bluuebunny/crossref_metadata_2025 huggingface dataset:
Oral (Drinking Water) Developmental Toxicity Study of Ammonium Perchlorate in Sprague-Dawley Rats
Authors: York Raymond G. , Funk Kathleen A. , Girard Michael F. , Mattie David , Strawson Joan E.
Published: June 2009

A developmental toxicity study was conducted with ammonium perchlorate (AP) in the drinking water at doses of 0.0, 0.01, 0.1, 1.0, and 30.0 mg/kg-day beginning 14 days before cohabitation and continuing through sacrifice. Twenty-four rats/group were cesarean-sectioned on day of gestation (DG) 21 and fetuses examined for visceral and skeletal alterations. An additional 16 litters/group were sacrificed on DG 21 for maternal and fetal serum TSH, T3, and T4(thyroid-stimulating hormone, triiodothyronine, and thyroxine) levels and thyroid histopathology. Clinical and necropsy observations, body weights, feed and water consumption, and cesarean-sectioning parameters were comparable among the groups with only delays in ossification observed in the 30 mg/kg-day group. Maternal thyroid weights were increased in the 30.0 mg/kg-day group. Decreased colloid was present in male and female fetal thyroids in the 1.0 and 30.0 mg/kg-day groups. Maternal TSH was increased and T4was decreased at all levels, and T3was reduced at 30.0 mg/kg-day. Fetal TSH was increased at 1.0 and 30.0 mg/kg-day, T4was reduced at 30.0 mg/kg-day, and T3was decreased at all levels. The maternal no-observable-adverse-effect level (NOAEL) was 1.0 mg/kg-day; exposures of 30.0 mg/kg-day increased absolute and relative maternal thyroid weights and histopathology findings. The developmental NOAEL was 1.0 mg/kg-day; developmental delays in ossification occurred in the 30.0 mg/kg-day group. The colloid depletion in the thyroids and increased TSH and decreased T3and T4levels at lower exposures were considered adaptive and not adverse. No adverse effects on development at occurred levels that did not cause maternal toxicity. AP is not a selective developmental toxicant.
Issues in Chemical and Biological Terrorism
Authors: Salem Harry
Published: June 2009

This manuscript describes the overview presented at the 23rd Annual Meeting of the American College of Toxicology in 2002. Although it is recognized that weapons of mass destruction that can be used against our military and civilian populations include chemical, biological, radiological, and nuclear (CBRN) agents, this overview is limited primarily to chemical and biological (CB) agents. The issues of CB terrorism are discussed in terms of When, What, How, and Who. The US Army has been providing chemical and biological solutions since 1917, and has since 1996 applied these solutions to homeland defense and domestic preparedness. The use of chemical and biological agents as terrorist weapons both in the United States and elsewhere in the world is reviewed. The CB threat spectrum is presented, as is the further categorization of biological threat agents by the Centers for Disease Control and Prevention (CDC). In addition, the CB agents considered to be a potential threat to our water supply are also presented. These are agents that are water soluble, stable, and resistant to water treatment and/or disinfection. The overview concludes with the chronological accomplishments of ECBC since 1917.
Efficient Parallelization of the Stochastic Simulation Algorithm for Chemically Reacting Systems On the Graphics Processing Unit
Authors: Hong Li  , Petzold Linda
Published: June 2009

The small number of some reactant molecules in biological systems formed by living cells can result in dynamical behavior which cannot be captured by traditional deterministic models. In such a problem, a more accurate simulation can be obtained with discrete stochastic simulation (Gillespie’s stochastic simulation algorithm — SSA). Many stochastic realizations are required to capture accurate statistical information of the solution. This carries a very high computational cost. The current generation of graphics processing units (GPU) is well-suited to this task. In this paper we describe our implementation and present some computational experiments illustrating the power of this technology for this important and challenging class of problems.
High-Performance Three-Dimensional Image Reconstruction for Molecular Structure Determination
Authors: Chung Julianne , Sternberg Philip , Chao Yang
Published: June 2009

We describe an efficient parallel implementation of a reliable iterative reconstruction algorithm for estimating the three-dimensional (3D) density map of a macromolecular complex from a large number of two-dimensional (2D) cryo-electron microscopy (Cryo-EM) images. Our algorithm is based on a hybrid regularization approach first developed by Björck and O’Leary—Simmons. Our implementation uses a special data structure to represent the 3D density map to improve data locality in the reconstruction computation. Our parallelization strategy allows both 2D images and 3D data to be distributed on a 2D processor grid. We have used our implementation successfully on several datasets of different sizes, and we are able to achieve scalable parallel performance on a distributed memory cluster using over 15,000 CPUs for the largest dataset.
Increasing the Locality of Iterative Methods and Its Application to the Simulation of Semiconductor Devices
Authors: Pichel J.C. , Heras D.B. , Cabaleiro J.C. , García-Loureiro A.J. , Rivera F.F.
Published: June 2009

