation radiation in the endoscopic retrograde cholangiopancreatography suite and 86/699 (12.3%) in the cardiac catheterisation laboratory. The mean (SD) duration of endoscopic retrograde cholangiopancreatography was 54.8 (29.1) min compared with 67.9 (42.8) min for cardiac catheterisation suite procedures (p = 0.058). The mean (SD) fluoroscopy time per procedure for endoscopic retrograde cholangiopancreatography was 5.5 (4.1) min compared with 12 (10.9) min in the cardiac catheterisation suite (p < 0.001). The combined net radiation exposure over 6 months was 0.28 mSv for endoscopic retrograde cholangiopancreatography procedures and 2.32 mSv in the cardiac catheterisation suite. The combined exposure was less than the maximum recommended exposure of 20 mSv per year.
The prevalence of anatomical variations that can cause inadvertent dural puncture when performing caudal block in Koreans: a study using magnetic resonance imaging
Authors: Joo J. , Kim J. , Lee J.
Published: November 2009

The purpose of this study was to investigate the prevalence of the anatomical abnormalities that can induce inadvertent dural puncture when performing caudal block. The anatomy of the lumbo‐sacral area was evaluated using magnetic resonance imaging. In 2462 of the 2669 patients imaged, the dural sac terminal was located between the upper half of the 1st sacral vertebra and the lower half of the 2nd sacral vertebra. In 22 cases (0.8%), the dural sac terminal and the spinal canal were located at or below the 3rd sacral vertebra, and these were cases of simple anatomical variations. As regards pathologic conditions, there was one case of sacral meningocoele and 46 cases of sacral perineural cyst. In 21 cases (0.8%) out of the 46 perineural cyst cases, the cyst could be found at or below the 3rd sacral vertebra level. Inadvertent dural puncture may happen when performing caudal block in patients with such abnormal anatomy.
Phase 2 study of two sequential three‐drug combinations containing bortezomib, cyclophosphamide and dexamethasone, followed by bortezomib, thalidomide and dexamethasone as frontline therapy for multiple myeloma
Authors: Bensinger William I. , Jagannath Sundar , Vescio Robert , Camacho Elber , Wolf Jeffrey , Irwin David , Capo Gerardo , McKinley Marti , Potts Phyllis , Vesole David H. , Mazumder Amitabha , Crowley John , Becker Pam , Hilger Jacqueline , Durie Brian G.M.
Published: November 2009

Novel sequential combination therapy for induction may improve the quality of response and therefore prolong survival in newly diagnosed multiple myeloma (MM) patients. We report results from a phase 2 study of two sequential three‐drug combinations. Forty‐four previously untreated, symptomatic MM patients received: bortezomib 1·3 mg/m2 (days 1, 4, 8, 11), cyclophosphamide 300 mg/m2 (days 1, 8), plus dexamethasone 40 mg (day of and day after bortezomib) for three 21‐day cycles, followed by bortezomib 1·0 mg/m2, dexamethasone 40 mg and thalidomide 100 mg daily for three cycles. Overall response rate for 42 evaluable patients was 95%, including 19% stringent complete response (sCR), 26% CR, and 57%≥ very good partial response. Twenty‐two patients have undergone stem‐cell transplantation. After a median follow‐up of 20·9 months, five patients have died; none was induction therapy‐related. Median event‐free survival (EFS) and overall survival (OS) have not been reached; estimated 1‐year EFS and OS rates were 81% and 91% respectively. Both three‐drug combinations were well tolerated; 82% of patients completed all six cycles. Toxicities were predictable and manageable; the most‐commonly reported grade 3/4 toxicity was neuropathy (11%). This novel sequential three‐drug combination therapy is effective and well‐tolerated in previously untreated MM patients.
Microglandular adenosis or microglandular adenoma? A molecular genetic analysis of a case associated with atypia and invasive carcinoma
Authors: Geyer Felipe C , Kushner Yael B , Lambros Maryou B , Natrajan Rachael , Mackay Alan , Tamber Narinder , Fenwick Kerry , Purnell Dave , Ashworth Alan , Walker Rosemary A , Reis‐Filho Jorge S
Published: November 2009

Aims:  Microglandular adenosis (MGA) is a rare breast lesion, which has long been considered to be hyperplastic. However, atypical forms of MGA (AMGA) and invasive carcinomas arising in the background of MGA are recorded. Recent studies have suggested that MGA may be a non‐obligate precursor of invasive carcinomas that are negative for hormone receptors and lack HER‐2 overexpression (triple‐negative phenotype). The aim of this study was to determine whether MGA is clonal and whether it harbours chromosomal aberrations similar to those found in matched invasive ductal carcinoma of no special type (IDC‐NST).

