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Background: Pre-treatment stratification and outcomes of neuroblastoma patients often depend on the assessment of image-defined risk factors (IDRFs) on MR Imaging, usually using Gadolinium-contrast materials which are cautioned in pediatrics. We aimed to address whether gadolinium contrast-enhanced sequences are necessary to identify the presence/absence of IDRFs. Methods: Patients with neuroblastoma with MR imaging were retrospectively identified from 2005 to 2021. Ninety confirmed IDRFs were evaluated in 23 patients. Corresponding MR studies were anonymized, randomized, and independently evaluated by 3 fellowship-trained pediatric radiologists. Each radiologist assessed the studies twice. At the first reading, all enhanced sequences were omitted, while in the second reading, the full study with enhanced sequences were included. Consensus reading was obtained among readers. Inter- and intra-rater agreements using Kappa statistics (κ) as well as the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of non-enhanced MR in assessing IDRFs with respect to enhanced MR were calculated. Results: There were substantial (ĸ: 0.64-0.73) intra-reader agreements, and moderate to substantial (ĸ: 0.57-0.62) inter-reader agreements among radiologists in identifying IDRFs using non-enhanced MR. Non-enhanced MR had a sensitivity of 87.8% (95% CI [79-94]), specificity of 93% (89-96), PPV of 82.3 (73-89), NPV of 95.4 (92-98), and accuracy of 91.6 (88-94) in identifying IDRFs. However, 5/23 patients (21.7%) had a change in staging with the inclusion of contrast sequences. Conclusion: Although contrast sequences have a role in IDRF assessment, the majority can be adequately assessed on MR without gadolinium-contrast enhancement. Validation in a larger cohort is an important next step. [ABSTRACT FROM AUTHOR]

Reading W.K. Clifford’s “The Ethics of Belief” in evidentialist terms is standard. However, evidentialist accounts face several longstanding interpretive issues over the Shipowner Story and Clifford’s Motto. This article defends an evidentialist reading. But what distinguishes it from others is that it interprets “The Ethics of Belief” according to Clifford’s “first principle of natural ethics”, a principle he articulates in prior writings, and which comes down to social trust. I reorient Clifford’s evidentialism by returning to his core moral principle and argue that doing so can establish coherence across Clifford’s writings on ethics and can help resolve the relevant interpretive issues. [ABSTRACT FROM AUTHOR]

Background: Meal pattern is a potential health determinant. Previously, mean values for properties of meal pattern, such as daily meal frequency, have been considered. Means, however, obscure variability between‐day (irregular or chaotic eating). This systematic review aimed to identify and critique published methods used to characterise between‐day variability in meal pattern, and to explore relationships between this and obesity, as well as associated health outcomes. Methods: Using relevant databases, a systematic search was undertaken for studies with adults and children in which between‐day variability in meal pattern was measured, and related to body weight, metabolic syndrome components and cognitive function. Results: In 34 papers identified (28 observational and six intervention studies), between‐day variability in meal pattern was characterised by a variety of methods. These ranged from single questions about intake regularity to more complex methods quantifying the degree of variability. Assumptions were made, such as there being three main meals, resulting in dissociation from the "clock time" of eating. In 24 of the papers, between‐day variability in meal pattern was associated with negative weight and health outcomes including higher weight, reduced thermogenic response to meals and poorer academic achievement. Conclusions: Between‐day variability in meal pattern is a promising research area that might inform low‐cost public health interventions. However, current methods of characterising between‐day variability tend to make assumptions and be inconsistent in the meal pattern properties considered. Well controlled dietary intervention studies are required to confirm causation. Highlights: This systematic review summarised the evidence about associations between day‐to‐day variability in meal pattern and body weight, components of the metabolic syndrome and cognitive function.Four databases were used to conduct an electronic search.Thirty‐four studies were included in this systematic review.Observational and intervention studies were included in this review.Studies included participants who were adults and children of healthy weight and living with overweight and obesity.Most studies demonstrated associations between the degree of meal pattern variability and negative health outcomes.However, different methods were used to characterise meal pattern variability. [ABSTRACT FROM AUTHOR]

Radial artery access has experienced increasing adoption and rapid expansion of indications for neurointerventional procedures. This access is an attractive neurointervention route to be considered, with many advantages over the traditional femoral access in terms of ease of vasculature navigation and decreased risk of complications such as significant bleeding. Although a promising technique for neurointerventional procedures, there are inherent and unique considerations as well as potential complications involved. The following case report highlights some of these vital concepts associated with radial artery access, including appropriate patient selection as well as assessment of arterial size in the context of neurointerventional techniques. Early identification of complications such as arterial injury and compartment syndrome, with an emphasis on appropriate draping and inter-procedure monitoring, is discussed as well as approaches for subsequent management. Finally, the issue of radiation safety in this emerging technique is considered. These concepts are critical for the successful use and the continued growth of radial artery access for neurointervention procedures. [ABSTRACT FROM AUTHOR]

