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Compelling evidence from around the world suggests that ethnic diversity is detrimental to neighborhood trust and cohesion. Much of this evidence derives from empirical associations found with static indicators of diversity, measuring the mix of ethnic groups at a single point in time, and controlling for a varied mix of individual and community‐level covariates. Less attention though has sought to understand how dynamic processes of migration and residential settlement both create diversity and influence trust and cohesion. In this study, census and survey data are used to analyze the demographic and economic characteristics and dynamics coinciding with diversity in local communities in Australia, and the implications for neighborhood trust and cohesion. Diverse communities are heavily concentrated in moderately and highly disadvantaged communities in large immigrant gateway cities. Highly diverse communities experience continual high levels of immigration and population turnover and contain young age structures and more diverse and transient housing and household structures. Survey analyses reveal that these characteristics substantially explain observed negative associations between diversity and neighborhood trust and cohesion. The results point to the near‐intractable difficulties in isolating the effects of diversity and the importance of understanding the dynamic demographic processes in the construction of neighborhood diversity, trust, and cohesion. [ABSTRACT FROM AUTHOR]

This article presents a multistate demographic approach for analyzing the longitudinal dynamics of housing and homelessness. The approach is applied to a sample of highly disadvantaged individuals in Australia to assess whether private housing markets and interpersonal support networks provide stable housing trajectories vis-à-vis public and community (social) housing. Discretetime competing risk survival models are specified to estimate the probabilities of exiting housing to six housing and homeless states. Model outputs are applied to a microsimulation model to estimate the duration of episodes and the cumulative incidence of subsequent episodes of housing and homelessness. The results suggest that private housing markets carry an increased risk of housing exit relative to social housing. The homes of family and friends are the most common destination, though this type of support is usually time limited and often precipitates episodes of homelessness. These findings warrant policy consideration as to how housing markets can provide better affordability and security for low income households. [ABSTRACT FROM AUTHOR]

Post-mortem studies have highlighted EC swelling, disruption of EC intercellular junctions, loss of EC contact with the basement membrane and significant EC apoptosis [[4]-[7]]. The net effect of this dysregulated immunothrombosis is the generation of platelet- and fibrin-rich thrombi and pulmonary vaso-occlusion In addition to this endotheliopathy, studies have shown that severe COVID-19 is associated with multifactorial platelet activation (Fig. Megakaryocytes and platelet-fibrin thrombi characterize multi-organ thrombosis at autopsy in COVID-19: A case series. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for coronavirus disease 2019 (COVID-19). [Extracted from the article]

The biological mechanisms involved in the pathogenesis of type 2 and type 3 von Willebrand disease (VWD) have been studied extensively. In contrast, although accounting for the majority of VWD cases, the pathobiology underlying partial quantitative VWD has remained somewhat elusive. However, important insights have been attained following several recent cohort studies that have investigated mechanisms in patients with type 1 VWD and low von Willebrand factor (VWF), respectively. These studies have demonstrated that reduced plasma VWF levels may result from either (1) decreased VWF biosynthesis and/or secretion in endothelial cells and (2) pathological increased VWF clearance. In addition, it has become clear that some patients with only mild to moderate reductions in plasma VWF levels in the 30 to 50 IU/dL range may have significant bleeding phenotypes. Importantly in these low VWF patients, bleeding risk fails to correlate with plasma VWF levels and inheritance is typically independent of the VWF gene. Although plasma VWF levels may increase to > 50 IU/dL with progressive aging or pregnancy in these subjects, emerging data suggest that this apparent normalization in VWF levels does not necessarily equate to a complete correction in bleeding phenotype in patients with partial quantitative VWD. In this review, these recent advances in our understanding of quantitative VWD pathogenesis are discussed. Furthermore, the translational implications of these emerging findings are considered, particularly with respect to designing personalized treatment plans for VWD patients undergoing elective procedures. [ABSTRACT FROM AUTHOR]

Biodiversity loss is a hallmark of our times, but predicting its consequences is challenging. Ecological interactions form complex networks with multiple direct and indirect paths through which the impacts of an extinction may propagate. Here we show that accounting for these multiple paths connecting species is necessary to predict how extinctions affect the integrity of ecological networks. Using an approach initially developed for the study of information flow, we estimate indirect effects in plant–pollinator networks and find that even those species with several direct interactions may have much of their influence over others through long indirect paths. Next, we perform extinction simulations in those networks and show that although traditional connectivity metrics fail in the prediction of coextinction patterns, accounting for indirect interaction paths allows predicting species' vulnerability to the cascading effects of an extinction event. Embracing the structural complexity of ecological systems contributes towards a more predictive ecology, which is of paramount importance amid the current biodiversity crisis. [ABSTRACT FROM AUTHOR]

Summary: Blood clot formation to stem bleeding from an injured blood vessel arises from a complex series of cellular and biochemical events, which, when dysregulated, predispose to an increased risk of thrombosis or bleeding. Similarly, haemostatic regulation of clot growth and size is exquisitely controlled by a series of anticoagulant 'checkpoints', that exert their inhibitory activity at distinct stages in the steps leading to clot formation. Although the major plasma protein constituents required for haemostasis have now been largely elucidated and the molecular events that lead to clot formation are well understood, defining a fuller appreciation of the importance, location and regulation of each haemostatic process remains a fertile area of ongoing research. In this review article, we first provide an overview of the original 'waterfall' or 'cascade' hypothesis of blood coagulation as it was defined in the 1960s. We subsequently discuss how this original model has been refined over time to incorporate accumulating data that has enabled a more nuanced consideration of the role of specific proteins, receptors and lipids in dictating the spatial and temporal development of a blood clot. [ABSTRACT FROM AUTHOR]

At the outbreak of the Second World War, Northern Ireland, as part of the United Kingdom, was committed to war. The independent Irish state, on the other hand, declared neutrality and introduced a particularly vigorous censorship regime designed to ensure that no comment or opinion emanating from its press could possibly be interpreted as contradictory to the state's neutrality. Historically Irish newspapers had largely relied on common, syndicated news agency material to report international events. Now, for the first time, they operated under two state-backed regimes with markedly different aims for presentation and comment on war news. This article reveals how the differing state-controlled mechanisms operating in Ireland affected the presentation and interpretation of news from common sources, particularly concentrating on the London-based Press Association, of the Dunkirk evacuation in 1940 and the Allied landings on D-Day in 1944. [ABSTRACT FROM AUTHOR]