Methods and results:  We report on a case comprising MGA, AMGA and a high‐grade IDC‐NST. The three components were separately microdissected and subjected to genetic analysis with high‐resolution microarray comparative genomic hybridisation. Identical genetic changes were detected in all components with subsequent acquisition of additional genetic aberrations in the invasive component, suggesting that MGA was the substrate for the development of the invasive carcinoma. Immunohistochemistry revealed concordant profiles across all components, characterized by triple‐negative phenotype and variable positivity for basal markers.

Conclusions:  Similar to adenomas, MGA is, at least in some cases, a clonal lesion and may be a non‐obligate precursor of a subgroup of high‐grade triple‐negative and basal‐like breast carcinomas.
CD98 expression is decreased in papillary carcinoma of the thyroid and Hashimoto’s thyroiditis
Authors: Anderson Catriona E , Graham Catriona , Herriot Michael M , Kamel Hassan M , Salter Donald M
Published: November 2009

Aims:  CD98 is a component of the large neutral amino acid transporter (LAT), which is a cell surface amino acid transporter. CD98 also binds to and activates β1‐integrin, promoting anchorage‐independent growth. CD98 expression is increased in a variety of carcinomas but its distribution in the normal and neoplastic thyroid gland has not been reported. The aim was to examine the immunohistochemical expression of CD98 in normal and diseased thyroid tissue.

Methods and results:  One hundred and forty thyroid cases were selected from the archives of the Department of Pathology, including normal controls, neoplasms (follicular adenoma, follicular carcinoma and papillary carcinoma) and non‐neoplastic conditions (multinodular goitre, Graves’ disease and Hashimoto’s thyroiditis). Immunohistochemistry for CD98 was performed and each case was scored for proportion of cells and intensity of immunoreactivity. In normal thyroid, there was moderately strong expression of CD98 in the lateral cell membranes of follicular cells. A similar pattern of expression was seen in follicular adenoma, minimally invasive follicular carcinoma, multinodular goitre and Graves’ disease. In most cases of papillary carcinoma and in the inflamed areas of Hashimoto’s thyroiditis, expression of CD98 was decreased.

Conclusions:  CD98 expression is down‐regulated in thyroid papillary carcinoma; this may relate to the better prognosis associated with many of these tumours.
A comparison between isolated blood dendritic cells and monocyte‐derived dendritic cells in pigs
Authors: Facci Marina R. , Auray Gael , Buchanan Rachelle , Van Kessel Jill , Thompson David R. , Mackenzie‐Dyck Sarah , Babiuk Lorne A. , Gerdts Volker
Published: November 2009

Various dendritic cell (DC) populations exist that differ in phenotype and ability to present antigen to T cells. For example, plasmacytoid DCs (pDCs) are less potent T cell activators compared with conventional DCs (cDCs). Here, we compared porcine blood DCs (BDCs), containing pDCs and cDCs, and monocyte‐derived DCs (MoDC), consisting of cDCs, in their phenotype, ability to uptake antigen, activation and maturation and their ability to present antigen to autologous T cells. Pigs represent an important animal model, whose immune system in many respects closely resembles that of humans. For example, the distribution of Toll‐like receptors is similar to that of humans, in contrast to that of mice. Here we demonstrate that both populations endocytose foreign material. Following lipopolysaccharide stimulation, CD80/86 and chemokine receptor (CCR)7 expression was increased in both populations as was the expression of the chemokine ligands (CCL)‐2, CCL‐4, CCL‐20 and CXCL‐2. Although basal and post‐stimulation protein concentrations of interleukins 6 and 8 and tumour necrosis factor‐α were higher in MoDCs, protein concentrations showed a higher fold increase in BDCs. Antigen‐specific proliferation of autologous T cells was induced by MoDCs and BDCs. Interestingly, while MoDCs induced stronger proliferation in naive T cells, no difference in proliferation was observed when primed T cells were studied. These results demonstrate that isolated porcine BDCs are highly responsive to stimulation with lipopolysaccharide and are functionally able to drive primed T‐cell proliferation to the same extent as MoDCs.
Dendritic cells activated by an anti‐inflammatory agent induce CD4+ T helper type 2 responses without impairing CD8+ memory and effector cytotoxic T‐lymphocyte responses
Authors: Wang Yang , Da’Dara Akram A. , Thomas Paul G. , Harn Donald A.
Published: November 2009

