Abrogation of HMX1 function causes rare oculoauricular syndrome associated with congenital cataract, anterior segment dysgenesis, and retinal dystrophy.

PURPOSE: To define the phenotypic manifestation, confirm the genetic basis, and delineate the pathogenic mechanisms underlying an oculoauricular syndrome (OAS). METHODS: Two individuals from a consanguineous family underwent comprehensive clinical phenotyping and electrodiagnostic testing (EDT). Genome-wide microarray analysis and Sanger sequencing of the candidate gene were used to identify the likely causal variant. Protein modelling, Western blotting, and dual luciferase assays were used to assess the pathogenic effect of the variant in vitro. RESULTS: Complex developmental ocular abnormalities of congenital cataract, anterior segment dysgenesis, iris coloboma, early-onset retinal dystrophy, and abnormal external ear cartilage presented in the affected family members. Genetic analyses identified a homozygous c.650A>C; p.(Gln217Pro) missense mutation within the highly conserved homeodomain of the H6 family homeobox 1 (HMX1) gene. Protein modelling predicts that the variant may have a detrimental effect on protein folding and/or stability. In vitro analyses were able to demonstrate that the mutation has no effect on protein expression but adversely alters function. CONCLUSIONS: Oculoauricular syndrome is an autosomal recessive condition that has a profound effect on the development of the external ear, anterior segment, and retina, leading to significant visual loss at an early age. This study has delineated the phenotype and confirmed HMX1 as the gene causative of OAS, enabling the description of only the second family with the condition. HMX1 is a key player in ocular development, possibly in both the pathway responsible for lens and retina development, and via the gene network integral to optic fissure closure.

IAS 14 - Segment Reporting; The Requirements and Implementation

The principal aim of this study is to clarify the requirements of segment reporting and compare the requirements with the actual! implementation on different business lines. The empirical part was concluded by interviewing randomly selected companies that are publicly listed on the Helsinki Exchanges. The theoretical part of the study (chapters 2 and 3) will give basic information about shifting to IAS -standards and the requirements of IAS -standards. In order to meet the principal aim, a pre-empiric research was conducted by studying the annual accounts (year 2002) of randomly selected companies that already follow the IAS -standards of reporting. The companies in the pre-empiric research consist of both domestic and foreign companies. The aim of the pre-empiric study was to give a basis for the interview process on the empiric part of the study. The study indicates that implementing segment reporting has not brought any major concerns or problems. This is due to the fact that most companies that were examined - being publicly listed companies - have traditionally had a clear division between their geographical and commercial segments, and also been obliged to give reports according to these segments. In case of changes in corporate structure, shifting on new lines of businesses or downsizing of operations, the problems in reporting according to IAS -standards, may arise. Such changes will also require changes on information systems, providing the essential information for segment reporting. According to this study, most companies choose the commercial segment as their primary segment for reporting. The pre-empiric study indicates, that most of the companies already following the IAS -standards, still have a lot of improvement to do, in order to meet all the IAS requirements.

Who's fault is it ? : An analysis of the press coverage of football betting scandals in France and the United Kingdom

Sport betting is a lucrative business for bookmakers, for the lucky (or wise) punters, but also for governments and for sport. While not new or even recent, the deviances linked to sport betting, primarily match-fixing, have gained increased media exposure in the past decade. This exploratory study is a qualitative content analysis of the press coverage of sport betting-related deviances in football in two countries (UK and France), using in each case two leading national publications over a period of five years. Data analysis indicates a mounting coverage of sport betting scandals, with teams, players and criminals increasingly framed as culprits, while authorities and federations primarily assume a positive role. As for the origin of sport betting deviances, French newspapers tend to blame the system (in an abstract way); British newspapers, in contrast, focus more on individual weaknesses, notably greed. This article contributed to the growing body of literature on the importance of these deviances and on the way they are perceived by sport organizations, legislators and the public at large.