Background: Image-defined risk factors (IDRFs) were introduced to provide a consensus approach for pre-treatment risk stratification on computed tomography (CT) and magnetic resonance imaging (MRI) in patients with neuroblastoma.To assess the intra- and inter-reader agreement of radiologists in identifying IDRFs on CT.Approval for this retrospective study was granted by our institutional research ethics board with a waiver of consent. CT studies of pediatric patients with neuroblastoma were assessed by seven radiologists in two rounds. Each CT was accompanied by a standard form to indicate presence or absence of IDRFs for each patient. At least a 4-week period between rounds, randomization, and relabeling of the CT studies was required to minimize recall bias. Finally, three of the seven radiologists conducted a subsequent consensus reading to determine true positive IDRFs in the cohort. Fleiss’ kappa statistic was used to evaluate readers’ agreements and Pearson’s correlation assessed the correlation between years of experiences of radiologists and their performance in accurately (intra-reader agreement) detecting IDRFs.A total of 31 children with a median age of 2.1 years (interquartile range (IQR) 1.1, 3.0; range 0-18; male=21 (67.7%)) were included and 251 total positive IDRFs were identified on their CT scans. The location of the primary tumor was in the neck in 1 patient (3.2%), within the chest in 2 patients (6.5%), within the abdomen in 27 patients (87.1%), and in the pelvis in 1 patient (3.2%). In determining IDRFs, the inter-reader agreement among radiologists was substantial: 0.65 (95% CI 0.60, 0.69) and the intra-reader agreement for each radiologist was substantial to near perfect, ranging from 0.67 (0.60, 0.70) to 0.86 (0.82, 0.90). The correlation between the number of years of experience of radiologists and their performances in accurately detecting IDRFs (their intra-reader agreements) was respectively low (r=45, P=0.30) for abdomino-pelvic IDRFs and high for organs’ infiltration IDRFs (r=0.74, P=0.05).The determination of IDRFs on CT is reproducible with significant agreement among radiologists. The two IDRF items with the lowest overall inter-reader agreements were “diaphragm infiltration” and “mesenteric infiltration.”Objective: Image-defined risk factors (IDRFs) were introduced to provide a consensus approach for pre-treatment risk stratification on computed tomography (CT) and magnetic resonance imaging (MRI) in patients with neuroblastoma.To assess the intra- and inter-reader agreement of radiologists in identifying IDRFs on CT.Approval for this retrospective study was granted by our institutional research ethics board with a waiver of consent. CT studies of pediatric patients with neuroblastoma were assessed by seven radiologists in two rounds. Each CT was accompanied by a standard form to indicate presence or absence of IDRFs for each patient. At least a 4-week period between rounds, randomization, and relabeling of the CT studies was required to minimize recall bias. Finally, three of the seven radiologists conducted a subsequent consensus reading to determine true positive IDRFs in the cohort. Fleiss’ kappa statistic was used to evaluate readers’ agreements and Pearson’s correlation assessed the correlation between years of experiences of radiologists and their performance in accurately (intra-reader agreement) detecting IDRFs.A total of 31 children with a median age of 2.1 years (interquartile range (IQR) 1.1, 3.0; range 0-18; male=21 (67.7%)) were included and 251 total positive IDRFs were identified on their CT scans. The location of the primary tumor was in the neck in 1 patient (3.2%), within the chest in 2 patients (6.5%), within the abdomen in 27 patients (87.1%), and in the pelvis in 1 patient (3.2%). In determining IDRFs, the inter-reader agreement among radiologists was substantial: 0.65 (95% CI 0.60, 0.69) and the intra-reader agreement for each radiologist was substantial to near perfect, ranging from 0.67 (0.60, 0.70) to 0.86 (0.82, 0.90). The correlation between the number of years of experience of radiologists and their performances in accurately detecting IDRFs (their intra-reader agreements) was respectively low (r=45, P=0.30) for abdomino-pelvic IDRFs and high for organs’ infiltration IDRFs (r=0.74, P=0.05).The determination of IDRFs on CT is reproducible with significant agreement among radiologists. The two IDRF items with the lowest overall inter-reader agreements were “diaphragm infiltration” and “mesenteric infiltration.”Materials and methods: Image-defined risk factors (IDRFs) were introduced to provide a consensus approach for pre-treatment risk stratification on computed tomography (CT) and magnetic resonance imaging (MRI) in patients with neuroblastoma.To assess the intra- and inter-reader agreement of radiologists in identifying IDRFs on CT.Approval for this retrospective study was granted by our institutional research ethics board with a waiver of consent. CT studies of pediatric patients with neuroblastoma were assessed by seven radiologists in two rounds. Each CT was accompanied by a standard form to indicate presence or absence of IDRFs for each patient. At least a 4-week period between rounds, randomization, and relabeling of the CT studies was required to minimize recall bias. Finally, three of the seven radiologists conducted a subsequent consensus reading to determine true positive IDRFs in the cohort. Fleiss’ kappa statistic was used to evaluate readers’ agreements and Pearson’s correlation assessed the correlation between years of experiences of radiologists and their performance in accurately (intra-reader agreement) detecting IDRFs.A total of 31 children with a median age of 2.1 years (interquartile range (IQR) 1.1, 3.0; range 0-18; male=21 (67.7%)) were included and 251 total positive IDRFs were identified on their CT scans. The location of the primary tumor was in the neck in 1 patient (3.2%), within the chest in 2 patients (6.5%), within the abdomen in 27 patients (87.1%), and in the pelvis in 1 patient (3.2%). In determining IDRFs, the inter-reader agreement among radiologists was substantial: 0.65 (95% CI 0.60, 0.69) and the intra-reader agreement for each radiologist was substantial to near perfect, ranging from 0.67 (0.60, 0.70) to 0.86 (0.82, 0.90). The correlation between the number of years of experience of radiologists and their performances in accurately detecting IDRFs (their intra-reader agreements) was respectively low (r=45, P=0.30) for abdomino-pelvic IDRFs and high for organs’ infiltration IDRFs (r=0.74, P=0.05).The determination of IDRFs on CT is reproducible with significant agreement among radiologists. The two IDRF items with the lowest overall inter-reader agreements were “diaphragm infiltration” and “mesenteric infiltration.”Results: Image-defined risk factors (IDRFs) were introduced to provide a consensus approach for pre-treatment risk stratification on computed tomography (CT) and magnetic resonance imaging (MRI) in patients with neuroblastoma.To assess the intra- and inter-reader agreement of radiologists in identifying IDRFs on CT.Approval for this retrospective study was granted by our institutional research ethics board with a waiver of consent. CT studies of pediatric patients with neuroblastoma were assessed by seven radiologists in two rounds. Each CT was accompanied by a standard form to indicate presence or absence of IDRFs for each patient. At least a 4-week period between rounds, randomization, and relabeling of the CT studies was required to minimize recall bias. Finally, three of the seven radiologists conducted a subsequent consensus reading to determine true positive IDRFs in the cohort. Fleiss’ kappa statistic was used to evaluate readers’ agreements and Pearson’s correlation assessed the correlation between years of experiences of radiologists and their performance in accurately (intra-reader agreement) detecting IDRFs.A total of 31 children with a median age of 2.1 years (interquartile range (IQR) 1.1, 3.0; range 0-18; male=21 (67.7%)) were included and 251 total positive IDRFs were identified on their CT scans. The location of the primary tumor was in the neck in 1 patient (3.2%), within the chest in 2 patients (6.5%), within the abdomen in 27 patients (87.1%), and in the pelvis in 1 patient (3.2%). In determining IDRFs, the inter-reader agreement among radiologists was substantial: 0.65 (95% CI 0.60, 0.69) and the intra-reader agreement for each radiologist was substantial to near perfect, ranging from 0.67 (0.60, 0.70) to 0.86 (0.82, 0.90). The correlation between the number of years of experience of radiologists and their performances in accurately detecting IDRFs (their intra-reader agreements) was respectively low (r=45, P=0.30) for abdomino-pelvic IDRFs and high for organs’ infiltration IDRFs (r=0.74, P=0.05).The determination of IDRFs on CT is reproducible with significant agreement among radiologists. The two IDRF items with the lowest overall inter-reader agreements were “diaphragm infiltration” and “mesenteric infiltration.”Conclusion: Image-defined risk factors (IDRFs) were introduced to provide a consensus approach for pre-treatment risk stratification on computed tomography (CT) and magnetic resonance imaging (MRI) in patients with neuroblastoma.To assess the intra- and inter-reader agreement of radiologists in identifying IDRFs on CT.Approval for this retrospective study was granted by our institutional research ethics board with a waiver of consent. CT studies of pediatric patients with neuroblastoma were assessed by seven radiologists in two rounds. Each CT was accompanied by a standard form to indicate presence or absence of IDRFs for each patient. At least a 4-week period between rounds, randomization, and relabeling of the CT studies was required to minimize recall bias. Finally, three of the seven radiologists conducted a subsequent consensus reading to determine true positive IDRFs in the cohort. Fleiss’ kappa statistic was used to evaluate readers’ agreements and Pearson’s correlation assessed the correlation between years of experiences of radiologists and their performance in accurately (intra-reader agreement) detecting IDRFs.A total of 31 children with a median age of 2.1 years (interquartile range (IQR) 1.1, 3.0; range 0-18; male=21 (67.7%)) were included and 251 total positive IDRFs were identified on their CT scans. The location of the primary tumor was in the neck in 1 patient (3.2%), within the chest in 2 patients (6.5%), within the abdomen in 27 patients (87.1%), and in the pelvis in 1 patient (3.2%). In determining IDRFs, the inter-reader agreement among radiologists was substantial: 0.65 (95% CI 0.60, 0.69) and the intra-reader agreement for each radiologist was substantial to near perfect, ranging from 0.67 (0.60, 0.70) to 0.86 (0.82, 0.90). The correlation between the number of years of experience of radiologists and their performances in accurately detecting IDRFs (their intra-reader agreements) was respectively low (r=45, P=0.30) for abdomino-pelvic IDRFs and high for organs’ infiltration IDRFs (r=0.74, P=0.05).The determination of IDRFs on CT is reproducible with significant agreement among radiologists. The two IDRF items with the lowest overall inter-reader agreements were “diaphragm infiltration” and “mesenteric infiltration.” [ABSTRACT FROM AUTHOR]

The expression of genetic information is tightly controlled by chromatin regulatory proteins, including those in the heterochromatin gene repression family. Many of these regulatory proteins work together on the chromatin substrate to precisely regulate gene expression during mammalian development, giving rise to many different tissues in higher organisms from a fixed genomic template. Here we identify and characterize the interactions of two related heterochromatin regulatory proteins, heterochromatin protein 1 alpha (HP1α) and M-phase phosphoprotein 8 (MPP8), with hepatoma-derived growth factor-related protein 2 (HRP2). We find in biochemical experiments that HRP2 copurifies and co-sediments with heterochromatin-associated proteins, including HP1α and MPP8. Using the Chromatin in vivo Assay in multiple cell types, we demonstrate that HP1α-mediated gene repression dynamics are altered by the presence of HRP2. Furthermore, the knockout of HRP2 in MDA-MB-231 cells results in significant changes to chromatin structure and stability, which alter gene expression patterns. Here, we detail a mechanism by which HRP2 contributes to epigenetic transcriptional regulation through engagement with heterochromatin-associated proteins to stabilize the chromatin landscape and influence gene expression. [ABSTRACT FROM AUTHOR]

