A pragmatic benchmarking study of an evidence-based personalised approach in 1938 adolescents with high-risk idiopathic scoliosis

Combining evidence-based medicine and shared decision making, current guidelines support an evidence-based personalised approach (EBPA) for idiopathic scoliosis in adolescents (AIS). EBPA is considered important for adolescents\u2019 compliance, which is particularly difficult in AIS. Benchmarking to existing Randomised Controlled Trials (RCTs) as paradigms of single treatments, we aimed to check the effectiveness and burden of care of an EBPA in high-risk AIS. This study\u2019s design features a retrospective observation of a prospective database including 25,361 spinal deformity patients < 18 years of age. Participants consisted of 1938 AIS, 11\u201345\u25e6 Cobb, Risser stage 0\u20132, who were studied until the end of growth. EBPA included therapies classified for burdensomeness according to current guidelines. Using the same inclusion criteria of the RCTs on exercises, plastic, and elastic bracing, out of the 1938 included, we benchmarked 590, 687, and 884 participants, respectively. We checked clinically significant results and burden of care, calculating Relative Risk of success (RR) and Number Needed to Treat (NNT) for efficacy (EA) and intent-to-treat analyses. At the end of growth, 19% of EBPA participants progressed, while 33% improved. EBPA showed 2.0 (1.7\u20132.5) and 2.9 (1.7\u20134.9) RR of success versus Weinstein and Coillard\u2019s studies control groups, respectively. Benchmarked to plastic or elastic bracing, EBPA had 1.4 (1.2\u20131.5) and 1.7 (1.2\u20132.5) RR of success, respectively. The EBPA treatment burden was greater than RCTs in 48% of patients, and reduced for 24% and 42% versus plastic and elastic bracing, respectively. EBPA showed to be from 40% to 70% more effective than benchmarked individual treatments, with low NNT. The burden of treatment was frequently reduced, but it had to be increased even more frequently

Global Analysis of Aerosol Properties Above Clouds

The seasonal and spatial varability of Aerosol Above Cloud (AAC) properties are derived from passive satellite data for the year 2008. A significant amount of aerosols are transported above liquid water clouds on the global scale. For particles in the fine mode (i.e., radius smaller than 0.3 m), including both clear sky and AAC retrievals increases the global mean aerosol optical thickness by 25(+/- 6%). The two main regions with man-made AAC are the tropical Southeast Atlantic, for biomass burning aerosols, and the North Pacific, mainly for pollutants. Man-made AAC are also detected over the Arctic during the spring. Mineral dust particles are detected above clouds within the so-called dust belt region (5-40 N). AAC may cause a warming effect and bias the retrieval of the cloud properties. This study will then help to better quantify the impacts of aerosols on clouds and climate

Is knee neuromuscular activity related to anterior cruciate ligament injury risk? A pilot study.

BACKGROUND: There is limited evidence on neuromuscular risk factors for anterior cruciate ligament (ACL) injuries, with most work mainly focusing on hamstrings and quadriceps muscle strength. This prospective pilot study explored if neuromuscular activation patterns of the quadriceps and hamstrings during a drop vertical jump influence ACL injury risk. METHODS: Forty-six female athletes performed a drop vertical jump at baseline. Injuries were monitored throughout a one-year follow-up. Neuromuscular activation patterns of the vastus medialis, vastus lateralis, hamstrings medialis and hamstrings lateralis, and selected landing kinematic and kinetic profiles (knee flexion, knee abduction and hip flexion angles, and knee abduction moments), were compared between athletes who sustained a non-contact ACL injury and those who remained injury free. Electromyogram vector fields were created to represent neuromuscular activation patterns of muscle pairs around the knee joint rather than only considering individual muscle activations, and compared using Statistical Parametric Mapping. RESULTS: Four athletes sustained an ACL injury. Significantly greater {hamstrings medials, hamstrings lateralis}, {vastus lateralis, hamstrings lateralis} and {hamstrings lateralis, vastus medialis} activations, mainly due to greater hamstrings lateralis activation, were found in the injured group around peak loading and just before take-off (P < 0.001). No group differences were found in knee flexion, knee abduction and hip flexion angles, or knee abduction moments. CONCLUSIONS: This pilot study revealed initial evidence that athletes already showed altered neuromuscular activation patterns prior to sustaining an ACL injury, namely increased lateral and posterior muscle activations

