bluuebunny/crossref_metadata_2025 huggingface dataset:
Oral Insulin Supplementation in Paediatric Short Bowel Disease: A Pilot Observational Study
Authors: Shamir Raanan , Kolacek Sanja , Koletzko Sibylle , Tavori Irit , Bader David , Litmanovitz Ita , Flidel‐Rimon Orna , Marks Kyla Anna , Sukhotnik Igor , Shehadeh Naim
Published: June 2009

Background and Aim:

Insulin is present in human milk, and oral insulin supplementation causes a dramatic adaptive gut growth in a rat model of short bowel syndrome (SBS). We conducted an open‐label pilot observational study to examine whether oral insulin supplementation to paediatric patients with SBS decreases the need for parenteral nutrition (PN).

Methods:

Between April 2004 and March 2006, 10 premature infants and children were recruited from 8 paediatric gastroenterology centres in Israel, Croatia, and Germany. Enrolled subjects received 1 unit of insulin (Actrapid, Novonordisk, Denmark)/kg body weight per dose × 4/day (every 6 hours) for 28 days. We monitored glucose blood levels, weight, enteral and parenteral intake of calories, carbohydrates, and lipids. In addition, blood levels of albumin, ALT, AST, GGT, ALP, total cholesterol, triglycerides, and anti‐insulin antibodies were recorded.

Results:

On average, enteral intake increased from 45.6% ± 30.6% to 58.9% ± 28.2% (not statistically significant), and ALT blood levels decreased from 194 ± 128 U to 136 ± 79 U (not statistically significant). Two (2/10) infants were weaned off PN. None of the children developed insulin antibodies.

Conclusions:

Oral insulin supplementation in paediatric SBS is not associated with short‐term side effects. Although clinical improvement was observed in a subset of children, whether these effects are due to insulin administration is uncertain. The efficacy of oral insulin remains to be determined in a double‐blind manner using a preparation that is resistant to degradation in the stomach.
Breast‐feeding: A Commentary by the ESPGHAN Committee on Nutrition
Authors:   ESPGHAN Committee on Nutrition:, Agostoni Carlo , Braegger Christian , Decsi Tamas , Kolacek Sanja , Koletzko Berthold , Michaelsen Kim Fleischer , Mihatsch Walter , Moreno Luis A , Puntis John , Shamir Raanan , Szajewska Hania , Turck Dominique , van Goudoever Johannes
Published: June 2009

This medical position article by the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition summarises the current status of breast‐feeding practice, the present knowledge on the composition of human milk, advisable duration of exclusive and partial breast‐feeding, growth of the breast‐fed infant, health benefits associated with breast‐feeding, nutritional supplementation for breast‐fed infants, and contraindications to breast‐feeding. This article emphasises the important role of paediatricians in the implementation of health policies devised to promote breast‐feeding.

The European Society for Paediatric Gastroenterology, Hepatology, and Nutrition Committee on Nutrition recognises breast‐feeding as the natural and advisable way of supporting the healthy growth and development of young children. This article delineates the health benefits of breast‐feeding, reduced risk of infectious diarrhoea and acute otitis media being the best documented.

Exclusive breast‐feeding for around 6 months is a desirable goal, but partial breast‐feeding as well as breast‐feeding for shorter periods of time are also valuable. Continuation of breast‐feeding after the introduction of complementary feeding is encouraged as long as mutually desired by mother and child.

The role of health care workers, including paediatricians, is to protect, promote, and support breast‐feeding. Health care workers should be trained in breast‐feeding issues and counselling, and they should encourage practices that do not undermine breast‐feeding. Societal standards and legal regulations that facilitate breast‐feeding should be promoted, such as providing maternity leave for at least 6 months and protecting working mothers.
Threonine Metabolism in the Intestine of Mice: Loss of Mucin 2 Induces the Threonine Catabolic Pathway
Authors: van der Sluis Maria , Schaart Maaike W , de Koning Barbara AE , Schierbeek Henk , Velcich Anna , Renes Ingrid B , van Goudoever Johannes B
Published: June 2009

Objectives:

Previous studies have shown that the intestine uses a major part of the dietary threonine intake for the synthesis of the structural component of the protective intestinal mucus layer, the secretory mucin Muc2. In this context, the high intestinal demand for dietary threonine probably results from its incorporation into secretory mucins rich in threonine residues. Therefore, we compared threonine utilization in the colon of Muc2 knockout (Muc2−/−) and wild‐type (Muc2+/+) mice to investigate the intestinal dietary threonine metabolism in the absence of Muc2, which results in inflammation of the colon.

Materials and Methods:

Concentrations and isotopic enrichment of threonine were measured by gas chromatography‐isotope ratio mass spectrometry in the serum, colon, and colonic content of mice given a bolus [U‐13C]threonine enterally.

Results:

We retrieved 37.8% and 40.9% of dietary threonine in Muc2+/+ and Muc2−/− mice, respectively, either as free or incorporated threonine. There were no major differences in the availability and concentration of free or incorporated threonine recovered in both serum and colon in both types of mice. However, the Muc2−/− mice did show overall significantly higher threonine oxidation rates compared with Muc2+/+ mice.

