bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of viroplasm formation during the early stages of rotavirus infection
Authors: Carreño-Torres José J , Gutiérrez Michelle , Arias Carlos F , López Susana , Isa Pavel
Published: November 2010

Background

During rotavirus replication cycle, electron-dense cytoplasmic inclusions named viroplasms are formed, and two non-structural proteins, NSP2 and NSP5, have been shown to localize in these membrane-free structures. In these inclusions, replication of dsRNA and packaging of pre-virion particles occur. Despite the importance of viroplasms in the replication cycle of rotavirus, the information regarding their formation, and the possible sites of their nucleation during the early stages of infection is scarce. Here, we analyzed the formation of viroplasms after infection of MA104 cells with the rotavirus strain RRV, using different multiplicities of infection (MOI), and different times post-infection. The possibility that viroplasms formation is nucleated by the entering viral particles was investigated using fluorescently labeled purified rotavirus particles.

Results

The immunofluorescent detection of viroplasms, using antibodies specific to NSP2 showed that both the number and size of viroplasms increased during infection, and depend on the MOI used. Small-size viroplasms predominated independently of the MOI or time post-infection, although at MOI's of 2.5 and 10 the proportion of larger viroplasms increased. Purified RRV particles were successfully labeled with the Cy5 mono reactive dye, without decrease in virus infectivity, and the labeled viruses were clearly observed by confocal microscope. PAGE gel analysis showed that most viral proteins were labeled; including the intermediate capsid protein VP6. Only 2 out of 117 Cy5-labeled virus particles colocalized with newly formed viroplasms at 4 hours post-infection.

Conclusions

The results presented in this work suggest that during rotavirus infection the number and size of viroplasm increases in an MOI-dependent manner. The Cy5 in vitro labeled virus particles were not found to colocalize with newly formed viroplasms, suggesting that they are not involved in viroplasm nucleation.
Investigations of barley stripe mosaic virus as a gene silencing vector in barley roots and in Brachypodium distachyon and oat
Authors: Pacak Andrzej , Geisler Katrin , Jørgensen Bodil , Barciszewska-Pacak Maria , Nilsson Lena , Nielsen Tom Hamborg , Johansen Elisabeth , Grønlund Mette , Jakobsen Iver , Albrechtsen Merete
Published: November 2010

Background

Gene silencing vectors based on Barley stripe mosaic virus (BSMV) are used extensively in cereals to study gene function, but nearly all studies have been limited to genes expressed in leaves of barley and wheat. However since many important aspects of plant biology are based on root-expressed genes we wanted to explore the potential of BSMV for silencing genes in root tissues. Furthermore, the newly completed genome sequence of the emerging cereal model species Brachypodium distachyon as well as the increasing amount of EST sequence information available for oat (Avena species) have created a need for tools to study gene function in these species.

Results

Here we demonstrate the successful BSMV-mediated virus induced gene silencing (VIGS) of three different genes in barley roots, i.e. the barley homologues of the IPS1, PHR1, and PHO2 genes known to participate in Pi uptake and reallocation in Arabidopsis. Attempts to silence two other genes, the Pi transporter gene HvPht1;1 and the endo-β-1,4-glucanase gene HvCel1, in barley roots were unsuccessful, probably due to instability of the plant gene inserts in the viral vector. In B. distachyon leaves, significant silencing of the PHYTOENE DESATURASE (BdPDS) gene was obtained as shown by photobleaching as well as quantitative RT-PCR analysis. On the other hand, only very limited silencing of the oat AsPDS gene was observed in both hexaploid (A. sativa) and diploid (A. strigosa) oat. Finally, two modifications of the BSMV vector are presented, allowing ligation-free cloning of DNA fragments into the BSMV-γ component.

Conclusions

Our results show that BSMV can be used as a vector for gene silencing in barley roots and in B. distachyon leaves and possibly roots, opening up possibilities for using VIGS to study cereal root biology and to exploit the wealth of genome information in the new cereal model plant B. distachyon. On the other hand, the silencing induced by BSMV in oat seemed too weak to be of practical use. The new BSMV vectors modified for ligation-free cloning will allow rapid insertion of plant gene fragments for future experiments.
The effect of muscle contusion on cortical bone and muscle perfusion following reamed, intramedullary nailing: a novel canine tibia fracture model
Authors: Koo Henry , Hupel Thomas , Zdero Rad , Tov Alexei , Schemitsch Emil H
Published: November 2010

Background

Management of tibial fractures associated with soft tissue injury remains controversial. Previous studies have assessed perfusion of the fractured tibia and surrounding soft tissues in the setting of a normal soft tissue envelope. The purpose of this study was to determine the effects of muscle contusion on blood flow to the tibial cortex and muscle during reamed, intramedullary nailing of a tibial fracture.

Methods

Eleven adult canines were distributed into two groups, Contusion or No-Contusion. The left tibia of each canine underwent segmental osteotomy followed by limited reaming and locked intramedullary nailing. Six of the 11 canines had the anterior muscle compartment contused in a standardized fashion. Laser doppler flowmetry was used to measure cortical bone and muscle perfusion during the index procedure and at 11 weeks post-operatively.

