bluuebunny/crossref_metadata_2025 huggingface dataset:
The application of the framework of Situational Crime Prevention to ‘organized crime’
Authors: von Lampe Klaus
Published: April 2011

This essay and review examines to what extent the conceptual framework of Situational Crime Prevention can be meaningfully applied to the phenomena variously labelled ‘organized crime’. Several approaches are identified which in different respects imply modifications to the situational framework in order to accommodate assumed specificities of ‘organized crime’, including ‘organized’ criminal activities transcending space and time, and ‘organized’ criminals being capable of selecting and shaping crime settings. It is argued that while a situational approach to the study of ‘organized crime’ is useful in some respects, in other respects the conceptual framework of Situational Crime Prevention needs to be modified to a point where its universal applicability is called into question.
Low-profile plate fixation in arthrodesis of the first metacarpophalangeal joint
Authors: Rasmussen C. , Roos S. , Boeckstyns M.
Published: April 2011

Fifty-one consecutive arthrodeses (46 patients) of the first metacarpophalangeal joint were retrospectively reviewed, after fixation with a Leibinger low-profile titanium plate, using a cup-and-cone technique. Primary bone union was achieved in 98%. Three cases required removal of the plate and one case a tenolysis. Follow-up time was 13–92 months (mean 52). There was no correlation between patient satisfaction and position of fusion. We conclude that this technique gives a high rate of union, a short period of immobilization and rehabilitation, and a reliable position at the site of fusion.
Hand hygiene and transmission of Pseudomonas aeruginosa on hands in a hospital environment
Authors: Jones Susan
Published: April 2011

Colonisation and infection with Pseudomonas aeruginosa from the water supply constitutes a risk in neonatal hospital units. This short research note demonstrates that the use of correct hand hygiene minimises the risk of contamination of hands with P. aeruginosa even when heavily contaminated wash water is used.
Fetal hemoglobin in sickle cell anemia
Authors: Akinsheye Idowu , Alsultan Abdulrahman , Solovieff Nadia , Ngo Duyen , Baldwin Clinton T. , Sebastiani Paola , Chui David H. K. , Steinberg Martin H.
Published: April 2011

Fetal hemoglobin (HbF) is the major genetic modulator of the hematologic and clinical features of sickle cell disease, an effect mediated by its exclusion from the sickle hemoglobin polymer. Fetal hemoglobin genes are genetically regulated, and the level of HbF and its distribution among sickle erythrocytes is highly variable. Some patients with sickle cell disease have exceptionally high levels of HbF that are associated with the Senegal and Saudi-Indian haplotype of the HBB-like gene cluster; some patients with different haplotypes can have similarly high HbF. In these patients, high HbF is associated with generally milder but not asymptomatic disease. Studying these persons might provide additional insights into HbF gene regulation. HbF appears to benefit some complications of disease more than others. This might be related to the premature destruction of erythrocytes that do not contain HbF, even though the total HbF concentration is high. Recent insights into HbF regulation have spurred new efforts to induce high HbF levels in sickle cell disease beyond those achievable with the current limited repertory of HbF inducers.
Quality of the parent-child interaction in young children with type 1 diabetes mellitus: study protocol
Authors: Nieuwesteeg Anke M , Pouwer Frans , van Bakel Hedwig JA , Emons Wilco HM , Aanstoot Henk-Jan , Odink Roelof , Hartman Esther E
Published: April 2011

Background

In young children with type 1 diabetes mellitus (T1DM) parents have full responsibility for the diabetes-management of their child (e.g. blood glucose monitoring, and administering insulin). Behavioral tasks in childhood, such as developing autonomy, and oppositional behavior (e.g. refusing food) may interfere with the diabetes-management to achieve an optimal blood glucose control. Furthermore, higher blood glucose levels are related to more behavioral problems. So parents might need to negotiate with their child on the diabetes-management to avoid this direct negative effect. This interference, the negotiations, and the parent's responsibility for diabetes may negatively affect the quality of parent-child interaction. Nevertheless, there is little knowledge about the quality of interaction between parents and young children with T1DM, and the possible impact this may have on glycemic control and psychosocial functioning of the child. While widely used global parent-child interaction observational methods are available, there is a need for an observational tool specifically tailored to the interaction patterns of parents and children with T1DM. The main aim of this study is to construct a disease-specific observational method to assess diabetes-specific parent-child interaction. Additional aim is to explore whether the quality of parent-child interactions is associated with the glycemic control, and psychosocial functioning (resilience, behavioral problems, and quality of life).

Methods/Design

First, we will examine which situations are most suitable for observing diabetes-specific interactions. Then, these situations will be video-taped in a pilot study (N = 15). Observed behaviors are described into rating scales, with each scale describing characteristics of parent-child interactional behaviors. Next, we apply the observational tool on a larger scale for further evaluation of the instrument (N = 120). The parents are asked twice (with two years in between) to fill out questionnaires about psychosocial functioning of their child with T1DM. Furthermore, glycemic control (HbA1c) will be obtained from their medical records.

