bluuebunny/crossref_metadata_2025 huggingface dataset:
Prophylactic antibiotic treatment is superior to therapy on-demand in experimental necrotising pancreatitis
Authors: Fritz Stefan , Hartwig Werner , Lehmann Ronny , Will-Schweiger Katja , Kommerell Mechthild , Hackert Thilo , Schneider Lutz , Büchler Markus W , Werner Jens
Published: November 2008

Introduction

High morbidity and mortality rates in patients with severe acute pancreatitis are mainly caused by bacterial superinfection of pancreatic necrosis and subsequent sepsis. The benefit of early prophylactic antibiotics remains controversial because clinical studies performed to date were statistically underpowered. Thus, the aim of this study was to evaluate on-demand versus prophylactic antibiotic treatment in a standardised experimental model.

Methods

Treatment groups received meropenem either therapeutically 24 hours after induction of necrotising pancreatitis or prophylactically before development of pancreatic superinfection. At 24 and 72 hours, pancreatic injury was investigated by histology and translocation by bacterial cultures of pancreatic tissue and mesenteric lymph nodes. Septic complications were evaluated by blood cultures and survival.

Results

Without antibiotic treatment, pancreatic superinfection was observed in almost all cases after induction of necrotising pancreatitis. The 72-hour-mortality rate was 42.9% and bacterial infection of mesenteric lymph nodes and bacteraemia was found in 87.5% of the surviving animals. Therapeutic administration of meropenem on-demand reduced bacteraemia to 50% and mortality to 27.3%. However, prophylactic antibiotic treatment significantly reduced bacteraemia to 25.0% (p = 0.04) and pancreatic superinfection as well as mortality to 0% (p < 0.001 and p = 0.05, respectively) compared with controls.

Conclusions

In the present study both prophylactic and delayed antibiotic treatment on-demand reduced septic complications in a standardised setting of experimental necrotising pancreatitis. However, pancreatic superinfection, bacteraemia and mortality rates were reduced significantly by early treatment. Thus, in the absence of statistically relevant and well-designed clinical trials, the study demonstrates that prophylactic antibiotic treatment is superior to antibiotic treatment on-demand.
Phenylephrine versus norepinephrine for initial hemodynamic support of patients with septic shock: a randomized, controlled trial
Authors: Morelli Andrea , Ertmer Christian , Rehberg Sebastian , Lange Matthias , Orecchioni Alessandra , Laderchi Amalia , Bachetoni Alessandra , D'Alessandro Mariadomenica , Van Aken Hugo , Pietropaoli Paolo , Westphal Martin
Published: November 2008

Introduction

Previous findings suggest that a delayed administration of phenylephrine replacing norepinephrine in septic shock patients causes a more pronounced hepatosplanchnic vasoconstriction as compared with norepinephrine. Nevertheless, a direct comparison between the two study drugs has not yet been performed. The aim of the present study was, therefore, to investigate the effects of a first-line therapy with either phenylephrine or norepinephrine on systemic and regional hemodynamics in patients with septic shock.

Methods

We performed a prospective, randomized, controlled trial in a multidisciplinary intensive care unit in a university hospital. We enrolled septic shock patients (n = 32) with a mean arterial pressure below 65 mmHg despite adequate volume resuscitation. Patients were randomly allocated to treatment with either norepinephrine or phenylephrine infusion (n = 16 each) titrated to achieve a mean arterial pressure between 65 and 75 mmHg. Data from right heart catheterization, a thermodye dilution catheter, gastric tonometry, acid-base homeostasis, as well as creatinine clearance and cardiac troponin were obtained at baseline and after 12 hours. Differences within and between groups were analyzed using a two-way analysis of variance for repeated measurements with group and time as factors. Time-independent variables were compared with one-way analysis of variance.

Results

No differences were found in any of the investigated parameters.

Conclusions

The present study suggests there are no differences in terms of cardiopulmonary performance, global oxygen transport, and regional hemodynamics when phenylephrine was administered instead of norepinephrine in the initial hemodynamic support of septic shock.

Trial registration

ClinicalTrial.gov NCT00639015
ArrayPlex: distributed, interactive and programmatic access to genome sequence, annotation, ontology, and analytical toolsets
Authors: Killion Patrick J , Iyer Vishwanath R
Published: November 2008

ArrayPlex is a software package that centrally provides a large number of flexible toolsets useful for functional genomics, including microarray data storage, quality assessments, data visualization, gene annotation retrieval, statistical tests, genomic sequence retrieval and motif analysis. It uses a client-server architecture based on open source components, provides graphical, command-line, and programmatic access to all needed resources, and is extensible by virtue of a documented application programming interface. ArrayPlex is available at http://sourceforge.net/projects/arrayplex/.
Characterization of the differentially methylated region of the Impactgene that exhibits Glires-specific imprinting
Authors: Okamura Kohji , Wintle Richard F , Scherer Stephen W
Published: November 2008

Background

Imprinted genes are exclusively expressed from one of the two parental alleles in a parent-of-origin-specific manner. In mammals, nearly 100 genes are documented to be imprinted. To understand the mechanism behind this gene regulation and to identify novel imprinted genes, common features of DNA sequences have been analyzed; however, the general features required for genomic imprinting have not yet been identified, possibly due to variability in underlying molecular mechanisms from locus to locus.