Results

Following a standardized contusion, muscle perfusion in the Contusion group was higher compared to the No-Contusion group at post-osteotomy and post-reaming (p < 0.05). Bone perfusion decreased to a larger extent in the Contusion group compared to the No-Contusion group following osteotomy (p < 0.05), and the difference in bone perfusion between the two groups remained significant throughout the entire procedure (p < 0.05). At 11 weeks, muscle perfusion was similar in both groups (p > 0.05). There was a sustained decrease in overall bone perfusion in the Contusion group at 11 weeks, compared to the No-Contusion group (p < 0.05).

Conclusions

Injury to the soft tissue envelope may have some deleterious effects on intraosseous circulation. This could have some influence on the fixation method for tibia fractures linked with significant soft tissue injury.
An animal paired crossover ePTFE arteriovenous graft model
Authors: Jahrome Abdelkarime K , Hoefer Imo , Moll Frans L , Houston Graeme J , Stonebridge Peter A , Blankestijn Peter J , de Borst Gert J
Published: November 2010

Purpose

Previously, we developed a porcine model for Arterio Venous Graft (AVG) failure to allow assessment of new access strategies. This model was limited concerning graft length. In the present technical report, we describe a modification of our model allowing the assessment of long AVGs.

Technique

In 4 pigs, AVGs of 15 cm length were created bilaterally in a cross-over fashion between the carotid artery and the contralateral jugular vein. Two days (2 pigs) and two weeks (2 pigs) after AV shunting, graft patency was evaluated by angiography, showing all four grafts to be patent, with no sign of angiographic or macroscopic narrowing at the anastomoses sites.

Conclusions

In this modified pig AVG failure model, implantation of a bilateral cross-over long AVG is a feasible approach. The present model offers a suitable tool to study local interventions or compare various long graft designs aimed at improvement of AVG patency.
Chromatin remodeling enzyme Brg1 is required for mouse lens fiber cell terminal differentiation and its denucleation
Authors: He Shuying , Pirity Melinda K , Wang Wei-Lin , Wolf Louise , Chauhan Bharesh K , Cveklova Kveta , Tamm Ernst R , Ashery-Padan Ruth , Metzger Daniel , Nakai Akira , Chambon Pierre , Zavadil Jiri , Cvekl Ales
Published: November 2010

Background

Brahma-related gene 1 (Brg1, also known as Smarca4 and Snf2β) encodes an adenosine-5'-triphosphate (ATP)-dependent catalytical subunit of the (switch/sucrose nonfermentable) (SWI/SNF) chromatin remodeling complexes. SWI/SNF complexes are recruited to chromatin through multiple mechanisms, including specific DNA-binding factors (for example, heat shock transcription factor 4 (Hsf4) and paired box gene 6 (Pax6)), chromatin structural proteins (for example, high-mobility group A1 (HMGA1)) and/or acetylated core histones. Previous studies have shown that a single amino acid substitution (K798R) in the Brg1 ATPase domain acts via a dominant-negative (dn) mechanism. Genetic studies have demonstrated that Brg1 is an essential gene for early (that is, prior implantation) mouse embryonic development. Brg1 also controls neural stem cell maintenance, terminal differentiation of multiple cell lineages and organs including the T-cells, glial cells and limbs.

Results

To examine the roles of Brg1 in mouse lens development, a dnBrg1 transgenic construct was expressed using the lens-specific αA-crystallin promoter in postmitotic lens fiber cells. Morphological studies revealed abnormal lens fiber cell differentiation in transgenic lenses resulting in cataract. Electron microscopic studies showed abnormal lens suture formation and incomplete karyolysis (that is, denucleation) of lens fiber cells. To identify genes regulated by Brg1, RNA expression profiling was performed in embryonic day 15.5 (E15.5) wild-type and dnBrg1 transgenic lenses. In addition, comparisons between differentially expressed genes in dnBrg1 transgenic, Pax6 heterozygous and Hsf4 homozygous lenses identified multiple genes coregulated by Brg1, Hsf4 and Pax6. DNase IIβ, a key enzyme required for lens fiber cell denucleation, was found to be downregulated in each of the Pax6, Brg1 and Hsf4 model systems. Lens-specific deletion of Brg1 using conditional gene targeting demonstrated that Brg1 was required for lens fiber cell differentiation, for expression of DNase IIβ, for lens fiber cell denucleation and indirectly for retinal development.

Conclusions

These studies demonstrate a cell-autonomous role for Brg1 in lens fiber cell terminal differentiation and identified DNase IIβ as a potential direct target of SWI/SNF complexes. Brg1 is directly or indirectly involved in processes that degrade lens fiber cell chromatin. The presence of nuclei and other organelles generates scattered light incompatible with the optical requirements for the lens.
No agreement of mixed venous and central venous saturation in sepsis, independent of sepsis origin
Authors: van Beest Paul A , van Ingen Jan , Boerma E Christiaan , Holman Nicole D , Groen Henk , Koopmans Matty , Spronk Peter E , Kuiper Michael A
Published: November 2010

Introduction

Controversy remains regarding the relationship between central venous saturation (ScvO2) and mixed venous saturation (SvO2) and their use and interchangeability in patients with sepsis or septic shock. We tested the hypothesis that ScvO2 does not reliably predict SvO2 in sepsis. Additionally we looked at the influence of the source (splanchnic or non-splanchnic) of sepsis on this relationship.