Discussion

A disease-specific observational tool will enable the detailed assessment of the quality of diabetes-specific parent-child interactions. The availability of such a tool will facilitate future (intervention) studies that will yield more knowledge about impact of parent-child interactions on psychosocial functioning, and glycemic control of children with T1DM.
Role of calcium supplementation during pregnancy in reducing risk of developing gestational hypertensive disorders: a meta-analysis of studies from developing countries
Authors: Imdad Aamer , Jabeen Afshan , Bhutta Zulfiqar A
Published: April 2011

Background

Hypertension in pregnancy stand alone or with proteinuria is one of the leading causes of maternal mortality and morbidity in the world. Epidemiological and clinical studies have shown that an inverse relationship exists between calcium intake and development of hypertension in pregnancy though the effect varies based on baseline calcium intake and pre-existing risk factors. The purpose of this review was to evaluate preventive effect of calcium supplementation during pregnancy on gestational hypertensive disorders and related maternal and neonatal mortality in developing countries.

Methods

A literature search was carried out on PubMed, Cochrane Library and WHO regional databases. Data were extracted into a standardized excel sheet. Identified studies were graded based on strengths and limitations of studies. All the included studies were from developing countries. Meta-analyses were generated where data were available from more than one study for an outcome. Primary outcomes were maternal mortality, eclampsia, pre-eclampsia, and severe preeclampsia. Neonatal outcomes like neonatal mortality, preterm birth, small for gestational age and low birth weight were also evaluated. We followed standardized guidelines of Child Health Epidemiology Reference Group (CHERG) to generate estimates of effectiveness of calcium supplementation during pregnancy in reducing maternal and neonatal mortality in developing countries, for inclusion in the Lives Saved Tool (LiST).

Results

Data from 10 randomized controlled trials were included in this review. Pooled analysis showed that calcium supplementation during pregnancy was associated with a significant reduction of 45% in risk of gestational hypertension [Relative risk (RR) 0.55; 95 % confidence interval (CI) 0.36-0.85] and 59% in the risk of pre-eclampsia [RR 0.41; 95 % CI 0.24-0.69] in developing countries. Calcium supplementation during pregnancy was also associated with a significant reduction in neonatal mortality [RR 0.70; 95 % CI 0.56-0.88] and risk of pre-term birth [RR 0.88, 95 % CI 0.78-0.99]. Recommendations for LiST for reduction in maternal mortality were based on risk reduction in gestational hypertensive related severe morbidity/mortality [RR 0.80; 95% CI 0.70-0.91] and that for neonatal mortality were based on risk reduction in all-cause neonatal mortality [RR 0.70; 95% CI 0.56-0.88].

Conclusion

Calcium supplementation during pregnancy is associated with a reduction in risk of gestational hypertension, pre-eclampsia neonatal mortality and pre-term birth in developing countries.
Effect of screening and management of diabetes during pregnancy on stillbirths
Authors: Syed Madiha , Javed Hasan , Yakoob Mohammad Yawar , Bhutta Zulfiqar A
Published: April 2011

Background

Diabetes during pregnancy is associated with significant risk of complications to the mother, fetus and newborn. We reviewed the potential impact of early detection and control of diabetes mellitus during pregnancy on stillbirths for possible inclusion in the Lives Saved Tool (LiST).

Methods

A systematic literature search up to July 2010 was done to identify all published randomized controlled trials and observational studies. A standardized data abstraction sheet was employed and data were abstracted by two independent authors. Meta-analyses were performed with different sub-group analyses. The analyses were graded according to the CHERG rules using the adapted GRADE criteria and recommendations made after assessing the overall quality of the studies included in the meta-analyses.

Results

A total of 70 studies were selected for data extraction including fourteen intervention studies and fifty six observational studies. No randomized controlled trials were identified evaluating early detection of diabetes mellitus in pregnancy versus standard screening (glucose challenge test between 24th to 28th week of gestation) in pregnancy. Intensive management of gestational diabetes (including specialized dietary advice, increased monitoring and tailored dietary therapy) during pregnancy (3 studies: 3791 participants) versus conventional management (dietary advice and insulin as required) was associated with a non-significant reduction in the risk of stillbirths (RR 0.20; 95% CI: 0.03-1.10) (‘moderate’ quality evidence). Optimal control of serum blood glucose versus sub-optimal control was associated with a significant reduction in the risk of perinatal mortality (2 studies, 5286 participants: RR=0.40, 95% CI 0.25- 0.63), but not stillbirths (3 studies, 2469 participants: RR=0.51, 95% CI 0.14-1.88). Preconception care of diabetes (information about need for optimization of glycemic control before pregnancy, assessment of diabetes complications, review of dietary habits, intensification of capillary blood glucose self-monitoring and optimization of insulin therapy) versus none (3 studies: 910 participants) was associated with a reduction in perinatal mortality (RR=0.29, 95% CI 0.14 -0.60). Using the Delphi process for estimating effect size of optimal diabetes recognition and management yielded a median effect size of 10% reduction in stillbirths.

Conclusions

Diabetes, especially pre-gestational diabetes with its attendant vascular complications, is a significant risk factor for stillbirth and perinatal death. Our review highlights the fact that very few studies of adequate quality are available that can provide estimates of the effect of screening for aid management of diabetes in pregnancy on stillbirth risk. Using the Delphi process we recommend a conservative 10% reduction in the risk of stillbirths, as a point estimate for inclusion in the LiST.
Preventive zinc supplementation in developing countries: impact on mortality and morbidity due to diarrhea, pneumonia and malaria
Authors: Yakoob Mohammad Yawar , Theodoratou Evropi , Jabeen Afshan , Imdad Aamer , Eisele Thomas P , Ferguson Joy , Jhass Arnoupe , Rudan Igor , Campbell Harry , Black Robert E , Bhutta Zulfiqar A
Published: April 2011

Background

Zinc deficiency is commonly prevalent in children in developing countries and plays a role in decreased immunity and increased risk of infection. Preventive zinc supplementation in healthy children can reduce mortality due to common causes like diarrhea, pneumonia and malaria. The main objective was to determine all-cause mortality and cause-specific mortality and morbidity in children under five in developing countries for preventive zinc supplementation.