According to the American Library Association, there are 119,000 libraries in the United States. But how many do we need? In this vision session report, Arizona State University Librarian James J. O’Donnell addresses this question through the lenses of discovery tools, usability, and marketing strategy. He also addresses the need for a more global and collaborative approach to collection building in libraries. This deliberately provocative talk provides several different ways to think about the answer to the title question—and several answers. [ABSTRACT FROM PUBLISHER]

The article presents the analysis of California Supreme Court case California Building Industry Association v. City of San Jose which deals with affordable housing ordinance. Topics discussed include U.S. Supreme Court case Koontz v. St. Johns River Water Management District on same; California Supreme Court's holding in light of Supreme Court precedent specifically in in Koontz; and analysis of implications of Koontz on land use planning.

The cardiovascular system is affected by a wide range of pathological processes, including neoplastic, inflammatory, ischemic, and congenital aetiology. Magnetic resonance imaging (MRI) and positron emission tomography (PET) are state-of-the-art imaging modalities used in the evaluation of these cardiovascular disorders. MRI has good spatial and temporal resolutions, tissue characterization and multi-planar imaging/reconstruction capabilities, which makes it useful in the evaluation of cardiac morphology, ventricular and valvar function, disease characterization, and evaluation of myocardial viability. FDG-PET provides valuable information on the metabolic activity of the cardiovascular diseases, including ischemia, inflammation, and neoplasm. MRI and FDG-PET can provide complementary information on the evaluation of several cardiovascular disorders. For example, in cardiac masses, FDG-PET provides the metabolic information for indeterminate cardiac masses. MRI can be used for localizing and characterizing abnormal hypermetabolic foci identified incidentally on PET scan and also for local staging. A recent advance in imaging technology has been the development of integrated PET/MRI systems that utilize the advantages of PET and MRI in a single examination. The goal of this manuscript is to provide a comprehensive review on the incremental value of PET and MRI in the evaluation of cardiovascular diseases. Main Messages: • MRI has good spatial and temporal resolutions, tissue characterization, and multi-planar reconstruction • FDG-PET provides valuable information on the metabolic activity of cardiovascular disorders • PET and MRI provide complementary information on the evaluation of cardiovascular disorders [ABSTRACT FROM AUTHOR]

In this issue of Blood, Kho et al provide further evidence that platelets play a major role in the pathogenesis of malaria infection. In particular, they demonstrate that platelets can kill circulating parasites of all major Plasmodium species in human malaria. Elucidating the molecular mechanisms underpinning this platelet-directed killing mechanism may offer the opportunity to develop novel adjunctive antimalarial therapies. [ABSTRACT FROM AUTHOR]

Massively parallel sequencing is rapidly emerging as an efficient way to quantify biodiversity at all levels, from genetic variation and expression to ecological community assemblage. However, the number of reads produced per sequencing run far exceeds the number required per sample for many applications, compelling researchers to sequence multiple samples per run in order to maximize efficiency. For studies that include a PCR step, this can be accomplished using primers that include an index sequence allowing sample origin to be determined after sequencing. The use of indexed primers assumes they behave no differently than standard primers; however, we found that indexed primers cause substantial template sequence-specific bias, resulting in radically different profiles of the same environmental sample. Likely the outcome of differential amplification efficiency due to primer-template mismatch, two indexed primer sets spuriously change the inferred sequence abundance from the same DNA extraction by up to 77.1%. We demonstrate that a double PCR approach alleviates these effects in applications where indexed primers are necessary. [ABSTRACT FROM AUTHOR]

Preserving biodiversity is a global challenge requiring data on species' distribution and abundance over large geographic and temporal scales. However, traditional methods to survey mobile species' distribution and abundance in marine environments are often inefficient, environmentally destructive, or resource-intensive. Metabarcoding of environmental DNA ( eDNA) offers a new means to assess biodiversity and on much larger scales, but adoption of this approach for surveying whole animal communities in large, dynamic aquatic systems has been slowed by significant unknowns surrounding error rates of detection and relevant spatial resolution of eDNA surveys. Here, we report the results of a 2.5 km eDNA transect surveying the vertebrate fauna present along a gradation of diverse marine habitats associated with a kelp forest ecosystem. Using PCR primers that target the mitochondrial 12S rRNA gene of marine fishes and mammals, we generated eDNA sequence data and compared it to simultaneous visual dive surveys. We find spatial concordance between individual species' eDNA and visual survey trends, and that eDNA is able to distinguish vertebrate community assemblages from habitats separated by as little as ~60 m. eDNA reliably detected vertebrates with low false-negative error rates (1/12 taxa) when compared to the surveys, and revealed cryptic species known to occupy the habitats but overlooked by visual methods. This study also presents an explicit accounting of false negatives and positives in metabarcoding data, which illustrate the influence of gene marker selection, replication, contamination, biases impacting eDNA count data and ecology of target species on eDNA detection rates in an open ecosystem. [ABSTRACT FROM AUTHOR]

Building related data tends to be generated, used and retained in a domain-specific manner. The lack of interoperability between data domains in the architecture, engineering and construction (AEC) industry inhibits the cross-domain use of data at an enterprise level. Semantic web technologies provide a possible solution to some of the noted interoperability issues. Traditional methods of information capture fail to take into account the wealth of soft information available throughout a building. Several sources of information are not included in performance assessment frameworks, including social media, occupant communication, mobile communication devices, occupancy patterns, human resource allocations and financial information. The paper suggests that improved data interoperability can aid the integration of untapped silos of information into existing structured performance measurement frameworks, leading to greater awareness of stakeholder concerns and building performance. An initial study of how building-related data can be published following semantic web principles and integrated with other ‘soft-data’ sources in a cross-domain manner is presented. The paper goes on to illustrate how data sources from outside the building operation domain can be used to supplement existing sources. Future work will include the creation of a semantic web based performance framework platform for building performance optimisation. [ABSTRACT FROM AUTHOR]