Conclusions:

In the absence of Muc2, dietary threonine is mainly used for constitutive protein synthesis or becomes a substrate for metabolic oxidation. This indicates that inflammation also requires high threonine amounts.
Vocal discrimination of potential mates by female giant pandas (Ailuropoda melanoleuca)
Authors: Charlton Benjamin D. , Huang Yan , Swaisgood Ronald R.
Published: June 2009

In the current study, we used male giant panda (Ailuropoda melanoleuca) bleats in a habituation–discrimination paradigm to determine whether females discriminate between the vocalizations of different males. We found that females habituated to the bleats of a specific male showed a significant dishabituation when they were presented with bleats from a novel male. Further playbacks, in which we standardized the mean fundamental frequency (pitch) and amplitude modulation of male bleats, indicated that amplitude modulation is the key feature that females attend to when discriminating between male callers. Our results show that female giant pandas can discriminate between the vocalizations of potential mates and provide a platform for further studies investigating the functional role of caller identity in giant panda sexual communication.
Is the cask of facilitation ready for bottling? A symposium on the connectivity and future directions of positive plant interactions
Authors: Pakeman Robin J. , Pugnaire Francisco I. , Michalet Richard , Lortie Chris J. , Schiffers Katja , Maestre Fernando T. , Travis Justin M. J.
Published: June 2009

The 2009 British Ecological Society's Annual Symposium entitled ‘Facilitation in Plant Communities’ was held at the University of Aberdeen, Scotland, from 20 to 22 April 2009. This was the first ever international meeting dedicated to the rapidly expanding field of facilitation. The aim of the symposium was to assess the current ‘state-of-play’ by contrasting findings from different systems and by looking outwards in an attempt to integrate this field with other related fields. It was also aimed at understanding how knowledge of facilitation can help understand community dynamics and be applied to ecosystem restoration. The symposium identified several key areas where future work is likely to be most profitable.
Rastering strategy for screening and centring of microcrystal samples of human membrane proteins with a sub-10 µm size X-ray synchrotron beam
Authors: Cherezov Vadim , Hanson Michael A. , Griffith Mark T. , Hilgart Mark C. , Sanishvili Ruslan , Nagarajan Venugopalan , Stepanov Sergey , Fischetti Robert F. , Kuhn Peter , Stevens Raymond C.
Published: June 2009

Crystallization of human membrane proteins in lipidic cubic phase often results in very small but highly ordered crystals. Advent of the sub-10 µm minibeam at the APS GM/CA CAT has enabled the collection of high quality diffraction data from such microcrystals. Herein we describe the challenges and solutions related to growing, manipulating and collecting data from optically invisible microcrystals embedded in an opaque frozen
in meso
material. Of critical importance is the use of the intense and small synchrotron beam to raster through and locate the crystal sample in an efficient and reliable manner. The resulting diffraction patterns have a significant reduction in background, with strong intensity and improvement in diffraction resolution compared with larger beam sizes. Three high-resolution structures of human G protein-coupled receptors serve as evidence of the utility of these techniques that will likely be useful for future structural determination efforts. We anticipate that further innovations of the technologies applied to microcrystallography will enable the solving of structures of ever more challenging targets.
Exact solution of an electro-osmotic flow problem in a cylindrical channel of polymer electrolyte membranes
Authors: Berg Peter , Ladipo Kehinde
Published: June 2009

The electric potential of counter-ions (protons) in an infinite cylindrical channel is presented as a solution of the Poisson–Boltzmann equation, involving a constant ion charge density along the wall. The distribution of protons is derived and used subsequently to compute the velocity profile and mass flow rate of the corresponding electro-osmotic flow, driven by an electric field. Analytical expressions are derived for all quantities, including the conductivity and water drag coefficient. This analysis relates especially to cylindrical nano-channels of polymer electrolyte membranes such as Nafion and addresses the validity of continuum models for these materials.
Quantity matters: male sex pheromone signals mate quality in the parasitic wasp
Nasonia vitripennis
Authors: Ruther Joachim , Matschke Michael , Garbe Leif-Alexander , Steiner Sven
Published: June 2009

Sexual selection theory asserts that females are well adapted to sense signals indicating the quality of potential mates. One crucial male quality parameter is functional fertility (i.e. the success of ejaculates in fertilizing eggs). The phenotype-linked fertility hypothesis (PLFH) predicts that functional fertility of males is reflected by phenotypic traits that influence female mate choice. Here, we show for
Nasonia vitripennis
, a parasitic wasp with haplodiploid sex determination and female-biased sex ratios, that females use olfactory cues to discriminate against sperm-limited males. We found sperm limitation in newly emerged and multiply mated males (seven or more previous matings) as indicated by a higher proportion of sons in the offspring fathered by these males. Sperm limitation correlated with clearly reduced pheromone titres. In behavioural bioassays, females oriented towards higher doses of the synthetic pheromone and were attracted more often to scent marks of males with a full sperm load than to those of sperm-limited males. Our data support the PLFH and suggest that
N. vitripennis
females are able to decrease the risk of getting constrained to produce suboptimal offspring sex ratios by orienting towards gradients of the male sex pheromone.
Inhibitory effects of aminoguanidine on thyroid follicular carcinoma development in inflamed capsular regions of rats treated with sulfadimethoxine after N‐bis(2‐hydroxypropyl)nitrosamine‐initiation
Authors: Imai Toshio , Hasumura Mai , Cho Young‐Man , Ota Yoshio , Takami Shigeaki , Hirose Masao , Nishikawa Akiyoshi
Published: June 2009