Data sources/ review methods

A literature search was carried out on PubMed, the Cochrane Library and the WHO regional databases to identify RCTs on zinc supplementation for greater than 3 months in children less than 5 years of age in developing countries and its effect on mortality was analyzed.

Results

The effect of preventive zinc supplementation on mortality was given in eight trials, while cause specific mortality data was given in five of these eight trials. Zinc supplementation alone was associated with a statistically insignificant 9% (RR = 0.91; 95% CI: 0.82, 1.01) reduction in all cause mortality in the intervention group as compared to controls using a random effect model. The impact on diarrhea-specific mortality of zinc alone was a non-significant 18% reduction (RR = 0.82; 95% CI: 0.64, 1.05) and 15% for pneumonia-specific mortality (RR = 0.85; 95% CI: 0.65, 1.11). The incidence of diarrhea showed a 13% reduction with preventive zinc supplementation (RR = 0.87; 95% CI: 0.81, 0.94) and a 19% reduction in pneumonia morbidity (RR = 0.81; 95% CI: 0.73, 0.90). Keeping in mind the direction of effect of zinc supplementation in reducing diarrhea and pneumonia related morbidity and mortality; we considered all the outcomes for selection of effectiveness estimate for inclusion in the LiST model. After application of the CHERG rules with consideration to quality of evidence and rule # 6, we used the most conservative estimates as a surrogate for mortality. We, therefore, conclude that zinc supplementation in children is associated with a reduction in diarrhea mortality of 13% and pneumonia mortality of 15% for inclusion in the LiST tool. Preventive zinc supplementation had no effect on malaria specific mortality (RR = 0.90; 95% CI: 0.77, 1.06) or incidence of malaria (RR=0.92; 95 % CI 0.82-1.04)

Conclusion

Zinc supplementation results in reductions in diarrhea and pneumonia mortality.
Nrf2 is overexpressed in pancreatic cancer: implications for cell proliferation and therapy
Authors: Lister Adam , Nedjadi Taoufik , Kitteringham Neil R , Campbell Fiona , Costello Eithne , Lloyd Bryony , Copple Ian M , Williams Samantha , Owen Andrew , Neoptolemos John P , Goldring Chris E , Park B Kevin
Published: April 2011

Background

Nrf2 is a key transcriptional regulator of a battery of genes that facilitate phase II/III drug metabolism and defence against oxidative stress. Nrf2 is largely regulated by Keap1, which directs Nrf2 for proteasomal degradation. The Nrf2/Keap1 system is dysregulated in lung, head and neck, and breast cancers and this affects cellular proliferation and response to therapy. Here, we have investigated the integrity of the Nrf2/Keap1 system in pancreatic cancer.

Results

Keap1, Nrf2 and the Nrf2 target genes AKR1c1 and GCLC were detected in a panel of five pancreatic cancer cell lines. Mutation analysis of NRF2 exon 2 and KEAP1 exons 2-6 in these cell lines identified no mutations in NRF2 and only synonomous mutations in KEAP1. RNAi depletion of Nrf2 caused a decrease in the proliferation of Suit-2, MiaPaca-2 and FAMPAC cells and enhanced sensitivity to gemcitabine (Suit-2), 5-flurouracil (FAMPAC), cisplatin (Suit-2 and FAMPAC) and gamma radiation (Suit-2). The expression of Nrf2 and Keap1 was also analysed in pancreatic ductal adenocarcinomas (n = 66 and 57, respectively) and matching normal benign epithelium (n = 21 cases). Whilst no significant correlation was seen between the expression levels of Keap1 and Nrf2 in the tumors, interestingly, Nrf2 staining was significantly greater in the cytoplasm of tumors compared to benign ducts (P < 0.001).

Conclusions

Expression of Nrf2 is up-regulated in pancreatic cancer cell lines and ductal adenocarcinomas. This may reflect a greater intrinsic capacity of these cells to respond to stress signals and resist chemotherapeutic interventions. Nrf2 also appears to support proliferation in certain pancreatic adenocarinomas. Therefore, strategies to pharmacologically manipulate the levels and/or activity of Nrf2 may have the potential to reduce pancreatic tumor growth, and increase sensitivity to therapeutics.
Enhanced neuroinflammation and pain hypersensitivity after peripheral nerve injury in rats expressing mutated superoxide dismutase 1
Authors: Berger Julie V , Deumens Ronald , Goursaud Stéphanie , Schäfer Sabrina , Lavand'homme Patricia , Joosten Elbert A , Hermans Emmanuel
Published: April 2011

Background

Neuroinflammation and nitroxidative stress are implicated in the pathophysiology of neuropathic pain. In view of both processes, microglial and astroglial activation in the spinal dorsal horn play a predominant role. The present study investigated the severity of neuropathic pain and the degree of glial activation in an inflammatory- and nitroxidative-prone animal model.

