bluuebunny/crossref_metadata_2025 huggingface dataset:
A multi‐centre study of candidate genes for wheeze and allergy: the International Study of Asthma and Allergies in Childhood Phase 2
Authors: Genuneit J. , Cantelmo J. L. , Weinmayr G. , Wong G. W. K. , Cooper P. J. , Riikjärv M.‐A. , Gotua M. , Kabesch M. , Von Mutius E. , Forastiere F. , Crane J. , Nystad W. , El‐Sharif N. , Batlles‐Garrido J. , García‐Marcos L. , García‐Hernández G. , Morales‐Suarez‐Varela M. , Nilsson L. , Bråbäck L. , Saraçlar Y. , Weiland S. K. , Cookson W. O. C. , Strachan D. , Moffatt M. F. ,   the ISAAC Phase 2 Study Group
Published: November 2009

Background
Common polymorphisms have been identified in genes suspected to play a role in asthma. We investigated their associations with wheeze and allergy in a case–control sample from Phase 2 of the International Study of Asthma and Allergies in Childhood.

Methods
We compared 1105 wheezing and 3137 non‐wheezing children aged 8–12 years from 17 study centres in 13 countries. Genotyping of 55 candidate single nucleotide polymorphisms (SNPs) in 14 genes was performed using the Sequenom System. Logistic regression models were fitted separately for each centre and each SNP. A combined per allele odds ratio and measures of heterogeneity between centres were derived by random effects meta‐analysis.

Results
Significant associations with wheeze in the past year were detected in only four genes (IL4R, TLR4, MS4A2, TLR9, P<0.05), with per allele odds ratios generally <1.3. Variants in IL4R and TLR4 were also related to allergen‐specific IgE, while polymorphisms in FCER1B (MS4A2) and TLR9 were not. There were also highly significant associations (P<0.001) between SPINK5 variants and visible eczema (but not IgE levels) and between IL13 variants and total IgE. Heterogeneity of effects across centres was rare, despite differences in allele frequencies.

Conclusions
Despite the biological plausibility of IgE‐related mechanisms in asthma, very few of the tested candidates showed evidence of association with both wheeze and increased IgE levels. We were unable to confirm associations of the positional candidates DPP10 and PHF11 with wheeze, although our study had ample power to detect the expected associations of IL13 variants with IgE and SPINK5 variants with eczema.
Immunotherapy with a modified birch pollen extract in allergic rhinoconjunctivitis: clinical and immunological effects
Authors: Ceuppens J. L. , Bullens D. , Kleinjans H. , Van Der Werf J. ,   the PURETHAL Birch Efficacy Study Group
Published: November 2009

Background
Modification of allergens by glutaraldehyde in extracts used for immunotherapy reduces the risk for side‐effects, but the therapeutic efficacy of such extracts still requires further evaluation. The aim of this study was to show the efficacy and safety of immunotherapy with a single‐strength glutaraldehyde‐modified aluminium hydroxide‐adsorbed extract of birch pollen.

Methods
In a multi‐centre, randomized, placebo‐controlled double‐blind setting, starting in 2001 between 1 August and 15 December, birch pollen‐allergic subjects (n=62) were injected subcutaneously with increasing doses of the allergen extract or placebo at weekly intervals over a 6‐week period (or longer if adverse reactions occurred). Maintenance dose was given monthly for at least 18 months till June 2003. Efficacy was evaluated on the basis of the clinical index score (CIS), a combined symptom and medication score.

Results
Fifty‐eight patients could be evaluated for clinical efficacy. Treatment with the birch pollen extract resulted in a lower CIS for the eye and nose during the peak birch pollen season of 2003, compared with placebo (reductions of 42% and 31%, respectively) (P=0.017 and 0.039). Active treatment induced IgG and IgG4 antibodies reacting with Bet v 1 (P<0.001). Sera from treated patients had a blocking effect on Bet v 1‐induced basophil activation (P<0.04). No major adverse reactions occurred, and local reactions, if occurring, were mild.

Conclusion
Immunotherapy with a modified slow‐release birch pollen extract, administered in a single‐strength preparation with a rapid dose increase, is safe and efficacious. IgG and IgG4 antibodies against native Bet v 1 are induced, which block basophil activation.
Phosphorus and nitrogen in a monomictic freshwater lake: employing cyanobacterial bioreporters to gain new insights into nutrient bioavailability
Authors: GILLOR OSNAT , HADAS ORA , POST ANTON F. , BELKIN SHIMSHON
Published: November 2009

1. It is an uncontested paradigm that an adequate supply of the macronutrients nitrogen (N) and phosphorus (P) is critical for maintaining phytoplankton primary production in aquatic ecosystems; it has also been suggested that there is an optimal total N : total P ratio for this globally significant process.

2. This ratio, normally assessed by chemical determination of the major dissolved N and P species, poses a dilemma: do chemical measurements actually reflect the bioavailable fraction of these nutrient pools? Accurate determination of the various N and P species and their fluxes into phytoplankton cells is notoriously difficult.

3. To provide a possible solution to this difficulty, we engineered strains of the cyanobacterium Synechococcus sp. strain PCC 7942 that ‘report’ on N and P bioavailability via a bioluminescent signal. These strains were used to quantify, for the first time, bioavailable concentrations of these essential macronutrients in a freshwater lake.

