bluuebunny/crossref_metadata_2025 huggingface dataset:
T‐helper 1 and T‐helper 2 adjuvants induce distinct differences in the magnitude, quality and kinetics of the early inflammatory response at the site of injection
Authors: Korsholm Karen Smith , Petersen Rune V. , Agger Else Marie , Andersen Peter
Published: July 2009

Vaccine adjuvants activate the innate immune system and thus influence subsequent adaptive T‐cell responses. However, little is known about the initial immune mechanisms preceding the adjuvant‐induced differentiation of T‐helper (Th) cells. The effect of a T‐helper 1 (Th1) adjuvant, dimethyldioctadecylammonium liposomes with monophosphoryl lipid‐A (DDA/MPL), and a T‐helper 2 adjuvant, aluminium hydroxide [Al(OH)3], on early, innate chemotactic signals and inflammatory cell influx at the site of injection was therefore investigated. Injection of the adjuvants into the peritoneal cavity of mice demonstrated distinct differences in the magnitude, quality and kinetics of the response. The inflammatory response to DDA/MPL was prominent, inducing high local levels of pro‐inflammatory cytokines, chemokines and a pronounced inflammatory exudate consisting of neutrophils, monocytes/macrophages and activated natural killer cells. This was in contrast to the response induced by Al(OH)3, which, although sharing some of the early chemokine signals, was more moderate and consisted almost exclusively of neutrophils and eosinophils. Notably, Al(OH)3 specifically induced the release of a significant amount of interleukin (IL)‐5, whereas DDA/MPL induced high amounts of tumour necrosis factor‐α (TNF‐α), IL‐1α and IL‐6. Finally, a microarray analysis confirmed that the effect of DDA/MPL was broader with more than five times as many genes being specifically up‐regulated after injection of DDA/MPL compared with Al(OH)3. Thus, the adjuvants induced qualitatively distinct local inflammatory signals early after injection.
Effect modification of endocrine disruptors and testicular germ cell tumour risk by hormone‐metabolizing genes
Authors: Chia V. M. , Li Y. , Quraishi S. M. , Graubard B. I. , Figueroa J. D. , Weber J‐P. , Chanock S. J. , Rubertone M. V. , Erickson R. L. , McGlynn K. A.
Published: July 2009

It has been hypothesized that the increased prevalence of testicular germ cell tumours (TGCT) may be attributable to endocrine disrupting chemicals, such as persistent organic pollutants (POPs); these may be modulated by hormone‐metabolizing enzymes. Using data from 568 cases and 698 controls enrolled in the US Servicemen’s Testicular Tumor Environmental and Endocrine Determinants Study, we examined associations between TGCT and POPs, including p,p′‐dichlorodiphenyldichloroethylene, chlordane‐related compounds and polychlorinated biphenyls (PCBs), modified by polymorphisms in five hormone‐metabolizing genes (CYP17A1, CYP1A1, HSD17B1, HSD17B4 and AR). Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression models that stratified associations of POP exposure and TGCT risk by genotype. Two polymorphisms in CYP1A1, rs1456432 and rs7495708, modified the association between trans‐nonachlor and total chlordanes and TGCT risk. Among men with a minor allele for rs1456432, those with the highest quartiles had an increased risk of TGCT (OR = 1.90, 95% CI, 1.01–3.56) compared with those with the lowest; there was no increased risk among men with the homozygous major allele genotype (p‐interactions = 0.024). Similar results were seen for rs7495708. HSD17B4 rs384346 modified the associations between TGCT risk and PCB‐118 and PCB‐138 concentrations: the 45–55% reductions in TGCT risk for men with the highest quartiles compared with the lowest quartiles were only present in those who had a major homozygous allele genotype (p‐interactions < 0.04). Thus, there are suggestions that certain CYP1A1 and HSD17B4 polymorphisms may modify the associations between POPs and TGCT risk. With false discovery rate values >0.2, however, caution is advisable when interpreting the findings of this study.
Does hybridization between divergent progenitors drive whole‐genome duplication?
Authors: BUGGS RICHARD J. A. , SOLTIS PAMELA S. , SOLTIS DOUGLAS E.
Published: July 2009

Hybridization and whole‐genome duplication are both potential mechanisms of rapid speciation which sometimes act in concert. Recent surveys, showing that homoploid hybrid species tend to be derived from parents that are less evolutionarily divergent than parents of polyploid hybrid species (allopolyploids), have been interpreted as supporting a hypothesis that high divergence between hybridizing species drives whole‐genome duplication. Here, we argue that such conclusions stem from problems in sampling (especially the omission of autopolyploids) and null model selection, and underestimate the importance of selection. The data simply demonstrate that hybridization between divergent parents has a higher probability of successfully producing a species if followed by polyploidization.
Identification of a Campylobacter jejuni‐secreted protein required for maximal invasion of host cells
Authors: Christensen Jeffrey E. , Pacheco Sophia A. , Konkel Michael E.
Published: July 2009