We have reported that thyroid capsular thickening with inflammation induced by an antithyroidal agent, sulfadimethoxine (SDM), might play a role in the development of invasive follicular carcinomas in rats initiated with N‐bis(2‐hydroxypropyl)nitrosamine (DHPN). Inducible nitric oxide synthase (iNOS) expressed in the inflamed capsular regions further appeared to be implicated in the tumor progression. In the present study, the effects of an iNOS inhibitor, aminoguanidine (AG), on thyroid carcinogenesis were examined. F344 male rats were treated with SDM in drinking water (0.1%) with or without concomitant dietary administration of AG (0.2%) for 4 and 10 weeks after subcutaneous injection of DHPN at 2800 mg/kg bodyweight. At week 4, thyroid capsular thickening with inflammation was observed and iNOS‐positive foci were found in the inflamed regions. In addition, single‐strand DNA‐positive inflammatory cells were scattered among neighboring follicular cells, indicating some cellular damage, at least partly in association with iNOS induction. Concurrent dietary administration of AG with SDM treatment slightly decreased the number of single‐strand DNA‐positive cells but did not alter the incidence and multiplicity of iNOS‐positive foci in the inflamed capsular regions at week 4. At week 10, however, invasive follicular carcinomas predominantly arose in the thickened capsule in the DHPN–SDM‐treated rats, and AG administration decreased (P < 0.05) their multiplicity. The carcinoma cells were partly positive for iNOS. These results thus suggested that iNOS induction in both inflammatory and tumor cells might play pivotal roles in tumor progression in this DHPN–SDM rat model. (Cancer Sci 2009; 100: 1794–1800)
Socio‐demographic risk factors for alcohol and drug dependence: the 10‐year follow‐up of the national comorbidity survey
Authors: Swendsen Joel , Conway Kevin P. , Degenhardt Louisa , Dierker Lisa , Glantz Meyer , Jin Robert , Merikangas Kathleen R. , Sampson Nancy , Kessler Ronald C.
Published: June 2009

Aims  Continued progress in etiological research and prevention science requires more precise information concerning the specific stages at which socio‐demographic variables are implicated most strongly in transition from initial substance use to dependence. The present study examines prospective associations between socio‐demographic variables and the subsequent onset of alcohol and drug dependence using data from the National Comorbidity Survey (NCS) and the NCS Follow‐up survey (NCS‐2).

Design  The NCS was a nationally representative survey of the prevalence and correlates of DSM‐III‐R mental and substance disorders in the United States carried out in 1990–2002. The NCS‐2 re‐interviewed a probability subsample of NCS respondents a decade after the baseline survey. Baseline NCS socio‐demographic characteristics and substance use history were examined as predictors of the first onset of DSM‐IV alcohol and drug dependence in the NCS‐2.

Participants  A total of 5001 NCS respondents were re‐interviewed in the NCS‐2 (87.6% of baseline sample).

Findings  Aggregate analyses demonstrated significant associations between some baseline socio‐demographic variables (young age, low education, non‐white ethnicity, occupational status) but not others (sex, number of children, residential area) and the subsequent onset of DSM‐IV alcohol or drug dependence. However, conditional models showed that these risk factors were limited to specific stages of baseline use. Moreover, many socio‐demographic variables that were not significant in the aggregate analyses were significant predictors of dependence when examined by stage of use.

Conclusions  The findings underscore the potential for socio‐demographic risk factors to have highly specific associations with different stages of the substance use trajectory.
Smoking cessation during alcohol treatment: a randomized trial of combination nicotine patch plus nicotine gum
Authors: Cooney Ned L. , Cooney Judith L. , Perry Bridget L. , Carbone Michael , Cohen Emily H. , Steinberg Howard R. , Pilkey David T. , Sevarino Kevin , Oncken Cheryl A. , Litt Mark D.
Published: June 2009

Aims  The primary aim was to compare the efficacy of smoking cessation treatment using a combination of active nicotine patch plus active nicotine gum versus therapy consisting of active nicotine patch plus placebo gum in a sample of alcohol‐dependent tobacco smokers in an early phase of out‐patient alcohol treatment. A secondary aim was to determine whether or not there were any carry‐over effects of combination nicotine replacement on drinking outcomes.

Design  Small‐scale randomized double‐blind placebo‐controlled clinical trial with 1‐year smoking and drinking outcome assessment.

Setting  Two out‐patient substance abuse clinics provided a treatment platform of behavioral alcohol and smoking treatment delivered in 3 months of weekly sessions followed by three monthly booster sessions.

Participants  Participants were 96 men and women with a diagnosis of alcohol abuse or dependence and smoking 15 or more cigarettes per day.

Intervention  All participants received open‐label transdermal nicotine patches and were randomized to receive either 2 mg nicotine gum or placebo gum under double‐blind conditions.

Findings  Analysis of 1‐year follow‐up data revealed that patients receiving nicotine patch plus active gum had better smoking outcomes than those receiving patch plus placebo gum on measures of time to smoking relapse and prolonged abstinence at 12 months. Alcohol outcomes were not significantly different across medication conditions.