4. Only a small fraction (0.01–1%) of the chemically determined P may actually be bioavailable to this unicellular cyanobacterium and, by inference, to the phytoplankton community in general. In contrast, bioavailable N comprises most of the dissolved N pool. Consequently, bioavailable N : P ratios based on these assays are higher then those based on chemical determinations, indicating that P limitation in Lake Kinneret is more extensive then previously thought.
Characterizing dispersal patterns in a threatened seabird with limited genetic structure
Authors: HALL LAURIE A. , PALSBØLL PER J. , BEISSINGER STEVEN R. , HARVEY JAMES T. , BÉRUBÉ MARTINE , RAPHAEL MARTIN G. , NELSON S. KIM , GOLIGHTLY RICHARD T. , MCFARLANE‐TRANQUILLA LAURA , NEWMAN SCOTT H. , PEERY M. ZACHARIAH
Published: November 2009

Genetic assignment methods provide an appealing approach for characterizing dispersal patterns on ecological time scales, but require sufficient genetic differentiation to accurately identify migrants and a large enough sample size of migrants to, for example, compare dispersal between sexes or age classes. We demonstrate that assignment methods can be rigorously used to characterize dispersal patterns in a marbled murrelet (Brachyramphus marmoratus) population from central California that numbers approximately 600 individuals and is only moderately differentiated (FST∼ 0.03) from larger populations to the north. We used coalescent simulations to select a significance level that resulted in a low and approximately equal expected number of type I and II errors and then used this significance level to identify a population of origin for 589 individuals genotyped at 13 microsatellite loci. The proportion of migrants in central California was greatest during winter when 83% of individuals were classified as migrants compared to lower proportions during the breeding (6%) and post‐breeding (8%) seasons. Dispersal was also biased toward young and female individuals, as is typical in birds. Migrants were rarely members of parent‐offspring pairs, suggesting that they contributed few young to the central California population. A greater number of migrants than expected under equilibrium conditions, a lack of individuals with mixed ancestry, and a small number of potential source populations (two), likely allowed us to use assignment methods to rigorously characterize dispersal patterns for a population that was larger and less differentiated than typically thought required for the identification of migrants.
Co‐evolution of multipartite interactions between an extended tmRNA tag and a robust Lon protease in Mycoplasma
Authors: Ge Zhiyun , Karzai A. Wali
Published: November 2009

Messenger RNAs that lack in‐frame stop codons promote ribosome stalling and accumulation of aberrant and potentially harmful polypeptides. The SmpB‐tmRNA quality control system has evolved to solve problems associated with non‐stop mRNAs, by rescuing stalled ribosomes and directing the addition of a peptide tag to the C‐termini of the associated proteins, marking them for proteolysis. In Escherichia coli, the ClpXP system is the major contributor to disposal of tmRNA‐tagged proteins. We have shown that the AAA+ Lon protease can also degrade tmRNA‐tagged proteins, but with much lower efficiency. Here, we present a unique case of enhanced recognition and degradation of an extended Mycoplasma pneumoniae (MP) tmRNA tag by the MP‐Lon protease. We demonstrate that MP‐Lon can efficiently and selectively degrade MP‐tmRNA‐tagged proteins. Most significantly, our studies reveal that the larger (27 amino acids long) MP‐tmRNA tag contains multiple discrete signalling motifs for efficient recognition and rapid degradation by Lon. We propose that higher‐affinity multipartite interactions between MP‐Lon and the extended MP‐tmRNA tag have co‐evolved from pre‐existing weaker interactions, as exhibited by Lon in E. coli, to better fulfil the function of MP‐Lon as the sole soluble cytoplasmic protease responsible for the degradation of tmRNA‐tagged proteins.
Active crustal shortening in NE Syria revealed by deformed terraces of the River Euphrates
Authors: Abou Romieh Mohammad , Westaway Rob , Daoud Mohamad , Radwan Yousef , Yassminh Rayan , Khalil Ahlam , Al‐Ashkar Abeer , Loughlin Susan , Arrell Katherine , Bridgland David
Published: November 2009

The Africa–Arabia plate boundary comprises the Red Sea oceanic spreading centre and the left‐lateral Dead Sea Fault Zone (DSFZ); however, previous work has indicated kinematic inconsistency between its continental and oceanic parts. The Palmyra Fold Belt (PFB) splays ENE from the DSFZ in SW Syria and persists for ∼400 km to the River Euphrates, but its significance within the regional pattern of active crustal deformation has hitherto been unclear. We report deformation of Euphrates terraces consistent with Quaternary right‐lateral transpression within the PFB, indicating anticlockwise rotation (estimated as 0.3° Ma−1 about 36.0°N 39.8°E) of the block between the PFB and the northern DSFZ relative to the Arabian Plate interior. The northern DSFZ is shown to be kinematically consistent with the combination of Euler vectors for the PFB and the Red Sea spreading, resolving the inconsistency previously evident. The SW PFB causes a significant earthquake hazard, previously unrecognized, to the city of Damascus.
North Arch volcanic fields near Hawaii are evidence favouring the restite‐root hypothesis for the origin of hotspot swells
Authors: Yamamoto Michiko , Morgan Jason Phipps
Published: November 2009

A pronounced regional bathymetric swell is a common feature of oceanic hotspot volcanism. Recently, the hypothesis of a buoyant sublithospheric swell‐root has been favoured, the root being either a ‘refracted plume’ of hot, buoyant and hence low‐viscosity plume material embedded within surrounding higher viscosity asthenosphere, or a ‘restite‐root’ composed of hot and more viscous residues to hotspot melt‐extraction from the hottest central portion of the upwelling plume. In this article, we present numerical experiments that show that these two scenarios predict different flow and melting patterns whenever the plume passes beneath an obliquely oriented fracture zone where the base of the overriding lithosphere changes in thickness. We find that the restite‐root hypothesis predicts an asymmetric spatial pattern of persistent ‘arch volcanism’ strikingly similar to that found in the Hawaiian chain surrounding the Molokai Fracture Zone. In contrast, the ‘refracted plume’ hypothesis predicts more chaotic patterns quite different from the off‐chain pattern of Hawaiian volcanism.
Social cohesion among kin, gene flow without dispersal and the evolution of population genetic structure in the killer whale (Orcinus orca)
Authors: PILOT M. , DAHLHEIM M. E. , HOELZEL A. R.
Published: November 2009