Irregular codes are present in many scientific applications, such as finite element simulations. In these simulations the solution of large sparse linear equation systems is required, which are often solved using iterative methods. The main kernel of the iterative methods is the sparse matrix—vector multiplication which frequently demands irregular data accesses. Therefore, techniques that increase the performance of this operation will have a great impact on the global performance of the iterative method and, as a consequence, on the simulations. In this paper a technique for improving the locality of sparse matrix codes is presented. The technique consists of reorganizing the data guided by a locality model instead of restructuring the code or changing the sparse matrix storage format. We have applied our proposal to different iterative methods provided by two standard numerical libraries. Results show an impact on the overall performance of the considered iterative method due to the increase in the locality of the sparse matrix—vector product. Noticeable reductions in the execution time have been achieved both in sequential and in parallel executions. This positive behavior allows the reordering technique to be successfully applied to real problems. We have focused on the simulation of semiconductor devices and in particular on the BIPS3D simulator. The technique was integrated into the simulator. Both sequential and parallel executions have been analyzed extensively in this paper. Noticeable reductions in the execution time required by the simulations are observed when using our reordered matrices in comparison with the original simulator.
Emotional, motivational and interpersonal responsiveness of children with autism in improvisational music therapy
Authors: Kim Jinah , Wigram Tony , Gold Christian
Published: June 2009

Through behavioural analysis, this study investigated the social-motivational aspects of musical interaction between the child and the therapist in improvisational music therapy by measuring emotional, motivational and interpersonal responsiveness in children with autism during joint engagement episodes. The randomized controlled study ( n = 10) employed a single subject comparison design in two different conditions, improvisational music therapy and toy play sessions, and DVD analysis of sessions. Improvisational music therapy produced markedly more and longer events of `joy', `emotional synchronicity' and `initiation of engagement' behaviours in the children than toy play sessions. In response to the therapist's interpersonal demands, `compliant (positive) responses' were observed more in music therapy than in toy play sessions, and `no responses' were twice as frequent in toy play sessions as in music therapy. The results of this exploratory study found significant evidence supporting the value of music therapy in promoting social, emotional and motivational development in children with autism.
Are there more bowel symptoms in children with autism compared to normal children and children with other developmental and neurological disorders?
Authors: Smith R.A. , Farnworth H. , Wright B. , Allgar V.
Published: June 2009

There is considerable controversy as to whether there is an association between bowel disorders and autism. Using a bowel symptom questionnaire we compared 51 children with autism spectrum disorder with control groups of 35 children from special school and 112 from mainstream school. There was a significant difference in the reporting of certain bowel symptoms (constipation, diarrhoea, flatulence) and food faddiness between the autism group and the mainstream school control group. There was no significant difference between the autism group and children in the special schools except for faddiness, which is an autism specific symptom and not a bowel symptom. This study confirms previously reported findings of an increase in bowel symptoms in children with autism. It would appear, however, that this is not specifically associated with autism as bowel symptoms were reported in similar frequency to a comparison group of children with other developmental and neurological disorders.
Social Value Orientation and Cooperation in Social Dilemmas: A Meta-Analysis
Authors: Balliet Daniel , Parks Craig , Joireman Jeff
Published: June 2009

This article reports a meta-analysis of 82 studies assessing the relationship between social value orientation (SVO) and cooperation in social dilemmas. A significant and small to medium effect size was found ( r = .30). Results supported a hypothesis that the effect size was larger when participants were not paid ( r = .39) than when they were paid ( r = .23). The effect size was also larger in give-some ( r = .29) as opposed to take-some ( r = .22) games. However, contrary to expectations, the effect was not larger in one-shot, as opposed to iterated games. Findings are discussed in the context of theory on SVO and directions for future research are outlined.
Reactions to Procedural Discrimination in an Intergroup Context: The Role of Group Membership of the Authority
Authors: Cheng Grand H.-L. , Fielding Kelly S. , Hogg Michael A. , Terry Deborah J.
Published: June 2009

The present research examined whether reactions to procedural discrimination (favoring self vs. favoring other procedures) are qualified by whether the authority is an ingroup or an outgroup member. We argue that because we tend to demonstrate ingroup bias in an intergroup context, we should react more positively when we are favored over an outgroup other than when an outgroup other is favored over us. Furthermore, we reason that because compared with outgroup authorities, ingroup authorities are perceived to be more related to us, we should react more strongly to procedural discrimination exercised by the ingroup authority. Across the two studies, results support our predictions. Results are discussed with reference to the social identity perspective and the group-value model.
Explanations of American punishment policies
Authors: Tonry Michael
Published: June 2009

None of the conventional explanations why American penal policies became so severe — rising crime rates, harsh public attitudes and cynical electoral politics — are persuasive. Nor are various `conditions of late modernity' such as the limited capacities of governments, increasing population diversity or increasing insecurity and risk aversion. All these things characterized every developed country in much of the period 1975—2000 and most did not adopt drastically harsher policies. Nor are such amorphous and over-generalized notions as `populist punitiveness', `penal populism' and neo-liberalism of much use. Some things do have explanatory power cross-nationally. Moderate penal policies and low imprisonment rates are associated with low levels of income inequality, high levels of trust and legitimacy, strong welfare states, professionalized as opposed to politicized criminal justice systems and consensual rather than conflictual political cultures. For each of those factors, the United States falls at the wrong end of the distribution. The question is, Why? Four answers stand out: the `paranoid style' in American politics; a Manichean moralism associated with fundamentalist religious views; the obsolescence of the American constitution; and the history of race relations in the USA.
Chronic myeloid leukemia (CML) with P190BCR-ABL: analysis of characteristics, outcomes, and prognostic significance
Authors: Verma Dushyant , Kantarjian Hagop M. , Jones Dan , Luthra Rajyalakshmi , Borthakur Gautam , Verstovsek Srdan , Rios Mary Beth , Cortes Jorge
Published: June 2009