Conclusions  Results of this study were consistent with results of larger trials of smokers without alcohol problems, showing that combination therapy (nicotine patch plus gum) is more effective than monotherapy (nicotine patch) for smoking cessation.
Patterns of differential gene expression in Brassica napus cultivars infected with Sclerotinia sclerotiorum
Authors: ZHAO JIANWEI , BUCHWALDT LONE , RIMMER SAMUEL ROGER , SHARPE ANDREW , MCGREGOR LINDA , BEKKAOUI DIANA , HEGEDUS DWAYNE
Published: June 2009

The fungal pathogen Sclerotinia sclerotiorum infects a broad range of dicotyledonous plant species and causes stem rot in Brassica napus. To elucidate the mechanisms underlying the defence response, the patterns of gene expression in the partially resistant B. napus cultivar ZhongYou 821 (ZY821) and the susceptible cultivar Westar were studied using a B. napus oligonucleotide microarray. Although maximum differential gene expression was observed at 48 h post‐inoculation (hpi) in both cultivars, increased transcript levels were detected in cv. ZY821 at the earlier stages of infection (6–12 hpi) for many genes, including those encoding defence‐associated proteins, such as chitinases, glucanases, osmotins and lectins, as well as genes encoding transcription factors belonging to the zinc finger, WRKY, APETALA2 (AP2) and MYB classes. In both cultivars, genes encoding enzymes involved in jasmonic acid, ethylene and auxin synthesis were induced, as were those for gibberellin degradation. In addition, changes in the expression of genes encoding enzymes involved in carbohydrate and energy metabolism appeared to be directed towards shuttling carbon reserves to the tricarboxylic acid cycle and generating reactive oxygen species. Transcripts from genes encoding enzymes involved in glucosinolate and phenylpropanoid biosynthesis were highly elevated in both cultivars, suggesting that secondary metabolites are also components of the response to S. sclerotiorum in B. napus.
Meta‐analysis: clinicopathological and prognostic significance of cyclooxygenase‐2 expression on oesophageal squamous cell carinoma
Authors: LI L. , ZHAO J. , WU Z. , WANG G. , CHEN G.
Published: June 2009

Background  Cyclooxygenase‐2 (COX‐2) is involved in oesophageal carcinogenesis, but the clinical and prognostic significance of COX‐2 expression in oesophageal squamous cell carcinoma (ESCC) remains controversial.

Aim  To evaluate the clinicopathological and prognostic role of COX‐2 expression in ESCC.

Methods  Studies assessing clinical or prognostic significance of COX‐2 expression in ESCC published until December 2008 were selected. A meta‐analysis was performed to clarify the impact of COX‐2 expression on clinicopathological parameters or overall survival (OS) in ESCC.

Results  A total of 19 studies met the inclusion criteria, among which 17 studies were about the clinicopathological significance of COX‐2 expression in ESCC, 12 studies were dealing with prognostic role of COX‐2 expression in ESCC and 10 studies evaluated both of them. Overexpression of COX‐2 was significantly correlated with not only the depth of invasion and TNM stage, with a combined odds ratio (OR) of 0.55 (95%CI: 0.34–0.90, Z = 2.41, P = 0.02) and 0.55 (95%CI: 0.32–0.95, Z = 2.13, P = 0.03) respectively but also the reduced OS with relative risk (RR) 1.42, 95% CI: 1.07–1.90, Z = 2.43, P = 0.02).

Conclusions  COX‐2 might play an important role in the progress of ESCC, overexpression of COX‐2 correlates with not only the depth of invasion and TNM stage but also the reduced OS. COX‐2 might be a potential therapy target for ESCC and work as a prognostic factor for ESCC patients, yet the clinicopathological and prognostic role of COX‐2 in ESCC still needs further confirmation by well‐designed prospective studies.
Influence of standard treatment on ileal and colonic antimicrobial defensin expression in active Crohn’s disease
Authors: KÜBLER I. , KOSLOWSKI M. J. , GERSEMANN M. , FELLERMANN K. , BEISNER J. , BECKER S. , ROTHFUSS K. , HERRLINGER K. R. , STANGE E. F. , WEHKAMP J.
Published: June 2009

Background  Crohn’s Disease (CD), a chronic intestinal inflammation, is currently treated primarily by therapeutics which are directed against inflammatory responses. Recent findings though suggest a central role of the innate immune barrier in the pathophysiology. Important factors providing this barrier are antimicrobial peptides like the α‐ and β‐defensins. Little is known about in vivo effects of common drugs on their expression.

Aim  To analyse the influence of corticosteroids, azathioprine and aminosalicylate treatment on ileal and colonic antimicrobial peptides in active CD and also assess the role of inflammation.

Methods  We measured the expression of antimicrobial peptides and pro‐inflammatory cytokines in 75 patients with active CD.

Results  Ileal and colonic α‐ and β‐defensins as well as LL37 remained unaffected by corticosteroids, azathioprine or aminosalicylate treatment. Additionally, we did not observe a negative coherency between Paneth cell α‐defensins and any measured cytokines. HBD2 and LL37 unlike HBD1 levels were linked to inflammatory cytokines and increased in highly inflamed samples.

Conclusions  Current oral drug treatment seems to have no major effect on the expression of antimicrobial peptides. In contrast to HBD2 and LL37, ileal levels of HD5 and HD6 and colonic HBD1 level are independent of current inflammation. Innovative drugs should aim to strengthen protective innate immunity.
Clinoform quantification for assessing the effects of external forcing on continental margin development
Authors: Kertznus Vanessa , Kneller Ben
Published: June 2009