Methods

Transgenic rats expressing mutated superoxide dismutase 1 (hSOD1G93A) are classically used as a model for amyotrophic lateral sclerosis (ALS). Because of the associated inflammatory- and nitroxidative-prone properties, this model was used to study thermal and mechanical hypersensitivity following partial sciatic nerve ligation (PSNL). Next to pain hypersensitivity assessment, microglial and astroglial activation states were moreover characterized, as well as inflammatory marker gene expression and the glutamate clearance system.

Results

PSNL induced thermal and mechanical hypersensitivity in both wild-type (WT) and transgenic rats. However, the degree of thermal hypersensitivity was found to be exacerbated in transgenic rats while mechanical hypersensitivity was only slightly and not significantly increased. Microglial Iba1 expression was found to be increased in the ipsilateral dorsal horn of the lumbar spinal cord after PSNL but such Iba1 up-regulation was enhanced in transgenic rats as compared WT rats, both at 3 days and at 21 days after injury. Moreover, mRNA levels of Nox2, a key enzyme in microglial activation, but also of pro-inflammatory markers (IL-1β and TLR4) were not modified in WT ligated rats at 21 days after PSNL as compared to WT sham group while transgenic ligated rats showed up-regulated gene expression of these 3 targets. On the other hand, the PSNL-induced increase in GFAP immunoreactivity spreading that was evidenced in WT rats was unexpectedly found to be attenuated in transgenic ligated rats. Finally, GLT-1 gene expression and uptake activity were shown to be similar between WT sham and WT ligated rats at 21 days after injury, while both parameters were significantly increased in the ipsilateral dorsal region of the lumbar spinal cord of hSOD1G93A rats.

Conclusions

Taken together, our findings show that exacerbated microglial activation and subsequent inflammatory and nitroxidative processes are associated with the severity of neuropathic pain symptoms.
The CCAAT/enhancer binding protein (C/EBP) δ is differently regulated by fibrillar and oligomeric forms of the Alzheimer amyloid-β peptide
Authors: Ramberg Veronica , Tracy Linda M , Samuelsson Malin , Nilsson Lars NG , Iverfeldt Kerstin
Published: April 2011

Background

The transcription factors CCAAT/enhancer binding proteins (C/EBP) α, β and δ have been shown to be expressed in brain and to be involved in regulation of inflammatory genes in concert with nuclear factor κB (NF-κB). In general, C/EBPα is down-regulated, whereas both C/EBPβ and δ are up-regulated in response to inflammatory stimuli. In Alzheimer's disease (AD) one of the hallmarks is chronic neuroinflammation mediated by astrocytes and microglial cells, most likely induced by the formation of amyloid-β (Aβ) deposits. The inflammatory response in AD has been ascribed both beneficial and detrimental roles. It is therefore important to delineate the inflammatory mediators and signaling pathways affected by Aβ deposits with the aim of defining new therapeutic targets.

Methods

Here we have investigated the effects of Aβ on expression of C/EBP family members with a focus on C/EBPδ in rat primary astro-microglial cultures and in a transgenic mouse model with high levels of fibrillar Aβ deposits (tg-ArcSwe) by western blot analysis. Effects on DNA binding activity were analyzed by electrophoretic mobility shift assay. Cross-talk between C/EBPδ and NF-κB was investigated by analyzing binding to a κB site using a biotin streptavidin-agarose pull-down assay.

Results

We show that exposure to fibril-enriched, but not oligomer-enriched, preparations of Aβ inhibit up-regulation of C/EBPδ expression in interleukin-1β-activated glial cultures. Furthermore, we observed that, in aged transgenic mice, C/EBPα was significantly down-regulated and C/EBPβ was significantly up-regulated. C/EBPδ, on the other hand, was selectively down-regulated in the forebrain, a part of the brain showing high levels of fibrillar Aβ deposits. In contrast, no difference in expression levels of C/EBPδ between wild type and transgenic mice was detected in the relatively spared hindbrain. Finally, we show that interleukin-1β-induced C/EBPδ DNA binding activity to both C/EBP and κB sites is abolished after exposure to Aβ.

Conclusions

These data suggest that both expression and function of C/EBPδ are dysregulated in Alzheimer's disease. C/EBPδ seems to be differently regulated in response to different conformations of Aβ. We propose that Aβ induces an imbalance between NF-κB and C/EBP transcription factors that may result in abnormal responses to inflammatory stimuli.
Full sequence analysis and characterization of the South Korean Norovirus GII-4 variant CUK-3
Authors: Park Jeong-Woong , Lee Sung-Geun , Lee Young-Min , Jheong Weon-Hwa , Ryu Sangryeol , Paik Soon-Young
Published: April 2011

Background

Many of researchers have focused on the emerging pathogen, Norovirus, since its first identification as the causing agent of nonbacterial acute gastroenteritis in humans. One of the virulence factors of norovirus, the great genetic diversity attributed to point mutations and recombinations, has brought forth the result of significant changes in the circulating norovirus genotype patterns.

Findings

In recognition of the necessity for tracking and monitoring of genetic diversity, a norovirus variant among the most prevalent genotype GII-4, Norovirus Hu/GII-4/CUK-3/2008/KR (CUK-3), was isolated from stool samples and analyzed on the level of whole genome sequence. Whole genome sequence analysis revealed three ORF composites of the whole genome, ORF1 (5100 bp), ORF2 (1623 bp), and ORF3 (807 bp). Each genetic relationship of CUK-3 variant analysis located the ORF1 (5,100 bp) in Cluster I, ORF2 (1623 bp) in Cluster I (2006b), ORF3 (807 bp) in Cluster I, and the whole genome sequence (about 5.1 kb) in Cluster I in the phylogenetic tree. And the phylogenetic analyses showed the same location of CUK-3 strain with the GII-4/2006b cluster in the phylogenetic tree.