The most common BCR-ABL transcripts in chronic myeloid leukemia (CML) are e13a2(b2a2) and e14a2(b3a2). Other transcripts such as e1a2 are rare and their outcome with tyrosine kinase inhibitors (TKI) therapy is undefined. We analyzed 1292 CML patients and identified 14 with only e1a2 transcripts, 9 in chronic phase (CP), 1 in accelerated phase (AP), and 4 in blast phase (BP). Of the CP, 4 achieved complete hematologic response (CHR); 2, complete cytogenetic response (CCyR); 2, partial cytogenetic response (PCyR), and 1 did not respond to imatinib. Five patients progressed to myeloid BP (3), lymphoid BP (1), or AP (1). The AP patient received various TKIs sequentially and achieved only CHR. BP patients received hyper-CVAD (hyperfractionated cyclophosphamide, vincristine, adriamycin, dexamethasone) plus imatinib/dasatinib or idarubicin plus cytarabine (Ara-C); 2 did not respond, 1 had CCyR, and 1 short-lasting complete molecular response (CMR). Overall, cytogenetic responses lasted 3 to 18 months; only 2 achieved major molecular response (MMR) on TKI. P190BCR-ABL CML is rare and is associated with an inferior outcome to therapy with TKI. These patients need to be identified as high-risk patients.
Protamine sulfate down-regulates thrombin generation by inhibiting factor V activation
Authors: Ni Ainle Fionnuala , Preston Roger J. S. , Jenkins P. Vincent , Nel Hendrik J. , Johnson Jennifer A. , Smith Owen P. , White Barry , Fallon Padraic G. , O'Donnell James S.
Published: June 2009

Protamine sulfate is a positively charged polypeptide widely used to reverse heparin-induced anticoagulation. Paradoxically, prospective randomized trials have shown that protamine administration for heparin neutralization is associated with increased bleeding, particularly after cardiothoracic surgery with cardiopulmonary bypass. The molecular mechanism(s) through which protamine mediates this anticoagulant effect has not been defined. In vivo administration of pharmacologic doses of protamine to BALB/c mice significantly reduced plasma thrombin generation and prolonged tail-bleeding time (from 120 to 199 seconds). Similarly, in pooled normal human plasma, protamine caused significant dose-dependent prolongations of both prothrombin time and activated partial thromboplastin time. Protamine also markedly attenuated tissue factor-initiated thrombin generation in human plasma, causing a significant decrease in endogenous thrombin potential (41% ± 7%). As expected, low-dose protamine effectively reversed the anticoagulant activity of unfractionated heparin in plasma. However, elevated protamine concentrations were associated with progressive dose-dependent reduction in thrombin generation. To assess the mechanism by which protamine mediates down-regulation of thrombin generation, the effect of protamine on factor V activation was assessed. Protamine was found to significantly reduce the rate of factor V activation by both thrombin and factor Xa. Protamine mediates its anticoagulant activity in plasma by down-regulation of thrombin generation via a novel mechanism, specifically inhibition of factor V activation.
Transcriptome sequencing of the Microarray Quality Control (MAQC) RNA reference samples using next generation sequencing
Authors: Mane Shrinivasrao P , Evans Clive , Cooper Kristal L , Crasta Oswald R , Folkerts Otto , Hutchison Stephen K , Harkins Timothy T , Thierry-Mieg Danielle , Thierry-Mieg Jean , Jensen Roderick V
Published: June 2009

Background

Transcriptome sequencing using next-generation sequencing platforms will soon be competing with DNA microarray technologies for global gene expression analysis. As a preliminary evaluation of these promising technologies, we performed deep sequencing of cDNA synthesized from the Microarray Quality Control (MAQC) reference RNA samples using Roche's 454 Genome Sequencer FLX.

Results

We generated more that 3.6 million sequence reads of average length 250 bp for the MAQC A and B samples and introduced a data analysis pipeline for translating cDNA read counts into gene expression levels. Using BLAST, 90% of the reads mapped to the human genome and 64% of the reads mapped to the RefSeq database of well annotated genes with e-values ≤ 10-20. We measured gene expression levels in the A and B samples by counting the numbers of reads that mapped to individual RefSeq genes in multiple sequencing runs to evaluate the MAQC quality metrics for reproducibility, sensitivity, specificity, and accuracy and compared the results with DNA microarrays and Quantitative RT-PCR (QRTPCR) from the MAQC studies. In addition, 88% of the reads were successfully aligned directly to the human genome using the AceView alignment programs with an average 90% sequence similarity to identify 137,899 unique exon junctions, including 22,193 new exon junctions not yet contained in the RefSeq database.