Evidence for coseismic events of recurrent prehistoric deformation along the Alhama de Murcia fault, southeastern Spain

The Alhama de Murcia fault is a 85 km long oblique-slip fault, and is related to historical and instrumental seismic activity. A paleoseismic analysis of the Lorca-Totana sector of the fault containing MSK I=VIII historical earthquakes was made in order to identify and quantify its seismic potential. We present 1) the results of the neotectonic, structural and geomorphological analyses and, 2) the results of trenching. In the study area, the Alhama de Murcia fault forms a depressed corridor between two strands, the northwestern fault with morphological and structural features of a reverse component of slip, bounding the La Tercia range to the South, and the southeastern fault strand with evidence of sinistral oblique strike-slip movement. The offset along this latter fault trapped the sediments in transit from the La Tercia range towards the Guadalentín depression. The most recent of these sediments are arranged in three generations of alluvial fans and terraces. The first two trenches were dug in the most recent sediments across the southeastern fault strand. The results indicate a coseismic reverse fault deformation that involved the sedimentary sequence up to the intermediate alluvial fan and the Holocene terrace deposits. The sedimentary evolution observed in the trenches suggests an event of temporary damming of the Colmenar creek drainage to the South due to uplifting of the hanging wall during coseismic activation of the fault. Trench, structural and sedimentological features provide evidence of at least three coseismic events, which occurred after 125,000 yr. The minimum vertical slip rate along the fault is 0.06 mm/yr and the average recurrence period should not exceed 40,000 yr in accordance with the results obtained by fan topographic profiling. Further absolute dating is ongoing to constrain these estimates.

Active tectonics of the Alhama de Murcia fault, Betic Cordillera, Spain

We present an overview of the knowledge of the structure and the seismic behavior of the Alhama de Murcia Fault (AMF). We utilize a fault traces map created from a LIDAR DEM combined with the geodynamic setting, the analysis of the morphology, the distribution of seismicity, the geological information from E 1:50000 geological maps and the available paleoseismic data to describe the recent activity of the AMF. We discuss the importance of uncertainties regarding the structure and kinematics of the AMF applied to the interpretation and spatial correlation of the paleoseismic data. In particular, we discuss the nature of the faults dipping to the SE (antithetic to the main faults of the AMF) in several segments that have been studied in the previous paleoseismic works. A special chapter is dedicated to the analysis of the tectonic source of the Lorca 2011 earthquake that took place in between two large segments of the fault.

SQualTrack: A Tool for Robust Fault Detection

One of the techniques used to detect faults in dynamic systems is analytical redundancy. An important difficulty in applying this technique to real systems is dealing with the uncertainties associated with the system itself and with the measurements. In this paper, this uncertainty is taken into account by the use of intervals for the parameters of the model and for the measurements. The method that is proposed in this paper checks the consistency between the system's behavior, obtained from the measurements, and the model's behavior; if they are inconsistent, then there is a fault. The problem of detecting faults is stated as a quantified real constraint satisfaction problem, which can be solved using the modal interval analysis (MIA). MIA is used because it provides powerful tools to extend the calculations over real functions to intervals. To improve the results of the detection of the faults, the simultaneous use of several sliding time windows is proposed. The result of implementing this method is semiqualitative tracking (SQualTrack), a fault-detection tool that is robust in the sense that it does not generate false alarms, i.e., if there are false alarms, they indicate either that the interval model does not represent the system adequately or that the interval measurements do not represent the true values of the variables adequately. SQualTrack is currently being used to detect faults in real processes. Some of these applications using real data have been developed within the European project advanced decision support system for chemical/petrochemical manufacturing processes and are also described in this paper

Estudi sociomorfològica a Manresa : el segment velar en algunes formes del PI i el PS dels verbs anar, fer, veure i haver

Des d’una perspectiva sociomorfològica, aquest estudi analitza la correlació que hi ha entre les variables socials de l’edat, el gènere i la classe social i un dels trets morfofonològics més característics del parlar dels joves de Manresa: la presència del segment velar /g/ en la primera persona del singular del present d’indicatiu, i en les persones primera, segona i tercera del singular i en la tercera del plural del present de subjuntiu dels verbs irregulars anar, fer, veure i haver (ex. vaic i vaigui).