Policy interventions geared toward improving the quality of gig economy work depend not only on how this work is classified in legal terms but also on a fine‐tuned understanding of the relevant factors that determine the quality of the gig 'work relationship'. Models that are used to evaluate standard work, however, are poorly adapted to gig work. This article proposes a 'work relationship' model adapted to the gig economy. The model is inspired by Dunlop's systems approach and is constructed from 24 in‐depth interviews with gig economy workers. A survey generated from the model was used to verify the relevance of 3 macro‐level and 12 micro‐level factors. Its main findings are that income, labour protections, voice and client behavior are the most significant factors in determining the quality of work and of work relations as determined by gig workers. [ABSTRACT FROM AUTHOR]

Having devoted over 35 years of my professional life to various projects on choroideremia (CHM), I began to reflect on the many lessons that I learned along the way. One of the most important is: we should pay careful attention to possible, unintended psychological harm in clinical research. This lesson was learned early and then reinforced when I engaged CHM patients in an investigator-sponsored Phase IB clinical trial of ocular gene therapy for choroideremia. My second lesson came from the trial itself in that preliminary data may not be sufficient to predict the risks to patients in a clinical trial. In the significant push to begin a gene therapy trial for CHM patients, writing grants, recruiting personnel, interacting with regulatory authorities, acquiring research equipment to test outcome measures, I missed a third lesson. There is significant bias when the principal investigator of an investigator-sponsored clinical trial is also the treating physician in the trial. Ideally, those two roles should be kept separate. Finally, having completed the clinical trial, I learned that gene replacement with an AAV vector may not be the only genetic therapy for CHM; an antisense oligonucleotide therapy may be possible in select cases. [ABSTRACT FROM AUTHOR]

The flow patterns of red blood cells through the spleen are intimately linked to clearance of senescent RBCs, with clearance principally occurring within the open flow through the red pulp and slits of the venous sinus system that exists in humans, rats, and dogs. Passage through interendothelial slits (IESs) of the sinus has been shown by MacDonald et al. (Microvasc Res 33:118–134, 1987) to be mediated by the caliber, i.e., slit opening width, of these slits. IES caliber within a given slit of a given sinus section has been shown to operate in an asynchronous manner. Here, we describe a model and simulation results that demonstrate how the supporting forces exerted on the sinus by the reticular meshwork of the red pulp, combined with asymmetrical contractility of stress fibers within the endothelial cells comprising the sinus, describe this vital and intriguing behavior. These results shed light on the function of the sinus slits in species such as humans, rats, and dogs that possess sinusoidal sinuses. Instead of assuming a passive mechanical filtering mechanism of the IESs, our proposed model provides a mechanically consistent explanation for the dynamically modulated IES opening/filtering mechanism observed in vivo. The overall perspective provided is also consistent with the view that IES passage serves as a self-protective mechanism in RBC vesiculation and inclusion removal. [ABSTRACT FROM AUTHOR]

This article discusses the sector-wide organization of contractual archaeologists in Québec, beginning with the formation of a workers' committee and leading subsequently to union accreditation. We theorize the difficulty of organizing these "precarious professionals" and suggest that self-organization outside of an industrial relations framework may be required to overcome barriers to their unionization. Deliberation, norm setting, and informal parlays with employers lead to clarifying class distinctions that professional identification often occludes, while self-organization increases worker confidence in collective action. [ABSTRACT FROM AUTHOR]

Radial arterial access has gained interest for neurovascular procedures in recent years. Although there are no randomized control trials for neurointervention procedures using radial access, there is growing literature demonstrating its feasibility and favorable outcomes. Equipment technical improvements, like the recently introduced BENCHMARK™ BMX®81 System, have made radial navigation safer, with improved maneuverability and support for a variety of procedures. We present a multicenter case series highlighting our institutional radial access experience comparing the BMX®81 with alternative catheters.Multicenter retrospective cohort study of 80 patients who underwent neurovascular procedures through a radial approach. In half of the cases a BENCHMARK™ BMX®81 System was used. The comparison group consisted of the BENCHMARK™071 and 96, Neuron MAX®088 and BALLAST™ systems. Procedures included endovascular thrombectomy, carotid and brachiocephalic artery stenting, middle meningeal artery embolization, flow diverter stenting, vertebral artery sacrifice, aneurysm coiling, and WEB™ device deployment.In our series, the BMX®81 was successful in the navigation of the anatomy to the target location in 95% of cases. No radial access or BMX®81 related complications were identified. There was no significant difference in fluoroscopy time between the BMX81 and the comparison group. Four patients in the comparison group had catheter-related complications due to vasospasm. Eighty-six percent of BMX®81 cases had satisfactory outcomes and no technical difficulties. The remainder presented technical difficulties, but none of these were considered secondary to the puncture site or support structure.The BENCHMARK™ BMX®81 System is a recently developed guiding catheter which has design and size features supporting radial access for a variety of neurovascular interventions. Early multicenter experience highlights the ease of use and versatility of this new catheter as an alternative to transfemoral access as well as other catheters used for radial access. [ABSTRACT FROM AUTHOR]

The obituary is about William Gregory Pearce, a respected ophthalmologist who specialized in genetic eye diseases. He worked at the Ocular Genetics Clinic at the University of Alberta and was known for his dedication to diagnosing patients with various genetic eye conditions. Pearce made significant contributions to the field, including mapping and identifying mutations in the CACNA1F gene as the cause of one form of X-linked congenital stationary night blindness. He also collaborated with other researchers and was involved in studying the Holocaust after his retirement. Pearce was described as a man of strong beliefs and passions, although he could be challenging at times. [Extracted from the article]

Retinitis pigmentosa 1–like 1 (RP1L1) is a component of the photoreceptor cilium. Pathogenic variants in RP1L1 lead to photoreceptor disease, suggesting an important role for RP1L1 in photoreceptor biology, though its exact function is unknown. To date, RP1L1 variants have been associated with occult macular dystrophy (a cone degeneration) and retinitis pigmentosa (a rod disease). Here, we summarize reported RP1L1 -associated photoreceptor conditions and disease-causing RP1L1 variants. We also discuss novel associations between RP1L1 and additional photoreceptor conditions—besides occult macular dystrophy and retinitis pigmentosa—and fit RP1L1 into the broader scope of photoreceptor disease. RP1L1 appears to have a complex relationship with other photoreceptor proteins and may modify disease phenotype. Ultimately, further exploration of the relationship between RP1L1 , other cilium components, and their impact on photoreceptor health is needed. [ABSTRACT FROM AUTHOR]

While Peirce's case for rejecting Descartes' approach to philosophical inquiry tends to be familiar, there is the need to return to it, especially considering that some critics claim that he misread Descartes' method of doubt. My aim in this article is to show that, after closely reinvestigating Peirce's case, it becomes clear that his reasons for rejecting Descartes' approach are stronger than critics generally take them to be. And after I spell out these reasons, I will show why we can defend Peirce's case and how we can resolve the longstanding controversy over whether Peirce misrepresented Descartes. [ABSTRACT FROM AUTHOR]