The effect of COVID-19 lockdowns on mental health is a major concern worldwide. Measuring the impacts, however, is difficult because of a lack of data that tracks and compares outcomes and potential protective social factors before and during lockdowns. We aim to quantify the impact of a second lockdown in 2020 in the Australian city of Melbourne on levels of depression, anxiety, and loneliness, and analyse whether social relations in the neighbourhood may buffer against the worst effects of lockdown. We draw on quasi-experimental data from a nationally-representative longitudinal survey conducted in Australia. We use a difference-in-difference approach with a number of control variables to estimate changes in mental health among respondents in Melbourne following the imposition of the lockdown. A measure of perceived neighbourhood social relations is included as an explanatory variable to analyse potential protective effects. Lockdown is estimated to have increased depressive symptoms by approximately 23% and feelings of loneliness by 4%. No effect on anxiety was detected. Levels of neighbourhood social relations were strongly negatively associated with mental health symptoms. A significant interaction between lockdown and neighbourhood social relations suggests that lockdown increased depressive symptoms by 21% for people with average perceived neighbourhood relations, compared with a 9.7% increase for people whose perceived relations is one standard deviation greater than average. The results add to evidence of the harsh impacts of the COVID-19 pandemic and associated lockdowns on mental health. Importantly, neighbourhood social relations and social cohesion more broadly may be an important source of social support in response to lockdowns. These findings provide important insights for researchers and policy-makers in how to understand and respond to the mental health impacts of COVID-19. • A lockdown in Melbourne, Australia in 2020 increased depressive symptoms. • Neighbourhood social relations are negatively associated with mental health. • Neighbourhoods may have had a protective effect on depression during lockdown. • The findings highlight the potential benefit of social and community investment. [ABSTRACT FROM AUTHOR]

Introduction: Synovitis, a common feature in haemophilia, is triggered by the presence of blood in joints, and represents the first step towards the development of chronic arthropathy. Synovitis may be detected early by means of ultrasound or magnetic resonance imaging scan; clinical joint scores are less sensitive in this setting. Regular long‐term prophylaxis with clotting factor concentrates, as primary prophylaxis and tailored to individual needs, has high efficacy in preventing synovitis. In general, higher factor levels lower bleeding risk, but no direct correlation between factor levels and synovitis incidence has been demonstrated. Aim: This study aimed to develop an expert consensus relating to the definition, pathophysiology, diagnosis, prevention, follow‐up and treatment of synovitis, recognising its relevance for joint health and taking into account existing knowledge gaps. Methods: A Delphi consensus study was designed and performed. An expert group prepared 22 statements based on existing literature; a wider expert panel subsequently voted on these. Results: Retention of panellists was high. Four statements required amending and consensus on all statements was achieved after three rounds of voting. Conclusion: This e‐Delphi consensus study addressed the importance of synovitis in joint health of people with haemophilia and highlighted knowledge gaps in this field. Studies on the natural course of synovitis are lacking and the biological mechanisms underlying this process are not yet fully elucidated. While basic and clinical research proceeds in this field, expert consensus can help guide clinicians in their routine clinical practice, and Delphi methodology is often used to produce best‐practice guidelines. [ABSTRACT FROM AUTHOR]

In this issue of Blood, Jäckel et al define an unexpected role for the microbiome in regulating murine plasma von Willebrand factor (VWF) levels. In particular, commensal gut microbiota are shown to regulate VWF synthesis in liver sinusoidal endothelial cells through a Toll-like receptor-2 (TLR2)--dependent pathway. Collectively, these novel findings provide important insights into the biological mechanisms through which commensal microbiota may modulate cardiovascular pathology. [ABSTRACT FROM AUTHOR]

The selective Aurora-A kinase inhibitor MLN8237 is in clinical trials for hematologic malignancies, ovarian cancer and other solid tumors. We previously showed that MLN8237 is potently antiproliferative toward standard monolayer-cultured glioblastoma cells. We have now investigated the effect of MLN8237 with and without temozolomide or ionizing radiation on the proliferation of glioblastoma tumor stem-like cells (neurospheres) using soft agar colony formation assays and normal human astrocytes by MTT assay. Western blotting was utilized to compare MLN8237 ICs to cellular Aurora-A and phosphoThrAurora-A levels. MLN8237 was more potently antiproliferative to neurosphere cells than to standard monolayer glioma cells, and was non-toxic to normal human astrocytes. Western blot analysis revealed that MLN8237 treatment inhibits phosphoThrAurora-A levels providing proof of drug target-hit in glioblastoma cells. Furthermore, phosphoThrAurora-A levels partially predicted the antiproliferative efficacy of MLN8237. We also found that Aurora-A inhibition by MLN8237 was synergistic with temozolomide and potentiated the effects of ionizing radiation on colony formation in neurosphere glioblastoma tumor stem-like cells. These results further support the potential of Aurora-A inhibitors as primary chemotherapy agents or biologic response modifiers in glioblastoma patients. [ABSTRACT FROM AUTHOR]

Abstract: Building managers have specific duties and certain outputs that are required of them. Without the necessary data, information, tools, and time, they are unable to adequately meet their organisational goals. Scenario modelling enables explicit and unambiguous coupling of building functions with other pivotal aspects of building operation in a method that specifically considers the education and technical expertise of building managers. This new method captures, transforms, and communicates the complex interdependencies of environmental and energy management in buildings through an easily navigable, holistic, and reproducible checking mechanism that compares actual performance with predicted performance and completes the “plan-do-check-act” cycle for building managers. Most important, the structured nature of this method caters to the diverse profile of building managers, making it applicable for widespread deployment. This paper demonstrates the benefit of using the new method by examining its application to a performance analysis of two existing buildings. [Copyright &y& Elsevier]