In social species, breeding system and gregarious behavior are key factors influencing the evolution of large‐scale population genetic structure. The killer whale is a highly social apex predator showing genetic differentiation in sympatry between populations of foraging specialists (ecotypes), and low levels of genetic diversity overall. Our comparative assessments of kinship, parentage and dispersal reveal high levels of kinship within local populations and ongoing male‐mediated gene flow among them, including among ecotypes that are maximally divergent within the mtDNA phylogeny. Dispersal from natal populations was rare, implying that gene flow occurs without dispersal, as a result of reproduction during temporary interactions. Discordance between nuclear and mitochondrial phylogenies was consistent with earlier studies suggesting a stochastic basis for the magnitude of mtDNA differentiation between matrilines. Taken together our results show how the killer whale breeding system, coupled with social, dispersal and foraging behaviour, contributes to the evolution of population genetic structure.
Effect of male age on sperm traits and sperm competition success in the guppy (Poecilia reticulata)
Authors: GASPARINI C. , MARINO I. A. M. , BOSCHETTO C. , PILASTRO A.
Published: November 2009

Deleterious mutations can accumulate in the germline with age, decreasing the genetic quality of sperm and imposing a cost on female fitness. If these mutations also affect sperm competition ability or sperm production, then females will benefit from polyandry as it incites sperm competition and, consequently, minimizes the mutational load in the offspring. We tested this hypothesis in the guppy (Poecilia reticulata), a species characterized by polyandry and intense sperm competition, by investigating whether age affects post‐copulatory male traits and sperm competition success. Females did not discriminate between old and young males in a mate choice experiment. While old males produced longer and slower sperm with larger reserves of strippable sperm, compared to young males, artificial insemination did not reveal any effect of age on sperm competition success. Altogether, these results do not support the hypothesis that polyandry evolved in response to costs associated with mating with old males in the guppy.
Rapid spread of male‐killing Wolbachia in the butterfly Hypolimnas bolina
Authors: DUPLOUY A. , HURST G. D. D. , O’NEILL S. L. , CHARLAT S.
Published: November 2009

Reproductive parasites such as Wolbachia can spread through uninfected host populations by increasing the relative fitness of the infected maternal lineage. However, empirical estimates of how fast this process occurs are limited. Here we use nucleotide sequences of male‐killing Wolbachia bacteria and co‐inherited mitochondria to address this issue in the island butterfly Hypolimnas bolina. We show that infected specimens scattered throughout the species range harbour the same Wolbachia and mitochondrial DNA as inferred from 6337 bp of the bacterial genome and 2985 bp of the mitochondrial genome, suggesting this strain of Wolbachia has spread across the South Pacific Islands at most 3000 years ago, and probably much more recently.
Need for sharp phenotypes in QTL detection for calving traits in dairy cattle
Authors: Seidenspinner T. , Bennewitz J. , Reinhardt F. , Thaller G.
Published: November 2009

The aim of the study was to investigate whether parity‐specific phenotypes provide a clearer picture of quantitative trait loci (QTL) affecting calving traits in German Holsteins than breeding values estimated across parities. In experiment I, approximate daughter yield deviations were calculated by applying a univariate sire model assuming unrelated sires used as phenotypes in a QTL mapping study. These results were compared with those obtained using deregressed estimated breeding values obtained from the routine German sire evaluation (experiment II). In experiment I, 17 chromosome‐wise significant QTL were found for the first parity, but only 12 for the second parity. Only three QTL for maternal stillbirth, located on BTA7, 15 and 23, showed an experiment‐wise significance. Experiment II revealed 15 chromosome‐wise significant QTL. The results differed markedly between first and second parity within experiment I, as well as between experiment I and II. The present study showed that parity‐specific daughter yield deviations are beneficial for mapping QTL for calving traits. Furthermore, it is expected that the use of sharper phenotypes will also be advantageous for QTL fine mapping and the identification of candidate genes.
Calculating economic values for growth and functional traits in non‐dairy sheep
Authors: Wolfová M. , Wolf J. , Milerski M.
Published: November 2009

A bio‐economic model including a computer program was developed where a large number of parameters can be modified to describe a great variety of production systems. Economic values for up to 27 traits can be calculated. Seasonal feeding is considered and protein requirement in addition to net energy may be taken into account when calculating feed requirement. Furthermore, the model allows for the evaluation of individual parts of the growth curve. The model was applied to the Czech Suffolk breed used in pure‐breeding. An extensive pasture system with spring lambing and sale of surplus progeny for slaughter after weaning or after a finishing period was assumed. The economic values (in Euro cent per ewe, per year and per genetic standard deviation of the trait) were as follows: 9.9 for birth weight, −72.6 for mature weight, 142, 32.1 and 16.9 for growth rates till weaning, in rearing of breeding animals and in fattening, respectively, 19.9 and 101 for conception rate of female lambs and ewes, respectively, 690 for litter size per ewe lambing, 172 for productive lifetime of ewes, 402 and 503 for survival rate of lambs at lambing and till weaning, respectively, and 16.5 for fleece weight.
Screening 52 single nucleotide polymorphisms for extreme value of glycolytic potential and drip loss in pigs
Authors: Kamiński S. , Koćwin‐Podsiadła M. , Sieczkowska H. , Help H. , Zybert A. , Krzęcio E. , Antosik K. , Brym P. , Wójcik E. , Adamczyk G.
Published: November 2009