Active seafloor hydrocarbon seepage from three distinct, positive seafloor features, termed knolls, in the Sigsbee Knolls area, Gulf of Mexico (GOM), was investigated in March 2015. The study sites included the Challenger Knoll, which was drilled by the Deep Sea Drilling Program (DSDP) in 1969 and showed the influence of salt tectonics on its evolution and the presence of subsurface petroleum. This study used gas flare mapping in the water column, detailed seafloor bathymetry, backscatter mapping, sub-bottom profiling, and remote sensing of surface water to locate seafloor areas of hydrocarbon emissions. Flares of gas bubbles were detected in the water column above all three knolls, making them the deepest reported gas emission sites in the GOM. Although surface oil slicks above the Sigsbee Knolls have been detected by satellite imaging in the past; in this study, neither satellite imagery nor ship-based observations detected floating oil, this suggests that oil seepage in the region is intermittent. High-resolution video surveys of the seafloor at Challenger Knoll, using a camera system mounted on a lowered tow-vehicle, documented the presence of seep-related chemosynthetic fauna including clam fields and microbial mats at the western part of the knoll. These findings are consistent with previous investigations that link hydrocarbon seepage at Challenger Knoll to salt tectonics. During visual seafloor inspections, no asphalt deposits, such as those known from sites in the Campeche Knoll area in the southern GOM, were observed. These findings indicate that hydrocarbon seepage is less pronounced in the Sigsbee Knolls region, central GOM, than is the case in hydrocarbon systems in the northern or southern GOM. [ABSTRACT FROM AUTHOR]

Objectives: Factors maintaining cognitive health are still largely unknown. In particular, the cognitive benefits associated with vitamin intake and vitamin supplementation are disputed. We investigated self-reported vitamin intake and serum vitamin levels with performance in cognitive factors sensitive to dementia progression in two large middle-aged general population cohorts. Methods: Survey data were used to assess regular vitamin intake in 4400 NCDS 1958 and 1177 TwinsUK cohort members, and serum homocysteine and B vitamin levels were measured in 675 individuals from the TwinsUK study. Principal component analysis was applied to cognitive test performance from both cohorts resulting in two dementia-sensitive cognitive factors reflecting visuospatial associative memory and verbal semantic memory. Results: In both cohorts, individuals who reported regular intake of vitamins, particularly B vitamins, showed significantly better performance in visuospatial associative memory and verbal semantic memory (P < 0.001). A significant association was also found between homocysteine levels, vitamin serum concentration and visuospatial associative memory performance which indicated that individuals with high B vitamin and homocysteine levels showed better visuospatial associative memory performance than individuals with low vitamin B levels (P < 0.05). Discussion: The findings demonstrate that early dementia-sensitive cognitive changes can be identified in middle-aged asymptomatic individuals and that regular vitamin intake is associated with improved cognitive performance. These findings reinforce the potential cognitive benefits of regular vitamin intake, which should be considered as an economically viable therapeutic strategy for maintaining cognitive health. [ABSTRACT FROM AUTHOR]

Dromiceiomimus brevitertius is a North American ornithomimid diagnosed primarily by the ratio of tibia length to femur length. It has recently, and perhaps incorrectly, been considered synonymous with Ornithomimus edmontonicus, with several authors questioning the utility of limb ratios in diagnosing taxa. While isolated ornithomimosaur material is common, specimens with sufficient diagnostic material to explore the question of synonymy are comparatively rare. The putative Dromiceiomimus specimen UALVP 16182 represents one of the few specimens in which diagnostic elements are available. It is therefore an important specimen for assessing the validity of Dromiceiomimus and for examining the utility of using limb proportions to diagnose ornithomimid taxa. In this paper, UALVP 16182 is described, the tibia/femur ratio is examined in closely related ornithomimid taxa, and the ratio is found to distinguish Dromiceiomimus from Gallimimus, Ornithomimus, and Struthiomimus. A phylogenetic analysis recovered Anserimimus and Ornithomimus as sister taxa with Dromiceiomimus as an outgroup. Comparison of the manus revealed differences in the morphology of metacarpal I and the flexor tubercle of manual ungual II-3. Differences also appear in the surangular and scapula. An examination of stratigraphic positions of various specimens indicates that Dromiceiomimus is generally higher in section than Ornithomimus, although there are too few specimens to be statistically significant. This study agrees with other studies in concluding that limb proportions are roughly isometric in small theropods like ornithomimids and that the tibia/femur ratio may therefore be useful for diagnosing certain small taxa. These findings suggest that Dromiceiomimus may indeed be a valid taxon. [ABSTRACT FROM AUTHOR]

Purpose: To test the effect of docosahexanoic acid (DHA) dietary supplementation on macular function in patients with Stargardt disease. Materials and Methods: A single center, double-masked, randomized placebo-controlled trial of 11 subjects (2 males, 9 females) with Stargardt disease in a crossover design (NCT00060749). Six participants were randomized to two sequences of three month periods of DHA supplementation (2000 mg/day) followed by three months of placebo. Five participants were randomized to the opposite sequence. All participants were evaluated with a food frequency and NEI-VF25 questionnaires, complete ophthalmic examination, multifocal electroretinography (ERG, primary outcome), 30-Hz flicker ERG, Humphrey 10-2 visual field, D15 color tests and serum lipid analysis. Results: During periods of DHA supplementation, serum rose and then fell with transition to periods of placebo. None of the participants experienced greater than 20% change from baseline values of the mfERG during periods of DHA supplementation or placebo, while the average change in peak amplitude and phase angle of the flicker ERG remained similar at all visits. No significant change was observed for any of the secondary outcome measures. Eight adverse events occurred but these were not considered to be due to the treatment. Conclusions: No perceived effect of DHA supplementation on macular function was observed in a small sample of Stargardt patients who were compliant with the protocol as estimated by changes in serum DHA. This study will help design future studies of the effect of DHA supplementation on retinal function in cohorts with retinal dystrophies. [ABSTRACT FROM AUTHOR]

The winery/grower relationship is one of the most critical in the industry and is often controlled by contracts, either verbal agreements or formal documents. Yet contracts are subject to opportunism and are said to be ‘incomplete’ due to bounded rationality. While monitoring efforts and contract incentives help mitigate opportunism, contracts need an enforceable and efficient legal systems to be effective. We survey 111 South African wineries to investigate why contracts are still widely used to coordinate grape supply relationships while these exchanges are likely to be characterised by high asset specificity and high uncertainty. We ask the question how Agency monitoring and incentives efforts are related to contract use in the South African wine industry, a country with a relatively weak legal system as defined by the World Bank. Employing multiple regression, we found that South African wineries tended to rely more on outcome based contracts, utilising ‘incentives’ rather than ‘monitoring’ to control their grape supply partners. Indeed, we also argue that trust is a substitute for monitoring efforts. We also found moderate support for trust and the legal system promoting the use of spot markets. These results provide some insights into how to structure grape supply contracts. [ABSTRACT FROM AUTHOR]

Pseudoxanthoma elasticum (PXE) is an autosomal recessive condition caused by mutations in the ABCC6 gene. Ocular features include angioid streaks, peau d'orange fundus, and drusen. We report a novel ABCC6 mutation causing PXE in a patient with a mixed phenotype of PXE and retinitis pigmentosa (RP). A 37-year-old female presented with decreased peripheral vision and nyctalopia. Ocular imaging revealed angioid streaks emanating from the optic nerve as well as peripheral pigmentary changes and bone spicules. Genetic testing revealed two mutations in ABCC6 in trans. No other mutation was identified. We present a rare case with ocular findings of PXE and RP in a patient with a novel ABCC6 mutation. The patient presented both with peripheral pigmentary changes and angioid streaks. Further investigation into this novel mutation would be beneficial to determine if the mutation is involved in the RP phenotype. [ABSTRACT FROM AUTHOR]