The Ebro continental margin is characterized by a complex pattern of well‐developed, highly progradational and aggradational, margin‐scale clinoforms. Analysis of conventional 3D seismic reflection data combined with quantitative analyses of margin growth rates, slope geometries, incisional features and shelf‐edge trajectories through time, provides further insights into the signal imposed by externally driven mechanisms on continental margin stratigraphy. Three phases of construction characterize the Ebro continental margin evolution since the Messinian Salinity Crisis. These phases reflect the changes in the climate/sea‐level cyclicity from the Pliocene to the Pleistocene and its effects on sediment supply and sedimentary processes. Nonetheless, morphodynamic feedbacks of the system had a profound effect on the mechanisms of margin growth and sediment distribution. The frequency and amplitude of the progradational pulses of the system follows the trend of climate/sea level as indicated by oxygen isotope records. Generally, major steps of progradation are coeval with pulses towards glacial development. However, the amplitudes of the peaks do not always correlate due to the effects of other variables that are less directly dependent on climate, in particular, modifications of the progradational trends by mass‐wasting processes. The increase in sediment supply and accommodation creation during the Pleistocene along with the progradation of the system into deeper water resulted in progressively steeper slope gradients. Consequently, mass‐wasting processes became the primary sediment delivery mechanism during the Pleistocene. In addition, cross‐shelf incised valleys are not observed throughout the succession, therefore, widely accepted mechanisms of sediment delivery across continental margins and the classic sequence stratigraphic model for margin development are called into question in this system. Quantification of the slope curvature throughout the succession reveal that sigmoidal clinoform profiles correspond to un‐modified slopes while exponential geometries result from a modification of the original shape of the slope by erosional processes.
Influence of point‐source sediment‐supply on modern shelf‐slope morphology: implications for interpretation of ancient shelf margins
Authors: Olariu Cornel , Steel Ronald J.
Published: June 2009

Present sea‐floor bathymetry indicates that the continental‐shelf and shelf‐break morphology have some unique and predictable characteristics in areas with and without high sediment supply. Using a global bathymetry dataset in open shelf areas in front of rivers that discharge over 25 × 106 tons of sediment per year, five distinct accretionary types of shelf‐break are distinguished based on along‐shelf gradient variability and inferred shelf‐break trajectory. Morphological characteristics of river‐mouth shelves (compared with adjacent areas lateral to the immediate fairway of the river) are: (1) an overall lower gradient and greater width, and (2) a relatively high slope gradient/shelf gradient ratio. The exceptions are shelves with active shelf‐edge deltas; these are narrower, steeper and have an attenuated shelf break in front of rivers. These observations are at seismic scale and have direct implications for the recognition and positioning of principal cross‐shelf, supply fairways on ancient shelves or shelf margins, and therefore the potential by‐pass routes for deepwater sands. Higher slope/shelf gradient ratios in areas of actively accreting margins, where the shelf‐break is more prominent and easier to recognize on seismic data compared with adjacent areas, predict areas with high sediment supply. Along‐strike morphological changes on supply‐dominated shelves suggest that identification of the sediment‐feed route and depocenter relative to the shelf break during a relative sea level cycle are critical for understanding/predicting the 3‐D architecture of the shelf‐slope‐basin floor clinoform.
Detailed mapping of marine erosional surfaces and the geometry of clinoforms on seismic data: a tool to identify the thickest reservoir sand
Authors: Rasmussen E. S.
Published: June 2009

Deltaic sediments of the Billund and Bastrup sands were deposited in a ramp setting in the storm‐dominated North Sea during the early Miocene. A marked relief in the hinterland and the relatively high precipitation resulted in a high sediment supply to the sea and progradation of major delta‐coastal plains south of the present‐day Norway. The focus of this study is on the forced regressive wedge system tracts of the two delta complexes, which show remarkably well‐developed marine erosional surfaces associated with sand‐rich packages characterised by steeply dipping clinoforms (up to 10°). The well‐developed clinoformal packages indicate that deposition occurred in water depths of 60–100 m even under a sea‐level fall. The sand‐rich delta lobes also demonstrate that it was a high‐energy environment and that wave‐generated re‐suspension at the delta front effectively re‐sorted the sediments and sand‐rich systems became separated from mud‐dominated portions of the delta complexes. The evolution of the above occurred in a basin that has been exposed by inversion tectonism. The sediment supply was consequently high. During deposition, eustatic sea‐level changes strongly controlled the evolution of sequences. The results found in this study may be applicable for mapping reservoir sands in ramp settings and in rift basins especially when looking for reservoir rocks in the basinal setting or when carrying out detailed reservoir mapping in already existing hydrocarbon fields.
Drug cross‐resistance and therapy‐induced resistance in chronic lymphocytic leukaemia by an enhanced method of individualised tumour response testing
Authors: Bosanquet Andrew G. , Richards Sue M. , Wade Rachel , Else Monica , Matutes Estella , Dyer Martin J. S. , Rassam Saad M. B. , Durant Justin , Scadding Sheila M. , Raper Steve L. , Dearden Claire E. , Catovsky Daniel
Published: June 2009

Previous results with individualised tumour response testing (ITRT) in vitro in chronic lymphocytic leukaemia (CLL) have consistently shown good correlation with patient response and survival. We describe here an improved test and report its use with samples from the Leukaemia Research Fund CLL4 randomised clinical trial and previously treated patients. ITRT was performed by the tumour response to anti‐neoplastic compounds (TRAC) assay, a modification of the differential staining cytotoxicity (DiSC) assay. Improvements included drying drugs into wells before assay and using the Octospot system to cytocentrifuge eight spots of cells onto one microscope slide. We successfully tested 765/782 (98%) cellular blood samples received within 48 h of phlebotomy. Cross‐resistance (Pearson’s r > 0·7) in untreated CLL was found between similar drugs. Mitoxantrone (r = 0·31), cyclophosphamide (r = 0·35) and pentostatin (r = 0·29) had low cross‐resistance with fludarabine. Treatment resulted in increased resistance to chlorambucil, cyclophosphamide, doxorubicin, mitoxantrone, corticosteroids, cladribine and fludarabine (P < 0·01) but not to pentostatin. These results provide further rationale for standard drug combinations such as fludarabine‐mitoxantrone and fludarabine‐mitoxantrone‐cyclophosphamide and suggest possible pentostatin salvage in fludarabine‐resistant patients. ITRT results could assist both in determining the best treatment for individual patients and in the design and rationale of future clinical trials.
Cytolytic T‐cell response to the PASD1 cancer testis antigen in patients with diffuse large B‐cell lymphoma
Authors: Ait‐Tahar Kamel , Liggins Amanda P. , Collins Graham P. , Campbell Andrew , Barnardo Martin , Lawrie Charles , Moir Donald , Hatton Chris , Banham Alison H. , Pulford Karen
Published: June 2009