Conclusion

Using the MAQC metrics for evaluating the performance of gene expression platforms, the ExpressSeq results for gene expression levels showed excellent reproducibility, sensitivity, and specificity that improved systematically with increasing shotgun sequencing depth, and quantitative accuracy that was comparable to DNA microarrays and QRTPCR. In addition, a careful mapping of the reads to the genome using the AceView alignment programs shed new light on the complexity of the human transcriptome including the discovery of thousands of new splice variants.
Host cell transcriptional profiling during malaria liver stage infection reveals a coordinated and sequential set of biological events
Authors: Albuquerque Sónia S , Carret Céline , Grosso Ana Rita , Tarun Alice S , Peng Xinxia , Kappe Stefan HI , Prudêncio Miguel , Mota Maria M
Published: June 2009

Background

Plasmodium sporozoites migrate to the liver where they traverse several hepatocytes before invading the one inside which they will develop and multiply into thousands of merozoites. Although this constitutes an essential step of malaria infection, the requirements of Plasmodium parasites in liver cells and how they use the host cell for their own survival and development are poorly understood.

Results

To gain new insights into the molecular host-parasite interactions that take place during malaria liver infection, we have used high-throughput microarray technology to determine the transcriptional profile of P. berghei-infected hepatoma cells. The data analysis shows differential expression patterns for 1064 host genes starting at 6 h and up to 24 h post infection, with the largest proportion correlating specifically with the early stages of the infection process. A considerable proportion of those genes were also found to be modulated in liver cells collected from P. yoelii- infected mice 24 and 40 h after infection, strengthening the data obtained with the in vitro model and highlighting genes and pathways involved in the host response to rodent Plasmodium parasites.

Conclusion

Our data reveal that host cell infection by Plasmodium sporozoites leads to a coordinated and sequential set of biological events, ranging from the initial stage of stress response up to the engagement of host metabolic processes and the maintenance of cell viability throughout infection.
Kalirin12 interacts with dynamin
Authors: Xin Xiaonan , Rabiner Chana A , Mains Richard E , Eipper Betty A
Published: June 2009

Background

Guanine nucleotide exchange factors (GEFs) and their target Rho GTPases regulate cytoskeletal changes and membrane trafficking. Dynamin, a large force-generating GTPase, plays an essential role in membrane tubulation and fission in cells. Kalirin12, a neuronal RhoGEF, is found in growth cones early in development and in dendritic spines later in development.

Results

The IgFn domain of Kalirin12, not present in other Kalirin isoforms, binds dynamin1 and dynamin2. An inactivating mutation in the GTPase domain of dynamin diminishes this interaction and the isolated GTPase domain of dynamin retains the ability to bind Kalirin12. Co-immunoprecipitation demonstrates an interaction of Kalirin12 and dynamin2 in embryonic brain. Purified recombinant Kalirin-IgFn domain inhibits the ability of purified rat brain dynamin to oligomerize in response to the presence of liposomes containing phosphatidylinositol-4,5-bisphosphate. Consistent with this, expression of exogenous Kalirin12 or its IgFn domain in PC12 cells disrupts clathrin-mediated transferrin endocytosis. Similarly, expression of exogenous Kalirin12 disrupts transferrin endocytosis in cortical neurons. Expression of Kalirin7, a shorter isoform which lacks the IgFn domain, was previously shown to inhibit clathrin-mediated endocytosis; the GTPase domain of dynamin does not interact with Kalirin7.

Conclusion

Kalirin12 may play a role in coordinating Rho GTPase-mediated changes in the actin cytoskeleton with dynamin-mediated changes in membrane trafficking.
The impact of a fast track area on quality and effectiveness outcomes: A Middle Eastern emergency department perspective
Authors: Devkaran Subashnie , Parsons Howard , Van Dyke Murray , Drennan Jonathan , Rajah Jaishen
Published: June 2009

Background

Emergency department (ED) overcrowding is a ubiquitous problem with serious public health implications. The fast track area is a novel method which aims to reduce waiting time, patient dissatisfaction and morbidity. |The study objective was to determine the impact of a fast track area (FTA) on both effectiveness measures (i.e. waiting times [WT] and length of stay [LOS]) and quality measures (i.e. LWBS rates and mortality rates) in non-urgent patients. The secondary objective was to assess if a FTA negatively impacted on urgent patients entering the ED.

Methods

The study took place in a 500 bed, urban, tertiary care hospital in Abu Dhabi, United Arab Emirates. This was a quasi-experimental, which examined the impact of a FTA on a pre-intervention control group (January 2005) (n = 4,779) versus a post-intervention study group (January 2006) (n = 5,706).

Results

Mean WTs of Canadian Triage Acuity Scale (CTAS) 4 patients decreased by 22 min (95% CI 21 min to 24 min, P < 0.001). Similarly, mean WTs of CTAS 5 patients decreased by 28 min (95% CI 19 min to 37 min, P < 0.001) post FTA. The mean WTs of urgent patients (CTAS 2/3) were also significantly reduced after the FTA was opened (P < 0.001). The LWBS rate was reduced from 4.7% to 0.7% (95% CI 3.37 to 4.64; P < 0.001). Opening a FTA had no significant impact on mortality rates (P = 0.88).

Conclusion

The FTA improved ED effectiveness (WTs and LOS) and quality measures (LWBS rates) whereas mortality rate remained unchanged.
Deaths among tuberculosis cases in Shanghai, China: who is at risk?
Authors: Shen Xin , DeRiemer Kathryn , Yuan Zheng'an , Shen Mei , Xia Zhen , Gui Xiaohong , Wang Lili , Mei Jian
Published: June 2009

Background

Information about the risk factors associated with death caused by tuberculosis (TB) or death with TB would allow improvements in the clinical care of TB patients and save lives. The present study sought to identify characteristics associated with increased risk of death during anti-TB treatment in Shanghai, a city in China with one of the country's highest TB mortality rates.