Low heritability of meat quality traits and the lack of their systematic registration in breeding programs have encouraged the search for single nucleotide polymorphisms (SNPs) located within genes coding the proteins involved in muscle and fat metabolism. In this report, a panel of 52 SNPs was used to find which alleles and genotypes are more/less frequent in groups of pigs differentiated by extreme value of glycolytic potential (GP) and drip loss (DL). The analysis was carried out in 52 fatteners (chosen from 246 pigs), of which 28 were Landrace and 27 Landrace × Yorkshire. Two designs were performed: I, fatteners were divided into two groups showing extreme value of GP (<125 versus >145), II, fatteners were divided into two groups showing extreme value of DL (<6.0 versus >6.0). Allele frequency differences between the phenotypic groups of extreme GL or DL were not influenced by the breed. The frequency of 52 SNPs alleles for each of group was calculated and a chi‐squared test was used to estimate the significance of differences in allele frequencies between alternative groups in each experimental design. Three SNPs (DECR1, PPARGC1, MC4R) and another two (CYP21, SFRS1) showed significant differences between groups of extreme GP and DL, respectively. To exemplify and validate potential associations of candidate SNPs for GP and DL, 293 fatteners representing three commercial breeds/crosses (95 Landrace, 66 Landrace × Yorkshire and 132 Landrace × Yorkshire × Duroc were genotyped for DECR1 and CYP21 by PCR‐RFLP assays. DECR1 showed significant associations with GP in Landrace and Landrace × Yorkshire × Duroc fatteners. CYP21 showed significant associations with DL in all breeds/crosses. Interestingly, the CYP21 polymorphism revealed adverse associations trend in Landrace × Yorkshire × Duroc pigs in comparison to Landrace and Landrace × Yorkshire fatteners.
Economic weights of production and functional traits for Holstein‐Friesian cattle in Hungary
Authors: Komlósi I. , Wolfová M. , Wolf J. , Farkas B. , Szendrei Z. , Béri B.
Published: November 2009

A bio‐economic model was used to estimate economic values of 15 milk production, functional, growth and carcass traits for Hungarian Holstein‐Friesian cattle. The calculations were carried out for the situation in Hungary from 2000 to 2007, assuming no production quotas. The marginal economic values were defined as partial derivatives of the profit function with respect to each trait in a production system with dairy cow herds and with sales of surplus male calves. The economic weights for maternal and direct components of traits were calculated multiplying the marginal economic values by the number of discounted expression summed over a 25‐year investment period for 2‐year‐old bulls (candidates for selection). The standardized economic weight (economic weight × genetic standard deviation) of the trait or trait component expressed as percentage of the sum of the standardized economic weights for all traits and trait components represented the relative economic importance of this trait or trait component. The highest relative economic importance was obtained for milk yield (25%), followed by productive lifetime of cows (23%), protein yield and the direct component of a cow’s total conception rate (9% each), the maternal effect of the total conception rate of cows and the somatic cell score (approximately 7% each), fat yield (5%) and mature weight of cows and daily gain in rearing of calves (approximately 4% each). Other functional traits (clinical mastitis incidence, calving difficulty score, total conception rate of heifers and calf mortality) reached a relative economic importance between 0.5% and 2%. Birth weight and dressing percentage were least important (<0.5%). Based on these results, the inclusion of productive lifetime and cow fertility in the breeding programme for Holstein‐Friesian cattle in Hungary is advisable.
Effects of Hydrogen Peroxide (H2O2) on Fresh and Cryopreserved Buffalo Sperm Functions During Incubation at 37°CIn Vitro
Authors: Garg A , Kumaresan A , Ansari MR
Published: November 2009

The magnitude of damage to buffalo spermatozoa during incubation with different levels of H2O2was assessed. A total number of 24 ejaculates from four Murrah buffalo bulls were analysed in the study. Each ejaculate was split into two parts (part I and II). Part I was extended in Tris–egg yolk–citrate extender (20% egg yolk:7% glycerol), equilibrated (4 h at 5°C) and cryopreserved in 0.5‐ml French straws and stored in liquid nitrogen. The other part was utilized for fresh semen studies. The sperm in fresh, equilibrated and frozen–thawed semen was separated by centrifugation (1500 g; 15 min) and were washed with sperm TALP. The sperm cells were re‐suspended in incubation TALP at the rate of 108sperm cells per millilitre and incubated with 0, 10, 25, and 50 μmH2O2per ml at 37°C. Sperm motility, viability and intact acrosome percentages were assessed at 15‐min intervals up to 60 min of incubation. Lipid peroxidation levels of sperm were assessed at 0 and 60 min of incubation. The results of the experiment revealed that sperm motility decreased drastically during incubation with H2O2. Among the different levels of H2O2, the 50‐μmH2O2‐incorporated group had significantly (p < 0.05) higher malonaldehyde (MDA) level than the other groups. In the 50‐μmH2O2‐incorporated group, the MDA levels in fresh, equilibrated and frozen–thawed semen after incubation for 60 min were 961.6 ± 12.7, 991.8 ± 10.3 and 1234.9 ± 9.6 nmper 109spermatozoa respectively. An inverse relationship was observed between sperm motility, viability, intact acrosome percentages and concentration of H2O2and duration of incubation. The decrease in sperm functions with duration of incubation and concentration of H2O2was significantly (p < 0.05) higher in frozen–thawed than fresh and equilibrated spermatozoa.
Extrarenal teratoid Wilms' tumor: Two cases in unusual locations, one associated with elevated serum AFP
Authors: Song Joon Seon , Kim In Koo , Kim Yong Man , Khang Shin‐Kwang , Kim Kyu‐Rae , Lee Yonghee
Published: November 2009