The European Legal Framework on Cybercrime

This article analyzes the European legal framework on cybercrime. Initially, it argues the challenges of cybercrime to traditional criminal justice systems. Subsequently, it focuses on the criminal law framework on cybercrime with a mainly European perspective. The European legal framework provides a three-path solution: the reduction of frictions among national legislations, the introduction of new investigative powers and the facilitation of international cooperation. The article presents and discusses each solution. Further, it argues that the effective implementation of the main legal instruments does not seem to depend on the legal enforceability of these international measures. Contrarily, other, non legal, factors such as national security, politics, the economy and the public opinion appear to stimulate the spontaneous implementation of the European legal framework. In this context, the added value of the EU action is rather low, although the Treaty of Lisbon and the Stockholm Programme may improve this situation in the long ter

VennPlex--a novel Venn diagram program for comparing and visualizing datasets with differentially regulated datapoints.

With the development of increasingly large and complex genomic and proteomic data sets, an enhancement in the complexity of available Venn diagram analytical programs is becoming increasingly important. Current freely available Venn diagram programs often fail to represent extra complexity among datasets, such as regulation pattern differences between different groups. Here we describe the development of VennPlex, a program that illustrates the often diverse numerical interactions among multiple, high-complexity datasets, using up to four data sets. VennPlex includes versatile output features, where grouped data points in specific regions can be easily exported into a spreadsheet. This program is able to facilitate the analysis of two to four gene sets and their corresponding expression values in a user-friendly manner. To demonstrate its unique experimental utility we applied VennPlex to a complex paradigm, i.e. a comparison of the effect of multiple oxygen tension environments (1–20% ambient oxygen) upon gene transcription of primary rat astrocytes. VennPlex accurately dissects complex data sets reliably into easily identifiable groups for straightforward analysis and data output. This program, which is an improvement over currently available Venn diagram programs, is able to rapidly extract important datasets that represent the variety of expression patterns available within the data sets, showing potential applications in fields like genomics, proteomics, and bioinformatics

The governance of justice and internal security in Scotland: Between the Scottish independence referendum and British decisions on the EU

This article examines how the governance of justice and internal security in Scotland could be affected by the outcome of the Scottish independence referendum in September 2014. The article argues that it is currently impossible to equate a specific result in the referendum with a given outcome for the governance of justice and internal security in Scotland. This is because of the complexities of the current arrangements in that policy area and the existence of several changes that presently affect them and are outside the control of the government and of the people of Scotland. This article also identifies an important paradox. In the policy domain of justice and internal security, a ‘no’ vote could, in a specific set of circumstances, actually lead to more changes than a victory of the ‘yes’ camp

Expression of zebrafish pax6b in pancreas is regulated by two enhancers containing highly conserved cis-elements bound by PDX1, PBX and PREP factors