Conclusions

In This study, a first concerning the full-length sequence of a NoV variant in South Korea is meaningful in that it can be used not only as a full-length NoV variant sequence standard for future comparison studies, but also as useful material for the public health field by enabling the diagnosis, vaccine development, and prediction of new emerging variants.
Discovering functional modules by identifying recurrent and mutually exclusive mutational patterns in tumors
Authors: Miller Christopher A , Settle Stephen H , Sulman Erik P , Aldape Kenneth D , Milosavljevic Aleksandar
Published: April 2011

Background

Assays of multiple tumor samples frequently reveal recurrent genomic aberrations, including point mutations and copy-number alterations, that affect individual genes. Analyses that extend beyond single genes are often restricted to examining pathways, interactions and functional modules that are already known.

Methods

We present a method that identifies functional modules without any information other than patterns of recurrent and mutually exclusive aberrations (RME patterns) that arise due to positive selection for key cancer phenotypes. Our algorithm efficiently constructs and searches networks of potential interactions and identifies significant modules (RME modules) by using the algorithmic significance test.

Results

We apply the method to the TCGA collection of 145 glioblastoma samples, resulting in extension of known pathways and discovery of new functional modules. The method predicts a role for EP300 that was previously unknown in glioblastoma. We demonstrate the clinical relevance of these results by validating that expression of EP300 is prognostic, predicting survival independent of age at diagnosis and tumor grade.

Conclusions

We have developed a sensitive, simple, and fast method for automatically detecting functional modules in tumors based solely on patterns of recurrent genomic aberration. Due to its ability to analyze very large amounts of diverse data, we expect it to be increasingly useful when applied to the many tumor panels scheduled to be assayed in the near future.
Thrombomodulin phenotype of a distinct monocyte subtype is an independent prognostic marker for disseminated intravascular coagulation
Authors: Hwang Sang Mee , Kim Ji-Eun , Han Kyou-Sup , Kim Hyun Kyung
Published: April 2011

Introduction

Thrombomodulin, which is expressed solely on monocytes, along with tissue factor (TF), takes part in coagulation and inflammation. Circulating blood monocytes can be divided into 3 major subtypes on the basis of their receptor phenotype: classical (CD14brightCD16negative, CMs), inflammatory (CD14brightCD16positive; IMs), and dendritic cell-like (CD14dimCD16positive DMs). Monocyte subtype is strongly regulated, and the balance may influence the clinical outcomes of disseminated intravascular coagulation (DIC). Therefore, we investigated the phenotypic difference in thrombomodulin and TF expression between different monocyte subtypes in coagulopathy severity and prognosis in patients suspected of having DIC.

Methods

In total, 98 patients suspected of having DIC were enrolled. The subtypes of circulating monocytes were identified using CD14 and CD16 and the thrombomodulin and TF expression in each subtype, expressed as mean fluorescence intensity, was measured by flow cytometry. Plasma level of tissue factor was measured by ELISA. In cultures of microbead-selected, CD14-positive peripheral monocytes, lipopolysaccharide (LPS)- or interleukin-10-induced expression profiles were analyzed, using flow cytometry.

Results

The proportion of monocyte subtypes did not significantly differ between the overt and non-overt DIC groups. The IM thrombomodulin expression level was prominent in the overt DIC group and was well correlated with other coagulation markers. Of note, IM thrombomodulin expression was found to be an independent prognostic marker in multivariate Cox regression analysis. In addition, in vitro culture of peripheral monocytes showed that LPS stimulation upregulated thrombomodulin expression and TF expression in distinct populations of monocytes.

Conclusions

These findings suggest that the IM thrombomodulin phenotype is a potential independent prognostic marker for DIC, and that thrombomodulin-induced upregulation of monocytes is a vestige of the physiological defense mechanism against hypercoagulopathy.
Characterization of DXZ4 conservation in primates implies important functional roles for CTCF binding, array expression and tandem repeat organization on the X chromosome
Authors: McLaughlin Christine R , Chadwick Brian P
Published: April 2011

Background

Comparative sequence analysis is a powerful means with which to identify functionally relevant non-coding DNA elements through conserved nucleotide sequence. The macrosatellite DXZ4 is a polymorphic, uninterrupted, tandem array of 3-kb repeat units located exclusively on the human X chromosome. While not obviously protein coding, its chromatin organization suggests differing roles for the array on the active and inactive X chromosomes.

Results

In order to identify important elements within DXZ4, we explored preservation of DNA sequence and chromatin conformation of the macrosatellite in primates. We found that DXZ4 DNA sequence conservation beyond New World monkeys is limited to the promoter and CTCF binding site, although DXZ4 remains a GC-rich tandem array. Investigation of chromatin organization in macaques revealed that DXZ4 in males and on the active X chromosome is packaged into heterochromatin, whereas on the inactive X, DXZ4 was euchromatic and bound by CTCF.