Teratoid Wilms' tumor is an unusual morphological entity characterized by a classic triphasic malignancy with predominantly heterologous tissue. The authors describe two cases of teratoid Wilms' tumor with an extrarenal site: one in a 13‐year‐old girl with vaginal spotting (patient 1) and another in a 1‐day‐old girl with a sacrococcygeal mass (patient 2). The tumors were located in the vagina and coccyx, respectively. Under the initial clinical diagnosis of sarcoma botryoides in patient 1 and teratoma in patient 2, the masses were removed. Microscopically, both tumors were composed of typical triphasic Wilms' tumor tissue with primitive cartilage and skeletal muscle, and squamous and columnar mucinous epithelia. The patient with sacrococcygeal mass (patient 2) had an elevated serum AFP level. The patients were given chemotherapy and have now remained disease free for 7 years 1 month, and 2 years 5 months after surgery, respectively. Familiarity with this rare variant of Wilms' tumor might be important in arriving at a correct diagnosis.
Observations in febrile children with round air space opacities
Authors: Fretzayas Andrew , Moustaki Maria , Alexopoulou Efthimia , Liapi Olga , Nicolaidou Polyxeni , Priftis Konstantinos N.
Published: November 2009

Background:  Community‐acquired pneumonia in children is rarely depicted as round opacity. The aim of the present study was therefore to describe the clinical and laboratory characteristics of round pneumonia in children.

Methods:  The clinical series consisted of 30 children aged 1–7 years (mean age, 3.4 ± 1.8 years) who were compared to an equal number of children with segmental or lobar pneumonia aged 3–11 years (mean age, 5.5 ± 2.7 years).

Results:  Round pneumonia was localized more often in the lower lobe (17/30), and the right side was more commonly affected (20/30). The same, however, was the case for the control group. The two groups were not different regarding the severity of the disease but cough was much more common in the control patients. The white blood cells were considerably higher in round pneumonia, whereas the other inflammatory indices were not significantly different. All round consolidations responded promptly to antibiotics and resolved radiographically in 8 weeks.

Conclusion:  Round consolidations in febrile children associated with elevated inflammatory indices seem to be attributed to round pneumonia, which responds promptly to antibiotics without complications.
Inflammatory bowel disease: a systematic review on the value of diagnostic testing in primary care
Authors: Jellema P. , van Tulder M. W. , van der Horst H. E. , Florie J. , Mulder C. J. , van der Windt D. A. W. M.
Published: November 2009

Aim  The clinical presentation of inflammatory bowel disease in primary care represents a diagnostic challenge as its symptoms are heterogeneous and common. To assist the primary care physician, we have summarized the available evidence on diagnostic tests in patients with abdominal symptoms.

Method  We searched PubMed and Embase and screened references. Studies were selected if the design was a primary diagnostic study. Patients were adults attending with nonacute abdominal symptoms. Tests included clinical assessment, blood or faecal tests or abdominal ultrasonography. Quality assessment using a modified version of the QUADAS tool and data extraction was performed by two reviewers independently. Diagnostic two‐by‐two tables and pooled estimates of sensitivity and specificity are given. We refrained from pooling when there was considerable clinical or statistical heterogeneity.

Results  A total of 24 studies were included. While the diagnostic performance of the individual symptoms was highly variable (range sensitivity 0.0–0.96, specificity 0.09–1.0), the performance of symptom‐based classification systems was both more consistent and better (sensitivity 0.65–1.0, specificity 0.17–0.82). Among faecal and blood tests, calprotectin was studied most frequently and showed the best results (sensitivity 0.61–1.0, specificity 0.71–1.0). Statistical pooling for ultrasonography resulted in a sensitivity of 0.73 (0.65–0.80) and a specificity of 0.95 (0.91–0.97).

Conclusion  Although calprotectin and ultrasonography showed consistent and promising findings, none of the studies was performed in primary care. To assist primary care physicians in diagnostic decision making, we urgently need high quality studies performed in primary care.
Laparoscopy for recurrent Crohn’s disease: how do the results compare with the results for primary Crohn’s disease?
Authors: Pinto R. A. , Shawki S. , Narita K. , Weiss E. G. , Wexner S. D.
Published: November 2009

Aim  To assess the feasibility and outcomes of reoperative laparoscopic‐assisted surgery for recurrent Crohn’s disease compared with index laparoscopic resections.

Method  A retrospective analysis of a prospectively maintained database was performed from 2001 to 2008 on patients who had primary laparoscopy (group I) or reoperative laparoscopy for Crohn’s disease (group II). Data collection included demographic and surgical data, and postoperative outcomes.