Results

We performed a thorough comparative genomic analysis of a single locus, Impact, which is imprinted only in Glires (rodents and lagomorphs). The fact that Glires and primates diverged from each other as recent as 70 million years ago makes comparisons between imprinted and non-imprinted orthologues relatively reliable. In species from the Glires clade, Impact bears a differentially methylated region, whereby the maternal allele is hypermethylated. Analysis of this region demonstrated that imprinting was not associated with the presence of direct tandem repeats nor with CpG dinucleotide density. In contrast, a CpG periodicity of 8 bp was observed in this region in species of the Glires clade compared to those of carnivores, artiodactyls, and primates.

Conclusions

We show that tandem repeats are dispensable, establishment of the differentially methylated region does not rely on G+C content and CpG density, and the CpG periodicity of 8 bp is meaningful to the imprinting. This interval has recently been reported to be optimal for de novo methylation by the Dnmt3a-Dnmt3L complex, suggesting its importance in the establishment of imprinting in Impact and other genes.
Efficacy of Oxaliplatin Plus Capecitabine or Infusional Fluorouracil/Leucovorin in Patients With Metastatic Colorectal Cancer: A Pooled Analysis of Randomized Trials
Authors: Arkenau Hendrik-Tobias , Arnold Dirk , Cassidy Jim , Diaz-Rubio Eduardo , Douillard Jean-Yves , Hochster Howard , Martoni Andrea , Grothey Axel , Hinke Axel , Schmiegel Wolff , Schmoll Hans-Joachim , Porschen Rainer
Published: November 2008

Purpose

Six randomized phase II and III trials have investigated the role of oxaliplatin (OX) in combination with capecitabine (CAP) or infusional fluorouracil (FU) in metastatic colorectal cancer. This meta-analysis compared the efficacy of CAP/OX compared with infusional FU/OX.

Patients and Methods

This analysis compared all published CAP/OX versus infusional FU/OX regimens. A total of 3,494 patients (FU, n = 1,737; CAP, n = 1,757) were analyzed for response rate (RR), progression-free (PFS), overall survival (OS), and toxicity.

Results

The fixed-effect pooled estimate for RR showed higher RR for FU-based regimens (Odds ratio [OR] = 0.85; 95% CI, 0.74 to 0.97; P = .02) whereas the analysis of chemotherapy-only trials, excluding the bevacizumab containing NO16966 and TREE 2 trials, led to an OR of 0.74 (95% CI, 0.60 to 0.92; P = .007). However, for PFS (hazard ratio [HR] = 1.04; 95% CI, 0.96 to 1.12; P = .17) and OS (HR = 1.04; 95% CI, 0.95 to 1.12; P = .41) all models suggested similar outcome within the range of noninferiority. Grade 3/4 toxicities (thrombocytopenia—HR = 2.07, 95% CI, 1.42 to 3.03; P < .0002; diarrhea—HR = 1.34; 95% CI, 1.08 to 1.66; P < .0009; and grade 2/3 hand-foot-syndrome [HFS]—HR = 3.54; 95% CI, 2.07 to 6.05; P < .00001) were less prominent with FU-based regimens whereas neutropenia (HR = 0.15; 95% CI, 0.11 to 0.19; P < .00001) was lower in the CAP regimens.

Conclusion

The combination of CAP and OX resulted in lower RR, but this did not affect PFS and OS, which were similar in both treatment arms. The toxicity analysis showed the characteristic toxicity of each of the different FU schedules, with thrombocytopenia and HFS consistently more prominent in the CAP regimens.
Natural History of Osteonecrosis of the Jaw in Patients With Multiple Myeloma
Authors: Badros Ashraf , Terpos Evangelos , Katodritou Eirini , Goloubeva Olga , Kastritis Efstathios , Verrou Evgenia , Zervas Kostas , Baer Maria R. , Meiller Timothy , Dimopoulos Meletios A.
Published: November 2008

Purpose

To evaluate the natural history of bisphosphonate-related osteonecrosis of the jaw (ONJ) in patients with multiple myeloma.

Patients and Methods

Ninety-seven patients with myeloma from the United States (n = 37) and Greece (n = 60) were observed prospectively for a minimum 3.2 years after ONJ. Patients characteristics were similar with regard to age, bisphosphonate use, and myeloma therapy, except more autologous transplantations were performed on patients in the United States than in Greece (73% v 28%; P < .0001).

Results

ONJ resolved in 60 patients (62%), resolved and recurred in 12 patients (12%), and did not heal in 25 patients (26%). Dental procedures preceded ONJ in 46 patients (47%) and were more common in those with single episodes (35 of 60, 58%) than recurrent or nonhealing (11 of 37, 30%; P = .007). Recurrent ONJ followed reinitiation of bisphosphonates in six of 12 patients. Greek patients had more bone pain than United States patients (60% v 30%, P = .001) and were less likely to restart bisphosphonates (5% v 35%, P < .0002). Myeloma relapses were more common in patients with recurrent/nonhealing than single-episode ONJ (84% v 62%; P = .02). Median overall survival from myeloma diagnosis was 10.8 years (95% CI; 9.3 years to not reached) and did not differ between patients with single, recurrent, and nonhealing ONJ (P = .2).