Methods

In this prospective observational two-center study we concurrently determined ScvO2 and SvO2 in a group of 53 patients with severe sepsis during the first 24 hours after admission to the intensive care units in 2 Dutch hospitals. We assessed correlation and agreement of ScvO2 and SvO2, including the difference, i.e. the gradient, between ScvO2 and SvO2 (ScvO2 - SvO2). Additionally, we compared the mean differences between ScvO2 and SvO2 of both splanchnic and non-splanchnic group.

Results

A total of 265 paired blood samples were obtained. ScvO2 overestimated SvO2 by less than 5% with wide limits of agreement. For changes in ScvO2 and SvO2 results were similar. The distribution of the (ScvO2 - SvO2) (< 0 or ≥ 0) was similar in survivors and nonsurvivors. The mean (ScvO2 - SvO2) in the splanchnic group was similar to the mean (ScvO2 - SvO2) in the non-splanchnic group (0.8 ± 3.9% vs. 2.5 ± 6.2%; P = 0.30). O2ER (P = 0.23) and its predictive value for outcome (P = 0.20) were similar in both groups.

Conclusions

ScvO2 does not reliably predict SvO2 in patients with severe sepsis. The trend of ScvO2 is not superior to the absolute value in this context. A positive difference (ScvO2 - SvO2) is not associated with improved outcome.
Generalized moveout approximation for qP- and qSV-waves in a homogeneous transversely isotropic medium
Authors: Stovas Alexey
Published: November 2010

The moveout approximations can be used in kinematic modeling, velocity analysis, and time migration. The generalized moveout approximation involves five approximation parameters and has several known approximations as special cases. A method is demonstrated for determining parameters of the generalized nonhyperbolic moveout approximation for qP- and qSV-waves in a homogeneous transversely isotropic medium with vertical symmetry axis (VTI medium). The additional parameters for the generalized approximation are computed from the hyperbolic asymptote at infinite offset. Comparison with a few well-known moveout approximations for higher-order terms in the Taylor series and asymptotic behavior shows that the generalized moveout approximation is superior to other nonhyperbolic approximations. A few numerical examples for qP- and qSV-waves in a VTI medium also indicate that the generalized approximation performs the best.
Influence of parameterization on inversion of surface wave dispersion curves and definition of an inversion strategy for sites with a strong VS contrast
Authors: Renalier F. , Jongmans D. , Savvaidis A. , Wathelet M. , Endrun B. , Cornou C.
Published: November 2010

Inversion of the fundamental mode of the Rayleigh wave dispersion curve does not provide a unique solution and the choice of the parameterization (number of layers, range of velocity, and thickness values for the layers) is of prime importance for obtaining reliable results. We analyzed shear-wave velocity profiles derived from borehole tests at 10 sites where soil layers overlay bedrock in various geologic contexts. One to three seismic layers with linear velocity laws could model all of them. Three synthetic models defined from this preliminary study were used to understand the influence of parameterization on the dispersion curve inversion. This analysis resulted in the definition of a two-step inversion procedure for sites exhibiting a strong impedance con-trast. In the first step, the dispersion curve is inverted with an increasing number of layers over half space. The evolution of the minimum misfit and bedrock depth with number of layers allows the estimation of the true bedrock depth range. In the second step, this information is introduced in inversions with linear velocity laws. Synthetic tests showed that applying this procedure requires the dispersion curve over a frequency range from [Formula: see text] to [Formula: see text], where [Formula: see text] is the site resonance frequency. The strategy was tested on two real cases for which Rayleigh wave dispersion curves were measured over this frequency range using passive and active seismic methods. The strategy was successful at the first site, while the bedrock depth was overestimated by 15% at the second site, probably resulting from the existence of a higher mode affecting the dispersion curve at low frequency.
Intensive home treatment, admission rates and use of mental health legislation
Authors: Forbes Naida F. , Cash Helen T. , Lawrie Stephen M.
Published: November 2010

Aims and method

We examined the local impact of introducing a home treatment team on the use of in-patient psychiatric resources and rates of detention under the Mental Health (Care and Treatment) (Scotland) Act 2003.

Results

Rates of admission to hospital and duration of hospital stay were unchanged. However, there was an increase in episodes of detention in the year following the team's introduction.

Clinical implications

Offering home treatment as an alternative to in-patient care may be associated with an increase in compulsory treatment. If true, this is incompatible with the ‘least restrictive alternative’ principle of the recently revised mental health legislation.
Associations of Insulin Resistance and Adiponectin With Mortality in Women With Breast Cancer
Authors: Duggan Catherine , Irwin Melinda L. , Xiao Liren , Henderson Katherine D. , Smith Ashley Wilder , Baumgartner Richard N. , Baumgartner Kathy B. , Bernstein Leslie , Ballard-Barbash Rachel , McTiernan Anne
Published: November 2010

Purpose

Overweight or obese breast cancer patients have a worse prognosis compared with normal-weight patients. This may be attributed to hyperinsulinemia and dysregulation of adipokine levels associated with overweight and obesity. Here, we evaluate whether low levels of adiponectin and a greater level of insulin resistance are associated with breast cancer mortality and all-cause mortality.