The food‐borne pathogen Campylobacter jejuni is dependent on a functional flagellum for motility and the export of virulence proteins that promote maximal host cell invasion. Both the flagellar and non‐flagellar proteins exported via the flagellar type III secretion system contain a sequence within the amino‐terminus that directs their export from the bacterial cell. Accordingly, we developed a genetic screen to identify C. jejuni genes that encode a type III secretion amino‐terminal sequence that utilizes the flagellar type III secretion system of Yersinia enterocolitica and a phospholipase reporter (yplA). We screened a library of 321 C. jejuni genes and identified proteins with putative type III secretion amino‐terminal sequences. One gene identified by the screen was Cj1242. We generated a mutation in Cj1242, and performed growth rate, motility, secretion and INT 407 cell adherence and internalization assays. The C. jejuni Cj1242 mutant was not altered in growth rate or motility when compared with the wild‐type strain, but displayed an altered secretion profile and a reduction in host cell internalization. Based on the phenotype of the C. jejuni Cj1242 mutant, we designated the protein Campylobacter invasion antigen C (CiaC). Collectively, our findings indicate that CiaC is a potentially important virulence factor.
Swallowing and respiratory pattern in young healthy individuals recorded with high temporal resolution
Authors: Boden K. , Hardemark Cedborg A. I. , Eriksson L. I. , Hedström H. Witt , Kuylenstierna R. , Sundman E. , Ekberg O.
Published: July 2009

Abstract  The coordination of swallowing and respiration is essential for a safe swallow. Swallowing consists of several subsecond events. To study this, it is important to use modalities with high temporal resolution. In this study, we have examined young healthy individuals with simultaneous videofluoroscopy, videomanometry and respiratory recording, all with high temporal resolution. The onset of 13 predetermined swallowing and respiratory events and the surrounding respiratory phase pattern were studied in different body positions and during different respiratory drives. An increased respiratory drive was induced by breathing 5% CO2. The results demonstrated a highly repeatable and fixed temporal coordination of the swallowing pattern despite body position and respiratory drive. Previous studies have demonstrated a period of centrally controlled apnoea during swallowing. This apnoea period has a variable length, varying from 1 to 5 s. During increased respiratory drive, we could demonstrate a significantly shorter period of apnoea during swallowing, mainly due to an earlier resumption of respiration. The high temporal recordings in this study have revealed that swallowing during expiration is present basically in all healthy individuals. This swallowing respiratory pattern seems to be appropriate for a safe swallow. This knowledge will be used as a reference for future studies on how swallowing and respiratory coordination might be altered due to ageing and diseases.
Association of the status of interstitial cells of Cajal and electrogastrogram parameters, gastric emptying and symptoms in patients with gastroparesis
Authors: Lin Z. , Sarosiek I. , Forster J. , Damjanov I. , Hou Q. , Mccallum R. W.
Published: July 2009

Abstract  Our goal was to investigate associations between the status of interstitial cells of Cajal (ICC) and electrogastrogram (EGG) parameters, gastric emptying and symptoms in a large cohort of patients with gastroparesis. Forty‐one patients with refractory gastroparesis who were referred for gastric electrical stimulation (GES) underwent full thickness gastric (antrum) biopsy during the surgery to place the GES device. The biopsy samples were stained with c‐kit and scored for the presence of ICC based on criteria obtained from 10 controls. All patients underwent EGG recordings, a 4‐h standardized scintigraphic gastric emptying study and symptom assessment prior to the surgery. Based on antral biopsy, 15 patients (36%) had almost no ICC (ICC− group) and 26 patients had adequate cell numbers (ICC+ group). EGG recordings in the ICC− group displayed significantly less normal slow waves than in the ICC+ group both in the fasting and fed states. Tachygastria in the ICC− group was significantly more than in the ICC+ group both in the fasting (32 ± 8%vs 11 ± 2%) and fed states (27 ± 9%vs 12 ± 2%). There was no statistical difference in gastric emptying, symptom severity of gastroparesis, aetiology, age and gender between the two groups. Severely depleted ICC occurs in up to 36% of gastroparetic patients and significantly correlates with an abnormal EGG. Severely depleted ICC does not correlate with the severity of gastroparesis as assessed by gastric emptying or symptom status but did result in a poorer symptomatic response to GES. These data suggest that the EGG may have a role for predicting ICC status during clinical evaluation of gastroparetic patients.
Neuropeptide S receptor 1 expression in the intestine and skin – putative role in peptide hormone secretion
Authors: Sundman L. , Saarialho‐kere U. , Vendelin J. , Lindfors K. , Assadi G. , Kaukinen K. , Westerholm‐ormio M. , Savilahti E. , Mäki M. , Alenius H. , D’amato M. , Pulkkinen V. , Kere J. , Saavalainen P.
Published: July 2009

Abstract  Neuropeptide S receptor 1 (NPSR1) was recently found to be genetically associated with inflammatory bowel disease in addition to asthma and related traits. Epithelia of several organs express NPSR1 isoforms A and B, including the intestine and the skin, and NPSR1 appears to be upregulated in inflammation. In this study, we used cell lines and tissue samples to characterize the expression of NPSR1 and its ligand neuropeptide S (NPS) in inflammation. We used polyclonal and monoclonal antibodies to investigate the expression of NPS and NPSR1 in intestinal diseases, such as celiac disease and food allergy, and in cutaneous inflammatory disorders. We found that NPSR1‐A was expressed by the enteroendocrine cells of the gut. Overall, the expression pattern of NPS was similar to its receptor suggesting an autocrine mechanism. In an NPSR1‐A overexpressing cell model, stimulation with NPS resulted in a dose‐dependent upregulation of glycoprotein hormone, alpha polypeptide (CGA), tachykinin 1 (TAC1), neurotensin (NTS) and galanin (GAL) encoding peptide hormones secreted by enteroendocrine cells. Because NPSR1 was also expressed in macrophages, neutrophils, and intraepithelial lymphocytes, we demonstrated that stimulation with the pro‐inflammatory cytokines tumour necrosis factor alpha and interferon gamma increased NPSR1 expression in the THP‐1 monocytic cells. In conclusion, similar to other neuropeptides and their receptors, NPSR1 signalling might play a dual role along the gut–brain axis. The NPS/NPSR1 pathway may participate in the regulation of the peptide hormone production in enteroendocrine cells of the small intestine.
Impact of delayed introduction of sulfadoxine–pyrimethamine and arthemeter–lumefantrine on malaria epidemiology in KwaZulu‐Natal, South Africa
Authors: Knight S. E. , Anyachebelu E. J. , Geddes R. , Maharaj R.
Published: July 2009