Conclusion

ONJ healed in 75% of patients. Patients with spontaneous ONJ have a higher risk of nonhealing and recurrence. Reinitiating bisphosphonates after healing of ONJ is a reasonable option in patients experiencing relapse who are at risk of skeletal complications. Further studies of the pathogenesis and healing of ONJ are needed.
Intervals Longer Than 20 Weeks From Breast-Conserving Surgery to Radiation Therapy Are Associated With Inferior Outcome for Women With Early-Stage Breast Cancer Who Are Not Receiving Chemotherapy
Authors: Olivotto Ivo A. , Lesperance Mary L. , Truong Pauline T. , Nichol Alan , Berrang Tanya , Tyldesley Scott , Germain François , Speers Caroline , Wai Elaine , Holloway Caroline , Kwan Winkle , Kennecke Hagen
Published: November 2008

Purpose

To determine the interval from breast-conserving surgery (BCS) to radiation therapy (RT) that affects local control or survival.

Patients and Methods

The 10-year Kaplan-Meier (KM) local recurrence-free survival (LRFS), distant recurrence-free survival (DRFS), and breast cancer–specific survival (BCSS) were computed for 6,428 women who had T1 to 2, N0 to 1, M0 breast cancer that was diagnosed in British Columbia between 1989 and 2003, and who were treated with BCS and RT without chemotherapy. Intervals from BCS to RT were grouped by weeks as follows: ≤ 4 (n = 83), greater than 4 to 8 (n = 2,288; reference group); greater than 8 to 12 (n = 2,606); greater than 12 to 16 (n = 961); greater than 16 to 20 (n = 358); and greater than 20 weeks (n = 132). Cox proportional hazards models and matching were used to control for confounding variables.

Results

The median follow-up time was 7.5 years. The 10-year KM outcomes were as follows: LRFS, 95.4%; DRFS, 90.5%; and BCSS, 92.5%. Compared with the greater than 4 to 8 weeks group, hazard ratios (HR) were not significantly different for any outcome among patients who were treated up to 20 weeks after BCS. However, LRFS (hazard ratio [HR], 2.00; P = .15), DRFS (HR, 1.86; P = .02) and BCSS (HR, 2.15; P = .009) were inferior for women with BCS-to-RT intervals greater than 20 weeks compared with those greater than 4 to 8 weeks. The matched analysis yielded similar results.

Conclusion

Outcomes were statistically similar for BCS-to-RT intervals up to 20 weeks, but they were inferior for intervals beyond 20 weeks. Time can be reasonably allowed for the breast to heal and for patients to consider treatment options, but RT should start within 20 weeks of BCS.
Adaptive genetic variation, stress and glucose regulation
Authors: Oriel Roxanne C. , Wiley Christopher D. , Dewey Michael J. , Vrana Paul B.
Published: November 2008

Elevated glucose levels in the presence of insulin are indicative of type 2 diabetes and the more inclusive metabolic syndrome. Alleles conferring susceptibility to these and other common conditions may be adaptations to past environments. It is possible that other mammals exhibiting environmental diversity harbor similar variants; therefore, we assessed glucose regulation in two species of deer mice (Peromyscus), a diverse endemic North American group. The prairie deer mouse, P. maniculatus bairdii (BW), and the Oldfield mouse, P. polionotus subgriseus (PO) differ in sexual dimorphism, behavior and habitat. PO animals exhibit better regulatory ability than BW animals, particularly among males, although both species display equivalent insulin levels/responses and non-fasted glucose levels. Hybrid males exhibit a PO glucose challenge response and subsequent analysis of consomic animals implicates Y chromosome variation as the genetic cause. Two pieces of evidence indicate that the male glucose regulatory differences are mediated by stress response: (1) fasting and handling alone account for most of the variation; (2) an inhibitor of glucocorticoid (GC) stress hormone synthesis eliminates these differences. PO males have GC levels that are twice those of BW males, indicating the presence of alleles that attenuate the GC response. We hypothesize that the interspecific physiological and behavioral differences are interrelated and that similar human variants exist.
Analysis of mouse models carrying the I26T and R160C substitutions in the transcriptional repressor HESX1 as models for septo-optic dysplasia and hypopituitarism
Authors: Sajedi Ezat , Gaston-Massuet Carles , Signore Massimo , Andoniadou Cynthia L. , Kelberman Daniel , Castro Sandra , Etchevers Heather C. , Gerrelli Dianne , Dattani Mehul T. , Martinez-Barbera Juan Pedro
Published: November 2008

A homozygous substitution of the highly conserved isoleucine at position 26 by threonine (I26T) in the transcriptional repressor HESX1 has been associated with anterior pituitary hypoplasia in a human patient, with no forebrain or eye defects. Two individuals carrying a homozygous substitution of the conserved arginine at position 160 by cysteine (R160C) manifest septo-optic dysplasia (SOD), a condition characterised by pituitary abnormalities associated with midline telencephalic structure defects and optic nerve hypoplasia. We have generated two knock-in mouse models containing either the I26T or R160C substitution in the genomic locus. Hesx1I26T/I26T embryos show pituitary defects comparable with Hesx1−/− mouse mutants, with frequent occurrence of ocular abnormalities, although the telencephalon develops normally. Hesx1R160C/R160C mutants display forebrain and pituitary defects that are identical to those observed in Hesx1−/− null mice. We also show that the expression pattern of HESX1 during early human development is very similar to that described in the mouse, suggesting that the function of HESX1 is conserved between the two species. Together, these results suggest that the I26T mutation yields a hypomorphic allele, whereas R160C produces a null allele and, consequently, a more severe phenotype in both mice and humans.
Book Reviews
Authors: Ginestet Cedric
Published: November 2008

Introduction to the taxometric method: A practical guide Ruscio J. Haslam N. Ruscio A. M. London: Erlbaum 2006, £24.50 Paperback ISBN: 978‐0‐8058‐5976‐8
Book Reviews
Authors: Rakow Tim
Published: November 2008