Conclusions

Collectively, these data suggest an important conserved role for DXZ4 on the X chromosome involving expression, CTCF binding and tandem organization.
Hepatic Glucokinase Expression Is Associated with Lipogenesis and Fatty Liver in Humans
Authors: Peter Andreas , Stefan Norbert , Cegan Alexander , Walenta Mareike , Wagner Silvia , Königsrainer Alfred , Königsrainer Ingmar , Machicao Fausto , Schick Fritz , Häring Hans-Ulrich , Schleicher Erwin
Published: April 2011

Background/Aims:

Glucokinase (GCK) phosphorylates glucose to form glucose 6-phosphate and thereby regulates hepatic glucose disposal and activates hepatic lipogenesis. Hepatic GCK activity is regulated on the level of GCK mRNA expression and by the inhibitory glucokinase regulatory protein. In this study, we aimed to investigate the relation between GCK mRNA expression and markers of lipogenesis as well as liver fat content in human liver biopsies. Additionally, we investigated whether genetic variation in the liver specific GCK promoter determines liver fat content in humans.

Methods:

Hepatic mRNA expression and liver triglyceride content was analyzed in 50 human liver biopsies. In a second cohort of 330 individuals, liver fat was precisely measured by 1H magnetic resonance spectroscopy.

Results:

Hepatic GCK mRNA expression is associated with triglyceride content in human liver biopsies (r = 0.50, P = 0.0002). Furthermore, hepatic GCK mRNA expression is associated with lipogenic gene expression (fatty acid synthase, r = 0.49, P = 0.0003; acetyl-coenzyme A carboxylase-α, r = 0.44, P = 0.0015, and acetyl-coenzyme A carboxylase-β, r = 0.48, P = 0.0004) and the de novo lipogenesis index (r = 0.36, P = 0.01). In support of these findings, the single-nucleotide polymorphism rs2041547 in the liver-specific GCK promoter is associated with liver fat content in prediabetic individuals (P = 0.047).

Conclusions:

In this study, we demonstrate for the first time that GCK mRNA expression is associated with markers of de novo lipogenesis and liver triglyceride content in humans. This suggests that increased GCK activity may induce fatty liver and its metabolic and hepatic consequences in humans. Thus, the widely used approach to nonspecifically activate β-cell and hepatic GCK to treat diabetes mellitus is therefore questionable and may cause serious side effects.
Reading theNew Yorker
Authors: Letter Joseph J.
Published: April 2011

This essay discusses the impact of using serialized reading texts, like magazines, in writing instruction. It explains an advanced expository writing course that uses the New Yorker magazine as a frame for addressing the significance of contemporaneity and performance in student writing. Ultimately, the magazine remediates between traditional readers and new media approaches.
The Undergraduate Literature Conference
Authors: Hersh Cara , Hiro Molly , Asarnow Herman
Published: April 2011

Written by the co-chairs of the Northwest Undergraduate Conference on Literature (NUCL), this article makes an argument for the value of the undergraduate conference: by fostering conversations about student work, undergraduate conferences offer one way of ameliorating the present crisis in the humanities. The writers also explain the more particular disciplinary, institutional, and departmental benefits of the conference, and suggest strategies for implementing such a conference on other campuses.
The Ethics of Violence
Authors: O'Connor Tom
Published: April 2011

This article analyzes classroom discussions of Boaz Yakin's 1994 film Fresh—an unsettling urban drama about a young boy (Fresh) who devises a creative escape from the drug dealers in his environment: he buys a large amount of cocaine that he uses to trick those dealers into thinking that they're all trying to break into each others' markets. In the end, he turns these negative and violent forces against each other and then enters the Witness Protection Program. The social commentary in the film is paramount since it highlights the disturbing cultural reasons why a twelve–year-old African American boy has to devise his own escape from the inner city. Most important, class discussions of (as well as the writing assignments focused on) Yakin's film necessarily confront the role that class hierarchies play in America as well as the cultural myths—like the unconditional individual—that affect many of our expectations and assumptions. Herein resides the film's pedagogical importance: it offers an intensely emotional and intellectual challenge to many of our foundational understandings of American values and cultural narratives. That is, it critiques the problematic rationalizations (like “the just-world phenomenon”) that seek to not only dis-empower but also neglect whole segments of American society.
β-Catenin is essential for Müllerian duct regression during male sexual differentiation
Authors: Kobayashi Akio , Stewart C. Allison , Wang Ying , Fujioka Kaoru , Thomas Nicholas C. , Jamin Soazik P. , Behringer Richard R.
Published: April 2011

During male sexual differentiation, the transforming growth factor-β (TGF-β) signaling molecule anti-Müllerian hormone (AMH; also known as Müllerian inhibiting substance, MIS) is secreted by the fetal testes and induces regression of the Müllerian ducts, the primordia of the female reproductive tract organs. Currently, the molecular identity of downstream events regulated by the AMH signaling pathway remains unclear. We found that male-specific Wnt4 expression in mouse Müllerian duct mesenchyme depends upon AMH signaling, implicating the WNT pathway as a downstream mediator of Müllerian duct regression. Inactivation of β-catenin, a mediator of the canonical WNT pathway, did not affect AMH signaling activation in the Müllerian duct mesenchyme, but did block Müllerian duct regression. These data suggest that β-catenin mediates AMH signaling for Müllerian duct regression during male sexual differentiation.
The 2050 Roadmap for Nuclear: Making a Global Difference
Authors: Cameron Ron , Taylor Martin
Published: April 2011