Objective  To investigate how delayed introduction of sulfadoxine–pyrimethamine (Fansidar®) and arthemeter–lumefantrine (Coartem®) as first‐line drugs for malaria in KwaZulu‐Natal contributed to the reported epidemics of 1985–1988 and 1997–2001.

Methods  Ecological study assessing the association between malaria incidence and the emergence and degree of resistance to chloroquine from 1982 to 1988 and to sulfadoxine–pyrimethamine from 1991 to 2001, when each was the first‐line malaria treatment.

Results  The relative risk for malaria infection after the level of drug resistance reached 10% was 4.5 (95% CI: 4.0–5.2) in the chloroquine period and 5.9 (95% CI: 5.7–6.1) in the sulfadoxine–pyrimethamine period. In the chloroquine period, the relative risk of death from malaria was tenfold (95% CI: 1.3–78.1) and the case fatality doubled after drug resistance had reached 10%. The risk of death during the sulfadoxine–pyrimethamine period was 10.8 (95% CI: 5.9–19.2) and case fatality 1.8 times higher after drug resistance had reached 10%, than before.

Conclusion  Malaria epidemics in KwaZulu‐Natal, South Africa have been exacerbated by failing drug regimens. The establishment of sentinel sites for monitoring drug failure and the prompt adoption of guidelines based on World Health Organization standards in drug resistance should improve malaria control.
Accuracy of WHO CD4 cell count criteria for virological failure of antiretroviral therapy
Authors: Keiser Olivia , MacPhail Patrick , Boulle Andrew , Wood Robin , Schechter Mauro , Dabis François , Sprinz Eduardo , Egger Matthias ,   for the ART‐LINC Collaboration of the International Databases to Evaluate AIDS (IeDEA)
Published: July 2009

Objectives  To examine the accuracy of the World Health Organization immunological criteria for virological failure of antiretroviral treatment.

Methods  Analysis of 10 treatment programmes in Africa and South America that monitor both CD4 cell counts and HIV‐1 viral load. Adult patients with at least two CD4 counts and viral load measurements between month 6 and 18 after starting a non‐nucleoside reverse transcriptase inhibitor‐based regimen were included. WHO immunological criteria include CD4 counts persistently <100 cells/μl, a fall below the baseline CD4 count, or a fall of >50% from the peak value. Virological failure was defined as two measurements ≥10 0000 copies/ml (higher threshold) or ≥500 copies/ml (lower threshold). Measures of accuracy with exact binomial 95% confidence intervals (CI) were calculated.

Results  A total of 2009 patients were included. During 1856 person‐years of follow up 63 patients met the immunological criteria and 35 patients (higher threshold) and 95 patients (lower threshold) met the virological criteria. Sensitivity [95% confidence interval (CI)] was 17.1% (6.6–33.6%) for the higher and 12.6% (6.7–21.0%) for the lower threshold. Corresponding results for specificity were 97.1% (96.3–97.8%) and 97.3% (96.5–98.0%), for positive predictive value 9.5% (3.6–19.6%) and 19.0% (10.2–30.9%) and for negative predictive value 98.5% (97.9–99.0%) and 95.7% (94.7–96.6%).

Conclusions  The positive predictive value of the WHO immunological criteria for virological failure of antiretroviral treatment in resource‐limited settings is poor, but the negative predictive value is high. Immunological criteria are more appropriate for ruling out than for ruling in virological failure in resource‐limited settings.
Low level genotypic chloroquine resistance near Malawi’s northern border with Tanzania
Authors: Bridges Daniel J. , Molyneux Malcolm , Nkhoma Standwell
Published: July 2009

We conducted a prevalence study of mutations in Plasmodium falciparum that are associated with antimalarial drug resistance at a rural site in Karonga near Malawi’s northern border with Tanzania. We found a higher prevalence of the key chloroquine resistance‐conferring mutation in the pfcrt gene (K76T) at this site in comparison with the prevalence in Blantyre, a city in the south of Malawi, far from an international border (9%vs. 0%; P < 0.0005). In contrast we found a lower prevalence of the quintuple dhfr/dhps mutation, which is highly predictive of SP treatment failure, at the Karonga site compared to Blantyre (76%vs. 88%; P < 0.005). The prevalence of the K76T pfcrt mutation at two Tanzanian sites close to the border with Malawi was recently reported to be over 50%. Our findings suggest a considerable ‘leakage’ of parasite antimalarial drug resistance across the border between two countries with different national malaria control policies and with different levels of resistance. Neighbouring countries should consider implementing common regional rather than national malaria treatment policies to prevent the spread of antimalarial drug resistance alleles across their borders.
Instability of the structure and allergenic protein content in Arizona cypress pollen
Authors: Shahali Y. , Pourpak Z. , Moin M. , Mari A. , Majd A.
Published: July 2009

Background:  The allergenic characteristics of pollen and their levels of expression may vary depending on the plant species, the degree of maturation and the influence of environmental factors such as climate and atmospheric pollution. The objective of this survey was the comparison of the structure and allergenic protein content in Arizona cypress (Cupressus arizonica, CA) pollen collected just after microsporangia dehiscence and 2 weeks later in urban areas.