Abstract: Within the operational phase buildings are now producing more data than ever before, from energy usage, utility information, occupancy patterns, weather data, etc. In order to manage a building holistically it is important to use knowledge from across these information sources. However, many barriers exist to their interoperability and there is little interaction between these islands of information. As part of moving building data to the cloud there is a critical need to reflect on the design of cloud-based data services and how they are designed from an interoperability perspective. If new cloud data services are designed in the same manner as traditional building management systems they will suffer from the data interoperability problems. Linked data technology leverages the existing open protocols and W3C standards of the Web architecture for sharing structured data on the web. In this paper we propose the use of linked data as an enabling technology for cloud-based building data services. The objective of linking building data in the cloud is to create an integrated well-connected graph of relevant information for managing a building. This paper describes the fundamentals of the approach and demonstrates the concept within a Small Medium sized Enterprise (SME) with an owner-occupied office building. [Copyright &y& Elsevier]

The article discusses both print and electronic book versions available for the works of Roman philosopher and political theorist Marcus Tullius Cicero. Texts by Cicero were traditionally used for two purposes, for the study of Latin language and culture, and by more experienced scholars in fields such as rhetoric and political philosophy. A discussion of the history of printed works of Cicero from the nineteenth-century to the present, including topics such as the digitalization of books by Project Gutenberg, Amazon.com, and how Portable Document Format (PDF) files changed the effectiveness of reading electronic books, is presented.

Increasing evidence links blood coagulation proteins with the regulation of acute and chronic inflammatory disease. Of particular interest are vitamin K-dependent proteases, which are generated as a hemostatic response to vascular injury, but can also initiate signal transduction via interactions with vascular receptors. The endothelial cell protein C receptor (EPCR) is a multi-ligand vitamin K-dependent protein receptor for zymogen and activated forms of plasma protein C and factor VII. Although the physiological role of the EPCR-FVII(a) interaction is not well-understood, protein C binding to EPCR facilitates rapid generation of APC in response to excessive thrombin generation, and is a central requirement for the multiple signal-transduction cascades initiated by APC on both vascular endothelial and innate immune cells. Exciting recent studies have highlighted the emerging role of EPCR in modulating the cytoprotective properties of APC in a number of diverse inflammatory disorders. In this review, we describe the structure-function relationships, signal transduction pathways, and cellular interactions that enable EPCR to modulate the anticoagulant and anti-inflammatory properties of its vitamin K-dependent protein ligands, and examine the relevance of EPCR to both thrombotic and inflammation-associated disease. [ABSTRACT FROM AUTHOR]

Anticoagulants are powerful and unavoidably dangerous drugs that must be carefully selected, monitored, and evaluated. Every patient undergoing treatment is at risk of excess bleeding, since the primary purpose of this class of drugs is to decrease clotting through a variety of biochemical and pharmacological mechanisms. Under the best of circumstances, significant numbers of patients (∼10%) experience toxicity on traditional warfarin oral anticoagulants. Beyond the obvious type A pharmacological toxicity, heparin products carry a seemingly paradoxical/novel risk of increased coagulopathy with limb- and life-threatening thromboembolic injuries (heparin-induced thrombocytopenia [HIT]). As a result of the great toxicity risk, many patients suffer injuries, and litigation is threatened or initiated, frequently against pharmacists and their employers. This article reviews the therapeutic use of old and novel anticoagulants, lists the types of litigation related thereto, and discusses the HIT risk associated with heparin products treatment. Litigation can result from adverse drug reactions and toxicity from anticoagulants. [ABSTRACT FROM PUBLISHER]

Abstract: P120 catenin (p120ctn) is an adherens junction protein recognized to regulate barrier function, but emerging evidence indicates that p120ctn may also exert control on other cellular functions such as transcriptional suppression of genes. We investigated the hypothesis that loss of p120ctn in human endothelial cells activates transcription of pro-inflammatory adhesion molecules. For study, siRNA targeted to p120ctn was transfected into brain microvascular (HBMECs) or pulmonary artery endothelial cells (HPAECs) for 24–120h, which depleted 50–80% of endogenous p120ctn. This loss of p120ctn resulted in increased promoter reporter activity of transcription factors, NFκB, AP-1, and Kaiso, as well as of target genes, MMP-1 and ICAM-1. Real-time RT-PCR analysis indicated that the mRNA for ICAM-1, VCAM-1, and E- and P-selectins were all upregulated during the period of 24–120h of p120ctn depletion, although the time-course and extent of the expression profiles differed. The upregulated mRNA of adhesion molecules corresponded with increased PMN adhesion to the EC surface and elevated ICAM-1 protein expression. We further explored the role of ERK1/2 as a potential signaling mechanism responsible for regulation of transcriptional activities by p120ctn. Results indicated that loss of p120ctn increased phosphorylated ERK1/2, and a MEK1 inhibitor (PD98059) prevented NFκB nuclear translocation. This implicates ERK1/2 in signaling the NFκB activation induced by p120ctn loss. The findings provide strong evidence that deficiency in p120ctn expression in endothelial cells is a potent stimulus for transcriptional upregulation of multiple adhesion molecules. We conclude that p120ctn functions to suppress transcription, which is an important and novel regulation in vascular endothelium. [Copyright &y& Elsevier]

Activated protein C (APC) has potent anticoagulant and anti-inflammatory properties that limit clot formation, inhibit apoptosis, and protect vascular endothelial cell barrier integrity. In this study, the role of N-linked glycans in modulating APC endothelial cytoprotective signaling via endothelial cell protein C receptor/protease-activated receptor 1 (PAR1) was investigated. Enzymatic digestion of APC N-linked glycans (PNG-APC) decreased the APC concentration required to achieve half-maximal inhibition of thrombin-induced endothelial cell barrier permeability by 6-fold. Furthermore, PNG-APC exhibited increased protection against staurosporine-induced endothelial cell apoptosis when compared with untreated APC. To investigate the specific N-linked glycans responsible, recombinant APC variants were generated in which each N-linked glycan attachment site was eliminated. Of these, APC-N329Q was up to 5-fold more efficient in protecting endothelial barrier function when compared with wild type APC. Based on these findings, an APC variant (APC-L38D/N329Q) was generated with minimal anticoagulant activity, but 5-fold enhanced endothelial barrier protective function and 30-fold improved anti-apoptotic function when compared with wild type APC. These data highlight the previously unidentified role of APC N-linked glycosylation in modulating endothelial cell protein C receptor-dependent cytoprotective signaling via PAR1. Furthermore, our data suggest that plasma β-protein C, characterized by aberrant N-linked glycosylation at Asn-329, may be particularly important for maintenance of APC cytoprotective functions in vivo. [ABSTRACT FROM AUTHOR]