Current trends in energy supply and use are patently unsustainable – economically, environmentally and socially. Without decisive action, energy-related emissions of carbon dioxide (CO2) will more than double by 2050 and increased oil demand will heighten concerns over the security of supplies. To change our current path will take an energy revolution and low-carbon energy technologies will have a crucial role to play. Nuclear power among other technologies needs to be widely deployed if we are to reach our greenhouse gas emission goals. Every major country and sector of the economy must be involved. But what level should we aim for, what are the roadblocks to be overcome and what are the milestones that we must achieve? This paper will discuss the nuclear roadmap to 2050, produced jointly by the IEA and NEA.
Strong Flow-Acoustic Resonances of Rectangular Cavities
Authors: Wittich D. J. , Cain Alan B. , Jumper Eric J.
Published: April 2011

Several studies relating to strongly resonating cavity shear layers in subsonic or supersonic flows are reviewed and discussed. Special consideration is given to cavity configurations which Rockwell and Naudascher (1978) branded “whistle-type” cavities, deep cavities and cavities mounted in the wall of an otherwise solid-walled duct (such as a wind tunnel). At certain flow conditions, each configuration can promote a strong, acoustic resonance which tends to favor a single dominant frequency in the pressure spectrum. The resultant shear layer motions and unsteady pressure fluctuations may be of large amplitude at the peak frequency. The empirical constants in Rossiter's formula and a similar frequency prediction formula for partially-covered cavities are also discussed.
ASP, The Art and Science of Practice: Taking the Measure of Lean: Efficiency and Effectiveness
Authors: Schonberger Richard J.
Published: April 2011

Part I: As a long-time (29 years and counting) researcher and writer about lean, I gave no thought to addressing lean efficiency and effectiveness until data began to show trouble in lean land. I saw that big, “best-managed” companies had mixed, long-term lean results, most of which were not good. The main measure of merit in my “leanness” research is the common one, inventory—a measure that is visible and countable in lean action zones and is readily available up the hierarchy as a standard, audited metric for publicly traded companies. Despite that, I have found the inventory metric to be subject to misunderstanding and misuse. In this two-part paper, I address the merits, uses, and abuses of this metric in terms of lean efficiency and lean effectiveness. With exceptions, inventory works well as a dominant, gratifying lean result and as a low-level indicator of lean efficiency. However, examples from five companies show inventory to be equivocal as an upper-management-level marker of lean effectiveness.

Part II: In part I of this two-part paper, I stated that lean's dominant purpose should be seen as cycle-time (wait-time) reduction, which—counted in units of inventory, its close relative—is visually prominent and easily measured at low (efficiency) levels and high (effectiveness) levels in the hierarchy. Part II continues with observations on lean's strategic value; additional cautions about uses of inventory trends at the executive level; examination of lean metrics in retailing, wholesaling, and services; and lean's relationship to quality and other elements of continuous-process improvement. More data from my “leanness studies” offer support for my observations.
People Skills: Optimizing Team Development and Performance
Authors: Levasseur Robert E.
Published: April 2011

This is another in a series of articles about some of the most effective models, methods, and processes of organization development (OD), also known as change management, a discipline that offers much to professionals intent on solving real-world problems. Because it is based on a systemic view of organizations, OD includes the whole universe of fuzzy people issues that increasingly determine the success or failure of efforts to implement otherwise flawless technical solutions. This article examines the stages of group development, the role that conflict plays in the process, and the importance of conflict management in group development and team performance. It also provides ideas for developing high-performing teams based on the application of established change management principles and practices.
Training Robust Decision Making in Immersive Environments
Authors: Patterson Robert , Pierce Byron , Bell Herbert H. , Andrews Dee , Winterbottom Marc
Published: April 2011

We provide a review and analysis of much of the published literature on decision making that is relevant to the design of immersive environments. This review draws from the basic and applied literature in order to provide insight for the design of such synthetic environments. Included in this review are articles and books cited in other works, and articles and books obtained from an Internet search. Issues discussed are (a) an overview of immersive decision environments; (b) dual-process decision making; (c) training robust intuitive decision making; (d) combining analytical and intuitive processing in immersive environments; and (e) concluding remarks. For the development of robust decision making in immersive environments, intuitive reasoning should be emphasized by creating an immersive situation and by providing for the development of automatic processing through implicit learning, with the latter reinforced by explicit thought processes. Considerations of the literature on decision making will provide insight for future design solutions for immersive decision environments.
Adaptive Automation Based on an Object-Oriented Task Model: Implementation and Evaluation in a Realistic C2 Environment
Authors: de Tjerk E. Greef , Henryk F. R. Arciszewski , Neerincx Mark A.
Published: April 2011

Staffing reduction initiatives and more complicated military operations lead to a higher cognitive workload in command and control (C2) environments. Extending automation with adaptive capabilities can aid the human in overcoming cognitive workload challenges. At present, most adaptive automation research has focused on laboratory experiments and only limited research has aimed to implement and validate adaptive automation in a real-world setting. The objective of the present study was to investigate the effects of adaptive automation in precisely such a setting, extending the scientific knowledge base of adaptive systems with an evaluation of a real-world adaptive task. Implementing adaptive automation in a real-world C2 setting required extending current adaptive automation theories with an object-oriented task model and a hybrid triggering mechanism. The extended model was evaluated with eight naval officers using a high-fidelity C2 environment and showed an overall efficiency effect of 60%. Furthermore, no negative side effects of adaptive automation have been found, and the data show that the scenarios were manipulated correctly. In addition, the positive efficiency effects appear most strongly in the more complicated asymmetrical scenarios (65%). This latter conclusion shows that adaptive automation can be a valuable contribution to future C2 systems.
The Hydrostatic Stress Board of Plastics Pipe Institute: The First 50 Years
Authors: Mruk Stanley A.
Published: April 2011