Methods

We evaluated deaths among culture positive pulmonary TB cases that were diagnosed in Shanghai during 2000–2004 and initiated anti-TB therapy. Demographic, clinical, mycobacteriological information and treatment outcomes were routinely collected through a mandatory reporting system.

Results

There were 7,999 culture positive pulmonary cases reported during the study period. The overall case fatality rate was 5.5% (440 cases), and approximately half (50.5%) of the deaths were attributed to causes other than TB. Eighty-six percent of the deaths were among TB cases age ≥ 60 years. The significant independent risk factors for mortality during anti-TB treatment were advancing age, male sex, sputum smear positivity, and the presence of a comorbidity.

Conclusion

More vigorous clinical management and prevention strategies by both the TB control program and other public health programs are essential to improve TB treatment outcomes. Earlier suspicion, diagnosis and treatment of TB, especially among persons older than 60 years of age and those with a comorbid condition, could reduce deaths among TB patients.
Risk of latent tuberculosis infection in children living in households with tuberculosis patients: a cross sectional survey in remote northern Lao People's Democratic Republic
Authors: Nguyen Tuan H , Odermatt Peter , Slesak Gunther , Barennes Hubert
Published: June 2009

Background

Tuberculosis is highly prevalent in Laos (289 per 100,000). We evaluated the risk of latent tuberculosis infection (LTBI) among children (0–15 years) living with tuberculosis patients in rural northern Laos.

Methods

In a cross sectional survey of 30 randomly selected villages, 72 tuberculosis patients were traced and their 317 contacts (148 were children) investigated using a questionnaire, a tuberculin skin tests (positive: > = 10 mm), a 3-day sputum examination for acid-fast bacilli (AFB), and chest radiography.

Results

None of the 148 contact-children received prophylaxis, one had cervical tuberculosis; the risk for LTBI was 31.0%. Awareness of the infectiousness of tuberculosis was low among patients (31%) and their contacts (31%), and risky behavior was common. After multivariate logistic analysis, increased LTBI was found in children with contact with sputum positive adults (OR: 3.3, 95% CI: 1.4–7.7), patients highly positive sputum prior to treatment (AFB >2+; OR: 4.7, 95% CI: 1.7–12.3), and living in ethnic minorities (OR: 5.4, 95% CI: 2.2–13.6).

Conclusion

The study supports the importance of contact tracing in remote settings with high TB prevalence. Suggestions to improve the children's detection rate, the use of existing guidelines, chemoprophylaxis of contact-children and the available interventions in Laos are discussed. Improving education and awareness of the infectiousness of TB in patients is urgently needed to reduce TB transmission.
The INSIG2 rs7566605 genetic variant does not play a major role in obesity in a sample of 24,722 individuals from four cohorts
Authors: Bressler Jan , Fornage Myriam , Hanis Craig L , Kao Wen Hong Linda , Lewis Cora E , McPherson Ruth , Dent Robert , Mosley Thomas H , Pennacchio Len A , Boerwinkle Eric
Published: June 2009

Background

In a genome-wide association study performed in the Framingham Offspring Cohort, individuals homozygous for the rs7566605 C allele located upstream of insulin-induced gene 2 (INSIG2) were reported to incur an increased risk of obesity. This finding was later replicated in four out of five populations examined. The goal of the study reported here was to assess the role of the INSIG2 single nucleotide polymorphism (SNP) in susceptibility to obesity in the prospective longitudinal Atherosclerosis Risk in Communities (ARIC) study (n = 14,566) and in three other cohorts: the Coronary Artery Risk Development in Young Adults (CARDIA) study (n = 3,888), the Genetic Epidemiology Network of Arteriopathy (GENOA) study (n = 4,766), and extremely obese and lean individuals ascertained at the University of Ottawa (n = 1,502). The combined study sample is comprised of 24,722 white, African-American, and Mexican-American participants.

Methods

Differences in mean body mass index (BMI) and other anthropometric measures including weight, waist circumference, and waist-to-hip ratio were assessed by a general linear model in individuals categorized by INSIG2 rs7566605 genotype. Multivariable logistic regression was used to predict the risk of obesity (BMI ≥ 30 kg/m2).

Results

There was no discernable variation in the frequencies of the three INSIG2 SNP genotypes observed between white, Hispanic, and African-American obese individuals and non-obese study subjects. When the relationship between rs7566605 and BMI considered either as a categorical variable or a continuous variable was examined, no significant association with obesity was found for participants in any of the four study populations or in a combined analysis (p = 0.38) under a recessive genetic model. There was also no association between the INSIG2 polymorphism and the obesity-related quantitative traits except for a reduced waist-to-hip ratio in white ARIC study participants homozygous for the C allele, and an increased waist-to-hip ratio in African-Americans in the ARIC cohort with the same genotype (p = 0.04 and p = 0.01, respectively). An association with waist-to-hip ratio was not seen when the combined study sample was analyzed (p = 0.74).

Conclusion

These results suggest that the INSIG2 rs7566605 variant does not play a major role in determining obesity risk in a racially and ethnically diverse sample of 24,722 individuals from four cohorts.
Mammographic density and epithelial histopathologic markers
Authors: Verheus Martijn , Maskarinec Gertraud , Erber Eva , Steude Jana S , Killeen Jeffrey , Hernandez Brenda Y , Cline J Mark
Published: June 2009

Background

We explored the association of mammographic density, a breast cancer risk factor, with hormonal and proliferation markers in benign tissue from tumor blocks of pre-and postmenopausal breast cancer cases.