Stegastes nigricans, a "farmerfish" that cultivates algal turf and defends territories from grazers and other intruders, can affect coral indirectly due to increased competition with farmed algal turf and/or reduced predation resulting from territorial aggression directed at corallivores. To investigate the indirect effects of this key ecosystem engineer on coral mortality and growth, we transplanted caged and exposed fragments of four coral species to patch reefs in French Polynesia on which we manipulated the presence of S. nigricans and turf, and to reefs naturally devoid of S. nigricans. Reef access was two to four times higher for herbivorous fishes, and two times higher for corallivorous fishes, when S. nigricans was removed, indicating that reef access is reduced for two important guilds of fishes when S. nigricans is present. Stegastes' territoriality indirectly benefited delicate acroporids (Monriporafloweri and Acropora striatci), yielding a twofold to fivefold reduction in skeletal loss due to lower predation frequencies in the presence of S. nigricans. Three corals, A. striata, M. floweri, and especially Ponies ausiraliensis, suffered mortality due to overgrowth significantly more frequently in the presence of farmed turf, but Pocillopora verrucosa did not. Algal abundance predicted the frequency of overgrowth for only A. stniata and P. australiensis. M. floweri were more likely to be overgrown when exposed (uncaged) in the presence of S. nigricans, suggesting an interaction modification, in this case that initial predation increased susceptibility to competition with turf. In this community, the presence of S. nignicans may increase algal overgrowth of massive Ponies by facilitating its turf competitors and simultaneously reduce predation of branching corals through territorial exclusion of corallivores. These indirect interactions may underlie previously documented community transitions from disturbance-resistant massive coral to recovering branching corals within S. nigricans territories. [ABSTRACT FROM AUTHOR]

Abstract: P120 catenin (p120ctn) belongs to the family of Armadillo repeat-containing proteins, which are believed to have dual functions of cell-cell adhesion and transcriptional regulation. In vascular endothelium, p120ctn is mostly recognized for its cell-cell adhesion function through its ability to regulate VE-cadherin. The current study investigated whether p120ctn in endothelial cells also has the capability to signal transcription events. Examination of several endothelial cell types indicated that Kaiso, a p120ctn-binding transcription factor, was abundantly expressed, with a predominant localization to the perinuclear region. Immunoprecipitation of endothelial cell lysates with a p120ctn antibody resulted in p120ctn–Kaiso complex formation, confirming the interactions of the two proteins. Transfection of the KBS (Kaiso-binding sequence) luciferase reporter plasmid into endothelial cells resulted in a 40% lower reporter activity compared to the mutant Kaiso-insensitive construct or empty vector pGL3, indicating that the suppressed reporter activity was attributed to endogenous Kaiso. The knock-down of p120ctn increased the KBS reporter activity 2-fold over control, but had no effects on the mutant KBS reporter activity. Furthermore, p120ctn knock-down also reduced Kaiso expression, suggesting that p120ctn functioned to stabilize Kaiso. Overall, the findings provide evidence that in endothelial cells, p120ctn has a transcription repression function through regulation of Kaiso, possibly as a cofactor with the transcription factor. [ABSTRACT FROM AUTHOR]

Background: Electronic clinical decision support (CDS) is increasingly establishing its role in evidence-based clinical practice. Considerable evidence supports its enhancement of efficiency in e-Prescribing, but some controversy remains. This study evaluated the practicality and identified the perceived benefits of, and barriers to, its future adoption in the West of Ireland. Methods: This cross sectional study was carried out by means of a 27-part questionnaire sent to 262 registered general practitioners in Counties Galway, Mayo and Roscommon. The survey domains encompassed general information of individual's practice, current use of CDS and the practitioner's attitudes towards adoption of CDS-eP. Descriptive and inferential analyses were performed to analyse the data collected. Results: The overall response rate was 37%. Nearly 92% of respondents employed electronic medical records in their practice. The majority acknowledged the value of electronic CDS in improving prescribing quality (71%) and reducing prescribing errors (84%). Despite a high degree of unfamiliarity (73%), the practitioners were open to the use of CDS-eP (94%) and willing to invest greater resources for its implementation (62%). Lack of a strategic implementation plan (78%) is the main perceived barrier to the incorporation of CDS-eP into clinical practice, followed by i) lack of financial incentives (70%), ii) lack of standardized product software (61%), iii) high sensitivity of drug-drug interaction or medication allergy markers (46%), iv) concern about overriding physicians' prescribing decisions(44%) and v) lack of convincing evidence on the systems' effectiveness (22%). Conclusions: Despite favourable attitudes towards the adoption of CDS-eP, multiple perceived barriers impede its incorporation into clinical practice. These merit further exploration, taking into consideration the structure of the Irish primary health care system, before CDS-eP can be recommended for routine clinical use in the West of Ireland. [ABSTRACT FROM AUTHOR]

Abstract: We present an approach that allows the estimation of vertical eddy diffusivity coefficients from buoy measurements made at two or more depths. By measuring the attenuation and phase lag of a scalar signal generated periodically at the surface as it propagates downwards, the vertical eddy diffusivity coefficients can be calculated as K v = ωΔz 2/2ln2(α2/α1), where α2/α1 is the ratio of the real amplitudes at frequency ω at the two depths separated by Δz = z 2 − z 1; as K V = ωΔz 2/2φ 2, where φ is the phase lag at the frequency ω; or as K v = iωΔz 2/ln2(U 2/U 1), where U 2/U 1 is the ratio of the complex signal amplitudes at the two depths. The method requires that horizontal fluxes be small at the ω frequency and that the signal-to-noise ratios at the two depths allow the determination of the amplitude and phase of ω. Application of this method to summertime 2004 western Long Island Sound oxygen and temperature buoy measurements at two depths provides a time-series of two-day average vertical eddy diffusivity estimates. Using these eddy diffusivities in conjunction with measured vertical concentration gradients, we obtain a time-series of vertical transport rates for oxygen and heat and estimate mean downward fluxes for June and July as 150–260 mMol m−2 day−1 and 100–400 W m−2 respectively. These estimates are of a similar magnitude to sub-pycnocline O2 and heat demands of 240±200 mMol m−2 day−1 and 180±60 W m−2 that we infer from simple budgets, implying that vertical transport is significant to both budgets. The eddy coefficients obtained from the independent O2 and temperature measurements have a 68% correlation, and the O2 flux estimates show a correlation of 41% to measured rates of change in bottom dissolved oxygen levels. Our results indicate that extended time-series of eddy diffusivity coefficients can be obtained from in situ buoy measurements and the method shows promise as a way to constrain the vertical transport variability in budgets of dissolved materials in estuaries. [Copyright &y& Elsevier]