Principles of statistical inference Cox D. R. Cambridge: Cambridge University Press 2006, £20.99 Paperback (ISBN‐13: 9780521685672; ISBN‐10: 0521685672)
Fetuin-A and BMD in Older Persons: The Health Aging and Body Composition (Health ABC) Study
Authors: Ix Joachim H , Wassel Christina L , Bauer Douglas C , Toroian Damon , Tylavsky Frances A , Cauley Jane A , Harris Tamara B , Price Paul A , Cummings Steven R , Shlipak Michael G
Published: November 2008

Fetuin-A is a hepatic secretory protein that promotes bone mineralization in vitro. Whether fetuin-A levels are associated with BMD in humans is unknown. The Health Aging and Body Composition study enrolled 3075 well-functioning black and white persons 70–79 yr of age and measured BMD. This cross-sectional study measured serum fetuin-A using ELISA among a random sample of 508 participants within sex and race strata. Multivariate linear regression analysis evaluated the associations of fetuin-A with BMD. Among women (n = 257), higher fetuin-A levels were significantly associated with higher total hip (p = 0.02), lumbar spine (p = 0.03), and whole body BMD (p = 0.01) in models adjusted for age, race, diabetes, alcohol and tobacco use, physical activity, body mass index, C-reactive protein levels, calcium supplement, and estrogen use. For example, each SD (0.38 g/liter) higher level of fetuin-A was associated with 0.016 g/cm2 higher total hip areal BMD. The association was of similar magnitude and direction for femoral neck BMD but did not reach statistical significance (p = 0.11). In contrast, among men (n = 251), fetuin-A had no significant associations with total hip (p = 0.79), lumbar spine (p = 0.35), whole body (p = 0.46), or femoral neck BMD (p = 0.54) in multivariable models. We conclude that higher fetuin-A levels are independently associated with higher BMD among well-functioning community-dwelling older women but not older men. Future studies should evaluate whether fetuin-A may refine fracture risk assessment in older women.
Divergent Effects of Glucocorticoids on Cortical and Trabecular Compartment BMD in Childhood Nephrotic Syndrome
Authors: Wetzsteon Rachel J , Shults Justine , Zemel Babette S , Gupta Pooja U , Burnham Jon M , Herskovitz Rita M , Howard Krista M , Leonard Mary B
Published: November 2008

Glucocorticoid (GC) effects on skeletal development have not been established. The objective of this pQCT study was to assess volumetric BMD (vBMD) and cortical dimensions in childhood steroid-sensitive nephrotic syndrome (SSNS), a disorder with minimal independent deleterious skeletal effects. Tibia pQCT was used to assess trabecular and cortical vBMD, cortical dimensions, and muscle area in 55 SSNS (age, 5–19 yr) and >650 control participants. Race-, sex-, and age-, or tibia length-specific Z-scores were generated for pQCT outcomes. Bone biomarkers included bone-specific alkaline phosphatase and urinary deoxypyridinoline. SSNS participants had lower height Z-scores (p < 0.0001) compared with controls. In SSNS, Z-scores for cortical area were greater (+0.37; 95% CI = 0.09, 0.66; p = 0.01), for cortical vBMD were greater (+1.17; 95% CI = 0.89, 1.45; p < 0.0001), and for trabecular vBMD were lower (−0.60; 95% CI, = −0.89, −0.31; p < 0.0001) compared with controls. Muscle area (+0.34; 95% CI = 0.08, 0.61; p = 0.01) and fat area (+0.56; 95% CI = 0.27, 0.84; p < 0.001) Z-scores were greater in SSNS, and adjustment for muscle area eliminated the greater cortical area in SSNS. Bone formation and resorption biomarkers were significantly and inversely associated with cortical vBMD in SSNS and controls and were significantly lower in the 34 SSNS participants taking GCs at the time of the study compared with controls. In conclusion, GCs in SSNS were associated with significantly greater cortical vBMD and cortical area and lower trabecular vBMD, with evidence of low bone turnover. Lower bone biomarkers were associated with greater cortical vBMD. Studies are needed to determine the fracture implications of these varied effects.
Focal Adhesion Kinase Is Important for Fluid Shear Stress-Induced Mechanotransduction in Osteoblasts
Authors: Young Suzanne RL , Gerard-O'Riley Rita , Kim Jae-Beom , Pavalko Fredrick M
Published: November 2008

Mechanical loading of bone is important for maintenance of bone mass and structural stability of the skeleton. When bone is mechanically loaded, movement of fluid within the spaces surrounding bone cells generates fluid shear stress (FSS) that stimulates osteoblasts, resulting in enhanced anabolic activity. The mechanisms by which osteoblasts convert the external stimulation of FSS into biochemical changes, a process known as mechanotransduction, remain poorly understood. Focal adhesions are prime candidates for transducing external stimuli. Focal adhesion kinase (FAK), a nonreceptor tyrosine kinase found in focal adhesions, may play a key role in mechanotransduction, although its function has not been directly examined in osteoblasts. We examined the role of FAK in osteoblast mechanotransduction using short interfering RNA (siRNA), overexpression of a dominant negative FAK, and FAK−/− osteoblasts to disrupt FAK function in calvarial osteoblasts. Osteoblasts were subjected to varying periods oscillatory fluid flow (OFF) from 5 min to 4 h, and several physiologically important readouts of mechanotransduction were analyzed including: extracellular signal-related kinase 1/2 phosphorylation, upregulation of c-fos, cyclooxygenase-2, and osteopontin, and release of prostaglandin E2. Osteoblasts with disrupted FAK signaling exhibited severely impaired mechanical responses in all endpoints examined. These data indicate the importance of FAK for both short and long periods of FSS-induced mechanotransduction in osteoblasts.
Vertebral Fracture Status and the World Health Organization Risk Factors for Predicting Osteoporotic Fracture Risk
Authors: Chen Peiqi , Krege John H , Adachi Jonathan D , Prior Jerilynn C , Tenenhouse Alan , Brown Jacques P , Papadimitropoulos Emmanuel , Kreiger Nancy , Olszynski Wojciech P , Josse Robert G , Goltzman David
Published: November 2008