Patients and Methods

We measured glucose, insulin, and adiponectin levels in fasting serum samples from 527 women enrolled in the Health, Eating, Activity, and Lifestyle (HEAL) Study, a multiethnic, prospective cohort study of women diagnosed with stage I-IIIA breast cancer. We evaluated the association between adiponectin and insulin and glucose levels (expressed as the Homeostatic Model Assessment [HOMA] score) represented as continuous measures and median split categories, along with breast cancer mortality and all-cause mortality, using Cox proportional hazards models.

Results

Increasing HOMA scores were associated with reduced breast cancer survival (hazard ratio [HR], 1.12; 95% CI, 1.05 to 1.20) and reduced all-cause survival (HR, 1.09; 95% CI, 1.02 to 1.15) after adjustment for possible confounders. Higher levels of adiponectin (above the median: 15.5 μg/mL) were associated with longer breast cancer survival (HR, 0.39; 95% CI, 0.15 to 0.95) after adjustment for covariates. A continuous measure of adiponectin was not associated with either breast cancer–specific or all-cause mortality.

Conclusion

Elevated HOMA scores and low levels of adiponectin, both associated with obesity, were associated with increased breast cancer mortality. To the best of our knowledge, this is the first demonstration of the association between low levels of adiponectin and increased breast cancer mortality in breast cancer survivors.
Diabetes Mellitus and Breast Cancer Outcomes: A Systematic Review and Meta-Analysis
Authors: Peairs Kimberly S. , Barone Bethany B. , Snyder Claire F. , Yeh Hsin-Chieh , Stein Kelly B. , Derr Rachel L. , Brancati Frederick L. , Wolff Antonio C.
Published: November 2010

Purpose

The goal of this study was to perform a systematic review and meta-analysis to examine the effect of pre-existing diabetes on breast cancer–related outcomes.

Methods

We searched EMBASE and MEDLINE databases from inception through July 1, 2009, using search terms related to diabetes mellitus, cancer, and prognostic outcome. Studies were included if they reported a prognostic outcome by diabetes status, evaluated a cancer population, and contained original data published in the English language. We performed a meta-analysis of pre-existing diabetes and its effect on all-cause mortality in patients with breast cancer and qualitatively summarized other prognostic outcomes.

Results

Of 8,828 titles identified, eight articles met inclusion/exclusion criteria and described outcomes in patients with breast cancer and diabetes. Pre-existing diabetes was significantly associated with all-cause mortality in six of seven studies. In a meta-analysis, patients with breast cancer and diabetes had a significantly higher all-cause mortality risk (pooled hazard ratio [HR], 1.49; 95% CI, 1.35 to 1.65) compared with their nondiabetic counterparts. Three of four studies found pre-existing diabetes to be associated with more advanced stage at presentation. Diabetes was also associated with altered regimens for breast cancer treatment and increased toxicity from chemotherapy.

Conclusion

Compared with their nondiabetic counterparts, patients with breast cancer and pre-existing diabetes have a greater risk of death and tend to present at later stages and receive altered treatment regimens. Studies are needed to investigate pathophysiologic interactions between diabetes and breast cancer and determine whether improvements in diabetes care can reduce mortality in patients with breast cancer.
Multicenter Phase III Randomized Trial Comparing Docetaxel and Trastuzumab With Docetaxel, Carboplatin, and Trastuzumab As First-Line Chemotherapy for Patients With HER2-Gene-Amplified Metastatic Breast Cancer (BCIRG 007 Study): Two Highly Active Therapeutic Regimens
Authors: Valero Vicente , Forbes John , Pegram Mark D. , Pienkowski Tadeusz , Eiermann Wolfgang , von Minckwitz Gunter , Roche Henri , Martin Miguel , Crown John , Mackey John R. , Fumoleau Pierre , Rolski Janusz , Mrsic-Krmpotic Zrinka , Jagiello-Gruszfeld Agnieszka , Riva Alessandro , Buyse Marc , Taupin Henry , Sauter Guido , Press Michael F. , Slamon Dennis J.
Published: November 2010

Purpose

Docetaxel-trastuzumab (TH) is effective therapy for HER2-amplified metastatic breast cancer (MBC). Preclinical findings of synergy between docetaxel, carboplatin, and trastuzumab (TCH) prompted a phase III randomized trial comparing TCH with TH in patients with HER2-amplified MBC.

Patients and Methods

Two hundred sixty-three patients were randomly assigned to receive eight 3-week cycles of TH (trastuzumab plus docetaxel 100 mg/m2) or TCH (trastuzumab plus carboplatin at area under the serum concentration-time curve 6 and docetaxel 75 mg/m2). Trastuzumab was given at 4 mg/kg loading dose followed by a 2 mg/kg dose once per week during chemotherapy, and then 6 mg/kg once every 3 weeks until progression.

Results

Patient characteristics were balanced between groups. There was no significant difference between TH and TCH in terms of the primary end point, time to progression (medians of 11.1 and 10.4 months, respectively; hazard ratio, 0.914; 95% CI, 0.694 to 1.203; P = .57), response rate (72% for both groups), or overall survival (medians of 37.1 and 37.4 months, respectively; P = .99). Rates of grades 3 or 4 adverse effects for TH and TCH, respectively, were neutropenic-related complications, 29% and 23%; thrombocytopenia, 2% and 15%; anemia, 5% and 11%; sensory neuropathy, 3% and 0.8%; fatigue, 5% and 12%; peripheral edema, 3.8% and 1.5%; and diarrhea, 2% and 10%. Two patients given TCH died of sepsis, and one patient given TH experienced sudden cardiac death. Absolute left ventricular ejection fraction decline > 15% was seen in 5.5% of patients on the TH arm and 6.7% of patients on the TCH arm.