Prehospital ticagrelor in ST-segment elevation myocardial infarction

Background:The direct-acting platelet P2Y receptor antagonist ticagrelor can reduce the incidence of major adverse cardiovascular events when administered at hospital admission to patients with ST-segment elevation myocardial infarction (STEMI). Whether prehospital administration of ticagrelor can improve coronary reperfusion and the clinical outcome is unknown. Methods: We conducted an international, multicenter, randomized, double-blind study involving 1862 patients with ongoing STEMI of less than 6 hours' duration, comparing prehospital (in the ambulance) versus in-hospital (in the catheterization laboratory) treatment with ticagrelor. The coprimary end points were the proportion of patients who did not have a 70% or greater resolution of ST-segment elevation before percutaneous coronary intervention (PCI) and the proportion of patients who did not have Thrombolysis in Myocardial Infarction flow grade 3 in the infarct-related artery at initial angiography. Secondary end points included the rates of major adverse cardiovascular events and definite stent thrombosis at 30 days. Results: The median time from randomization to angiography was 48 minutes, and the median time difference between the two treatment strategies was 31 minutes. The two coprimary end points did not differ significantly between the prehospital and in-hospital groups. The absence of ST-segment elevation resolution of 70% or greater after PCI (a secondary end point) was reported for 42.5% and 47.5% of the patients, respectively. The rates of major adverse cardiovascular events did not differ significantly between the two study groups. The rates of definite stent thrombosis were lower in the prehospital group than in the in-hospital group (0% vs. 0.8% in the first 24 hours; 0.2% vs. 1.2% at 30 days). Rates of major bleeding events were low and virtually identical in the two groups, regardless of the bleeding definition used

On Fault Tolerance Methods for Networks-on-Chip

Technology scaling has proceeded into dimensions in which the reliability of manufactured devices is becoming endangered. The reliability decrease is a consequence of physical limitations, relative increase of variations, and decreasing noise margins, among others. A promising solution for bringing the reliability of circuits back to a desired level is the use of design methods which introduce tolerance against possible faults in an integrated circuit. This thesis studies and presents fault tolerance methods for network-onchip (NoC) which is a design paradigm targeted for very large systems-onchip. In a NoC resources, such as processors and memories, are connected to a communication network; comparable to the Internet. Fault tolerance in such a system can be achieved at many abstraction levels. The thesis studies the origin of faults in modern technologies and explains the classification to transient, intermittent and permanent faults. A survey of fault tolerance methods is presented to demonstrate the diversity of available methods. Networks-on-chip are approached by exploring their main design choices: the selection of a topology, routing protocol, and flow control method. Fault tolerance methods for NoCs are studied at different layers of the OSI reference model. The data link layer provides a reliable communication link over a physical channel. Error control coding is an efficient fault tolerance method especially against transient faults at this abstraction level. Error control coding methods suitable for on-chip communication are studied and their implementations presented. Error control coding loses its effectiveness in the presence of intermittent and permanent faults. Therefore, other solutions against them are presented. The introduction of spare wires and split transmissions are shown to provide good tolerance against intermittent and permanent errors and their combination to error control coding is illustrated. At the network layer positioned above the data link layer, fault tolerance can be achieved with the design of fault tolerant network topologies and routing algorithms. Both of these approaches are presented in the thesis together with realizations in the both categories. The thesis concludes that an optimal fault tolerance solution contains carefully co-designed elements from different abstraction levels

A and B mode ultrasonography in preoperative evaluation of lens and posterior segment of dogs eyes with cataract