Prevalence of pro‐inflammatory diseases is rising in developed country populations. The increase in these diseases has fuelled the search for new, immune suppressive, anti‐inflammatory therapies, which do not impact, or minimally impact, CD4+ and/or CD8+ T‐cell‐mediated immunity. The goal of this study was to determine if antigen‐presenting cells (APCs) activated by the anti‐inflammatory oligosaccharide, lacto‐N‐fucopentaose III (LNFPIII), would have an impaired ability to drive CD4+ T helper (Th) or CD8+ memory and effector T‐cell responses. To investigate this we activated splenic dendritic cells (SDCs) with LNFPIII and examined their ability to drive antigen‐specific CD4+ Th, and CD8+ memory and cytotoxic T‐cell (CTL) responses compared with lipopolysaccharide (LPS) ‐stimulated SDCs. The LNFPIII‐activated SDCs had altered co‐stimulatory molecule expression compared with LPS‐stimulated SDCs, while the levels of SDC chemokines following activation by either compound were similar. LNFPIII‐activated SDCs produced significantly lower levels of interleukin‐12 but surprisingly higher levels of interleukin‐6 than LPS‐activated SDCs. Similar to previous studies using bone‐marrow‐derived DCs, LNFPIII‐activated SDCs induced strong Th2 responses in vivo and ex vivo. LNFPIII activation of APCs was independent of the Toll‐interleukin‐1 receptor adaptor myeloid differentiating factor 88. Importantly, LNFPIII‐matured DCs induced CD8+ memory and effector CTL responses similar to those driven by LPS‐matured DCs, including the frequency of interferon‐γ‐producing CD8+ T cells and induction of CTL effectors. Treatment of APCs by the anti‐inflammatory glycan LNFPIII did not impair their ability to drive CD8+ effector and memory cell‐mediated immunity.
Mesenteric lymph nodes are not required for an intestinal immunoglobulin A response to oral cholera toxin
Authors: Hahn Anika , Thiessen Nadja , Pabst Reinhard , Buettner Manuela , Bode Ulrike
Published: November 2009

Stimulation of the adaptive immune system in the gut is thought to be mainly initiated in the Peyer’s patches as well as in the mesenteric lymph nodes (mLNs) and results in immunoglobulin A (IgA) secretion by plasma cells in the lamina propria. However, the precise role of the mLNs in the development of IgA immune responses is poorly understood. Thus, cholera toxin (CT) was administered to mLN‐resected and mLN‐bearing animals and the IgA response to CT in the intestine and serum was examined. Levels of CT‐specific IgA antibodies and the numbers of cells producing these antibodies in the intestine were increased in mLN‐resected rats. Particularly in the distal parts of the intestine, the jejunum and the ileum, IgA responses to orally administered antigens developed were stronger in the intestine after removal of the mLNs. This strongly indicates that the mLNs play a critical role in modulating the expansion of specific IgA responses. After removal of the mLNs, the lymph from the gut flows directly into the blood. It was investigated whether the spleen is involved in the initiation of an immune response to orally administered CT after removal of the mLNs. In the spleens of mLN‐resected animals, proliferation was up‐regulated, and germinal centres were formed in the follicles. However, CT‐specific IgM+ cells, but no IgA+ cells, developed. Additionally, an increase of CT‐specific IgM in the serum was found in mLN‐resected animals. Thus, the data indicate that the spleen is involved in the immune response to CT after mLN resection.
Natural colourant from Shiraia bambusicola: stability and antimicrobial activity of hypocrellin extract
Authors: Su Yujie , Yin Xiaoyan , Rao Shengqi , Cai Yujie , Reuhs Brad , Yang Yanjun
Published: November 2009