Conclusion

Adding carboplatin did not enhance TH antitumor activity.TH (docetaxel, 100 mg/m2) and TCH (docetaxel, 75 mg/m2) demonstrated efficacy with acceptable toxicity in women with HER2-amplified MBC.
Phase II Study of Irinotecan and Temozolomide in Children With Relapsed or Refractory Neuroblastoma: A Children's Oncology Group Study
Authors: Bagatell Rochelle , London Wendy B. , Wagner Lars M. , Voss Stephan D. , Stewart Clinton F. , Maris John M. , Kretschmar Cynthia , Cohn Susan L.
Published: November 2010

Purpose

This phase II study was conducted to determine the response rate associated with use of irinotecan and temozolomide for children with relapsed/refractory neuroblastoma.

Patients and Methods

Patients with relapsed/refractory neuroblastoma measurable by cross-sectional imaging (stratum 1) or assessable by bone marrow aspirate/biopsy or metaiodobenzylguanidine (MIBG) scan (stratum 2) received irinotecan (10 mg/m2/dose 5 days a week for 2 weeks) and temozolomide (100 mg/m2/dose for 5 days) every 3 weeks. Response was assessed after three and six courses using International Neuroblastoma Response Criteria. Of the first 25 evaluable patients on a given stratum, five or more patients with complete or partial responses were required to conclude that further study would be merited.

Results

Fifty-five eligible patients were enrolled. The objective response rate was 15%. Fourteen patients (50%) on stratum 1 and 15 patients (56%) on stratum 2 had stable disease. Objective responses were observed in three of the first 25 evaluable patients on stratum 1 and five of the first 25 evaluable patients on stratum 2. Less than 6% of patients experienced ≥ grade 3 diarrhea. Although neutropenia was observed, less than 10% of patients developed evidence of infection while neutropenic.

Conclusion

The combination of irinotecan and temozolomide was well tolerated. The objective response rate of 19% in stratum 2 suggests that this combination may be effective for patients with neuroblastoma detectable by MIBG or marrow analysis. Although fewer objective responses were observed in patients with disease measurable by computed tomography/magnetic resonance imaging, patients in both strata seem to have derived clinical benefit from this therapy.
Laminins, via heparan sulfate proteoglycans, participate in zebrafish myotome morphogenesis by modulating the pattern of Bmp responsiveness
Authors: Dolez Morgane , Nicolas Jean-François , Hirsinger Estelle
Published: November 2010

In zebrafish, Hedgehog-induced Engrailed expression defines a muscle fibre population that includes both slow and fast fibre types and exhibits an organisational role on myotome and surrounding tissues, such as motoneurons and lateral line. This Engrailed-positive population is restricted in the myotome to a central domain. To understand how this population is established, we have analysed the phenotype of the sly/lamc1 mutation in the Laminin γ1 chain that was shown to specifically affect Engrailed expression in pioneers. We find that the sly mutation affects Engrailed expression in the entire central domain and that Hedgehog signalling does not mediate this effect. We show that Bmp-responding cells are excluded from the central domain and that this pattern is modulated by laminins, but not by Hedgehog signalling. Knockdown of Bmp signalling rescues Engrailed expression in the sly mutant and ectopically activates Engrailed expression in slow and fast lineages in wild-type embryos. Last, extracellular matrix-associated heparan sulfate proteoglycans are absent in sly and their enzymatic removal mimics the sly phenotype. Our results therefore show that laminins, via heparan sulfate proteoglycans, are instrumental in patterning Bmp responsiveness and that Bmp signalling restricts Engrailed expression to the central domain. This study underlines the importance of extracellular cues for the precise spatial modulation of cell response to morphogens.
brother of cdo (umleitung) is cell-autonomously required for Hedgehog-mediated ventral CNS patterning in the zebrafish
Authors: Bergeron Sadie A. , Tyurina Oksana V. , Miller Emily , Bagas Andrea , Karlstrom Rolf O.
Published: November 2010

The transmembrane protein Brother of Cdo (Boc) has been implicated in Shh-mediated commissural axon guidance, and can both positively and negatively regulate Hedgehog (Hh) target gene transcription, however, little is known about in vivo requirements for Boc during vertebrate embryogenesis. The zebrafish umleitung (umlty54) mutant was identified by defects in retinotectal axon projections. Here, we show that the uml locus encodes Boc and that Boc function is cell-autonomously required for Hh-mediated neural patterning. Our phenotypic analysis suggests that Boc is required as a positive regulator of Hh signaling in the spinal cord, hypothalamus, pituitary, somites and upper jaw, but that Boc might negatively regulate Hh signals in the lower jaw. This study reveals a role for Boc in ventral CNS cells that receive high levels of Hh and uncovers previously unknown roles for Boc in vertebrate embryogenesis.
Stability of inhibin A and unconjugated oestriol in the second trimester of pregnancy
Authors: Brown Louise F , Shearing Catherine H , Tydeman Graham
Published: November 2010

Background

The introduction of a second trimester quadruple test for fetal Down's syndrome adds the measurement of serum inhibin A (InhA) and unconjugated oestriol (UE3) to the existing repertoire of alphafetoprotein and intact human chorionic gonadotrophin. The aim of this study was to assess the stability of InhA and UE3 in whole blood and serum.