Methods

Breast cancer cases were recruited from a case-control study on breast density. Mammographic density was assessed on digitized prediagnostic mammograms using a computer-assisted method. For 279 participants of the original study, we obtained tumor blocks and prepared tissue microarrays (TMA), but benign tissue cores were only available for 159 women. The TMAs were immunostained for estrogen receptor alpha (ERα) and beta (ERβ), progesterone receptor (PR), HER2/neu, Ki-67, and Proliferating Cell Nuclear Antigen (PCNA). We applied general linear models to compute breast density according to marker expression.

Results

A substantial proportion of the samples were in the low or no staining categories. None of the results was statistically significant, but women with PR and ERβ staining had 3.4% and 2.4% higher percent density. The respective values for Caucasians were 5.7% and 11.6% but less in Japanese women (3.5% and -1.1%). Percent density was 3.4% higher in women with any Ki-67 staining and 2.2% in those with positive PCNA staining.

Conclusion

This study detected little evidence for an association between mammographic density and expression of steroid receptors and proliferation markers in breast tissue, but it illustrated the problems of locating tumor blocks and benign breast tissue samples for epidemiologic research. Given the suggestive findings, future studies examining estrogen effects in tissue, cell proliferation, and density in the breast may be informative.
Assessing the disease burden of Yi people by years of life lost in Shilin county of Yunnan province, China
Authors: Zhou Shang-Cheng , Cai Le , Wan Chong-Hua , Lv Yi-Ling , Fang Peng-Qian
Published: June 2009

Background

Years of Life Lost (YLL) is one of the methods used to estimate the duration of time lost due to premature death. While previous studies of disease burden have been reported using YLL, there have been no studies investigating YLL of Yi people in rural China. Yunnan Province ranks first in terms of Yi people in China. This paper uses YLL to estimate the disease burden of Yi people in Shilin county of Yunnan Province. This study aims to address the differentials about YLL between Yi people and Han people for providing useful information for health planning.

Methods

We applied the Global Burden of Disease (GBD) method created by WHO. YLL rate per 1,000 were calculated from medical death certificates in 2003 in Shilin Yi Nationality Autonomous County (Shilin county).

Results

The male had greater YLL rate per 1,000 than did the female almost in each age group. It demonstrated a higher premature mortality burden due to injuries in Shilin county. Among the top non-communicable diseases, respiratory diseases are the most common mortality burden. Yi people are still suffering from maternal conditions, with two times the burden rates of Han people. For Yi people, while malignant neoplasm was one of the least burden of disease for male, it was the greatest for female, which is the opposite to Han people.

Conclusion

Strategies of economic development should be reviewed to enhance the prevention and treatment of injuries, maternal conditions and respiratory diseases for Yi people.
Reproducibility and repeatability of measuring the electrical impedance of the pregnant human cervix-the effect of probe size and applied pressure
Authors: Jokhi Roobin P , Ghule Vidita V , Brown Brian H , Anumba Dilly OC
Published: June 2009

Background

The utility of cervical electrical impedance spectroscopy (EIS) as a diagnostic tool is being investigated in clinical trials. We sought to assess the reliability of two different sizes of tetrapolar probes used in measuring cervical impedance.

Methods

Cervical transfer impedance was measured at 14 frequencies between 76 and 625 000 Hz from 11 pregnant subjects at term. Repeated measurements were taken with two probes (3 mm and 12 mm diameter) applied softly (approximately 0.7 Newton of force), and firmly (approximately 2.2 Newton) to the surface of the cervix by two observers. The intra-class correlation coefficient (ICC), coefficient of variation (CV) and repeatability standard deviations (SD) were derived from these measurements and compared.

Results

Measurements taken by one observer were highly repeatable for both probes as demonstrated by high ICC and low CV values. Probe performance was improved further by firm application. Firm application of the 3 mm probe resulted in ICC values that ranged from 0.936 to 0.986 (p = 0.0001) and CV values between 1.0 and 3.4%. Firm pressure with the 12 mm probe resulted in ICC values that ranged between 0.914 and 0.988 (p = 0.0001) with CV values between 0.7 and 2.1%. In addition, the repeatability SD was low across all frequencies implying that there was low intra-observer variability. Measurements taken by 2 observers with firm application of the 12 mm probe demonstrated moderate reproducibility between 9.8 and 156 kHz, the frequency range in which previous clinical studies have shown predictive association between high cervical resistivity and vaginal delivery: ICC values ranged between 0.528 and 0.638 (p < 0.05), CV values were between 3.3 and 5.2% and reproducibility SD values were also low. In contrast the 3 mm probe demonstrated poor reproducibility at all study frequencies.