The activities and the policies issued by the Hydrostatic Stress Board (HSB) of the Plastics Pipe Institute have significantly enhanced the reliability of pressure rated thermoplastics pipe and the quality of ASTM, American Water Works Association, and other standards that cover such pipes. HSB policies define procedures for the forecasting of the long-term hydrostatic strength of thermoplastics piping materials and for the reducing of this strength into a hydrostatic design stress (HDS). HSB policies have been developed and are periodically updated under the light of our most current understanding of the factors that affect significant strength under actual service conditions. In support of the development of the most appropriate policies the HSB has also conducted various investigative activities. This paper reports on the major contributions that have been made by the HSB. Furthermore, it does so with reference to an overview of the factors that are now recognized as affecting the significant strength under actual service conditions and those that need to be considered when reducing a particular measure of strength into the most appropriate value of a HDS for an intended application.
Post-operative hypothalamic lesions and obesity in childhood craniopharyngioma: results of the multinational prospective trial KRANIOPHARYNGEOM 2000 after 3-year follow-up
Authors: Müller Hermann L , Gebhardt Ursel , Teske Carmen , Faldum Andreas , Zwiener Isabella , Warmuth-Metz Monika , Pietsch Torsten , Pohl Fabian , Sörensen Niels , Calaminus Gabriele
Published: April 2011

Background

Hypothalamic obesity has major impact on prognosis and quality of life (QoL) in childhood craniopharyngioma.

Patients and methods

For this study, 120 patients were prospectively recruited during 2001 and 2007 and evaluated after 3 years of follow-up (KRANIOPHARYNGEOM 2000). Body mass index (BMI) and QoL at diagnosis and 36 months after diagnosis were analysed based on the reference assessment of tumour localisation and post-surgical hypothalamic lesions. Treatment was analysed based on the neurosurgical strategy of 50 participating neurosurgical centres, the centre size based on the patient load.

Results

BMI SDS at diagnosis was similar in patients with or without hypothalamic involvement. Surgical lesions of anterior and posterior hypothalamic areas were associated with higher increase in BMI SDS during 36 months post-diagnosis compared with patients without or only anterior lesion (+1.8 BMISD, P=0.033, +2.1 BMISD; P=0.011), negative impact on QoL in patients with posterior hypothalamic lesions. Surgical strategies varied among the 50 neurosurgical centres (three large-sized, 24 middle-sized and 23 small-sized centres). Patients treated in small-sized centres presented with a higher rate of hypothalamic involvement compared with those treated in the middle- and large-sized centres. Treatment in large-sized centres was less radical, and the rates of complete resection and hypothalamic surgical lesions were lower in large-sized centres than those of the middle- and small-sized centres. However, a multivariable analysis showed that pre-operative hypothalamic involvement was the only independent risk factor for severe obesity (P=0.002).

Conclusions

Radical neurosurgical strategies leading to posterior hypothalamic lesions are not recommended due to the potential to exacerbate hypothalamic obesity and impaired QoL. Treatment should be confined to experienced multidisciplinary teams.
Association of bone microarchitecture with parathyroid hormone concentration and calcium intake in men: the STRAMBO study
Authors: Chaitou A , Boutroy S , Vilayphiou N , Varennes A , Richard M , Blaizot S , Munoz F , Delmas P D , Goudable J , Chapurlat R , Szulc P
Published: April 2011

Objective

In the elderly, vitamin D deficit, low calcium intake, and impaired bone microarchitecture are associated with higher risk of hip fracture. We assessed the association of bone microarchitecture with calcium intake and serum concentrations of 25-hydroxycholecalciferol (25OHD) and parathyroid hormone (PTH) in men.

Design

Cross-sectional analysis was performed in 1064 men aged 20–87 years not taking vitamin D or calcium supplements.

Methods

Daily calcium intake was assessed using a food frequency questionnaire. Bone microarchitecture was assessed at distal radius and tibia by high-resolution peripheral quantitative computed tomography. We measured serum and urinary levels of biochemical bone turnover markers (BTMs). Statistical models were adjusted for age, weight, height, and glomerular filtration rate.

Results

In 500 men aged <65 years, lower 25OHD levels and low calcium intake were associated with lower trabecular volumetric bone mineral density (Dtrab) at the distal tibia, due to lower trabecular number (Tb.N). Low calcium intake was associated with lower cortical thickness (Ct.Th). Higher PTH level was associated with higher BTM levels. In 563 men aged ≥65 years, the highest PTH quartile was associated with lower Ct.Th (tibia), lower Dtrab (both sites), and lower Tb.N (radius) compared with the lowest quartile. Low calcium intake was associated with lower Tb.N and more heterogenous trabecular distribution. BTM positively correlated with the PTH concentration.

Conclusion

In older men, elevated PTH concentration is associated with high bone turnover, poor trabecular microarchitecture (radius and tibia), and, at the distal tibia, lower Ct.Th. Low calcium intake is associated with lower Tb.N and more heterogenous trabecular distribution.