Results  One hundred and thirty patients were included in this study, distributed as follows: group I, 80 patients with a mean age of 35 years; and group II, 50 patients with a mean age of 42 years. Preoperative American Society of Anesthesiologists score and body mass index were similar in both groups. Patients in group II had a longer period of disease (15.5 vs 8.9 years in groups I and II, respectively; P = 0.0002). Immunosuppressive therapy had been utilized in 66 (82.5%) and in 42 (84%) patients in groups I and II, respectively. Ileocolic resection was the most commonly performed procedure in both groups (82%), followed by subtotal colectomy. Conversion rates were 18.7 and 32% in groups I and II, respectively (P = 0.09). The mean operative time (182 vs 201 min) and mean blood loss (161 vs 202 ml) were not significantly different (P > 0.05); however, the overall incisional length was significantly longer in group II (6.7 vs 11.4 cm, P = 0.045). A stoma was created in 17 and 16% of patients in groups I and II, respectively. Overall, early postoperative complications were not statistically significantly different between the two groups (P > 0.05); anastomotic leak occurred in four (5%) and one (2%) patients (P = 0.65), and abdominal abscess in three (3.75%) and four (8%) patients (P = 0.56), in groups I and II, respectively. Reoperative rates were 10 and 6% (P = 0.53), and mean hospital stay was similar in groups I and II respectively (6.7 vs 7.5 days, respectively; P = 0.3266). There was no mortality.

Conclusion  The results of laparoscopic‐assisted resection for recurrent Crohn’s disease are similar to those for primary resection.
Inguinal lymph node metastases are recognized with high frequency in rectal adenocarcinoma invading the dentate line. The histological features at the invasive front may predict inguinal lymph node metastasis
Authors: Hamano T. , Homma Y. , Otsuki Y. , Shimizu S. , Kobayashi H. , Kobayashi Y.
Published: November 2009

Aim  Inguinal lymph node (ILN) metastasis occurs with high frequency in some of the patients with lower rectal cancer. The aim of this study was to identify risk factors for ILN metastasis in patients with low rectal adenocarcinoma.

Method  We retrospectively analysed 156 patients with lower rectal adenocarcinoma who underwent radical resection (R0) at a single institution.

Results  Twenty‐five (16%) patients had a tumour that invaded the dentate line, seven of whom had ILN metastasis. Invasion of the dentate line was significantly associated with a high rate of ILN metastasis, worse prognosis and local recurrence than with a tumour not invading the dentate line (P = 0.03). A Cox proportional hazard regression analysis revealed the histological characteristics at the invading front (Hif) also to be a risk factor for ILN metastasis.

Conclusion  Tumours which invade the dentate line have a high rate of ILN metastases and worse cancer specific end‐points. The presence of poorly differentiated or mucinous adenocarcinoma components is an indication for bilateral groin irradiation.
In humans the adiponectin receptor R2 is expressed predominantly in adipose tissue and linked to the adipose tissue expression of MMIF‐1
Authors: Kos K. , Wong S. P. Y. , Huda M. S. B , Çakir M. , Jernas M. , Carlsson L. , Kerrigan D. , Wilding J. P. H. , Pinkney J. H.
Published: November 2009

In this study, the regional adipose tissue‐adiponectin (AT‐ADN) and adiponectin receptor (R1 and R2) expression and their relation with metabolic parameters, circulating and AT‐derived cytokine expressions were compared. Paired subcutaneous adipose tissue (SCAT) and visceral adipose tissue (VAT) were taken from 18 lean and 39 obese humans, AT‐mRNA expression of adipokines analysed by RT‐PCR and corresponding serum levels by enzyme‐linked immunosorbent assay (ELISA). R1 and R2 adipocyte expression was compared with 17 other human tissues.

ADN‐gene expression was lower in VAT than SCAT [mean (SD) 1.54 (1.1) vs. 2.84 (0.87); p < 0.001], and lower in obese subjects (VAT : p = 0.01;SCAT : p < 0.001). SCAT‐ADN correlated positively with serum ADN (r = 0.33;p = 0.036) but not VAT‐ADN. AT expressions of ADN and macrophage migration inhibiting factor (MMIF), IL18 and cluster of differentiation factor 14 (CD14) in both depots showed inverse correlations. R1 and R2 were expressed ubiquitously and R2 highest in SCAT, and this is much higher (×100) than R1 (×100). R expression was similar in lean and obese subjects and unrelated to the metabolic syndrome, however, receptors correlated with VAT‐MMIF (R 1: r = 0.4;p = 0.008;R 2: r = 0.35,p = 0.02) and SCAT‐MMIF expression (R 2: r = 0.43;p = 0.004).

Unlike ADN, its receptors are expressed in many human tissues. Human R2 expression is not highest in the liver but in AT where it is associated with MMIF expression. The adiponectin‐dependent insulin‐sensitizing action of thiazolidinediones is thus probably to differ amongst species with weaker effects on the human liver.
Frequency of zoledronic acid to prevent further bone loss in osteoporotic patients undergoing androgen deprivation therapy for prostate cancer
Authors: Wadhwa Vivek K. , Weston Robin , Parr Nigel J.
Published: November 2009

Study Type – Therapy (RCT) Level of Evidence 1b

OBJECTIVE

To evaluate the efficacy of zoledronic acid (ZA) in osteoporotic patients with prostate cancer receiving either luteinizing hormone‐releasing hormone agonists (LHRHA, which accelerate bone loss) or bicalutamide (which preserves bone mineral density, BMD) as androgen‐deprivation therapy is the mainstay of treatment for advanced prostate cancer, and many patients are osteoporotic at presentation, with others becoming so on treatment.

PATIENTS AND METHODS

Fifty‐eight osteoporotic men with non‐metastatic prostate cancer were followed for 3 years. Patients were randomly assigned to receive either LHRHA (29) or bicalutamide (29). All received 4 mg ZA 3‐monthly for 1 year. BMD was measured by dual energy X‐ray absorptiometry at four times: 1 year before ZA; immediately before ZA; after five infusions; and 1 year afterwards. Bone turnover markers (BTMs) were measured at 3‐monthly intervals on ZA and 1 year later. All patients had radiography of the thoracolumbar spine at baseline and after ZA.