Vertebral fractures are the most common osteoporotic fracture, and patients with prevalent vertebral fractures have a greater risk of future fractures. However, radiographically determined vertebral fractures are not identified as a distinct risk factor in the World Health Organization (WHO) fracture risk assessment tool. The objective of this study was to evaluate and compare potential risk factors including morphometric spine fracture status and the WHO risk factors for predicting 5-yr fracture risk. We hypothesized that spine fracture status provides prognostic information in addition to consideration of the WHO risk factors alone. A randomly selected, population-based community cohort of 2761 noninstitutionalized men and women ≥50 yr of age living within 50 km of one of nine regional centers was enrolled in the Canadian Multicentre Osteoporosis Study (CaMOS), a prospective and longitudinal cohort study following subjects for 5 yr. Prevalent and incident spine fractures were identified from lateral spine radiographs. Incident nonvertebral fragility fractures were determined by an annual, mailed fracture questionnaire with validation, and nonvertebral fragility fracture was defined by investigators as a fracture with minimal trauma. A model considering the WHO risk factors plus spine fracture status provided greater prognostic information regarding future fracture risk than a model considering the WHO risk factors alone. In univariate analyses, age, BMD, and spine fracture status had the highest gradient of risk. A model considering these three risk factors captured almost all of the predictive information provided by a model considering spine fracture status plus the WHO risk factors and provided greater predictive information than a model considering the WHO risk factors alone. The use of spine fracture status along with age and BMD predicted future fracture risk with greater simplicity and higher prognostic accuracy than consideration of the risk factors included in the WHO tool.
Evidence for Shared Genetic Influences on Self-Reported ADHD and Autistic Symptoms in Young Adult Australian Twins
Authors: Reiersen Angela M. , Constantino John N. , Grimmer Marisa , Martin Nicholas. G. , Todd Richard D.
Published: November 2008

Recent clinic-based and population-based studies have shown evidence of association between ADHD and autistic symptoms in children and adolescents as well as evidence for genetic overlap between these disorders. The objective of the current study was to confirm the association between autistic and ADHD symptoms in a young adult twin sample assessed by self-report, and investigate whether shared genetic and/or environmental factors can explain the association. We performed twin-based structural equation modeling using self-report data from 11 Social Responsiveness Scale (SRS) items and 12 DSM-IV ADHD inattentive and impulsive symptom items obtained from 674 young adult Australian twins. Phenotypic correlation between autistic and ADHD symptoms was moderate. The most parsimonious univariate models for SRS and ADHD included additive genetic effects and unique environmental effects, without sex differences. ADHD and autistic traits were both moderately heritable. In a bivariate model, genetic correlation (rg) between SRS and ADHD was 0.72. Our results suggest that in young adults, a substantial proportion of the genetic influences on self-reported autistic and ADHD symptoms may be shared between the two disorders.
Clones in the Classroom: A Daily Diary Study of the Nonshared Environmental Relationship Between Monozygotic Twin Differences in School Experience and Achievement
Authors: Asbury Kathryn , Almeida David , Hibel Jacob , Harlaar Nicole , Plomin Robert
Published: November 2008

Do genetically identical children experience the same classroom differently? Are nonshared classroom experiences associated with differences in achievement? We designed a telephone diary measure which we administered every school day for 2 weeks to 122 10-year-olds in 61 monozygotic (MZ) twin pairs. Each pair shared genes, a classroom, peers and a teacher. We found that MZ twins did experience their classrooms differently (rMZ < 0.65 for all measures of classroom experience). Furthermore, MZ differences in peer problems were significantly associated with MZ differences in Mathematics achievement (ES = 8%); differences in positivity about school were significantly associated with differences in Mathematics (ES = 15%) and Science (ES = 8%) achievement; and differences in ‘flow’ in Science lessons were associated with differences in Science achievement (ES = 12%). In a multiple regression analysis, MZ differences in positivity about school significantly predicted MZ differences in Mathematics achievement (R2= 0.16,p< .01) and MZ differences in ‘flow’ in Science significantly predicted MZ differences in Science achievement (R2= 0.10,p< .05). These results indicate that MZ twins experience the classroom differently and that differences in their experience are associated with differences in their achievement.
CD36Gene Promoter Polymorphisms Are Associated With Low Density Lipoprotein-Cholesterol in Normal Twins and After a Low-Calorie Diet in Obese Subjects
Authors: Goyenechea Estibaliz , Collins Laura J. , Parra Dolores , Liu Gaifen , Snieder Harold , Swaminathan Ramasamyiyer , Spector Tim D. , Martínez J. Alfredo , O'Dell Sandra D.
Published: November 2008