The article discusses the consumption and production of information in the academic discipline of the humanities. The author reflects on the role of electronic and digital media in humanities research. Other topics include humanistic education, distribution of materials, and scholarly performance.

The article offers information on a study which found that lobular neoplasia (LN) on core needle biopsy does not require excision. The authors conducted ninety-one biopsies for calcifications and seven were performed for mass lesions. It concludes that excision of LN is not needed if careful radiographic-pathologic correlation is made and strict histologic criteria are followed when making the diagnosis.

For many years, an association between ABO histo-blood group and risk of thrombosis has been recognized. Blood group non-O (A, B, and AB) individuals have consistently been found to demonstrate increased incidence of both arterial and venous thrombotic disease, compared to group O individuals. This increased risk is attributable to the fact that ABO blood group influences plasma levels of a coagulation glycoprotein named von Willebrand factor (VWF). VWF levels are 25 percent higher in non-O compared to group O individuals. The mechanism by which ABO group determines plasma VWF levels has not been determined. ABO(H) carbohydrate antigenic determinants, however, are expressed on the N-linked glycan chains of circulating plasma VWF. This review will focus on the carbohydrate structures of VWF and recent studies suggesting that subtle variations in these structures (particularly differences in ABO blood group antigen expression) may have clinically significant effects on VWF proteolysis and clearance. [ABSTRACT FROM AUTHOR]

With an analytic model, this paper describes the subtidal circulation in tidally dominated channels of different lengths, with arbitrary lateral depth variations. The focus is on an important parameter associated with the reversal of the exchange flows. This parameter (δ) is defined as the ratio between the channel length and one-quarter of the tidal wavelength, which is determined by water depth and tidal frequency. In this study, a standard bottom drag coefficient, CD = 0.0025, is used. For a channel with δ smaller than 0.6–0.7 (short channels), the exchange flow at the open end has an inward transport in deep water and an outward transport in shallow water. This situation is just the opposite of channels with a δ value larger than 0.6–0.7 (long channels). For a channel with a δ value of about 0.35–0.5, the exchange flow at the open end reaches the maximum of a short channel. For a channel with a δ value of about 0.85–1.0, the exchange flow at the open end reaches the maximum of a long channel, with the inward flux of water occurring over the shoal area and the outward flow in the deep-water area. However, near the closed end of a long channel, the exchange flow appears as that in a short channel—that is, the exchange flow changes direction along the channel from the head to the open end of the channel. For a channel with a δ value of about 0.6–0.7, the tidally induced subtidal exchange flow at the open end reaches its minimum when there is little flow across the open end and the water residence time reaches its maximum. The mean sea level increases toward the closed end for all δ values. However, the spatial gradient of the mean sea level in a short channel is much smaller than that of a long channel. The differences between short and long channels are caused by a shift in dynamical balance of momentum or, equivalently, a change in tidal wave characteristics from a progressive wave to a standing wave. [ABSTRACT FROM AUTHOR]

Abstract: Behavior maintained under a differential-reinforcement-of-low-rate (DRL) 72-s operant schedule, which reinforces responses with interresponse times greater than 72s, exhibits a rather unique sensitivity to antidepressant drugs. Antidepressants from a number of pharmacological classes, including tricyclic antidepressants, selective serotonin or norepinephrine reuptake inhibitors, monoamine oxidase inhibitors, as well as a number of atypical antidepressants and putative antidepressants, reduce response rate and increase reinforcement rate of rats under this schedule. These effects are observed acutely but persist or are augmented with repeated treatment. By contrast, drugs from a number of other psychotherapeutic classes do not, in general, produce similar effects. This includes anxiolytic, sedative, stimulant, opioid, antihistaminic, and anticholinergic drugs, which can produce false positive results in some preclinical tests for antidepressant efficacy. There are conflicting data regarding the utility of DRL behavior for discriminating the effects of antidepressant and antipsychotic drugs. This results in part from methodological differences among studies, but likely also reflects the overlap between the neuropharmacological and clinical effects of some antipsychotic and antidepressant drugs. DRL behavior also has proven useful for identifying neurochemical and neuroanatomical mediators of antidepressant effects on behavior. Consistent with clinical data, it appears that activation of noradrenergic or serotonergic systems provides for parallel means of producing antidepressant-like effects on DRL behavior. Finally, the results of studies using DRL behavior highlight important roles for central beta-1 adrenergic receptors, as well as 5-HT1A, 5-HT1B, 5-HT2A, and 5-HT2C receptors, in the mediation of antidepressant-like behavioral effects. [Copyright &y& Elsevier]

Despite initial promise, the development of type 4 phosphodiesterase (PDE4) inhibitors as antidepressants has not advanced significantly. This is due to an incomplete understanding of the functional importance of PDE4 subtypes and high-affinity and low-affinity inhibitor-binding conformers. However, recent developments have rekindled interest in the therapeutic potential of PDE4 inhibitors. First, PDE4 has been shown to be involved in cAMP signaling pathways that are affected by antidepressants. Second, data obtained using mouse knockout lines indicate that PDE4D and PDE4B mediate antidepressant effects. Third, it appears that the interaction of inhibitors with the high-affinity binding conformer of PDE4 is particularly important for antidepressant efficacy. These developments highlight the difficulties of dissociating the actions of PDE4 inhibitors and provide a guide for future research. [Copyright &y& Elsevier]