Conclusion

Measuring cervical resistivity by a single observer with both the 3 and 12 mm probes is highly repeatable whilst inter-observer reproducibility is poor with the 3 mm probe but moderately good when the 12 mm probe is firmly applied to the cervix in the frequency range 9.8 to 156 kHz, consistent with our observations of probe performance in clinical trials.
Interleukin-6 as an early marker for fat embolism
Authors: Yoga R , Theis JC , Walton M , Sutherland W
Published: June 2009

Background

Fat Embolism is a complication of long bone fractures, intramedullary fixation and joint arthroplasty. It may progress to fat embolism syndrome, which is rare but involves significant morbidity and can occasionally be fatal. Fat Embolism can be detected at the time of embolization by transoesophageal echocardiography or atrial blood sampling. Later, a combination of clinical signs and symptoms will point towards fat embolism but there is no specific test to confirm the diagnosis. We investigated serum Interleukin-6 (IL-6) as a possible early marker for fat embolism.

Methods

An animal study was conducted to simulate a hip replacement in 31 adult male Sprague Dawley rats. The procedure was performed under general anesthesia and the animals divided into 3 groups: control, uncemented and cemented. Following surgery and recovery from anaesthesia, the rats allowed to freely mobilize in their cages. Blood was taken before surgery and at 6 hours, 12 hours and 24 hours to measure serum IL-6 levels. The rats were euthanized at 24 hours and lungs removed and stained for fat. The amount of fat seen was then correlated with serum IL-6 levels.

Results

No rats in the control group had fat emboli. Numerous fat emboli were seen in both the uncemented and cemented implant groups. The interleukin levels were raised in all groups reaching a peak at 12 hours after surgery reaching 100 pg/ml in the control group and around 250 pg/ml in the uncemented and cemented implant groups. The IL-6 levels in the control group were significantly lower than any of the implant groups at 12 and 24 hours. At these time points, the serum IL-6 correlated with the amount of fat seen on lung histology.

Conclusion

Serum IL-6 is a possible early marker of fat embolism.
Hook-up of GluA2, GRIP and liprin-α for cholinergic muscarinic receptor-dependent LTD in the hippocampus
Authors: Wu Long-Jun , Wang Yu-Tian , Zhuo Min
Published: June 2009

The molecular mechanism underlying muscarinic acetylcholine receptor-dependent LTD (mAChR-LTD) in the hippocampus is less studied. In a recent study, a novel mechanism is described. The induction of mAChR-LTD required the activation of protein tyrosine phosphatase (PTP), and the expression was mediated by AMPA receptor endocytosis via interactions between GluA2, GRIP and liprin-α. The hook-up of these proteins may result in the recruitment of leukocyte common antigen-related receptor (LAR), a PTP that is known to be involved in AMPA receptor trafficking. Interestingly, the similar molecular interaction cannot be applied to mGluR-LTD, despite the fact that the same G-protein involved in LTD is activated by both mAChR and mGluR. This discovery provides key molecular insights for cholinergic dependent cognitive function, and mAChR-LTD can serve as a useful cellular model for studying the roles of cholinergic mechanism in learning and memory.
Association of Parathyroid Adenoma and Pregnancy with Preeclampsia
Authors: Hultin Hella , Hellman Per , Lundgren Ewa , Olovsson Matts , Ekbom Anders , Rastad Jonas , Montgomery Scott M.
Published: June 2009

Objective: Case reports have described associations between calcium metabolism disturbances and primary hyperparathyroidism with preeclampsia, suggesting parathyroid involvement in preeclampsia etiology. This study examines whether parathyroid adenoma, the main cause of hyperparathyroidism, diagnosed and treated before pregnancy is associated with preeclampsia.

Design: We conducted a register-based study to assess the association between parathyroid adenoma and subsequent preeclampsia.

Setting: Births among Sweden’s general population were studied.

Population: The study population included 52 women with a diagnosis of parathyroid adenoma and 519 without, all of whom had a subsequent singleton pregnancy between 1973 and 1997.

Methods: We performed a conditional logistic regression investigating the association of parathyroid adenoma with subsequent preeclampsia in the first singleton pregnancy with adjustment for potential confounding factors.

Main Outcome Measure: The main outcome was a diagnosis of preeclampsia that does not include women with prior chronic hypertension. To ensure that treatment of parathyroid adenoma was completed before pregnancy, those with a diagnosis of parathyroid adenoma made less than 2 yr before delivery (and the matched comparison women) were excluded.

Results: Statistically, parathyroid adenoma prior to delivery is significantly (P < 0.001) associated with preeclampsia, producing an adjusted odds ratio of 6.89 (95% confidence interval, 2.30, 20.58).

Conclusion: A history of parathyroid adenoma should be viewed as a risk for preeclampsia.

A history of parathyroid adenoma is associated with an increased risk for pre-eclampsia in subsequent pregnancies.
The Hippo pathway regulates apical-domain size independently of its growth-control function
Authors: Genevet Alice , Polesello Cédric , Blight Ken , Robertson Francesca , Collinson Lucy M. , Pichaud Franck , Tapon Nicolas
Published: June 2009