Methods:  The morphology and structure of pollen were examined by scanning electron microscopy. Pollen protein content was quantitatively and qualitatively investigated by Bradford protein assay, SDS‐PAGE and densitometric analysis respectively. Fifteen allergic subjects, according to their clinical history of seasonal rhino‐conjunctivitis and bronchial asthma have been selected for skin prick testing and ImmunoCap using CA standard allergen and for immunoblotting using extracts of CA mature pollen collected from Tehran.

Results:  After 2 weeks, numerous cracks and collapses appeared in pollen surfaces. Western blotting performed by using extracts of pollen collected from Tehran, revealed that sera‐specific immunoglobulin E of all allergic subjects reacted to a 35 kDa protein. The presence of this new major allergen and the decrease of Cup a 1 provide reliable explications about the low efficiency of standard commercial allergens in the diagnosis of the CA pollen allergy in Tehran.

Conclusion:  The instability of the pollen structure and protein content affects CA pollen allergenic properties. This study also suggests that to optimize CA standard allergen preparations, the eventual variability of pollen allergenic components have to be considered for each region.
Clostridium difficile‐associated disease in allogeneic hematopoietic stem‐cell transplant recipients: risk associations, protective associations, and outcomes
Authors: Dubberke Erik R. , Reske Kimberlay A. , Srivastava Anand , Sadhu Justin , Gatti Robert , Young Rebecca M. , Rakes Lauren C. , Dieckgraefe Brian , DiPersio John , Fraser Victoria J.
Published: July 2009

Dubberke ER, Reske KA, Srivastava A, Sadhu J, Gatti R, Young RM, Rakes LC, Dieckgraefe B, DiPersio J, Fraser VJ. Clostridium difficile‐associated disease in allogeneic hematopoietic stem‐cell transplant recipients: risk associations, protective associations, and outcomes. Clin Transplant 2009. DOI: 10.1111/j.1399‐0012.2009.01035.x © 2009 John Wiley & Sons A/S.

Abstract:  The purpose of this study was to evaluate risk factors, protective factors, and outcomes associated with Clostridium difficile‐associated disease (CDAD) in allogeneic hematopoietic stem‐cell transplant (HSCT) recipients. A case–control study was performed with 37 CDAD cases and 67 controls. In the multivariable logistic regression analysis, receipt of a third or fourth generation cephalosporin was associated with increased risk of CDAD (OR = 4.6, 95% CI 1.6–13.1). Receipt of growth factors was associated with decreased risk of CDAD (OR=0.1, 95% CI 0.02–0.3). Cases were more likely to develop a blood stream infection after CDAD than were controls at any point before discharge (p < 0.001). CDAD cases were more likely than controls to develop new onset graft‐vs.‐host disease (GVHD) (p < 0.001), new onset severe GVHD (p < 0.001), or new onset gut GVHD (p = 0.007) after CDAD/discharge. Severe CDAD was a risk factor for death at 180 d in multivariable Cox proportional hazards regression (HR=2.6, 95% CI 1.1–6.2). CDAD is a significant cause of morbidity and mortality in allogeneic HSCT patients, but modifiable risk factors exist. Further study is needed to determine the best methods of decreasing patients’ risk of CDAD.
Effects of acorn tannin content on infection by the fungus Ciboria batschiana
Authors: Takahashi A. , Ichihara Y. , Isagi Y. , Shimada T.
Published: July 2009

Ciboria batschiana, a fructicolous Discomycete, is a pathogen of Quercus serrata acorns, which contain considerable amounts of tannins in the cotyledons. It was hypothesized that the severity of C. batschiana infection may differ according to individual acorn tannin content. To examine this hypothesis, we investigated the relationship between survival of acorns to C. batschiana and tannin content, estimated non‐destructively using near infrared spectroscopy analysis. In addition, an inoculation experiment showed that acorns with higher tannin contents were more resistant to C. batschiana than those with lower tannin contents. We conclude that infection success of C. batschiana differs with tannin content of individual acorns.
Abnormal Expression of TIMP‐2, SOD, Vimentin and PAI Proteins in Cloned Bovine Placentae
Authors: Kim H‐R , Naruse K , Lee H‐R , Han R‐X , Park C‐S , Jin D‐I
Published: July 2009

Contents

Cloned mammals suffer from high rates of placental abnormality and foetal loss during pregnancy. We previously used 2‐D gel electrophoresis and mass spectrometry for global proteomic analysis of cloned and normal bovine placentae to identify differential protein expression patterns. Here, we used Western blot analysis to confirm the expression levels of several pregnancy‐related proteins putatively identified as being differentially expressed in somatic cell nuclear transfer (SCNT) vs normal bovine placentae. The expression levels of tissue inhibitor of metalloproteinase‐2 (TIMP‐2), its downstream protein, matrix metalloproteinase‐2 (MMP‐2), superoxide dismutase (SOD), vimentin and plasminogen activator inhibitor‐1 (PAI) were analysed in the placentae of SCNT cloned Korean native cattle that died immediately after birth and in normal placentae obtained by AI. Our results revealed that TIMP‐2 and SOD were up‐regulated in SCNT placenta compared with normal placenta, whereas MMP‐2 levels were comparable in cloned and normal placentae, and vimentin and PAI were significantly down‐regulated in SCNT compared with normal placentae. Our results suggest that key proteins of placental development are abnormally expressed in SCNT cloned bovine placentae, probably resulting in abnormal placental function and clonal mortality.
Biliary deposition of Liesegang rings presenting as a polypoid mass in the liver: Previously unrecognized lesion
Authors: Onodera Manabu , Sato Yasunori , Ikeda Hiroko , Zen Yoh , Sakai Seisyo , Syoji Masao , Sakamoto Koya , Tani Takashi , Asaka Masahiro , Nakanuma Yasuni
Published: July 2009