Common polymorphisms of theCD36fatty acid transporter gene have been associated with lipid metabolism and cardiovascular disease. Association of aCD36promoter single nucleotide polymorphism genotype with anthropometry and serum lipids was investigated in normal subjects, and in obese subjects during an 8-week low calorie diet and 6-month weight-maintenance period. 2728 normal female Twins UK subjects (mean body mass index 24.8 ± 4.4 kg/m2; age 47.3 ± 12.5 y) and 183 obese male and female Spanish subjects (mean body mass index 30.6 ± 3.0 kg/m2; age 35.0 ± 5.0 y) were genotyped for theCD36-22674T/C(rs2151916) promoter single nucleotide polymorphism. In the Twins UK full cohort, theC-allele was associated with lower low density lipoprotein-cholesterol (p= .02,N= 2396). No associations were found in the obese Spanish subjects at baseline, but 6 months after the end of the low-calorie diet, theC-allele was associated with lower total- (p= .03) and low density lipoprotein-cholesterol (p= .01) and higher high density lipoprotein-cholesterol (p= .01). Intake of saturated fatty acids was lower in carriers of theC-allele at baseline, but not significantly so (p= .11). However, 6 months after the end of the low-calorie diet, elements of the lipid profile were correlated with saturated fatty acid intake: total cholesterolr= .21,p= .060; low density lipoprotein-cholesterol:r= .25,p= .043; high density lipoprotein-cholesterol:r= –.26,p= .007.CD36promoter SNP allele –22674Cis therefore associated with lower serum low-density lipoprotein-cholesterol in normal female twins and with improved lipid profile during weight loss and maintenance in obese subjects.
Obstetric Events as a Risk Factor for Febrile Seizures: A Community-Based Twin Study
Authors: Helbig Ingo , Lawrence Kate M. , Connellan Mary M. , Torn-Broers Yvonne , Vadlamudi Lata , Eckhaus Jazmin , Milne Roger L. , Hopper John L. , Berkovic Samuel F.
Published: November 2008

Adverse events during the perinatal period have traditionally been thought to contribute to the risk of febrile seizures although an association has not been found in large epidemiological studies. Disease-discordant twins provide a means to assess the role of non-shared environmental factors while matching for confounding factors and avoiding difficulties of epidemiological studies in singletons. This study aimed to examine the association of obstetric events and febrile seizures in a community-based twin study. Twenty-one twin pairs discordant for febrile seizures were ascertained from a community-based twin register. Obstetric events were scored using the McNeil-Sjöström Scale for Obstetric Complications and expressed as a summary score (OC score). The frequency of individual obstetric events in affected and unaffected twins, the within-pair differences in OC scores and other markers of perinatal risk including birthweight, birth order and Apgar scores were examined. No significant difference was found in the frequency of individual obstetric events, nor in OC scores between affected and unaffected twins. No differences in birth weight, birth order, 1- or 5-minute Apgar scores were observed. Our results confirm previous findings that obstetric events are not associated with the risk of febrile seizures.
Weight Growth Charts from Birth to 6 Years of Age in Japanese Triplets
Authors: Yokoyama Yoshie , Sugimoto Masako , Silventoinen Karri , Kaprio Jaakko
Published: November 2008

We analyzed the characteristics of weight growth and present the weight growth charts from birth to 6 years of age in Japanese triplets. The study included 366 mothers and their 1098 triplet children, who were born between 1978 and 2006. Data were collected through a mailed questionnaire sent to the mothers asking for information recorded in medical records. For these births, data on triplets' weight growth, gestational age, sex, parity, and maternal age at delivery were obtained from records in the Maternal and Child Health Handbooks, which is provided by the authorities after a report of pregnancy. Birthweight proved to be the strongest contribution on weight of triplets from 1 to 6 years of age. In addition, gestational age was also a significant contributing factor to weight from birth to 6 years of age. Moreover, males had a higher weight from birth to 6 years of age than females. Compared to the 50th percentile of the growth standard for the general population of Japan, the weight deficit of the triplets was more than 40% at birth (male, –1.28 kg; female, –1.28 kg), decreased within the first 1 year of age, and fluctuated between 4% and 9% until 6 years of age (male, –1.82 kg; female, –1.78 kg). In conclusion, triplets have lower birth weight than singletons and in spite of the rapid catch-up growth during first year of life they are behind singletons even in mid-childhood. This study provides growth curves for use in triplets.
Experimental determination of coupled thermal-mechanical effects on fracture toughness of sandstone
Authors: Zuo Jian-ping , Xie He-ping , Zhou Hong-wei
Published: November 2008

In situ observations of the microscopic failure evolvement of sandstone under the coupled thermal-mechanical loadings were carried out by a scanning electron microscope (SEM). These results indicate that the effects of temperatures on cracking behavior and fracture toughness of sandstone are obvious. And, it is found that a critical transforming temperature is about 150°C for the fracture toughness of sandstone. That is, the fracture toughness value is to increase exponentially when the range of the temperature is from 25 to 150°C, but decreases exponentially when the range of the temperature is from 150 to 300°C. Therefore, in the present work the exponential relationships between fracture toughness and temperature are reported first. This is in good agreement with existing experimental evidence for the growth of micro cracks and thermal cracking.
Erosion Test Evaluation by Noncumulative Mass Loss Data
Authors: Meged Y.
Published: November 2008