Methods

To determine whole blood stability, five extra blood specimens were obtained from each of 10 women attending an antenatal clinic. Samples were stored at room temperature for either two hours, one, three, five or seven days and centrifuged prior to analysis. Serum stability was studied by the analysis of surplus serum from 14 routine second trimester screening samples: seven stored at room temperature and seven stored at 4°C. An aliquot from each specimen was analysed two hours, one, three, five or seven days post centrifugation. Specimens were analysed for InhA and UE3 using the Beckman Access 2® Immunoassay analyser.

Results

No significant difference ( P > 0.05) was shown in InhA or UE3 concentrations between the initial time point on the day of venepuncture and each of the subsequent analyses at one, three, five and seven days following collection for either whole blood or serum.

Conclusions

InhA and UE3 are stable in whole blood and serum for seven days.
Diagnostic value of pleural effusion ischaemia-modified albumin in patients with cardiac failure
Authors: Ozsu Savas , Gulsoy Ayhan , Karahan S Caner , Mentese Ahmet , Nuhoglu Irfan , Ozlu Tevfik
Published: November 2010

Background

Ischaemia-modified albumin (IMA) is a relatively new marker of ischaemia. IMA has not been studied previously in pleural effusions due to congestive heart failure (CHF). The aim of our study was to assess the diagnostic value of IMA in the pleural fluid (PF) and serum for the identification of pleural effusion due to CHF.

Methods

The concentrations of pleural fluid and serum IMA were measured in a total of 40 patients: 10 with CHF and 30 with non-cardiac failure (10 with acute pulmonary embolism, 10 with parapneumonic effusion and 10 with malignancy). The area under the curve (AUC) quantified the overall diagnostic accuracy of the tests.

Results

The study demonstrated that IMA concentration was higher in both pleural fluid and serum of CHF patients compared with non-cardiac patients. PF and serum IMA demonstrated AUCs of 0.927 (95% CI: 0.844–1.00, P < 0.001), and 0.792 (95% CI: 0.653–0.930, P = 0.006), respectively, for diagnosing effusions due to CHF. The sensitivity and specificity of PF-IMA for CHF at the cut-off concentration of ≥1.0 absorbance units was 90% and 80%, respectively. Its negative predictive value (NPV) was quite high (96%). Positive correlation was found between PF-IMA concentrations and serum-IMA ( r = 0.540, P < 0.001).

Conclusions

Measuring IMA concentrations in serum and pleural fluid may be helpful in distinguishing pleural effusion due to a cardiac or non-cardiac aetiology.
Serum prolactin and macroprolactin in heart failure: no relation to established laboratory or clinical parameters
Authors: Landberg Eva , Dahlström Ulf , Alehagen Urban
Published: November 2010

Background

A few smaller studies have reported that the prolactin concentration is elevated in connection with heart failure. As heart failure is combined with disturbances of several biological systems any or all of which may also influence prolactin concentrations, we wanted to evaluate the relation of prolactin to prognosis in elderly patients.

Methods

A total of 462 elderly patients from a primary health-care centre, all with symptoms of heart failure, were included. In addition to clinical examination including echocardiography, concentrations of prolactin, macroprolactin, C-reactive protein, thyroid-stimulating hormone and N-terminal pro B-type natriuretric peptide (NT-proBNP) were measured. Patients were then followed for 10 y, and all incidents of cardiovascular mortality were registered.

Results

After excluding patients with macroprolactin, hyperprolactinaemia was found in 3.7% of the patients. There were no differences in prolactin concentrations or in the frequency of macroprolactin between patients with heart failure and those with normal cardiac function, defined as left ventricular ejection fraction of at least 50%. No significant correlation could be found between NT-proBNP and prolactin. Neither could any association be found between cardiovascular mortality and prolactin concentration during 10 y of follow-up.

Conclusions

Prolactin concentrations were not associated with cardiovascular mortality or any clinical or biochemical marker of heart failure. Macroprolactin was found in similar frequency among patients with and without heart failure, and showed no correlation with mortality risk.
The Southampton Dupuytren's Clinic: audit of an effective multidisciplinary model
Authors: Warwick David , Belward Pete , Vadher Jane , Setty Kemp
Published: November 2010

Introduction

The Southampton Dupuytren's Clinic (SDC) was preceded by a four-month period when the therapist accompanied the surgeon in Clinic to learn about Dupuytren's Disease (DD) and to develop a specific proforma to collect details of the patient, the condition and the planned treatment.

Methods

A special clinic was set up for general practitioner referrals for patients with DD. Each patient was seen by the therapist. A detailed history and examination were recorded on the proforma. Treatment options to include the outcome, risks and benefits of surgery were clearly explained, supported by a handout. The patient was then seen by the surgeon to arrange management.

Results

One hundred and ninety-four patients were allocated to the SDC. In all, 5% failed to attend; 8% had an alternative diagnosis made; and 16% with DD were discharged as the disease was not advanced enough for intervention or the patient decided not to have surgery. The therapist then allocated 71% for surgical assessment. The surgeon, to efficiently allocate personnel and theatre resources, listed 22% for skin graft, 8% for fasciotomy, 70% for fasciectomy, 35% for consultant to perform, 35% for fellow/registrar to perform, and 30% for the consultant to train the registrar.