BACKGROUND: PAX6 is a transcription factor playing a crucial role in the development of the eye and in the differentiation of the pancreatic endocrine cells as well as of enteroendocrine cells. Studies on the mouse Pax6 gene have shown that sequences upstream from the P0 promoter are required for expression in the lens and the pancreas; but there remain discrepancies regarding the precise location of the pancreatic regulatory elements. RESULTS: Due to genome duplication in the evolution of ray-finned fishes, zebrafish has two pax6 genes, pax6a and pax6b. While both zebrafish pax6 genes are expressed in the developing eye and nervous system, only pax6b is expressed in the endocrine cells of the pancreas. To investigate the cause of this differential expression, we used a combination of in silico, in vivo and in vitro approaches. We show that the pax6b P0 promoter targets expression to endocrine pancreatic cells and also to enteroendocrine cells, retinal neurons and the telencephalon of transgenic zebrafish. Deletion analyses indicate that strong pancreatic expression of the pax6b gene relies on the combined action of two conserved regulatory enhancers, called regions A and C. By means of gel shift assays, we detected binding of the homeoproteins PDX1, PBX and PREP to several cis-elements of these regions. In constrast, regions A and C of the zebrafish pax6a gene are not active in the pancreas, this difference being attributable to sequence divergences within two cis-elements binding the pancreatic homeoprotein PDX1. CONCLUSION: Our data indicate a conserved role of enhancers A and C in the pancreatic expression of pax6b and emphasize the importance of the homeoproteins PBX and PREP cooperating with PDX1, in activating pax6b expression in endocrine pancreatic cells. This study also provides a striking example of how adaptative evolution of gene regulatory sequences upon gene duplication progressively leads to subfunctionalization of the paralogous gene pair

Anti-Allergic Cromones Inhibit Histamine and Eicosanoid Release from Activated Human and Murine Mast Cells by Releasing Annexin A1

PMCID: PMC3601088This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Integrated annotation and analysis of genomic features reveal new types of functional elements and large-scale epigenetic phenomena in the developing zebrafish

Zebrafish, a popular model for embryonic development and for modelling human diseases, has so far lacked a systematic functional annotation programme akin to those in other animal models. To address this, we formed the international DANIO-CODE consortium and created the first central repository to store and process zebrafish developmental functional genomic data. Our Data Coordination Center (https://danio-code.zfin.org) combines a total of 1,802 sets of unpublished and reanalysed published genomics data, which we used to improve existing annotations and show its utility in experimental design. We identified over 140,000 cis-regulatory elements in development, including novel classes with distinct features dependent on their activity in time and space. We delineated the distinction between regulatory elements active during zygotic genome activation and those active during organogenesis, identifying new aspects of how they relate to each other. Finally, we matched regulatory elements and epigenomic landscapes between zebrafish and mouse and predict functional relationships between them beyond sequence similarity, extending the utility of zebrafish developmental genomics to mammals

Protein profiling in hepatocellular carcinoma by label-free quantitative proteomics in two west african populations.

Background Hepatocellular Carcinoma is the third most common cause of cancer related death worldwide, often diagnosed by measuring serum AFP; a poor performance stand-alone biomarker. With the aim of improving on this, our study focuses on plasma proteins identified by Mass Spectrometry in order to investigate and validate differences seen in the respective proteomes of controls and subjects with LC and HCC. Methods Mass Spectrometry analysis using liquid chromatography electro spray ionization quadrupole time-of-flight was conducted on 339 subjects using a pooled expression profiling approach. ELISA assays were performed on four significantly differentially expressed proteins to validate their expression profiles in subjects from the Gambia and a pilot group from Nigeria. Results from this were collated for statistical multiplexing using logistic regression analysis. Results Twenty-six proteins were identified as differentially expressed between the three subject groups. Direct measurements of four; hemopexin, alpha-1-antitrypsin, apolipoprotein A1 and complement component 3 confirmed their change in abundance in LC and HCC versus control patients. These trends were independently replicated in the pilot validation subjects from Nigeria. The statistical multiplexing of these proteins demonstrated performance comparable to or greater than ALT in identifying liver cirrhosis or carcinogenesis. This exercise also proposed preliminary cut offs with achievable sensitivity, specificity and AUC statistics greater than reported AFP averages. Conclusions The validated changes of expression in these proteins have the potential for development into high-performance tests usable in the diagnosis and or monitoring of HCC and LC patients. The identification of sustained expression trends strengthens the suggestion of these four proteins as worthy candidates for further investigation in the context of liver disease. The statistical combinations also provide a novel inroad of analyses able to propose definitive cut-offs and combinations for evaluation of performance