Erosion tests are generally represented by cumulative erosion-time curves. These curves are evaluated by means of several criteria, such as nominal incubation time (NIT), maximum erosion rate (MER), time to reach a mean depth of erosion of 100 μm (t100) and terminal erosion rate (TER). These criteria are applied to assess the precision, and to obtain values of normalized erosion resistance (NER). The drawbacks of this evaluation method stem from the fact that these criteria are: 1. Point values–t100 and NIT2. Local values–MER and TER3. Rare value–TER4. With rather large variation–NIT5. Dependent on reference materials—NER.In order to overcome these drawbacks an alternative method is suggested. This method is based on noncumulative mass loss data, measured at equal test time intervals, along a specified test duration. These values are applied to study the erosion process and to characterize each material. This method is illustrated by analysis of erosion test results of four materials. The main advantage of this method is its ability to evaluate the erosion process on a micro-scale, thereby supplementing the prevailing method.
Competing for Coffee Space: Development‐Induced Displacement in the Central Highlands of Vietnam*
Authors: Doutriaux Sylvie , Geisler Charles , Shively Gerald
Published: November 2008

Abstract  Vietnam has emerged as the world's second largest producer of coffee. The benefits of this expanding coffee economy are substantial but not universal; their distribution follows ethnic lines despite government commitment to equalize welfare. Focusing on Dak Lak Province in Vietnam's Central Highlands, we investigate this commercial transformation and the “competition for coffee space” that it has occasioned. Combined ethno‐history and household income analyses suggest markedly different benefits between native and non‐native ethnic groups, despite generally larger landholdings among the former. We interpret these finding through the conceptual lens of in‐situ development‐induced displacement.
On Diversity, Empathy, and Community: The Relevance of Johann Gottfried Herder
Authors: Bahr Howard M. , Durrant Marie B. , Evans Matthew T. , Maughan Suzanne L.
Published: November 2008

Abstract  The writings of Johann Gottfried Herder (1744–1803) foreshadowed several of the dominant theories of sociology, social psychology, aesthetics, linguistics and literary theory. His ideas impacted generations of thinkers, but today he is uncelebrated, mostly unknown. His writings on populism, expressionism, and pluralism are relevant to contemporary sociology, especially community sociology. Here we consider his views on the nature and meaning of community, and his methods of studying and interpreting communities. These include an emphasis on the essential particularity of human communities and their connection to wider systems and networks. Herder urges special attention to the elements of context (place, time, language, culture) within which communities are situated. Herder's is an embedded particularism, a focus on individuality and diversity within larger unities. He also sensitizes us to the multivalence and multiplicity of social phenomena. As the proper stance for community research he counsels involvement and empathy rather than objectivity and emotional distance, and he urges researchers to be sensitive to data from all of their senses, not merely sight. Drawing upon Herder's writings, we conclude with several important methodological principles relevant to improving current work on the nature and conceptualization of communities.
State Welfare Rules, TANF Exits, and Geographic Context: Does Place Matter?*
Authors: Irving Shelley K.
Published: November 2008

Abstract  This research compares the likelihood of exiting TANF with and without employment and the effects of important state TANF rules on welfare exits in more disadvantaged (large Rustbelt cities and poor southern nonmetro) and less disadvantaged (other metro and other nonmetro) areas during the 1996–2003 post‐welfare reform period. Hierarchical competing risk models using individual‐level data from the 1996–99 and 2001–03 Panels of the Survey of Income and Program Participation merged with state‐level data from various sources show that female TANF participants in poor southern nonmetro areas are the least likely to exit TANF with work, and participants in large Rustbelt cities are less likely to exit TANF with work than those in other metro areas. Non‐work TANF exits are more likely to occur in other nonmetro areas than in other metro areas. Importantly, the effects of state welfare rules on TANF exits differ across places of residence. For example, stringent time limit policies promote work exits in large Rustbelt cities but promote non‐work exits in poor southern nonmetro areas. More lenient earned income disregards are significantly related to remaining on TANF in poor southern nonmetro areas but promote work exits in all other places. Findings from this paper imply that states should not take a “one‐size‐fits‐all approach” to reduce welfare caseloads.
TheCaenorhabditis elegans ing-3Gene Regulates Ionizing Radiation-Induced Germ-Cell Apoptosis in a p53-Associated Pathway
Authors: Luo Jingjing , Shah Sitar , Riabowol Karl , Mains Paul E
Published: November 2008

The inhibitor of growth (ING) family of type II tumor suppressors are encoded by five genes in mammals and by three genes in Caenorhabditis elegans. All ING proteins contain a highly conserved plant homeodomain (PHD) zinc finger. ING proteins are activated by stresses, including ionizing radiation, leading to the activation of p53. ING proteins in mammals and yeast have recently been shown to read the histone code in a methylation-sensitive manner to regulate gene expression. Here we identify and characterize ing-3, the C. elegans gene with the highest sequence identity to the human ING3 gene. ING-3 colocalizes with chromatin in embryos, the germline, and somatic cells. The ing-3 gene is part of an operon but is also transcribed from its own promoter. Both ing-3(RNAi) and ing-3 mutant strains demonstrate that the gene likely functions in concert with the C. elegans p53 homolog, cep-1, to induce germ-cell apoptosis in response to ionizing radiation. Somatically, the ing-3 mutant has a weak kinker uncoordinated (kinker Unc) phenotype, indicating a possible neuronal function.
Formation and Longevity of Chimeric and Duplicate Genes inDrosophila melanogaster
Authors: Rogers Rebekah L , Bedford Trevor , Hartl Daniel L
Published: November 2008