RESULTS

Patients on LHRHA showed a 4.9% decrease in BMD before ZA, a 1.6% increase after ZA and a 3.0% decrease 1 year later, compared to 2.0% increase, 7.8% increase and 1.9% decrease, respectively, in those on bicalutamide. BTMs decreased significantly after ZA. Seven patients (12%) had vertebral fractures at baseline, with none deteriorating at 1 year; two (3.5%) developed mandibular osteonecrosis.

CONCLUSION

Before ZA, BMD decreased on LHRHA, but was maintained on bicalutamide. Treatment with 3‐monthly ZA increased BMD and suppressed BTMs in osteoporotic patients both on LHRHA and bicalutamide, but to a greater extent in the latter. However, 1 year after the last infusion, BMD declined, suggesting that annual administration is inadequate in these patients. The optimum frequency might be related to BMD at time of bisphosphonate initiation.
Very long half‐life plasminogen activator inhibitor type 1 reduces bleeding in a mouse model
Authors: Jankun Jerzy , Selman Steven H. , Keck Rick W. , Łysiak‐Szydłowska Wiesława , Skrzypczak‐Jankun Ewa
Published: November 2009

OBJECTIVE

To investigate the potential for the future clinical use of a very long half‐life plasminogen activator inhibitor type 1 (VLHL PAI‐1) as a haemostatic agent.

MATERIALS AND METHODS

We developed a VLHL PAI‐1 (half‐life >700 h) recombinant mutant of PAI‐1 and assessed VLHL PAI‐1 for its ability to inhibit fibrinolysis in vitro using human, rabbit, mouse and rat blood. Fibrin clot lysis time, monitored by thromboelastometry, was determined at various concentrations of VLHL PAI‐1. Also, we determined total bleeding time and total blood loss of control, VLHL PAI‐1‐, tissue‐type plasminogen activator (tPA)‐ and tPA + VLHL PAI‐1‐treated mice.

RESULTS

Using a thromboelastometer, mouse blood was most similar to human blood in its coagulation and fibrinolytic characteristics. We evaluated the affect of VLHL PAI‐1 on haemostasis using the mouse model and showed that VLHL PAI‐1 is an effective inhibitor of fibrin clot degradation. It reduced time of bleeding and total blood loss.

CONCLUSION

VLHL PAI‐1 may provide an important physiological mechanism to protect clots from premature dissolution in surgical and trauma settings.
Bipolar transurethral resection of the prostate causes less bleeding than the monopolar technique: a single‐centre randomized trial of 202 patients
Authors: Fagerström Tim , Nyman Claes R. , Hahn Robert G.
Published: November 2009

Study Type – Therapy (RCT) Level of Evidence 1b

OBJECTIVE

To compare bipolar with the conventional monopolar transurethral resection of the prostate (TURP) for blood loss and speed of resection.

PATIENTS AND METHODS

In all, 202 consecutive patients from the hospital waiting list were randomized to undergo TURP using either a bipolar system (Surgmaster TURis, Olympus, Tokyo, Japan) or a monopolar system (24 F, Storz, Tübingen, Germany). The blood loss during and after surgery was measured using a photometer. Other variables compared included indices of resection speed and transfusion rate.

RESULTS

There were no statistically significant differences in operative duration, resection weight, resection speed or radicality of resection. However, the median blood loss was 235 mL for the bipolar and 350 mL for monopolar TURP (P < 0.001). The decrease in blood haemoglobin concentration during the day of surgery was smaller in the bipolar group (5.5% vs 9.6%P < 0.001). Fewer patients were transfused with erythrocytes (4% vs 11%, P < 0.01), which can be explained by the much lower 75th percentile for blood loss in the bipolar group (at 472 vs 855 mL, respectively).

CONCLUSIONS

Bipolar TURP using the TURis system was performed with the same speed as monopolar TURP but caused 34% less bleeding, the difference being greatest (81%) for the largest blood losses. Bipolar TURP also required fewer erythrocyte transfusions than the conventional monopolar technique.
Advanced patient age is associated with inferior cancer‐specific survival after radical nephroureterectomy
Authors: Shariat Shahrokh F. , Godoy Guilherme , Lotan Yair , Droller Michael , Karakiewicz Pierre I. , Raman Jay D. , Isbarn Hendrik , Weizer Alon , Remzi Mesut , Roscigno Marco , Kikuchi Eiji , Bolenz Christian , Bensalah Karim , Koppie Theresa M. , Kassouf Wassim , Wheat Jeffrey C. , Zigeuner Richard , Langner Cord , Wood Christopher G. , Margulis Vitaly
Published: November 2009

Study Type – Prognosis (case series) Level of Evidence 4

OBJECTIVE

To assess the impact of patient age on outcomes after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC).

PATIENTS AND METHODS

Data were collected on 1453 patients treated with RNU at 13 centres. Pathological slides were reviewed by dedicated genitourinary pathologists according to standardized criteria. Age at RNU was analysed both as a continuous and categorical variable (<50, n = 85; 50–59.9, n = 229; 60–69.9, n = 416; 70–79.9, n = 523; ≥80 years, n = 200).