Liesegang rings (LR) are acellular, laminated structures that may be deposited within and around cysts and inflamed or necrotic tissue. Previous reports have shown that the kidney and breast are commonly affected organs of LR. Herein is reported a rare case of biliary deposition of LR presenting as a tumor‐like polypoid mass in the liver. A 70‐year‐old man was found to have a cystic lesion, measuring 3.0 cm in diameter, in the lateral segment of the liver. The lesion was accompanied by a solid mass, 1.8 cm in diameter, within the cystic cavity. Lateral segmentectomy of the liver was performed because clinical examinations could not exclude the possibility of hepatobiliary cystadenoma or cystadenocarcinoma. Pathology of the resected specimen indicated a soft polypoid mass, connecting to the cystically dilated bile duct with elongated stalk‐like structures. Histologically the surface of the mass was covered by non‐neoplastic biliary‐type epithelium. Beneath the epithelium, extensive deposition of numerous ring‐like laminated structures, which exhibited an identical appearance to LR, was observed. This is a unique and previously unrecognized lesion involving the occurrence of LR deposition in the hepatobiliary tracts, which further formed a grossly visible mass resembling a hepatic tumor.
Malignant pleural mesothelioma initially diagnosed on cervical lymph node biopsy
Authors: Ogata Sho , Hiroi Sadayuki , Tominaga Akira , Aida Shinsuke , Kobayashi Ayako , Tamura Katsumi , Abe Yoshiyuki , Kawai Toshiaki
Published: July 2009

Reported herein is a case of malignant pleural mesothelioma, initially diagnosed on cervical lymph node biopsy. A 58‐year‐old man, without obvious evidence of asbestos exposure, exhibited repeated pleural effusion (cause unclear), which was resolved by diuretics. A neck mass was apparent and was identified pathologically as a lymph node metastasis of malignant mesothelioma. F‐18 fluorodeoxyglucose positron emission tomography/CT established the diagnosis of malignant pleural mesothelioma. Two conclusions emerge from this report: (i) cervical lymph node metastasis of pleural mesothelioma, although rare, should be included in differential diagnosis; and (ii) positron emission tomography/CT is useful for establishing a diagnosis of mesothelioma.
Breast‐feeding and overweight in Singapore school children
Authors: Sabanayagam Charumathi , Shankar Anoop , Chong Yap‐Seng , Wong Tien Yin , Saw Seang Mei
Published: July 2009

Background:  Studies from developed Western countries have shown inconsistent associations between breast‐feeding and overweight/obesity in children and adolescents. Few data are available from Asian populations. The purpose of the present study was therefore to evaluate the association between breast‐feeding and overweight/obesity in a study of 10–12‐year‐old children in Singapore.

Methods:  A total of 797 school children (49% girls, 76% Chinese) who participated in the Singapore Cohort Study of the Risk Factors for Myopia (SCORM) were examined. Overweight/obesity (n = 179) was defined as age–sex‐specific body mass index (BMI) cut‐offs corresponding to BMI of 25 kg/m2 for overweight and 30 kg/m2 for obesity at age 18 based on the International Obesity Task Force (IOTF) reference.

Results:  The prevalence of overweight/obesity was 22.5%. Overall, breast‐feeding was not found to be associated with overweight/obesity. After adjusting for potential confounders, the multivariable odds ratio (95% confidence interval) of overweight/obesity was 1.14 (0.80–1.63) for ever breast‐fed compared with never breast‐fed, 1.00 (0.57–1.72) for breast‐fed for >3 months compared to ≤3 months and 0.79 (0.47–1.34) for exclusive/mostly breast‐fed compared to partly breast‐fed.

Conclusions:  No significant associations were detected among breast‐feeding, its type, and duration with overweight/obesity in this Asian cohort of 10–12‐year‐old children.
Pediatric models for adult target‐controlled infusion pumps
Authors: ANDERSON BRIAN J.
Published: July 2009

Target‐controlled infusion (TCI) pumps currently do not satisfactorily cater for the pediatric population, particularly for those under 5 years. Growth and development are two major aspects of children not readily apparent in adults, and these two aspects influence clearance (CL) and volume of distribution (V). In simple terms, V determines initial dose, and CL determines infusion rate at steady state. Three major covariates (size, age, and organ function) contribute to parameter variability in children. Size can be standardized for clearance in a 70‐kg person using the allometric ¾ power model. Remifentanil, a drug cleared by hydrolysis, can be modeled in all age groups by simple application of this model using a standardized clearance of 2790 ml·min−1 for a 70‐kg person. Allometry alone is insufficient to predict clearance in neonates and infants from adult parameters for most drugs used in anesthesia. The addition of a model describing maturation is required. The sigmoid Emax or Hill model has been found useful for describing this maturation process. Propofol maturation has been described with a mature clearance of 1.83 l·min−1·70kg−1, a maturation half‐time (TM50) of 44 weeks and a Hill coefficient of 4.9. Organ function also affects clearance, and propofol clearance is reduced in neonates and infants after cardiac surgery. Although pharmacokinetics (PK) in children is receiving increasing attention and is eminently programmable into a TCI device, pharmacodynamic (PD) measures in children remain poorly defined, partly because the depth of anesthesia monitoring are inadequate. Both PK and PD are necessary for safe use of TCI pumps.
GeoChip‐based analysis of functional microbial communities during the reoxidation of a bioreduced uranium‐contaminated aquifer
Authors: Van Nostrand Joy D. , Wu Wei‐Min , Wu Liyou , Deng Ye , Carley Jack , Carroll Sue , He Zhili , Gu Baohua , Luo Jian , Criddle Craig S. , Watson David B. , Jardine Philip M. , Marsh Terence L. , Tiedje James M. , Hazen Terry C. , Zhou Jizhong
Published: July 2009