Conclusions

We consider that triage and assessment of patients with DD is improved by a multidisciplinary approach: a hand therapist, to quantify deformity and functional deficit, and explain the purpose, risks and outcome of surgery; and a hand surgeon, to decide the type and duration of surgery and the appropriate grade of surgeon.
Public Participation in the Regulation of Genetically Modified Organisms: A Matter of Substance or Form?
Authors: Cardwell Michael
Published: November 2010

The regulatory regime for GMOs contains provisions which grant to the public formal rights of participation. Such rights are examined at international level (in particular, the Cartagena Protocol and the Aarhus Convention), at European Community level and with specific reference to the United Kingdom. It would seem clear that their overall effect is materially to enhance the role of civil society (the more so where locus standi is conferred on NGOs); and, in addition, United Kingdom case law indicates that environmental consultation exercises are to be taken seriously (as is well illustrated by the decisions in Berkeley v Secretary of State for the Environment and R (on the application of Greenpeace Ltd) v Secretary of State for the Environment). On the other hand, there must remain some doubt as to the extent to which the views of the public are being fed into the decision-making process itself, while the cost of challenging legislation once enacted may prove to be prohibitive. Further, on a more general level, questions may be raised as to the efficacy of public engagement in technical and/or scientific issues; and, notwithstanding that the regulation of GMOs remains ‘work in progress’, many of the major decisions which offered opportunities for public participation have already been taken.
Environmental Principles and Environmental Justice
Authors: Pedersen Ole W.
Published: November 2010

This article offers an analysis of the compatibility between the emerging concept of environmental justice and a number of more well established environmental principles. These include the precautionary principle, the polluter pays principle and sustainable development. The article argues that, for all three principles, a comparison with environmental justice gives rise to conflicts as well as conformity. The main reason for this is the ambiguity and inconsistency of environmental justice and the three principles.
The Right to Access DNA Testing by Alleged Innocent Victims of Wrongful Convictions in the United Kingdom?
Authors: Naughton Michael , Tan Gabe
Published: November 2010

This article identifies two distinct cases of alleged wrongful conviction that were investigated by the University of Bristol Innocence Project (UoBIP) where the Criminal Cases Review Commission (CCRC), the official body that deals with alleged miscarriages of justice in England, Wales and Northern Ireland, has failed to utilise DeoxyriboNucleic Acid (DNA) testing that may exonerate the applicant: a case where numerous crime scene exhibits exist that has never been subjected to any DNA testing; and a case that has not been subjected to the full range of DNA tests that could be conducted to validate the applicant's claim of factual innocence. It draws from the right to share the benefits of scientific advancements contained in the International Bill of Rights to argue that access to official DNA testing for alleged innocent victims of wrongful convictions is vital to determine the reliability of contested convictions in the UK. From this perspective, the CCRC can be conceived to have denied the applicants in the cases cited the opportunity to prove their innocence. It is concluded that the interests of justice require that all attempts must be made to ensure the reliability of criminal convictions, meaning in this context that convicted persons maintaining innocence must have access to the most appropriate and up-to-date DNA techniques that could help exonerate them if they are innocent and even lead to the conviction of the real perpetrators of the crimes that they were convicted of.
Homicidal Poisoning in Japan: Offender and Crime Characteristics
Authors: Zaitsu Wataru
Published: November 2010

The purpose of this study was to examine empirically those who committed homicidal poisoning in Japan (N = 96). Typically, offenders were middle-aged (mean 43.2 years), had a fixed residence (99 per cent), had no criminal record (81 per cent), were employed (68 per cent), and married (56 per cent): 54 per cent of the offenders were female. The offenders could be differentiated by categorical principal component analysis (CATPCA) into two poisoning themes: ‘instrumental’ (N = 65) and ‘expressive’ (N = 31). In ‘instrumental’ poisoning, the offenders were likely to induce a coma in a victim using medical supplies such as hypnotics, and then murder the victim, usually by strangling or stabbing. There were more co-offenders among ‘instrumental’ poisoners than among ‘expressive’ poisoners. The offenders who committed ‘expressive’ poisoning were inclined to poison victims serially or collectively in the workplace during daytime. These offenders were more likely to live with a parent/parents and exhibit mental health problems than those who committed ‘instrumental’ poisoning.
A Virtual Environment to Test Police and Public Awareness of Anti-Social Behaviour Indicators
Authors: Smith Shamus P. , Carter Tim
Published: November 2010