Amyloid-β (Aβ) plaques are a neuropathological hallmark of Alzheimer's disease (AD); however, a significant number of cognitively normal older adults can also have Aβ plaques. Thus, distinguishing AD from cognitively normal individuals with Aβ plaques (NwAβ) based on Aβ plaque detection is challenging. It has been observed that butyrylcholinesterase (BChE) accumulates in plaques preferentially in AD. Thus, detecting BChE-associated plaques has the potential as an improved AD biomarker. We present Aβ, thioflavin-S, and BChE quantification of 26 postmortem brain tissues; AD (n = 8), NwAβ (n = 6), cognitively normal without plaques (n = 8), and other common dementias including corticobasal degeneration, frontotemporal dementia with tau, dementia with Lewy bodies, and vascular dementia. Pathology burden in the orbitofrontal cortex, entorhinal cortex, amygdala, and hippocampal formation was determined and compared. The predictive value of Aβ and BChE quantification was determined, via receiver-operating characteristic plots, to evaluate their AD diagnostic performance using sensitivity, specificity, and area under curve (AUC) metrics. In general, Aβ and BChE-associated pathology were greater in AD, particularly in the orbitofrontal cortex. In this region, the largest increase (9.3-fold) was in BChE-associated pathology, observed between NwAβ and AD, due to the virtual absence of BChE-associated plaques in NwAβ brains. Furthermore, BChE did not associate with pathology of the other dementias. In this sample, BChE-associated pathology provided better diagnostic performance (AUC = 1.0, sensitivity/specificity = 100% /100%) when compared to Aβ (AUC = 0.98, 100% /85.7%). These findings highlight the predictive value of BChE as a biomarker for AD that could facilitate timely disease diagnosis and management. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to synthesize and evaluate specific agents for molecular imaging of butyrylcholinesterase (BuChE), known to be associated with neuritic plaques and neurofibrillary tangles in Alzheimer's disease (AD). In this study, these agents were tested in a normal rat model. The distribution of radiolabel was compared with known BuChE histochemical distribution in the rat brain.Procedures: Iodobenzoate esters were synthesized and tested, through spectrophotometric analysis, as specific substrates for BuChE. These compounds were converted to the corresponding (123)I esters from tributyltin intermediates and purified for studies in the rat model. Whole body dynamic scintigraphic images were obtained for biodistribution studies. Autoradiograms of brain sections were obtained and compared to histochemical distribution of the enzyme in this model system.Results: The three iodobenzoate esters studied were specific substrates for BuChE. Whole body biodistribution studies with (123)I-labeled compounds showed rapid disappearance from the body while radioactivity was retained in the head region. Brain section autoradiography of animals injected with these labeled compounds indicated that most areas known to contain BuChE corresponded to areas of radioactivity accumulation.Conclusion: BuChE-specific radiolabeled iodobenzoates enter the brain and, in general, label areas known to exhibit BuChE activity in histochemical studies. Such molecules may represent a new direction for the development of agents for the molecular imaging of BuChE in the living brain, especially in regions where BuChE-containing neuropathological structures appear in AD. [ABSTRACT FROM AUTHOR]

Analysis of the magnitude of oil discharged from natural hydrocarbon seeps can improve understanding of the carbon cycle and the Gulf of Mexico (GOM) ecosystem. With use of a large archive of remote sensing data, in combination with geophysical and multibeam data, we identified, mapped, and characterized natural hydrocarbon seeps in the Macondo prospect region near the wreck site of the drill-rig Deepwater Horizon (DWH). Satellite image processing and the cluster analysis revealed locations of previously undetected seep zones. Including duplicate detections, a total of 562 individual gas plumes were also observed in multibeam surveys. In total, SAR imagery confirmed 52 oil-producing seep zones in the study area. In almost all cases gas plumes were associated with oil-producing seep zones. The cluster of seeps in the vicinity of lease block MC302 appeared to host the most persistent and prolific oil vents. Oil slicks and gas plumes observed over the DWH site were consistent with discharges of residual oil from the wreckage. In contrast with highly persistent oil seeps observed in the Green Canyon and Garden Banks lease areas, the seeps in the vicinity of Macondo Prospect were intermittent. The difference in the number of seeps and the quantity of surface oil detected in Green Canyon was almost two orders of magnitude greater than in Mississippi Canyon. [ABSTRACT FROM AUTHOR]

Flatfishes bury themselves under a thin layer of sand to hide from predators or to ambush prey. We investigated the role of undulation frequency of the body in burial in five species of flatfishes ( Isopsetta isolepis, Lepidopsetta bilineata, Hippoglossoides elassodon, Parophrys vetulus , and Psettichthys melanostictus ). High-speed videos show that undulations begin cranially and pass caudally while burying, as in forward swimming in many other fishes. The flatfishes also flick the posterior edge of their dorsal and anal fins during burial, which may increase the total surface area covered by substrate. We built a simple physical model – a flexible, oval silicone plate with a motorized, variable-speed actuator – to isolate the effect of undulation frequency on burial. In both the model and actuated dead flatfish, increased undulation frequency resulted in an increase in the area of sand coverage. Complete coverage required an undulation frequency of no more than 10 Hz for our models, and that was also sufficient for live flatfishes. The model shows that undulation is sufficient to bury the animal, but live flatfishes showed a superior ability to bury, which we attribute to the action of the median fins. [ABSTRACT FROM AUTHOR]

This article contends that what differentiates Wizard of the Crow from Ngũgĩ's earlier writings lies in the manner in which his populism has moved from the national to the global scale. Ngũgĩ accomplishes this by figuring dystopia as comic rather than tragic, privileging the social body over the individual in a way that transcends limitations surrounding the nation-state. Focusing on the novel's incorporation of scientific idioms as well as on themes of temporal fixity, the article points to a restaging of Ngũgĩ's earlier, more provincial, representations of resistance through the incorporation of utopian dissociative features that make it structurally and politically allegorical and also futuristic without conforming to the obsession with the sovereign individual common to Western anti-utopias. The crux of this movement, I argue, occurs through the figure of the cybogre, a fusion of technology and myth that pits cosmic spiritual elements against the limits of human technical (re)creativity. [ABSTRACT FROM AUTHOR]

We report the case of a 42 year-old man with a right middle cerebral artery territory infarct secondary to dissection of the right internal carotid artery who was followed throughout presentation, acute management and recovery. Cervical artery dissection (CAD) is one the most common causes of ischemic stroke in young and middle aged patients. Furthermore, spontaneous dissection of the carotid and vertebral arteries have a largely unknown pathogenesis. This case highlights how CAD may complicate treatment decisions concerning the effectiveness of thrombolytic therapy, the role of endovascular treatment, optimal antithrombotic therapy, and prevention of recurrence.. [ABSTRACT FROM AUTHOR]

This review is based on a presentation that was made at a meeting concerning hydration. It summarizes the epidemiological evidence for selected beverages in relation to cardiovascular and/or metabolic health. The review focuses on tea, cocoa, milk, orange juice, alcohol, and beverages sweetened with sugars. These beverage types were chosen because of their widespread consumption, with tea, cocoa, orange juice, and milk being of potential benefit while alcohol and sugars may be detrimental. There is reasonably consistent evidence of reduced risk of cardiovascular disease (CVD) in association with high consumption of tea, with the tea flavonoids appearing to be responsible for these benefits. There is also a growing evidence base for cocoa flavanols to have beneficial cardiovascular effects. The bulk of the evidence supporting these conclusions is epidemiological and needs to be confirmed with randomized controlled trials. Milk is associated with reduced risk of CVD, particularly in relation to blood pressure, with certain milk tripeptides being implicated in having effects to reduce angiotensin action. Further work is needed to confirm these potentially beneficial effects. There is some evidence of potentially beneficial effects of orange juice on aspects of cardiovascular function, but this is by no means convincing, and further evidence is needed from randomized controlled trials, together with the elucidation of whether any benefits are linked to the citrus flavanones or simply to the vitamin C content. While there is some evidence that red wine may convey some health benefits, there is also clear evidence that alcoholic beverages can have undesirable effects on blood pressure and increase the risk of CVD. It is possible that low to moderate intakes of alcoholic beverages may be beneficial. There is some evidence that beverages sweetened with sugars may contribute to increased energy intake and weight gain, and there is also an indication from longitudinal cohort studies that they are associated with an increased risk of developing type 2 diabetes. The mechanism of this latter association has not been explained. In conclusion, there is a substantial amount of epidemiological evidence for benefits of tea and cocoa in relation to cardiovascular health. There is a growing literature describing randomized controlled trials, but more evidence is needed. Potential cardiovascular and metabolic health benefits of milk and orange juice needs further investigation. The associations of higher alcohol intakes and consumption of beverages sweetened with sugars and their increased health risks are of concern, and more attention should be focused on this area. [ABSTRACT FROM AUTHOR]