A red pigment, hypocrellin extract, was studied as a natural food additive for the first time. The colour of hypocrellin extract changed with pH value, from bright red in acidic to green in alkaline condition. It was stable to heat, and natural light, but was susceptible under direct sun rays. Hypocrellin extract was resistant to oxidant (H2O2), but was sensitive to reducer such as Na2SO3. No evident influences of food additives in common use on the stability of hypocrellin extract were observed. Most tested metal ions hardly affected pigment stability except for Fe2+, Fe3+, Al3+and Cu2+. It possessed excellent light‐induced antimicrobial activity to the Gram‐positive bacteria usually troublesome in food industry. However, no antimicrobial activity was observed to the Gram‐negative bacteria. Our findings demonstrated that hypocrellin extract may be used as a natural colourant or preservative in food and other allied industries.
Shelf‐life of vacuum packed Alaskan, Scottish and Norwegian cold‐smoked salmon available on the Italian market
Authors: Bernardi Cristian , Ripamonti Barbara , Campagnoli Anna , Stella Simone , Cattaneo Patrizia
Published: November 2009

Fourteen vacuum packed cold smoked salmon products of different origin purchased in Italian retail were analysed at about half shelf‐life (HSL) and at the expiry date (ED). On ED, eight on fourteen samples had concentration of total volatile basic nitrogen (TVBN) indicating spoilage (values >40 mg N/100 g and up to 71.3 mg N/100 g) and only five samples were not rancid (thiobarbituric acid reactive substances, TBARS <8 nmol/g). Total psychrotrophic count (TPC) at HSL was acceptable (<106 CFU/g) in most samples; at ED, in 13 samples, TPC was very high (range 1.2 × 106– 6.0 × 108 CFU/g) and Lactobacilli were the most representative bacteria. No pathogens were detected. Significant negative differences in declared weight (over 8%) were determined in nine samples. The two months shelf‐life attributed to smoked salmon marketed in Italy proved to be, generally, too long and the consumer is at risk to buy a product in early stage of spoilage.
Industrial processing effects on chestnut fruits (Castanea sativa Mill.). 2. Crude protein, free amino acids and phenolic phytochemicals
Authors: Do Carmo Barbosa Mendes de Vasconcelos Maria , Bennett Richard N. , Rosa Eduardo A. S. , Ferreira‐Cardoso Jorge V.
Published: November 2009

The aim of this study was to analyse the effects of industrial processing on the composition of proteins, free amino acids and phenolics in Castanea sativa Mill. fruits of 2 years. The Portuguese cultivars were Judia, Longal, Martaínha and Lada, and the European cultivars were ‘Spanish’ (Puga do Bolo) and ‘Italian’ (Viterbes). At all processing stages the fruits contained low contents of protein (4.1–5.4 g 100 g−1 d.m.). The essential amino acid Thr had the highest values (3.6–10.0 mg 100 g−1 f.w.), while the highest non‐essential amino acid was Asn (14.9–36.4 g 100 g−1 f.w.). Total phenolics (6.6–18.3 mg g−1 f.w.) were more significantly affected by the processing stage factor. In 2007 the gallic acid contents were more affected by the processing stage and interaction factors (cultivar × processing stage), whereas the cultivar factor had more of an effect on ellagic acid. Industrial processing has some negative effects, specifically reducing the contents of some amino acids.
Microbiological characteristics of poultry patties in relation to packaging atmospheres
Authors: Mastromatteo Marianna , Lucera Annalisa , Sinigaglia Milena , Corbo Maria Rosaria
Published: November 2009

Microbial characteristics under different atmospheres (vacuum, air, MAP1: 80% O2/20% CO2 and MAP2: 5% O2/65% N2/30% CO2) of poultry patties made of a mixture of ostrich, chicken and turkey meat were evaluated. The meat preparations were examined for changes in pH, colour properties (CIE L*, a*, b*), headspace composition, and bacterial counts (total viable cell, psychrotrophs, Enterobacteriaceae, lactic acid bacteria, Staphylococcus spp., Brochothrix thermosphacta, Pseudomonas spp.). The use of a high O2 atmosphere (MAP1) quickly leads to a loss of the appealing red colour. A limited alteration occurred with use of MAP2 and vacuum. For total viable counts a cell load higher than 8 log cfu g−1 for the samples packaged in air, MAP1 and MAP2 at the end of storage was observed. Whereas, for the vacuum packed samples the cell load never reached values higher than 8 log cfu g−1. Enterobacteriaceae, B. thermosphacta and Pseudomonas spp. cell load was less with the vacuum (7.60, 5.06 and 7.17 log cfu g−1, respectively) and MAP2 packaging (7.08, 5.60 and 7.40 log cfu g−1, respectively). However, the high microbial loads suggest that an improvement of the microbiological quality of poultry meat is necessary if the producers are going to propose this new meat preparation on the market.