Anti-social behaviour is a problem in many modern-day communities. However, the ability of the police and other associated agencies to tackle this problem is limited due to the difficulties of gaining experience through training in the field, which is time-consuming and often dangerous. Virtual environment technology can provide a safe and controlled environment to assist police officer training in simulated urban environments. Public perceptions of anti-social behaviour are also important and virtual environments can be used to allow police practitioners to gain insight into how the public experience anti-social behaviour. A virtual environment system has been constructed to support police officers becoming more observant and confident at spotting indicators of anti-social behaviour. An evaluation study was conducted with practitioners and members of the public to compare the virtual environment with a paper-based alternative. Performance metrics were collected during the study and post-session questionnaires were used to evaluate the perceptions of 36 participants in regard to their experiences with the system. Performance in the virtual environment was comparable with a paper-based method. In addition, both practitioner and public participants positively received the virtual environment, with the majority indicating a preference for virtual environment simulations over conventional paper-based activities. This has implications for the further use of virtual environments as such systems can provide dynamic experiences over a wide variety of scenario-based environments.
Policing Possession of Child Pornography Online: Investigating the Training and Resources Dedicated to the Investigation of Cyber Crime
Authors: Marcum Catherine D. , Higgins George E. , Freiburger Tina L. , Ricketts Melissa L.
Published: November 2010

The internet is not a single network, limited to one specific type of information or restrictive of the types of users who can access its information. Conversely, the internet is an intercontinental information highway that has enabled people of all ages to communicate with family and friends with lightning-fast speed, share and collect information, and connect with people and companies thousands of miles from their computer (Roberts, Foehr, Rideout, & Brodie, 1999; Rosenbaum et al., 2000; Smith & Rupp, 2002). However, this growth of information technology has introduced a new form of criminality to the criminal justice system: cyber crime (Denning, 1998). The purpose of this research study is to investigate the prevalence of cyber criminality, specifically possession of child pornography, in law enforcement jurisdictions and the types of training which local and State law enforcement agencies currently offer to effectively combat these technological crimes.
Culpability, Kingston and the Law Commission
Authors: Crosby Cath
Published: November 2010

This article considers the basis upon which a person should be held to be criminally liable, and to do so, it is necessary to examine the leading theories of character and choice that underpin the State holding a person to be culpable of a criminal offence, i.e. the link between culpability and fault. The case of R v Kingston1 is used to examine the application of these leading theories and it is observed that choice theorists would not excuse such a defendant from criminal liability even though his capacity to make a choice to refrain from law breaking was made extremely difficult by external factors beyond his control. Only character theory could possibly offer exculpation in such circumstances on the basis that the defendant acted ‘out of character’ and his deed did not deserve the full censure and punishment of the criminal law. The Court of Appeal in R v Kingston would have been prepared to excuse, but the House of Lords, and most recently the Law Commission have adopted a pragmatic approach to the involuntarily intoxicated offender. This case serves as a reminder that while justice is the aim of the criminal justice system, it is not an absolute standard.
Stop and Search: Disproportionality, Discretion and Generalisations
Authors: Ellis Darren
Published: November 2010

It has long been recognised that discretion is vital to good police work. However, in Britain (and many other countries), practices of discretion in the stop and search context have come under much scrutiny as it has widely been linked to racist practices, i.e. a disproportionate amount of Black and minority ethnic individuals are stopped and searched compared to White people. In a bid to counteract the discretionary practices that are seen to be linked to racist stops and searches, police officers are required (in stops and searches under section 1 of the PACE code A) to have ‘reasonable grounds for suspicion’. This article evaluates what has been claimed as the tension between the required reasonable grounds for suspicion and the need to draw on generalisations (police discretion) for effective policing.
Blood Alcohol Concentration Levels among Dui Arrestees: Are There Differences When Considering Race and Gender?
Authors: Moore Robert
Published: November 2010

Many studies and treatment programmes associated with driving under the influence (DUI) of alcohol have focused on Caucasian males, either minimising or casually addressing minorities and females who historically may have not consumed alcohol and driven at equivalent BAC levels. The current study examines arrest report data in order to compare the mean blood alcohol concentration (BAC) levels for individuals arrested for DUI when considering race and gender. Examination of arrest data revealed that while females were less frequently arrested for driving under the influence of alcohol, female intoxication levels as measured by their blood alcohol concentration (BAC) at the time of their arrest were equivalent to their male counterparts ( t (242) = 1.214, p = 0.226). Further, when considering for arrestee's race there was no statistically significant difference between the mean BAC levels of Caucasians when compared with African Americans and other minorities ( F (2, 241) = 0.358, p = 0.700).
Massachusetts Justice Policy Recommendations: Addressing Disproportionate Minority Contact
Authors: Barrett James M.
Published: November 2010

This article makes several policy recommendations relating to the state of the criminal justice system in Massachusetts to address the problem of disproportionate minority contact (DMC). The article provides some recent historical perspectives, as well as accepted sociological theory to help clarify this problem. In responding to crime, law enforcement officials are confronted with a great many challenges and officer safety is paramount in any officer interaction, remaining a primary focus of police training nationally and internationally. However, an increasingly mobile society creates challenges extending beyond officer safety which have liability and other ramifications if not understood. These challenges include the varying opinions and attitudes ingrained in some minority groups that have developed over time as a result of both perceived and experienced contact with the American criminal justice system.

Without proper training, suburban practitioners serving predominantly Caucasian communities will have no cultural context from which to deal with the new, varied population that social mobility brings. The article recommends cultural diversity training to extend practitioners' ability to interpret the language, behaviours and actions of the various peoples with whom they are not intimately familiar and to make conscious decisions based upon real knowledge rather than attribute intent based upon biases and stereotypes.

The article further recommends that Massachusetts should examine national best practices and endeavour to improve and standardise the way in which data are collected, compiled and disseminated and the government should seek out these successful programmes and attach a representative to each to act as a conduit to various state agencies.