Historically, duplicate genes have been regarded as a major source of novel genetic material. However, recent work suggests that chimeric genes formed through the fusion of pieces of different genes may also contribute to the evolution of novel functions. To compare the contribution of chimeric and duplicate genes to genome evolution, we measured their prevalence and persistence within Drosophila melanogaster. We find that ∼80.4 duplicates form per million years, but most are rapidly eliminated from the genome, leaving only 4.1% to be preserved by natural selection. Chimeras form at a comparatively modest rate of ∼11.4 per million years but follow a similar pattern of decay, with ultimately only 1.4% of chimeras preserved. We propose two mechanisms of chimeric gene formation, which rely entirely on local, DNA-based mutations to explain the structure and placement of the youngest chimeric genes observed. One involves imprecise excision of an unpaired duplication during large-loop mismatch repair, while the other invokes a process akin to replication slippage to form a chimeric gene in a single event. Our results paint a dynamic picture of both chimeras and duplicate genes within the genome and suggest that chimeric genes contribute substantially to genomic novelty.
Stm1 Modulates mRNA Decay and Dhh1 Function in Saccharomyces cerevisiae
Authors: Balagopal Vidya , Parker Roy
Published: November 2008

The control of mRNA degradation and translation are important for the regulation of gene expression. mRNA degradation is often initiated by deadenylation, which leads to decapping and 5′–3′ decay. In the budding yeast Saccharomyces cerevisae, decapping is promoted by the Dhh1 and Pat1 proteins, which appear to both inhibit translation initiation and promote decapping. To understand the function of these factors, we identified the ribosome binding protein Stm1 as a multicopy suppressor of the temperature sensitivity of the pat1Δ strain. Stm1 loss-of-function alleles and overexpression strains show several genetic interactions with Pat1 and Dhh1 alleles in a manner consistent with Stm1 working upstream of Dhh1 to promote Dhh1 function. Consistent with Stm1 affecting Dhh1 function, stm1Δ strains are defective in the degradation of the EDC1 and COX17 mRNAs, whose decay is strongly affected by the loss of Dhh1. These results identify Stm1 as an additional component of the mRNA degradation machinery and suggest a possible connection of mRNA decapping to ribosome function.
Teaching Synthetic Biology, Bioinformatics and Engineering to Undergraduates: The Interdisciplinary Build-a-Genome Course
Authors: Dymond Jessica S , Scheifele Lisa Z , Richardson Sarah , Lee Pablo , Chandrasegaran Srinivasan , Bader Joel S , Boeke Jef D
Published: November 2008

A major challenge in undergraduate life science curricula is the continual evaluation and development of courses that reflect the constantly shifting face of contemporary biological research. Synthetic biology offers an excellent framework within which students may participate in cutting-edge interdisciplinary research and is therefore an attractive addition to the undergraduate biology curriculum. This new discipline offers the promise of a deeper understanding of gene function, gene order, and chromosome structure through the de novo synthesis of genetic information, much as synthetic approaches informed organic chemistry. While considerable progress has been achieved in the synthesis of entire viral and prokaryotic genomes, fabrication of eukaryotic genomes requires synthesis on a scale that is orders of magnitude higher. These high-throughput but labor-intensive projects serve as an ideal way to introduce undergraduates to hands-on synthetic biology research. We are pursuing synthesis of Saccharomyces cerevisiae chromosomes in an undergraduate laboratory setting, the Build-a-Genome course, thereby exposing students to the engineering of biology on a genomewide scale while focusing on a limited region of the genome. A synthetic chromosome III sequence was designed, ordered from commercial suppliers in the form of oligonucleotides, and subsequently assembled by students into ∼750-bp fragments. Once trained in assembly of such DNA “building blocks” by PCR, the students accomplish high-yield gene synthesis, becoming not only technically proficient but also constructively critical and capable of adapting their protocols as independent researchers. Regular “lab meeting” sessions help prepare them for future roles in laboratory science.
Physicians' Contact With Families After the Death of Pediatric Patients: A Survey of Pediatric Critical Care Practitioners' Beliefs and Self-Reported Practices
Authors: Borasino Santiago , Morrison Wynne , Silberman Jordan , Nelson Robert M. , Feudtner Chris
Published: November 2008

OBJECTIVES. Although research with bereaved families has shown that they appreciate contact with clinicians after the child's death, this realm of clinical practice remains empirically uncharted. The objective of this study was to describe pediatric critical care practitioners' attitudes and self-reported practices regarding contacting families after a patient's death.

METHODS. A total of 376 board-certified members of the American Academy of Pediatrics Section of Critical Care received e-mail invitations to complete a Web-based questionnaire; 204 members responded (effective response rate: 54.3%).

RESULTS. Most (95%) participants reported 0 to 1 patient deaths per week. A total of 79% of the respondents reported contacting families at least sometimes, 71.9% had attended funerals, and only 2.5% thought that it was inappropriate for clinicians to attend funerals. A total of 75.9% agreed that follow-up contact helps the family, whereas 47.3% agreed that follow-up contact helps the physicians. The most common methods of follow-up contact included the passive measures of providing contact information; active methods such as meeting with the family, calling them by telephone, or writing a letter or note were used less often. In multivariable analysis, respondents were more likely to report contact with a family after the death of a child when they affirmed the belief that such contact was useful to the family or to the physician or when they were female physicians. Regarding reported funeral attendance after the death of a patient, multivariable analysis revealed similar patterns of association but to an attenuated and nonstatistically significant degree.

CONCLUSIONS. A high proportion of pediatric critical care physicians have contacted bereaved families and attended funerals after the death of a child patient. These practices were consistently associated with the belief that such follow-up contact helps the family or the practitioner.