Summary. ABO blood group determines plasma von Willebrand factor (VWF) levels and ABH antigens are present on VWF. To investigate whether ABO influences the rate of VWF synthesis, we performed stable transfection of A transferase in a phenotypically group-O endothelial cell line (EAhy926). A transferase expression did not affect the rate of VWF synthesis. Although high levels of A antigen were expressed on the cell surface, no A determinants were added to VWF synthesized within these cells. Further studies demonstrated H structures were not present on EAhy926-derived VWF, despite the fact that H antigen is constitutively expressed by these cells. [ABSTRACT FROM AUTHOR]

We describe the use of a commercially available telemetry and data acquisition system to record heart rate, body temperature and activity of freely behaving rats with transmitters that operate without batteries (transponders). The system uses PDT 4000HR E-Mitters (Mini Mitter, OR, USA) to acquire animal temperature, heart rate and motor activity data. E-Mitters obtain power from a radiofrequency field produced by an ER-4000 energizer/receiver so that transponders can collect data on heart rate, body temperature and gross motor activity. ER-4000 energizers/receivers are designed to be placed below the animals'' cage. Data output from receivers is managed by a Windows PC-based data acquisition system, VitalView™. In this study, we report that a good correlation exists between VitalView™ and Powerlab for the determination of heart rate and between intra-abdominal (telemetric) and colonic body temperature (rectal digital thermometer) in rats. Assessment of this system by using agents that have well-documented effects on heart rate, body temperature and locomotor activity have also been determined. An additional feature of VitalView™ is the incorporation of behavioural inputs (feeding monitors to monitor duration and frequency of feeding and a lickometer to monitor drinking bouts) into the data acquisition system designed primarily to acquire data from the implanted transponders. Circadian rhythms for all parameters were established in rats with E-Mitters implanted. VitalView™ may be used for the determination of multiple parameters in freely behaving animals using transponders, which operate without batteries. This capability is unique in its field and represents a recent advance in biotelemetric monitoring of laboratory animals. [Copyright &y& Elsevier]

Summary. Previous reports on the effect of Secretor and Lewis blood groups on plasma factor VIII–von Willebrand factor (FVIII–VWF) levels have produced conflicting findings. To determine whether either or both loci can influence plasma FVIII–VWF complex levels, we studied the relationship between Secretor and Lewis genotypes, determined definitively using polymerase chain reaction–restriction fragment length polymorphism analysis, and plasma FVIII coagulant activity (FVIII:C) and VWF antigen (VWF:Ag) levels in 136 healthy volunteers. Overall, significantly higher VWF:Ag levels were found in those individuals homozygous for the Se allele (genotype SeSe ) than in those heterozygous for the Se allele (P < 0·001). To minimize any confounding influence of ABO genotype/phenotype, we investigated the relationship between Secretor genotype and plasma FVIII–VWF levels within individuals of the same ABO blood group genotype. In the subgroup analysis of group O 1 O 1 individuals alone, VWF:Ag levels were again significantly higher in those individuals with Secretor genotype SeSe than in those either heterozygous or homozygous for the se null allele. Among A 1 O 1 subjects, homozygous Secretor s also had significantly higher VWF:Ag levels. In contrast, we found no relationship between Lewis genotype and either VWF:Ag or FVIII:C levels. This study is the first based on genotypic rather than serological analysis, and resolves the previously confounding effects of the Lewis and Secretor loci on plasma FVIII–VWF complex levels. [ABSTRACT FROM AUTHOR]

Elevated plasma factor VIII coagulant activity (FVIII:C, > 150 IU/dl) is a risk factor for venous thromboembolism (VTE). We hypothesized that increased FVIII:C may exert a prothrombotic effect by increasing basal thrombin generation. To test this hypothesis we have measured prothrombin fragment 1 + 2 (F1 + 2) and thrombin–antithrombin complex (TAT) in three groups: (i) patients with objectively confirmed VTE and elevated FVIII:C; (ii) patients with VTE and no detectable thrombophilia; and (iii) healthy age- and sex-matched control subjets. In the group of patients with elevated FVIII:C, TAT and F1 + 2 levels were increased in 85% and 78% of individuals respectively. This frequency of coagulation activation is dramatically higher than that reported for other recognized constitutional thrombophilias. In the group of patients with VTE but no proven thrombophilia, increased thrombin generation was present in 30% of individuals. Basal thrombin generation was significantly higher in patients with elevated FVIII:C compared with individuals with VTE but no documented thrombophilia (median TAT = 8·65 µg/l versus 2·95 µg/l, median F1 + 2 = 1·5 nmol/l versus 0·87 nmol/l; P < 0·0001, P < 0·001). Overall FVIII:C levels were strongly correlated with levels of thrombin generation (r= 0·5, P < 0001). The clinical significance of such markedly increased F1 + 2 and TAT levels in patients with high FVIII:C levels remains unclear. [ABSTRACT FROM AUTHOR]

Assesses the usefulness of attention-deficit/hyperactivity disorder (ADHD) symptoms in a Diagnostic and Statistics Manual of Mental Disorder (DSM-IV) self-report checklist for predicting membership in a group previously diagnosed with adult ADHD. Application of predictive power analysis; Average number of symptoms of inattention and of hyperactivity-impulsivity endorsed by the group.