The identification of immunogenic cancer testis antigens (CTAs) as immunotherapeutic targets represents one approach to improve treatment options for diffuse large B‐cell lymphoma (DLBCL). We previously identified PASD1 [PAS (Per ARNT Sim) domain containing 1 (PASD1)], a DLBCL‐associated CTA that was expressed in a range of hematopoietic malignancies. The aim of the present study was to investigate the presence of a cytotoxic T‐cell (CTL) response to PASD1 in DLBCL patients. A significant γ‐interferon (IFN) release was detected in 21/29 HLA‐A*0201‐positive DLBCL patients (18 de novo DLBCL, two transformed DLBCL and one T‐cell rich B‐cell lymphoma) following short‐term culture of their peripheral blood mononuclear cells stimulated with five HLA‐A*0201‐restricted PASD1 peptides. No significant responses were detected in 21 HLA‐A*0201‐negative DLBCL patients (12 de novo DLBCL, seven transformed DLBCL, two T‐cell rich B‐cell lymphoma) or six normal subjects. CTL cell lines were able to lyse PASD1‐positive tumour cells in a major histocompatibility complex‐Class I dependent manner. The presence of a γ‐IFN response correlated with PASD1 protein expression in the tumour cells in 12/15 cases studied. This is the first report of a CTL response to a CTA in DLBCL. Our results provide additional valuable evidence supporting PASD1 as a potential immunotherapeutic target for the treatment of DLBCL and other malignancies.
Does fibrinogen add to prediction of cardiovascular disease? Results from the Scottish Heart Health Extended Cohort Study
Authors: Woodward Mark , Tunstall‐Pedoe Hugh , Rumley Ann , Lowe Gordon D. O.
Published: June 2009

Plasma fibrinogen is an established risk factor for cardiovascular disease (CVD), but it has not been established whether it adds predictive value to risk scores. In the Scottish Heart Health Extended Cohort Study, we measured plasma fibrinogen in 13 060 men and women, aged 30–74 years, initially free of CVD. After follow‐up for a median of 19·2 years, 2626 subjects had at least one CVD event. After adjusting for classical CVD risk factors and socio‐economic status, the hazard ratios (95% confidence interval) for a one unit (g/l) increase in plasma fibrinogen were 1·09 (1·02, 1·16) for men and 1·10 (1·02, 1·19) for women. Although fibrinogen added significantly to the discrimination of the Framingham risk score for women, it failed to do so for men. Fibrinogen did not add significantly to the ASSIGN risk score. Fibrinogen added between 1·3% and 3·2% to the classification of CVD status by the existing risk scores. We conclude that the added value of fibrinogen to two currently used risk scores is low; hence population screening with fibrinogen for this purpose is unlikely to be clinically useful or cost‐effective.
Budesonide and formoterol inhibit inflammatory mediator production by bronchial epithelial cells infected with rhinovirus
Authors: Skevaki C. L. , Christodoulou I. , Spyridaki I. S. , Tiniakou I. , Georgiou V. , Xepapadaki P. , Kafetzis D. A. , Papadopoulos N. G.
Published: June 2009

Background
Rhinoviruses (RVs) are responsible for the majority of acute asthma and chronic obstructive pulmonary disease (COPD) exacerbations. RVs infect the lower airways and induce the production of pro‐inflammatory and remodelling‐associated mediators. Budesonide (BUD) and formoterol (FORM) synergize in controlling asthma and COPD exacerbations; however, their effects on virus‐induced inflammation and remodelling are less known.

Objective
We investigated whether BUD and FORM synergize in suppressing RV‐induced inflammation and remodelling in the airways.

Methods
In vitro models of RV infection of BEAS‐2B and primary normal human bronchial epithelial (NHBE) cells were used. We assessed the effects of individual and combined drugs administered post‐infection, at a clinically relevant concentration range (10−6–10−10 m), on the production of CCL5, CXCL10, CXCL8, IL‐6 and the remodelling‐associated VEGF and bFGF, using ELISA and RT‐PCR.

Results
BUD effectively suppressed RV‐mediated induction of all mediators studied, in a concentration‐dependent manner. FORM alone suppressed the production of CXCL8 and bFGF. The combination of BUD and FORM had concentration‐dependent, additive or synergistic effects in the suppression of RV‐induced CCL5, CXCL8 and CXCL10 in both cell types as well as VEGF in NHBE only. Combination treatment also resulted in an enhanced suppression of RV‐induced IL‐6, and CCL5 at the mRNA level as compared with BUD or FORM alone.