A pilot‐scale system was established for in situ biostimulation of U(VI) reduction by ethanol addition at the US Department of Energy's (DOE's) Field Research Center (Oak Ridge, TN). After achieving U(VI) reduction, stability of the bioreduced U(IV) was evaluated under conditions of (i) resting (no ethanol injection), (ii) reoxidation by introducing dissolved oxygen (DO), and (iii) reinjection of ethanol. GeoChip, a functional gene array with probes for N, S and C cycling, metal resistance and contaminant degradation genes, was used for monitoring groundwater microbial communities. High diversity of all major functional groups was observed during all experimental phases. The microbial community was extremely responsive to ethanol, showing a substantial change in community structure with increased gene number and diversity after ethanol injections resumed. While gene numbers showed considerable variations, the relative abundance (i.e. percentage of each gene category) of most gene groups changed little. During the reoxidation period, U(VI) increased, suggesting reoxidation of reduced U(IV). However, when introduction of DO was stopped, U(VI) reduction resumed and returned to pre‐reoxidation levels. These findings suggest that the community in this system can be stimulated and that the ability to reduce U(VI) can be maintained by the addition of electron donors. This biostimulation approach may potentially offer an effective means for the bioremediation of U(VI)‐contaminated sites.
Key targets of hormonal treatment of prostate cancer. Part 2: the androgen receptor and 5α‐reductase
Authors: Vis André N. , Schröder Fritz H.
Published: July 2009

OBJECTIVE

The inhibition of 5α‐reductase (5AR) blocks the synthesis of the most powerful intracellular androgen, dihydrotestosterone (DHT). The prostate has two 5AR isoenzymes (5AR1 and 5AR2) that change in expression and cellular location during the development of prostate cancer and tumour progression. The objective of this review is to provide an understanding of the pharmacological properties and the potential clinical benefits of 5AR inhibition.

METHODS

We searched Pubmed for data obtained from pharmacological, preclinical and clinical studies.

RESULTS

5AR1 expression increases with increasing aggressiveness and extension of malignant prostatic disease. Conversely, 5AR2 expression decreases from benign prostatic tissue to localized prostate cancer. The efficacy of 5AR2 monotherapy with finasteride alone or in combination with an androgen receptor antagonist on more final outcome measures seems to be limited. Combining an androgen receptor antagonist with a 5AR inhibitor in patients with asymptomatic, locally advanced or recurrent prostate cancer might be a reasonable first therapeutic hormonal approach. As plasma testosterone levels are maintained, beneficial effects on quality of life, potency and sexual function are expected. From studies on the dual 5AR inhibitor dutasteride, the drug produces a biochemical response in some men who progressed under androgen‐deprivation therapy, and is generally well tolerated.

CONCLUSIONS

Achieving more potent suppression of intracellular DHT synthesis by 5AR inhibition is expected to provide clinical benefit to patients. Previous studies have shown that 5AR inhibition, by dutasteride in particular, halts/delays the progression of disease, and might even cause regression of disease in patients with advanced prostate cancer.
Secondary neoplasms of the urinary system and male genital organs
Authors: Morichetti Doriana , Mazzucchelli Roberta , Lopez‐Beltran Antonio , Cheng Liang , Scarpelli Marina , Kirkali Ziya , Montorsi Francesco , Montironi Rodolfo
Published: July 2009

BACKGROUND AND AIMS

In this review we discuss those secondary tumours involving the urinary system and male genital organs that can pose differential diagnostic difficulties with primary lesions, and highlight morphological and ancillary features that could be helpful in reaching a proper assignment of primary origin.

materials AND METHODS

Based on MEDLINE database searches all reports of secondary tumours involving the urinary system (kidney and bladder) and male genital organs (prostate, testis and penis) were examined.

RESULTS and discussion

Involvement by a secondary tumour occurs either as a metastasis or by direct extension. Among non‐genitourinary primary sites, colorectal, pulmonary, skin (melanoma) and breast are the most common contributors. Secondary spread from a genitourinary site primary tumour to another genitourinary organ occurs most frequently between the prostate and urinary bladder, given the intimate topographic proximity of the two. The prognosis is very poor, as the secondary tumour usually occurs in patients with carcinoma in the late stages. Few secondary tumours have distinctive histological and immunohistochemical features, making it difficult to make the appropriate diagnosis. Hence, knowledge of the history and clinical setting are particularly important in these cases.