The ability to accurately quantitate and experimentally examine epigenetic modifications across the human genome has exploded in the past decade. This has given rise to a wealth of new information concerning the contributions of epigenetic regulatory networks to the pathogenesis of human disease. In particular, immunological disorders have strong developmental roots in chromatin regulatory pathways. In this review, we focus on the epigenetic signatures and new discoveries revealing the epigenetic compositions of specific immunological cancers and autoimmune diseases. We also comment on the conserved epigenetic roots among diverse immunological disorders and suggest inhibition strategies that may be relevant for future treatment. Finally, we highlight emerging experimental tools with the capability to examine the mechanisms of chromatin regulatory enzymes with a high level of temporal control. The knowledge of genetic and epigenetic defects in immunological disease combined with new experimental approaches will elucidate the contribution of individual enzymes in complex epigenetic regulatory networks. This could lead to new diagnostic and therapeutic approaches for some very diverse and difficult to treat human diseases. [ABSTRACT FROM AUTHOR]

Introduction: Usher syndrome is a genetically heterogeneous condition and represents the most common cause of inherited combined vision and hearing loss. Deficits manifest as sensorineural hearing loss that typically develops at a young age and retinitis pigmentosa that can lead to peripheral vision loss and night blindness. As a result, this syndrome can have a significant impact on a patient's quality of life. Previous studies have described an association between Usher syndrome and Fuchs' heterochromic iridocyclitis, a form of non-granulomatous uveitis that generally presents in a unilateral manner. We present a rare finding of bilateral uveitis and, to the best of our knowledge, the first report of granulomatous uveitis as a feature in a patient with Usher syndrome. Case presentation: A 45-year-old Caucasian woman with a known history of retinitis pigmentosa presented to our clinic with suspected Usher syndrome, given her report of long-standing hearing loss. Aside from a mild loss in visual acuity, our patient was otherwise asymptomatic. Visual field testing, audiology and electroretinography findings supported the diagnosis of Usher syndrome. With slit lamp examination she was found to have bilateral keratic precipitates, with large, greasy-white, mutton-fat keratic precipitates on the endothelial surface of her left eye. A thorough work-up that included blood tests and imaging was negative for an alternative cause of her uveitis. Conclusion: We present a rare finding of bilateral uveitis and what we believe to be the first reported instance of mutton-fat keratic precipitates and granulomatous uveitis as a feature in a patient with Usher syndrome. By identifying atypical presentations of the disease, we hope to contribute to the range of ophthalmic conditions that may be seen in association with Usher syndrome. [ABSTRACT FROM AUTHOR]

Objective: To assess whether flow-mediated dilatation (FMD) affected cardiovascular (CV) parameters after consuming fructose or sucralose. Data source: Finometer. Design of study: Randomized, cross-over, single-blind design. Setting: School of biomedical sciences, University of Nottingham, UK. Period: July, 2009. Materials and methods: Ten healthy, white European males were studied twice. A Finometer continuously recorded CV parameters. Following 30 min baseline, a BP cuff, around mid-point of right arm was inflated 50 mmHg above Systolic BP for 5 min. Upon deflation, FMD measurements were made. Volunteers then consumed 500 ml of fructose or sucralose containing drink. Forty min later, 2nd FMD was done. Results: Pre-fructose FMD: SBP increased in late-occlusion and post-occlusion period (POP). HR and CO decreased and SV and TPR increased during POP (P < 0.01 & 0.001). Post-fructose: DBP rose (2 mmHg; P = 0.04) during occlusion; HR (P = 0.02) and CO (P < 0.05) increased whereas TPR decreased (0.023; P < 0.04) in recovery period. Pre-sucralose: SBP, DBP and MAP increased in POP and thereafter. Decreased HR and CO and increased TPR and SV were noted (P < 0.01 & 0.001). Post-sucralose: SBP rose in POP and thereafter (5 mmHg; P < 0.01); MAP (3 mmHg; P = 0.04) and SV (P = 0.05) increased in POP. Conclusions: Attenuated BP and TPR, after fructose, indicate fructose's possible vascular effects. [ABSTRACT FROM AUTHOR]

Cholinesterase inhibitors are the standard of care for Alzheimer's disease (AD). Acetylcholinesterase (AChE) catalyzes the hydrolysis of the cholinergic neurotransmitter acetylcholine. However, the related enzyme butyrylcholinesterase (BuChE) also breaks down acetylcholine and is likewise targeted by the same clinical cholinesterase inhibitors. The lack of clinical efficacy for the highly specific and potent AChE inhibitor, (-) huperzine A, is intriguing, given the known cholinergic deficit in AD. Based on the proven efficacy of inhibitors affecting both cholinesterases and the apparent failure of specific AChE inhibition, focused BuChE inhibition seems important for more effective treatment of AD. Therefore, BuChE-selective inhibitors provide promise for improved benefit. [ABSTRACT FROM AUTHOR]

The ability to distinguish cells and tissues of interest is critical for understanding their biological importance. In genetic model organisms, a prominent approach for discerning particular cells or tissues from others is the use of cell or tissue-specific enhancers to drive fluorescent reporters. This approach, however, is often limited by the brightness of the fluorescent reporter. To augment the ability to visualize cells or tissues of interest in Drosophila melanogaster, homo-hexameric GFP and mCherry reporters were developed for the GAL4, Q, and LexA transcription systems and functionally validated in vivo. The GFP and mCherry homo-hexameric fusion proteins exhibited significantly enhanced fluorescence as compared to monomeric fluorescent reporters and could be visualized by direct fluorescence throughout the cytoplasm of neurons, including the fine processes of axons and dendrites. These high-sensitivity fluorescent reporters of cell morphology can be utilized for a variety of purposes, especially facilitating fluorescence-based genetic screens for cell morphology phenotypes. These results suggest that the strategy of fusing monomeric fluorescent proteins in tandem to enhance brightness should be generalizable to other fluorescent proteins and other genetic model organisms. [ABSTRACT FROM AUTHOR]

Aim: Ingestion of fructose and mental arithmetic can increase blood pressure (BP); the present study assessed the effect of fructose ingestion on cardiovascular (CV) response to mental stress. Effects were compared with sucralose used as a control. Materials and methods: Ten healthy, white European males were studied twice. A Finometer recorded CV parameters, noninvasively, throughout the study period. After the 30-min baseline, a mental arithmetic task (MAT), a series of arithmetic questions displayed as PowerPoint slides, was presented. Subjects, while resting on a bed, answered 20 questions in 2 min; 15 min after MAT-1, volunteers consumed 500 mL of lemon-flavoured drink containing either fructose (0.75 g/kg body weight) or sucralose. Thirty minutes after drinking, MAT-2, using different questions, was administered; measurements continued for 30 min afterwards. The same protocol was repeated with new questions on a different day with the alternative drink, containing either fructose or sucralose. Results: Fructose and sucralose increased BP and total peripheral resistance (TPR). MATs increased BP, heart rate, and cardiac index, whereas TPR decreased. CV responses to mental arithmetic were not affected by fructose or sucralose, except for an attenuated increase in SBP during MAT-2 after fructose. Conclusion: Pressor effects of fructose (or sucralose) and MATs are not additive. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the possibility of duplications or deletions within the CHM gene as a cause of choroideremia (CHM). Materials and Methods: Eight males and one female subject were identified in whom clinical features were consistent with a clinical diagnosis of CHM. In all cases, sequencing of the coding region and adjacent intronic splice sites did not identify a mutation. In some cases, supplemental immunoblot analysis of protein from peripheral blood leukocytes with anti-REP-1 antibody confirmed absence of Rab escort protein-1, REP-1. A multiplex ligation-dependent probe amplification assay (MLPA) for the CHM gene was developed to test for deletions and duplications within the CHM gene. Results: A duplication of exons 3-8 of the CHM gene (NM_000390.2) was identified in one case. Discussion: While likely an uncommon event, duplication within the CHM gene could be considered as an explanation for CHM cases in which no mutation is found by sequence analysis. [ABSTRACT FROM AUTHOR]