Conclusion
BUD and FORM suppress RV‐induced chemokines and growth factors in bronchial epithelial cells in a concentration‐dependent, synergistic or additive manner. These data further support the combined use of BUD and FORM in asthma and COPD and intensification of this therapy during exacerbations.
Prevalence of clinical remission in patients with sporadic idiopathic hypoparathyroidism
Authors: Goswami Ravinder , Goel Siya , Tomar Neeraj , Gupta Nandita , Lumb Vanshika , Sharma Yagya Dutta
Published: June 2009

Background  Remission of disease activity is a characteristic feature of autoimmune endocrine disorders such as Graves’ disease, Addison’s disease and occasionally in patients with premature ovarian failure. Autoimmunity is also implicated in sporadic idiopathic hypoparathyroidism (SIH) with clinical remission of disease reported in three cases.

Objective  To assess the rate of remission in patients with sporadic idiopathic hypoparathyroidism and review the cases reported so far.

Subjects and methods  Subjects included 53 patients (M:F, 24:29) with SIH who had been symptomatic for at least 1 year (range 1–31 years). They were treated with calcium and 1‐α‐(OH)D3/cholecalciferol therapy and had a mean duration of follow up of 5·0 ± 3·2 years. Treatment was withdrawn in two stages in the patients who maintained normal levels of serum total calcium during the preceding year of treatment. In stage‐1, the dose of therapy was reduced to half and subsequently all treatment was stopped (stage 2) in those patients who maintained normal serum total calcium levels on the reduced dose. Remission of SIH was defined as maintenance of normal serum total (≥2·12 mmol/l) and ionized calcium, inorganic phosphorus and serum intact parathyroid hormone (iPTH) for at least 3 months after withdrawal of calcium and 1‐α‐(OH)D3/cholecalciferol therapy. Calcium sensing receptor autoantibodies (CaSRAb) were determined by Western blot.

Results  Two of the 53 patients (3·8%) with SIH stayed in remission for 1 year after complete withdrawal of therapy. CaSRAb was absent in both the cases. The clinical features, age at onset and duration of hypocalcaemic symptoms in cases with remission were comparable to those who did no show remission.

Conclusion  Sporadic idiopathic hypoparathyroidism is not irreversible as is widely believed and spontaneous remission of disease may occur in 3·8% of patients.
High cortisol levels in hyperglycaemic myocardial infarct patients signify stress hyperglycaemia and predict subsequent normalization of glucose tolerance
Authors: Carmen Wong K. Y. , Wong Vincent , Ho Jui T. , Torpy David J. , McLean Mark , Cheung N. Wah
Published: June 2009

Context  It is unclear if people who develop stress hyperglycaemia have underlying abnormal glucose metabolism, an exaggerated hormonal response to stress, or both. Similarly, it is unknown whether stress hyperglycaemia predicts future glucose intolerance.

Objective  To determine the relationship between illness severity and plasma cortisol concentration with the degree of hyperglycaemia in subjects experiencing acute myocardial infarction (AMI), and their later glucose metabolic status.

Patients and design  This analysis comprised 55 patients from the HI‐5 Study – a randomized control trial of insulin‐glucose infusion therapy for AMI patients with hyperglycaemia.

Main outcome measures  Blood glucose level (BGL) as well as total and free cortisol levels on admission were measured. Patients not previously known to have diabetes were assessed for abnormal glucose metabolism following discharge.

Results  Patients with ST segment‐elevation myocardial infarction (STEMI) and higher peak creatinine kinase level had a higher mean admission total and free cortisol level. As many as 38·5% of subjects were found to have newly diagnosed glucose intolerance at follow up. After multiple logistic regression, admission BGL was found to be a positive predictor (P = 0·027) whereas total cortisol level (P = 0·01) was a negative predictor for glucose intolerance.

Conclusions  Both the level of hyperglycaemia and cortisol levels on admission are predictive for the subsequent abnormal glucose tolerance development in hyperglycaemic AMI patients. Hyperglycaemia in patients who are more unwell (i.e. higher cortisol) reflects the stressed state rather than underlying glucose intolerance. Conversely, if the patient is less sick (i.e. lower cortisol), hyperglycaemia is more likely to reflect underlying glucose intolerance.
Short‐term overt hypothyroidism induces sympathovagal imbalance in thyroidectomized differentiated thyroid carcinoma patients
Authors: Heemstra Karen A. , Burggraaf Jacobus , Van Der Klaauw Agatha A. , Romijn Johannes A. , Smit Johannes W.A. , Corssmit Eleonora P.M.
Published: June 2009

Context  Thyroid hormone impacts on the cardiovascular system. (Subclinical) hyperthyroidism results in sympathovagal imbalance due to decreased vagal tone. However, conflicting data have been reported on the effects of hypothyroidism on the activity of the autonomic nervous system (ANS). In hypothyroidism, both increased and decreased sympathetic activity and increased vagal tone have been found.

Objective  To study the effects of acute short‐term overt hypothyroidism and thyroxine replacement therapy on the ANS by measuring urinary excretion of catecholamines and heart rate variability (HRV).

Design  Prospective study.

Setting  University hospital.

Patients  We studied 11 patients, previously treated with thyroidectomy for differentiated thyroid carcinoma, during hypothyroidism caused by cessation of thyroxine substitution for 4 weeks and during thyroxine replacement therapy, and 21 matched healthy controls.

Main outcome measures  The activity of the ANS was assessed by measuring urinary excretion of catecholamines and HRV at rest and during a challenge of the ANS by a mental stress test.