Most in vitro investigations of endothelial cell function have been based on the behaviour of human umbilical vein endothelial cells (HUVEC) in primary tissue culture. However, it is becoming apparent that there is a marked degree of heterogeneity among endothelial cells derived from different vascular beds. We have studied primary HUVEC from 45 umbilical cords. Contrary to previously published reports, we were unable to detect ABO antigens on the surface of cultured HUVEC from group A or B cords. This was not due to an absence of precursor H substance which was uniformly expressed on HUVEC in primary tissue culture. Further investigation revealed an absence of A enzyme activity in A type HUVEC and a level of mRNA only just detectable by RT-PCR. The absence of functional A enzyme activity was confirmed by demonstrating the absence of A substance on von Willebrand factor secreted by A type cells. HUVEC appear to be the only vascular endothelial cells that do not express ABO blood group antigens. We speculate that this may help protect the cord from maternal antibodies during gestation. The lack of ABO blood group antigens on HUVEC may significantly affect their surface function, and therefore care should be taken when extrapolating conclusions from results obtained with these cells (the most widely used human endothelial cell model in vitro) to the properties of adult endothelial cells.Copyright © 2000 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Haemorrhage is a frequent manifestation of amyloidosis. We performed a retrospective clinical analysis of 337 patients with systemic immunoglobulin light-chain (AL)-amyloidosis, in whom whole-body serum amyloid P component (SAP) scintigraphy and a clotting screen had been performed. Abnormal bleeding was noted in 94 cases (28%), and the coagulation screen was abnormal in 172 cases (51%). The most common abnormalities were prolongation of the thrombin time (TT; 108 cases, 32%) and the prothrombin time (PT; 82 cases, 24%). In multivariate analysis, a prolonged PT was the only coagulation abnormality associated with abnormal bleeding (P = 0·0012), but this was independent of the whole-body amyloid load. Prolongation of the TT was associated with hepatic amyloid infiltration (P < 0·00001), with proteinuria (P < 0·001) and low serum albumin (P < 0·00001). In 154 patients who were studied further, subnormal factor X activity (FX:C) was found in 22 cases (14%). In cases with subnormal FX:C, the corresponding factor X antigen (FX:Ag) measurements were consistently higher (median FX:Ag/FX:C 2·5, range 0·81–9·25, n = 16) than cases with normal FX:C (median FX:Ag/FX:C 0·96, range 0·65–1·29, n = 28, P < 0·0001). No evidence was found of an FX inhibitor. Of the 48/154 (31%) cases with a prolonged TT, the reptilase time was also prolonged in 38/48 cases (79%). These data show that haemorrhage and abnormal coagulation are common in AL-amyloidosis and are multifactorial in origin. We provide evidence suggesting that hepatic amyloid infiltration and nephrotic syndrome are determinants of the TT. In most patients, prolongation of the PT was explained by reduction in FX:C, but this was not wholly explained by a reduction in FX:Ag. [ABSTRACT FROM AUTHOR]

Abstract Rationale: Rolipram, a selective inhibitor of cyclic AMP-specific phosphodiesterase (PDE4), has been shown to enhance scopolamine-induced impairment of working memory. However, its effect on reference memory, which appears to be related to the level of cyclic AMP (cAMP), has not been investigated yet; in addition, the mechanism involved in its effects on memory remains to be elucidated. Objectives: To investigate the effects of rolipram on working and reference memories impaired by scopolamine and the involvement of cAMP. Methods: By administration (IP) of rolipram and forskolin, an activator of adenylyl cyclase (AC), the effects of both drugs on the number of correct choices and errors in experiment 1 and, the frequency of both working memory errors and reference memory errors in experiment 2 were observed in two eight-arm radial maze tasks in rats. Results: In experiment 1, rolipram (0.01-1.0 mg/kg) attenuated the scopolamine-induced (0.5 mg/kg) increase in the total number of errors in dose- and time-dependent manners. The minimum effective dose of rolipram was 0.05 mg/kg and the effects lasted nearly 60 min. By contrast, forskolin (1.010.0 mg/kg) failed significantly to affect any of the above indices altered by scopolamine. In experiment 2, rolipram (0.05 and 0.1 mg/kg) decreased the frequencies of both working and reference memory errors that were elevated by scopolamine. Forskolin did not alter either type of error at a dose that increased the exploration time. Conclusion: Rolipram may exert its effects of reversing both working and reference memory impairments via increased cyclic AMP concentrations in certain signal transduction pathways, rather than by a generalized increase in cAMP. [ABSTRACT FROM AUTHOR]

Even seemingly homogeneous on the surface, the oceans display high environmental heterogeneity across space and time. Indeed, different soft barriers structure the marine environment, which offers an appealing opportunity to study various evolutionary processes such as population differentiation and speciation. Here, we focus on Amphiprion clarkii (Actinopterygii; Perciformes), the most widespread of clownfishes that exhibits the highest colour polymorphism. Clownfishes can only disperse during a short pelagic larval phase before their sedentary adult lifestyle, which might limit connectivity among populations, thus facilitating speciation events. Consequently, the taxonomic status of A. clarkii has been under debate. We used whole‐genome resequencing data of 67 A. clarkii specimens spread across the Indian and Pacific Oceans to characterize the species' population structure, demographic history and colour polymorphism. We found that A. clarkii spread from the Indo‐Pacific Ocean to the Pacific and Indian Oceans following a stepping‐stone dispersal and that gene flow was pervasive throughout its demographic history. Interestingly, colour patterns differed noticeably among the Indonesian populations and the two populations at the extreme of the sampling distribution (i.e. Maldives and New Caledonia), which exhibited more comparable colour patterns despite their geographic and genetic distances. Our study emphasizes how whole‐genome studies can uncover the intricate evolutionary past of wide‐ranging species with diverse phenotypes, shedding light on the complex nature of the species concept paradigm. [ABSTRACT FROM AUTHOR]

ABSTRACT. Using a multi-trial, free-recall paradigm (Rey Auditory-Verbal Learning Test; Lezak, 1983), the acquisition and retention by learning disabled (LD) young adults with a Halstead Impairment Index < or equal to 0.3 (low LD) or ≥ 0.4 (high LD) was compared with that of nondisabled and head-injured (HI) young adults. Significant group differences, particularly during the last three acquisition trials, confirmed the effectiveness of this method in revealing subtle learning and retention deficits, Analyses of Thai I recall showed group differences in the prerecency but not the recency portion of the serial position curve, thus implicating long-term but not short-term memory differences between the groups. Analyses of pair frequency (Steinberg & Tulving, 1977) data showed that the three clinical groups had difficulty organizing the to-be-learned material for effective retrieval. Following an interpolated task, retention was poorer for the clinical groups than for the nondisabled and varied inversely with the ° of neuropsychological impairment. Finally, during retention, the nondisabled and low LD groups retained and used the list organization established during acquisition whereas the high LD and HI groups did not. [ABSTRACT FROM AUTHOR]