RESULTS

Patients aged <50 years were less likely to have undergone previous ureteroscopy and to have a history of bladder cancer (P ≤ 0.026). Advanced age was associated with infiltrative architecture and female gender (P ≤ 0.003). Patients aged >70 years were less likely to undergo lymphadenectomy and to receive adjuvant chemotherapy (P ≤ 0.026). In multivariable analyses, being older was associated with decreased all‐cause (AC) survival (>60 years) and cancer‐specific survival (CSS; >80 years) after controlling for the effects of standard pathological features (P ≤ 0.006). However, addition of age did not improve the predictive accuracy of a base model that included standard pathological features for prediction of either disease recurrence, AC survival or CSS.

CONCLUSIONS

Being older at the time of RNU was associated with decreased survival. This finding could be due to a change in the biological potential of the tumour cell, a decrease in the host’s defence mechanisms, or differences in care patterns. Further work is needed to improve our understanding of UTUC outcomes in this growing segment of the population and to develop strategies to improve cancer control in the elderly.
The effect of age and gender on bladder cancer: a critical review of the literature
Authors: Shariat Shahrokh F. , Sfakianos John P. , Droller Michael J. , Karakiewicz Pierre I. , Meryn Siegfried , Bochner Bernard H.
Published: November 2009

While patient age and gender are important factors in the clinical decision‐making for treating urothelial carcinoma of the bladder (UCB), there are no evidence‐based recommendations to guide healthcare professionals. We review previous reports on the influence of age and gender on the incidence, biology, mortality and treatment of UCB. Using MEDLINE, we searched for previous reports published between January 1966 and July 2009. While men are three to four times more likely to develop UCB than women, women present with more advanced disease and have worse survival rates. The disparity among genders is proposed to be the result of a differential exposure to carcinogens (i.e. tobacco and chemicals) as well as reflecting genetic, anatomical, hormonal, societal and environmental factors. Inpatient length of stay, referral patterns for haematuria and surgical outcomes suggest that inferior quality of care for women might be an additional cause of gender inequalities. Age is the greatest single risk factor for developing UCB and dying from it once diagnosed. Elderly patients face both clinical and institutional barriers to appropriate treatment; they receive less aggressive treatment and sub‐therapeutic dosing. Much evidence suggests that chronological age alone is an inadequate indicator in determining the clinical and behavioural response of older patients to UCB and its treatment. Epidemiological and mechanistic molecular studies should be encouraged to design, analyse and report gender‐ and age‐specific associations. Improved bladder cancer awareness in the lay and medical communities, careful patient selection, treatment tailored to the needs and the physiological and physical reserve of the individual patient, and proactive postoperative care are particularly important. We must strive to develop transdisciplinary collaborative efforts to provide tailored gender‐ and age‐specific care for patients with UCB.
Measurement delay associated with the Guardian® RT continuous glucose monitoring system
Authors: Wei C. , Lunn D. J. , Acerini C. L. , Allen J. M. , Larsen A. M. , Wilinska M. E. , Dunger D. B. , Hovorka R.
Published: November 2009

Diabet. Med.

Aims  Using compartment modelling, we assessed the time delay between blood glucose and sensor glucose measured by the Guardian® RT continuous glucose monitoring system in young subjects with Type 1 diabetes (T1D).

Methods  Twelve children and adolescents with T1D treated by continuous subcutaneous insulin infusion (male/female 7/5; age 13.1 ± 4.2 years; body mass index 21.9 ± 4.3 kg/m2; mean ± sd) were studied over 19 h in a Clinical Research Facility. Guardian® RT was calibrated every 6 h and sensor glucose measured every 5 min. Reference blood glucose was measured every 15 min using a YSI 2300 STAT Plus Analyser. A population compartment model of sensor glucose–blood glucose kinetics was adopted to estimate the time delay, the calibration scale and the calibration shift.

Results  The population median of the time delay was 15.8 (interquartile range 15.2, 16.5) min, which was corroborated by correlation analysis between blood glucose and 15‐min delayed sensor glucose. The delay has a relatively low intersubject variability, with 95% of individuals predicted to have delays between 10.4 and 24.3 min. Population medians (interquartile range) for the scale and shift are 0.800 (0.777, 0.823) (unitless) and 1.66 (1.47, 1.84) mmol/l, respectively.

Conclusions  In young subjects with T1D, the total time delay associated with the Guardian® RT system was approximately 15 min. This is twice that expected on physiological grounds, suggesting a 5‐ to 10‐min delay because of data processing. Delays above 25 min are rarely to be observed.
Determinants and Accounting Consequences of Forming a Governance Committee: Evidence from the United States
Authors: Huang Henry , Lobo Gerald J. , Zhou Jian
Published: November 2009

Manuscript Type: Empirical

Research Question/Issue: This study examines the determinants of forming a governance committee and whether such a committee constrains managerial opportunism.

Research Findings/Insights: This study examines a sample of S&P 1,500 firms over the period of 1996 to 2002. It finds that firms with a larger, more independent, and more active board, higher agency costs (as indicated by lower managerial ownership and lower takeover vulnerability), and past occurrence of class‐action lawsuits are more likely to voluntarily form a governance committee. This study also provides evidence that having a governance committee brings real consequences in that it constrains managerial opportunism by reducing aggressive financial reporting.

Theoretical/Academic Implications: Consistent with substitution theory, this study documents that a firm is more likely to form a governance committee to compensate for its severe agency problems. It also demonstrates that delegating some corporate governance duties to a specific board committee could improve the effectiveness of board monitoring.

Practitioner/Policy Implications: This study provides insights to regulators who are interested in regulating board structure. It suggests that whether a firm needs to form a governance committee is endogenously determined by the firm's characteristics when the firm has an independent board. In addition, this study documents that a voluntarily formed governance committee is able to mitigate agency costs in the form of constraining managerial accounting discretion.