Abstract: Synthetic derivatives of phenothiazine have been used for over a century as well-tolerated drugs against a variety of human ailments from psychosis to cancer. This implies a considerable diversity in the mechanisms of action produced by structural changes to the phenothiazine scaffold. For example, chlorpromazine treatment of psychosis is related to its interaction with dopaminergic receptors. On the other hand, antagonistic action of such drugs on cholinergic receptor systems would be counter-productive for treatment of Alzheimer’s disease. In a search for phenothiazines that are inhibitors of cholinesterases, especially butyrylcholinesterase, with potential to treat Alzheimer’s disease, we wished to ascertain that such molecules could be devoid of neurotransmitter receptor interactions. To that end, a number of our synthetic N-10-carbonyl phenothiazine derivatives, with cholinesterase inhibitory activity, were tested for interaction with a variety of neurotransmitter receptor systems. We demonstrate that phenothiazines can be prepared without significant neurotransmitter receptor interactions while retaining high potency as cholinesterase ligands for treatment of Alzheimer’s disease. [Copyright &y& Elsevier]

As an opportunistic Gram-negative pathogen, Pseudomonas aeruginosa must be able to adapt and survive changes and stressors in its environment during the course of infection. To aid survival in the hostile host environment, P. aeruginosa has evolved defense mechanisms, including the production of an exopolysaccharide capsule and the secretion of a myriad of degradative proteases and lipases. The production of outer membrane-derived vesicles (OMVs) serves as a secretion mechanism for virulence factors as well as a general bacterial response to envelope-acting stressors. This study investigated the effect of sublethal physiological stressors on OMV production by P. aeruginosa and whether the Pseudomonas quinolone signal (PQS) and the MucD periplasmic protease are critical mechanistic factors in this response. Exposure to some environmental stressors was determined to increase the level of OMV production as well as the activity of AlgU, the sigma factor that controls MucD expression. Overexpression of AlgU was shown to be sufficient to induce OMV production; however, stress-induced OMV production was not dependent on activation of AlgU, since stress caused increased vesiculation in strains lacking algU. We further determined that MucD levels were not an indicator of OMV production under acute stress, and PQS was not required for OMV production under stress or unstressed conditions. Finally, an investigation of the response of P. aeruginosa to oxidative stress revealed that peroxide-induced OMV production requires the presence of B-band but not A-band lipopolysaccharide. Together, these results demonstrate that distinct mechanisms exist for stress-induced OMV production in P. aeruginosa. [ABSTRACT FROM AUTHOR]

Cholinesterases are associated with pathology characteristic of conditions such as Alzheimer's disease and are therefore, considered targets for neuroimaging. Ester derivatives of N-methylpiperidinol are promising potential imaging agents; however, methodology is lacking for evaluating these compounds in vitro. Here, we report the synthesis and evaluation of a series of N-methylpiperidinyl thioesters, possessing comparable properties to their corresponding esters, which can be directly evaluated for cholinesterase kinetics and histochemical distribution in human brain tissue. N-methylpiperidinyl esters and thioesters were synthesized and they demonstrated comparable cholinesterase kinetics. Furthermore, thioesters were capable, using histochemical method, to visualize cholinesterase activity in human brain tissue. N-methylpiperidinyl thioesters can be rapidly evaluated for cholinesterase kinetics and visualization of enzyme distribution in brain tissue which may facilitate development of cholinesterase imaging agents for application to conditions such as Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Detection of oil floating on the ocean surface, and particularly thick layers of it, is crucial for emergency response to oil spills. While detection of oil on the ocean surface is possible under moderate sea-state conditions using a variety of remote-sensing methods, estimation of oil layer thickness is technically challenging. In this paper, we used synthetic aperture radar (SAR) imagery collected during the Deepwater Horizon oil spill and the Texture Classifier Neural Network Algorithm (TCNNA) to identify the spill's extent. We then developed an oil emulsion detection algorithm using TCNNA outputs to enhance the contrast of pixels within the oil slick in order to identify SAR image signatures that may correspond to regions of thick, emulsified oil. These locations were found to be largely consistent with ship-based observations and optical and thermal remote-sensing instrument data. The detection method identifies regions of increased radar backscattering within larger areas of oil-covered water. Detection was dependent on SAR incident angles and SAR beam mode configuration. L-band SAR was found to have the largest window of incidence angles (19-38° off nadir) useful for detecting oil emulsions. C-band SAR showed a narrower window (20-32° off nadir) than L-band, while X-band SAR had the narrowest window (20-31° off nadir). The results suggest that in case of future spills in the ocean, SAR data may be used to identify oil emulsions to help make management decisions. [ABSTRACT FROM AUTHOR]

Abstract: Microbes have evolved over millennia to become adapted and specialized to the environments that they occupy. These environments may include water or soil, extreme environments such as hydrothermal vents, and can even include a host organism. To become adapted to these locations, microbes have evolved specific tools to mediate interactions with the environment. One such tool that prokaryotes have evolved includes the production of membrane vesicles (MVs). MVs are 10–300 nm spherical blebs derived from the outermost membrane and have known functions in protein secretion, immune activation and suppression, stress response, attachment, internalization and virulence. In this review, we consider the highly conserved role of membrane vesicles derived from Gram-negative, Gram-positive and archaeal species as a mechanism to facilitate intermicrobial and microbe-host interaction. We examine both the offensive and defensive capabilities of MVs in regard to the interaction of MVs with both host and microbial cells in their environment. [Copyright &y& Elsevier]

Acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) catalyze the hydrolysis of the neurotransmitter acetylcholine and, thereby, function as coregulators of cholinergic neurotransmission. For both enzymes, hydrolysis takes place neae the bottom of a 20 Å deep active site gorge. A number of amino acid residues within the gorge have been identified as important in facilitating efficient catalysis and inhibitor binding. Of particular interest is the catalytic triad, consisting of serine, histidine, and glutamate residues, that mediates hydrolysis. Another site influencing the catalytic process is located above the catalytic tnad toward the periphery of the active site gorge. This peripheral site (P-site) contains a number of aromatic amino acid residues as well as an aspartate residue that is able to interact with cationic substrates and guide them down the gorge to the catalytic triad. In human AChE, certain aryl residues in the vicinity of the anionic aspartate residue (D74), such as W286, have been implicated in ligand binding and have therefore been considered part of the P-site of the enzyme. The present study was undertaken to explore the P-site of human BuChE and determine whether, like AChE, aromatic side chains near the peripheral aspartate (D70) of this enzyme contribute to ligand binding. Results obtained, utilizing inhibitor competition studies and BuChE mutant species, indicate the participation of aryl residues (F329 and Y332) in the E-helix component of the BuChE active site gorge, along with the anionic aspartate residue (D70), in binding ligands to the P-site of the enzyme. [ABSTRACT FROM AUTHOR]

Purpose: To describe the phenotype and genotype of patients with autosomal recessive bestrophinopathy. Methodology: The phenotype of the subjects was described after a complete ophthalmological examination, and in various cases, ancillary testing of the visual field, optical coherent tomography, full field electroretinography and electrophysiology. Genetic analysis was carried out by screening the Bestrophin-1 ( BEST1) gene for mutations by dideoxy sequencing and segregation analysis. Results: We identified three previously described mutations (Ala195Val, Leu191Pro and Arg141His) and two potentially pathogenic changes (Trp93Pro and Trp287Ter) in the Best-1 gene. Two patients carried compound heterozygous mutations, Trp93Pro/Ala195Val, and Leu191Pro/Trp287Ter. Two sisters were homozygous for an Arg141His mutation. All individuals with Best1 gene mutations had signs of maculopathy. Conclusions: Our observations expand the limited number of phenotypes associated with mutations in the Best1 gene. Patients with compound heteroyzygous Best1 mutations developed atypical forms of Best disease. Two siblings with homozygous Arg141His mutation developed symptoms of typical Best vitelliform dystrophy while their parents had clinical features of mild maculopathy. [ABSTRACT FROM AUTHOR]