The Hippo pathway, identified in Drosophila and conserved in vertebrates, regulates tissue growth by promoting cell cycle exit and apoptosis. In addition to their well-characterised overproliferation phenotype, adult Drosophila epithelial cells mutant for the kinases Hippo and Warts have hypertrophic apical domains. Here we examine the molecular basis of this apical hypertrophy and its impact on cell proliferation. In the wing imaginal disc epithelium, we observe increased staining for members of the apical polarity complexes aPKC and Crumbs as well as adherens junction components when Hippo activity is compromised, while basolateral markers are not affected. This increase in apical proteins is correlated with a hypertrophy of the apical domain and adherens junctions. The cell surface localisation of the Notch receptor is also increased in mutant clones, opening the possibility that aberrant receptor signalling may participate in overgrowth of hpo-deficient tissue. Interestingly, however, although the polarity determinant Crumbs is required for the accumulation of apical proteins, this does not appear to significantly contribute to the overproliferation defect elicited by loss of Hippo signalling. Therefore, Hippo signalling controls growth and apical domain size by distinct mechanisms.
Cul4 and DDB1 regulate Orc2 localization, BrdU incorporation and Dup stability during gene amplification inDrosophilafollicle cells
Authors: Lin Hsiu-Chen , Wu June-Tai , Tan Bertrand Chin-Ming , Chien Cheng-Ting
Published: June 2009

In higher eukaryotes, the pre-replication complex (pre-RC) component Cdt1 is the major regulator in licensing control for DNA replication. The Cul4-DDB1-based ubiquitin ligase mediates Cdt1 ubiquitylation for subsequent proteolysis. During the initiation of chorion gene amplification, Double-parked (Dup), the Drosophila ortholog of Cdt1, is restricted to chorion gene foci. We found that Dup accumulated in nuclei in Cul4 mutant follicle cells, and the accumulation was less prominent in DDB1 mutant cells. Loss of Cul4 or DDB1 activity in follicle cells also compromised chorion gene amplification and induced ectopic genomic DNA replication. The focal localization of Orc2, a subunit of the origin recognition complex, is frequently absent in Cul4 mutant follicle cells. Therefore, Cul4 and DDB1 have differential functions during chorion gene amplification.
Comparison of rapid casting solutions for lead and brass alloys using three-dimensional printing
Authors: Singh R , Singh J P
Published: June 2009

The purpose of the present investigation is to study and compare the feasibility of decreasing the shell wall thickness for rapid casting solution of brass and lead alloys using three-dimensional printing (3DP) technology. Starting from the identification of components/benchmarks, technological prototypes have been produced at different shell thicknesses using lead and brass alloys. Measurements on a coordinate measuring machine helped in calculating the dimensional tolerances of the castings produced. Some important mechanical properties are also compared to verify the suitability of the castings and further results are supported by microstructure analysis. The study suggested that the production of sound casting for minimum wall thickness depends on pouring temperature and weight density. It has been observed that IT grades comparable to machining can be obtained with 3DP for lower pouring temperature alloys. Further feasibility of obtaining minimum shell thickness is more dependent on pouring temperature than weight density. Based on improved dimensional accuracy and microstructure analysis, the saving of costs up to 45.75 per cent and time up to 43 per cent can be achieved over the recommended one in the case of lead alloy for the selected benchmark/component. For brass alloy casting saving of costs and time up to 40.05 and 32.84 per cent, respectively, has been achieved.
Indentation in lightweight composite sandwich beams
Authors: Saadati M , Sadighi M
Published: June 2009

Indentation law is the relationship between force and deflection under the load on a sandwich beam in a fully backed state (on rigid ground), which plays an important role in low-velocity impact models. In the classical method, the Winkler model, which is based on analysing a beam on elastic foundation, is used for measuring the linear part of indentation law and core compression yielding load. This load is assumed to be the same as three-point bending (3PB) state core compression yielding load. In the present article, the sandwich beam is divided into three regions: two faces and a core. Faces are modelled with classical beam theory separately and the core is modelled with two-dimensional elasticity theory, which is known as sandwich panel higher-order theory (SPHOT). A simply supported and fully backed sandwich beam with concentrated loading is solved with Fourier series, and closed-form solutions for core compression, shear, and normal stresses of the core are obtained. The obtained core yielding load by SPHOT is compared with the classical method using the commercial finite element code ANSYS and also with recently reported researches in the literature. The results show that SPHOT predicts more accurate core yielding load and better indentation law compared with other theories and are in good agreement with the results of finite element simulation. In addition, differences between SPHOT theory and the classical method for indentation are investigated in terms of geometry and material properties of sandwich elements. The bottom face effect is determined in core compression in the 3PB state. It is shown that core compression in the 3PB state is lower than fully backed indentation and fully backed indentation is lower than classical prediction.
A hierarchical classification scheme for computationally efficient damage classification
Authors: Coelho C K , Das S , Chattopadhyay A
Published: June 2009

This article presents a methodology for data mining of sensor signals in a structural health monitoring (SHM) framework for damage classification using a machine-learning-based approach called support vector machines (SVMs). A hierarchical decision tree structure is constructed for damage classification and experiments were conducted on metallic and composite test specimens with surface mounted piezoelectric transducers. Damage was induced in the specimens by fatigue, impact, and tensile loading; in addition, specimens with seeded delaminations were also considered. Data were collected from the surface mounted sensors at different severities of induced damage. A matching pursuit decomposition (MPD) algorithm was used as a feature extraction technique to preprocess the sensor data and extract the input vectors used in classification. Using this binary tree framework, the computational intensity of each successive classifier is reduced and the efficiency of the algorithm as a whole is increased. The results obtained using this classification show that this type of architecture works well for large data sets because a reduced number of comparisons are required. Due to the hierarchical set-up of the classifiers, performance of the classifier as a whole is heavily dependent on the performance of the classifier at higher levels in the classification tree.