CONCLUSION

The urinary system and male genital organs are not common sites for secondary tumours. They often go either undiagnosed or misdiagnosed in the clinical follow‐up of patients with cancer. Accurate diagnosis is essential because of differing therapeutic approaches compared with a primary neoplasm.
Androgen receptor expression is associated with prostate cancer‐specific survival in castrate patients with metastatic disease
Authors: Donovan Michael J. , Osman Iman , Khan Faisal M. , Vengrenyuk Yevgen , Capodieci Paola , Koscuiszka Michael , Anand Aseem , Cordon‐Cardo Carlos , Costa Jose , Scher Howard I.
Published: July 2009

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

OBJECTIVE

To investigate whether baseline (before treatment) clinical variables and tumour specimen characteristics (including the androgen receptor, AR) from patients with castrate‐resistant metastatic prostate cancer can be used to predict the time to prostate cancer‐specific mortality and overall survival, as AR levels in prostate cancer have been associated with disease progression, including prostate‐specific antigen (PSA) recurrence and systemic metastasis.

PATIENTS AND METHODS

Haematoxylin and eosin (H&E) slides/blocks and outcome data from a 104 castrate patients with metastatic disease (43 prostatectomy and 61 prostate needle biopsy samples), were independently reviewed; H&E morphometry and quantitative immunofluorescence were used to assess the samples. Sections were analysed with a multiplex quantitative immunofluorescence (IF) assay for cytokeratin‐18 (epithelial cells), 4′,6‐diamidino‐2‐phenylindole (nuclei), p63/high molecular weight keratin (basal cells), AR and α‐methyl CoA‐racemase. Images were acquired with spectral imaging software and processed for quantification with IF algorithms.

RESULTS

The median follow‐up was 12 years from diagnosis; 49 men (47%) baseline PSA levels of ≥ 20 ng/mL, 55 (53%) had a Gleason sum of 8, 63 (60%) died from the disease and 40% were alive (censored). In all, 66 patients had evaluable IF features, and the association with outcome was evaluated by univariate Cox modelling and support‐vector regression. PSA was the only clinical variable associated with outcome (concordance index, CoI, 0.41; P < 0.05, log‐rank test). The amount of AR present within tumour nuclei (regardless of tissue provenance and primary treatment) significantly correlated with a greater risk of a shorter time to prostate cancer‐specific mortality (CoI 0.36; P < 0.05 log‐rank test). There were no H&E features that correlated with mortality.

CONCLUSION

By univariate analysis, increased nuclear AR expression in either the diagnostic biopsy and/or radical prostatectomy specimen, from patients with advanced disease, was associated with a reduced time to prostate cancer‐specific mortality.
Archetypes of famine and response
Authors: Howe Paul
Published: July 2009

Famines have long been characterised by rapidly shifting dynamics: sudden price spirals, sharp increases in mortality, the media frenzy that often accompanies such spikes, the swift scaling up of aid flows, and a subsequent decline in interest. In arguing that these aspects of famine have been largely ignored in recent years due to attention to the ‘famine process’, this paper attempts to make these dynamics more explicit by applying systems thinking. It uses standard archetypes of systems thinking to explain six situations—watch, price spiral, aid magnet, media frenzy, overshoot, and peaks—that are present in many famine contexts. It illustrates their application with examples from crises in Ethiopia, Malawi, Niger, and Sudan. The paper contends that the systems approach offers a tool for analysing the larger patterns in famines and for pinpointing the most appropriate responses to them, based on an awareness of the dynamics of the crises.
An exploratory study on perceptions of seismic risk and mitigation in two districts of Istanbul
Authors: Eraybar Korel , Okazaki Kenji , Ilki Alper
Published: July 2009

Istanbul is one of the world's cities most vulnerable to seismic events. According to seismologists, the probability of a severe earthquake in the next 30 years is approximately 40 per cent. Following an outline of the seismicity of this vital Turkish city and a summary of current seismic risks and mitigation studies, this paper presents the results of a survey conducted in two districts of Istanbul, Avcilar and Bakirkoy. The survey comprised some 60 questions on the seismic risk perceptions of individuals and requested basic personal data, such as on age, education level, employment type, financial income, and gender. Despite various differences among the survey population, such as academic background and level of financial income, responses were surprisingly similar, especially in terms of having no plan for a safer house. The data may help those planning mitigation programmes and public awareness campaigns on preparedness and particularly mitigation in highly vulnerable regions.
IMMORTALITY WITHOUT BOREDOM
Authors: Bortolotti Lisa , Nagasawa Yujin
Published: July 2009

In this paper we address Bernard Williams' argument for the undesirability of immortality. Williams argues that unavoidable and pervasive boredom would characterise the immortal life of an individual with unchanging categorical desires. We resist this conclusion on the basis of the distinction between habitual and situational boredom and a psychologically realistic account of significant factors in the formation of boredom. We conclude that Williams has offered no persuasive argument for the necessity of boredom in the immortal life.1
WHAT IS PHYSICALISM?
Authors: Göcke Benedikt Paul
Published: July 2009

Although ‘most contemporary analytic philosophers [endorse] a physicalist picture of the world’ (A. Newen; V. Hoffmann; M. Esfeld, ‘Preface to Mental Causation, Externalism and Self‐Knowledge’, Erkenntnis, 67 (2007), p. 147), it is unclear what exactly the physicalist thesis states. The response that physicalism is the thesis that everything is physical does not solve the problem but is a precise statement of the problem because ‘the claim is hopelessly vague’ (G. Hellman; F. Thompson, ‘Physicalism: Ontology, Determination, and Reduction’, Journal of Philosophy, 72 (1975), p. 552). I argue that physicalism in fact should be the thesis that every existing particular essentially exemplifies properties the exemplification of which does not conceptually entail the existence of conscious beings. Physicalism thus is a purely philosophical thesis with no intrinsic relation to physics.1
WHAT IS NATURAL ABOUT FOOT'S ETHICAL NATURALISM?
Authors: Hacker‐Wright John
Published: July 2009