Results  Urinary dopamine excretion was significantly lower during hypothyroidism. Although in the patients total variability was unchanged, HRV analysis showed a significantly lower low frequency/high frequency ratio, indicating sympathovagal imbalance with sympathetic withdrawal. The mental stress test in the patients resulted in a significant increase in heart rate to the extent of 16–18%. This response was not different between the hypothyroid state and during thyroxine replacement therapy suggesting that cardiovascular reflexes in these patients remain intact.

Conclusion  Acute short‐term overt hypothyroidism results in sympathovagal imbalance with sympathetic withdrawal, with preservation of the cardiovascular reflexes to (mental) stress.
Partitioning of metals (Cd, Co, Cu, Ni, Pb, Zn) in soils: concepts, methodologies, prediction and applications – a review
Authors: Degryse F. , Smolders E. , Parker D. R.
Published: June 2009

Prediction of the fate of metals in soil requires knowledge of their solid–liquid partitioning. This paper reviews analytical methods and models for measuring or predicting the solid–liquid partitioning of metals in aerobic soils, and collates experimental data. The partitioning is often expressed with an empirical distribution coefficient or Kd, which gives the ratio of the concentration in the solid phase to that in the solution phase. The Kd value of a metal reflects the net effect of various reactions in the solid and liquid phases and varies by orders of magnitude among soils. The Kd value can be derived from the solid–liquid distribution of added metal or that of the soil‐borne metal. Only part of the solid‐phase metal is rapidly exchangeable with the solution phase. Various methods have been developed to quantify this ‘labile’ phase, and Kd values based on this phase often correlate better with soil properties than Kd values based on total concentration, and are more appropriate to express metal ion buffering in solute transport models. The in situ soil solution is the preferred solution phase for Kd determinations. Alternatively, water or dilute‐salt extracts can be used, but these may underestimate in situ concentrations of dissolved metals because of dilution of metal‐complexing ligands such as dissolved organic matter. Multi‐surface models and empirical models have been proposed to predict metal partitioning from soil properties. Though soil pH is the most important soil property determining the retention of the free metal ion, Kd values based on total dissolved metal in solution may show little pH dependence for metal ions that have strong affinity for dissolved organic matter. The Kd coefficient is used as an equilibrium constant in risk assessment models. However, slow dissociation of metal complexes in solution and slow exchange of metals between labile and non‐labile pools in the solid phase may invalidate this equilibrium assumption.
Linking individual response to biotic interactions with community structure: a trait‐based framework
Authors: Gross Nicolas , Kunstler Georges , Liancourt Pierre , De Bello Francesco , Suding Katharine Nash , Lavorel Sandra
Published: June 2009

1.  Due to species‐specificity of the outcomes of biotic interactions, it is difficult to generalize from observed biotic interactions at the individual plant level to the effect of those interactions at the community level. To evaluate the importance of biotic interactions in shaping plant communities, it is necessary to understand how the outcomes of the complex interactions observed at the individual level can influence community structure.

2.  Here, we propose a trait‐based framework that identifies and organises mechanisms affecting community structure (here described with relative abundances of plant functional traits – i.e. the distribution of trait values at the community level). We applied our approach to a single leaf trait, specific leaf area (SLA), to link individual responses to plant interactions with community structure (SLA distribution observed at the community level) and to test whether biotic interactions can predict the functional composition of subalpine grasslands. We evaluated the generality of our model through a cross‐validation with a set of eight subalpine grasslands independent from the four fields used to build the model.

3.  We found that competition and facilitation were able to explain the functional composition of subalpine grasslands, and the relevant fitness components (survival or growth) explaining this link changed depending on the limiting resources. When soil water availability was limiting, positive plant‐plant interactions acting on survival were able to explain community structure. In contrast, when no water limitation was observed competition acting on individual growth was the main driver of community structure.

4.  Our framework enables evaluation of the consequences of biotic interactions observed at individual level on community structure, thereby indicating when and where different types of plant‐plant interactions are important.
ATP‐induced osteoclast function: the formation of sealing‐zone like structure and the secretion of lytic granules via microtubule‐deacetylation under the control of Syk
Authors: Hazama Ryoichi , Qu Xiujuan , Yokoyama Kunio , Tanaka Chisato , Kinoshita Emi , He Jinsong , Takahashi Shusuke , Tohyama Kaoru , Yamamura Hirohei , Tohyama Yumi
Published: June 2009

Osteoclasts are bone‐resorbing cells which play an exclusive role in bone remodeling, but the molecular mechanisms of osteolysis, how osteoclasts are activated and how the lytic granules are finally released towards the bone matrix are poorly understood. Here we show that an energy molecule ATP induces osteolysis via P2X7‐nucleotide receptor and that deacetylation of α‐tubulin is essential for the whole process of osteolysis under the control of a tyrosine kinase Syk. By developing a traceable and reproducible in vitro analyzing system for osteoclast function, we found that ATP‐signaling gives rise to two events simultaneously (i) cytoskeletal reorganization for the formation of sealing zones, ring‐like adhesion structures which delimit the contact surface, and (ii) the delivery and secretion of lytic granules towards the delimited site on the matrix. We further found that deacetylation of α‐tubulin is a critical reaction for osteoclast function. Pharmacological inhibition of α‐tubulin deacetylation resulted in (i) failure of the sealing‐zone like structure formation and (ii) ceased secretion of lytic granules. Additionally, kinetics of deacetylation was found to be regulated by Syk. These data suggest a novel P2X7 microtubular regulation pathway related to Syk for a therapeutic target in osteolytic diseases.