This paper points to spatial foundations of trade union power in a re-urbanizing economy. Globalization has not simply undermined the power of organized labour, but, in addition, has shifted the opportunities of it exercising power to the urban level. Thus we may be seeing the emergence of a new geography of working class organization in which industrial sectors of the labour movement have been disorganized by capital and the state while other sectors have retained structural power due to the importance of union members' labour to the urban process. This is particularly the case in 'global cities' where centralization of capital and agglomeration of functions remains a necessity for capital and where competitive city building entails re-direction of capital investment in the 'fixed environment for production' (Harvey, 1985). Developed abstractly, the argument is made concrete in a discussion of transit planning and transit strikes in New York (2005) and Toronto (2008). The paper concludes on a strategic register with an argument for an urbanization of trade union consciousness. [ABSTRACT FROM AUTHOR]

Wine is a highly differentiated experience good with limited availability of information about its true quality until the time of consumption. As a consequence, buyers must use proxies of a wine's value to make the best possible purchase decisions. This paper uses hedonic price analysis to generate implicit prices for a sensory quality rating as well as regional reputation for three varieties of premium New Zealand wine. Results suggest that a favourable evaluation for a wine is associated with a significant price premium for the three wine varieties included in this analysis. The increasing magnitude of the quality-rating coefficient for pinot noir and chardonnay provides evidence that the quality price premium for these two varieties has been growing over time. Regional reputation appears to have the most influence among chardonnays, a result that is not surprising given the distinct regional variation associated with this variety in New Zealand. Interestingly, the quality-rating premium is smaller in magnitude and the regional reputation effects are less significant for sauvignon blanc. Our results are consistent with the hypothesis that ‘local knowledge’ may have much less influence over price for a variety that is predominately sold in the export market. [ABSTRACT FROM PUBLISHER]

Objective: To determine haemodynamic effects of inflation of a blood pressure cuff on right forearm of healthy, non-smoking, white European and Pakistani males and to identify ethnic differences in response. Methodology: Twenty healthy white Europeans (WEU) and Pakistanis (PAK) were studied twice. During the experiment, volunteer rested in bed with a Finometer's finger cuff attached around middle phalanx of left hand's middle finger and brachial arterial cuff around ipsilateral upper arm, another cuff was placed around middle part of contralateral forearm. Following baseline recording for 15 min, right arm cuff inflated to 50 mmHg above systolic BP for 5 min, while recordings continued throughout this period and for 15 min thereafter, non-invasively. Results: Lower baseline cardiac output (5.8 vs 6.5 l/min; P=0.04; (PAK)) and higher stroke volume (102 vs 96 ml; P=0.04; WEU)) were noted in afternoon compared to the morning. WEU had higher SV (102 ml) than PAK (90 ml) (P=0.03) in afternoon. During morning experiments, inflation of occlusion cuff resulted in 5% increase in TPR (0.054 units; P<0.001) and 2% decrease in SV (3 ml; P<0.01) from the baseline in PAK; WEU had an increase in DBP (2 mmHg; 3%; P<0.001) MAP (3 mmHg; 3%; P<0.001) and TPR (0.063 units; 3%; P<0.001). Increases in DBP (2 mmHg; 3%; P<0.001) MAP (2 mmHg; 2%; P<0.001) (both groups) and TPR 0.046 units (4%; P<0.001(WEU)); (0.041 units; 3%; P<0.01 (PAK)) and decreases in CI (283ml; 4%; P<0.001(WEU)) and SV (2.2ml; 2%; P< 0.001(WEU);2.6 ml; 2%;P<0.001 (PAK)) during occlusion were noted in the afternoon. Conclusion: There is no difference in baseline BP, CO, HR and TPR of WEU and PAK except for higher WEU SV in the afternoon. Inflation of the forearm occlusion cuff resulted in significant increase in BP, TPR and decrease in SV in both groups. Time of the day had no effect. [ABSTRACT FROM AUTHOR]

Abstract: Synthetic Aperture Radar (SAR) images obtained from satellites are a reliable tool for localizing natural hydrocarbon seeps. For this study, we used the Texture Classifier Neural Network Algorithm (TCNNA) to interpret SAR data from the RADARSAT satellite and a geostatistical clustering analysis to compare seeps detected in 579 SAR images covering the northern Gulf of Mexico (GOM). Geostatistical analysis results indicate that, in a typical active seep formation, oil vents would be found within a seep formation ∼2.5km in diameter. Repeated observations of slicks at a given seep formation indicate that advection of rising oil in the water column causes an offset from the vent depending on water depth. At 500m, the radial offset is up to 1400m; at 2000m, it is up to 3270m. Observations with submersibles showed that, in 100% of the cases, the calculated seep formations that are matched with active oil seeps correspond to anomalies interpreted from surface amplitude maps and migration pathways in the seismic data. However, episodically, larger releases from persistent seeps occurred, and also some other seep formations showed intermittent releases. Our analysis indicates that active oil seeps detected with SAR represent a subset of the total array of geophysical features generated by hydrocarbon migration on the northern continental slope of the Gulf of Mexico. [ABSTRACT FROM AUTHOR]

Abstract: The benthic component of an interdisciplinary expedition on icebreaker USCG HEALY analyzed box core samples and seafloor photographs to quantify deep-sea assemblages in the Canada Basin and Chukchi Borderland area. Soft bottom metazoan macrofauna (>250μm) were collected with 33 box cores at 11 stations ranging from 817 to 3961m water depth in the high-Arctic Canada Basin from 28 June to 25 July 2005. Megabenthic epifauna was quantified with a digital camera platform suspended <5m above the bottom at six stations (940–3800m water depth), of which the shallowest and northernmost one targeted a pockmark ∼40m deep by 800m wide. A total of 99 macrofauna taxa were identified, including at least three previously undescribed species of polychaetes. Total macrofauna abundance ranged from 0.6 to 50 individuals 0.06m−2 (89–2722indm−2) and total biomass ranged from 0.2 to 1.6g wet weight 0.06m−2 (<0.1–26.1gwetweightm−2). Macrofauna diversity numbered between 8 and 55 taxa per station. Abundance, biomass, number of taxa, and diversity indices of macrofauna declined significantly with water depth. Polychaetes, crustaceans and bivalves dominated the macrofaunal densities, biomass and species numbers. The megafauna visible in the seabed photographs was assigned to a total of 67 provisional taxa; the lowest taxon count per station was 11, and the highest was 51 at the pockmark station. Epifauna abundance was also highest in this pockmark (mean 5.8indm−2) and generally lower at deepest stations (0.1–0.9indm−2), but was skewed by large numbers of the holothuroid Kolga hyalina. Epifauna observed in the center of the pockmark was significantly different from all other station groups, but did not include known chemosynthetic fauna or bacterial mats. Multivariate analysis indicated that station groupings “Chukchi slope”, “Canada Basin abyss” and the “Chukchi Cap” were significantly different in community composition in the macrofauna box corer samples, but could not be similarly distinguished as such in the epifauna photographs. [Copyright &y& Elsevier]

Abstract: Histopathology of young individuals affected by choroideremia is rarely available to allow correlation with the clinical presentation. A 30-year-old man with choroideremia died in a motor vehicle accident and one eye was subjected to histopathological examination. Immunoblot analysis of protein derived from white blood cells of a living brother, also affected with choroideremia, confirmed the absence of Rab escort protein-1, the normal CHM gene product. Direct sequencing of the coding region and adjacent splice sites of the CHM gene was undertaken on genomic DNA from the living brother and revealed a transition mutation, C to T, in exon 6 (R253X) which resulted in a stop codon and was predicted to truncate the protein product. Histopathological examination of the eye of the deceased brother showed relative independent degeneration of choriocapillaris, retinal pigment epithelium, and retina, similar to observations in the mouse model of choroideremia. In addition, mild T-lymphocytic infiltration was found within the choroid. The ophthalmic features and the pathology of choroideremia are discussed in light of new findings in the current case. [Copyright &y& Elsevier]