Philippa Foot's Natural Goodness is in the midst of a cool reception. It appears that this is due to the fact that Foot's naturalism draws on a picture of the biological world at odds with the view embraced by most scientists and philosophers. Foot's readers commonly assume that the account of the biological world that she must want to adhere to, and that she nevertheless mistakenly departs from, is the account offered by contemporary neo‐Darwinian biological sciences. But as is evident in her notion of function, Foot does not employ an evolutionary view of the biological world. I will attempt to show, first, that it is for good reason that Foot is not operating with an evolutionary view of function; her views do not aim to unseat evolutionary views of function, but instead simply have quite different theoretical goals. Second, I aim to underline the importance to Foot's naturalism of the fact that we are practically reasoning creatures. The profundity of Foot's ethical naturalism rests in how she approaches our nature as practically reasoning creatures. In this aspect of Foot's thought, there is a significant Kantian strain that is surprising to find in someone who calls herself an ethical naturalist.1
POLITICAL OBLIGATION AND THE PARTICULARITY PROBLEM
Authors: Markie P. J.
Published: July 2009

Natural duty theorists of political obligation try to base a moral duty to obey the law on some natural duty, such as the duty to promote justice. Their critics say they confront an insurmountable obstacle in the particularity problem: Since natural duties do not bind us to some persons and institutions more strongly than to others, they cannot support a duty to one particular state or society. I solve the particularity problem, by developing a version of the political obligation thesis, giving a natural duty argument for it and showing that the particularity problem does not arise for the argument. I reply to some likely objections to my view.
Exchange Rate Volatility and Output Volatility: A Theoretical Approach*
Authors: Grydaki Maria , Fountas Stilianos
Published: July 2009

This paper makes an attempt to determine the factors influencing exchange rate and exchange rate uncertainty, as well as output and output variability. In the context of a small open economy under flexible exchange rates regime it is found that the level both of exchange rate and output is affected by monetary and inflationary shocks, as well as shocks in government spending, output, and trade balance. Further, the uncertainty of exchange rate and output is associated positively with the uncertainty of all shocks while the contemporaneous occurrence of selected shocks imposes either a positive or negative impact on exchange rate and output volatility. Finally, it is shown that the effect of the determinants either of exchange rate volatility or output volatility is very sensitive to the parameter values.
Fiscal Convergence, Business Cycle Volatility, and Growth
Authors: Furceri Davide
Published: July 2009

This paper analyzes the effects of fiscal convergence on business cycle volatility and growth. Using a panel of 11 EMU and 21 OECD countries and 40 years of data, we find that countries with similar government budget positions tend to have smoother business cycles. That is, fiscal convergence (in the form of persistently similar ratios of government surplus/deficit to GDP) is systematically associated with smoother business cycles. We also find evidence that reduced business cycle volatility through higher fiscal convergence stimulates growth. Our empirical results are economically and statistically significant, and robust.
A HISTORY OF RESEARCH INTO CANARIAN ROCK ART: OPENING UP NEW THOUGHTS
Authors: FARRUJIA DE LA ROSA A. JOSÉ
Published: July 2009

Research into the history of Canarian rock art presents major problems, both theoretical and methodological. This paper analyses the evolution of research into Canarian rock art from a historical and diachronic perspective. It also addresses the connection established between the Canary Islands, North Africa and the Atlantic area, focusing on the theoretical models developed to explain these relationships. The analysis therefore covers a period of seven centuries (fourteenth–twentieth centuries).
THE DOUET ALIGNMENT ON THE ISLAND OF HOEDIC (MORBIHAN, FRANCE): NEW INSIGHTS INTO STANDING STONE ALIGNMENTS IN BRITTANY
Authors: LARGE JEAN‐MARC , MENS EMMANUEL
Published: July 2009

The island of Hoedic in southern Brittany has numerous archaeological remains of later prehistoric date. It became famous through the discovery in the 1930s of a Mesolithic cemetery, but the island also has abundant archaeological evidence from the earliest Neolithic period onwards. These include several megalithic monuments, the most significant being alignments of standing stones. One of these alignments has recently been excavated, and investigation of another is in progress. The discoveries resulting from this work provide new insights into the origin of the phenomenon, its chronological and cultural context and the techniques that were used to create these structures. Above all, it offers a new approach to considering the meaning of these alignments.
RADIOCARBON‐DATED DESTRUCTION LAYERS: A SKELETON FOR IRON AGE CHRONOLOGY IN THE LEVANT
Authors: FINKELSTEIN ISRAEL , PIASETZKY ELI
Published: July 2009

We present a full‐sequence radiocarbon‐based chronological system for the Iron Age in the Levant, anchored on the dating of ten destruction layers for the years 1130–730 BC. We establish the sequence using two methods – the ‘uncalibrated weighted average’ and the Bayesian modelling. Utilizing four dating tools in combination – radiocarbon measurements, field stratigraphy, pottery typology and ancient Near Eastern historical records – facilitates solutions to chronological problems that are far beyond the resolving power of 14C dating alone. The results shed light on disputed issues related to biblical and ancient Near Eastern history, such as the expansion of the early Israelite polity from the highlands to the lowlands; the nature of the Shoshenq I campaign to Canaan; and the evolution of the conflict between northern Israel and Aram Damascus.