Ultrasonography of the lens and posterior segment is an indispensable step in the preoperative evaluation of dogs with cataracts, since ophthalmoscopy is not feasible when there is opacification of the lens. This study evaluated the echographic conditions of cataractous lens and fundus of the eye in dogs affected by cataracts. The study was conducted in 30 dogs (56 eyes), 10 males and 20 females, with different types of cataracts at different stages of development. Echography in A and B modes, simultaneously, was carried out for the examination of the lens and posterior segment. The examinations revealed anterior cortical, posterior cortical and nuclear cataract in 12 eyes (21.4%), anterior cortical, posterior cortical, nuclear and posterior capsular in 23 eyes (41%), anterior cortical, posterior cortical and posterior capsular cataract in one eye (1.7%), anterior cortical and nuclear cataract in one eye (1.7%), anterior cortical, nuclear and posterior capsular cataract in five eyes (8.9%), and anterior cortical cataract in seven eyes (12.5%). Abnormal ultrasonographic alterations were observed in the posterior segment in 26 eyes evaluated (46.4%). Vitreal degeneration was detected in 12 eyes (21.4%), images of vitreal exudate or hemorrhage in seven eyes (12.5%), persistence of hyaloid artery in four eyes (7.1%) and lens subluxation in three eyes (5.3%). The results obtained reiterate the importance of ultrasonography in canine patients presented for cataract surgery given that alterations of the posterior segment are difficult to identify in a clinical examination when the lens is opacified.

Genesis and Evolution of Brittle Structures In Southwestern Finland and Western South Africa. Insights into Fault Reactivation, Fluid Flow and Structural Maturity in Precambrian Cratons

The bedrock of old crystalline cratons is characteristically saturated with brittle structures formed during successive superimposed episodes of deformation and under varying stress regimes. As a result, the crust effectively deforms through the reactivation of pre-existing structures rather than by through the activation, or generation, of new ones, and is said to be in a state of 'structural maturity'. By combining data from Olkiluoto Island, southwestern Finland, which has been investigated as the potential site of a deep geological repository for high-level nuclear waste, with observations from southern Sweden, it can be concluded that the southern part of the Svecofennian shield had already attained structural maturity during the Mesoproterozoic era. This indicates that the phase of activation of the crust, i.e. the time interval during which new fractures were generated, was brief in comparison to the subsequent reactivation phase. Structural maturity of the bedrock was also attained relatively rapidly in Namaqualand, western South Africa, after the formation of first brittle structures during Neoproterozoic time. Subsequent brittle deformation in Namaqualand was controlled by the reactivation of pre-existing strike-slip faults.In such settings, seismic events are likely to occur through reactivation of pre-existing zones that are favourably oriented with respect to prevailing stresses. In Namaqualand, this is shown for present day seismicity by slip tendency analysis, and at Olkiluoto, for a Neoproterozoic earthquake reactivating a Mesoproterozoic fault. By combining detailed field observations with the results of paleostress inversions and relative and absolute time constraints, seven distinctm superimposed paleostress regimes have been recognized in the Olkiluoto region. From oldest to youngest these are: (1) NW-SE to NNW-SSE transpression, which prevailed soon after 1.75 Ga, when the crust had sufficiently cooled down to allow brittle deformation to occur. During this phase conjugate NNW-SSE and NE-SW striking strike-slip faults were active simultaneous with reactivation of SE-dipping low-angle shear zones and foliation planes. This was followed by (2) N-S to NE-SW transpression, which caused partial reactivation of structures formed in the first event; (3) NW-SE extension during the Gothian orogeny and at the time of rapakivi magmatism and intrusion of diabase dikes; (4) NE-SW transtension that occurred between 1.60 and 1.30 Ga and which also formed the NW-SE-trending Satakunta graben located some 20 km north of Olkiluoto. Greisen-type veins also formed during this phase. (5) NE-SW compression that postdates both the formation of the 1.56 Ga rapakivi granites and 1.27 Ga olivine diabases of the region; (6) E-W transpression during the early stages of the Mesoproterozoic Sveconorwegian orogeny and which also predated (7) almost coaxial E-W extension attributed to the collapse of the Sveconorwegian orogeny. The kinematic analysis of fracture systems in crystalline bedrock also provides a robust framework for evaluating fluid-rock interaction in the brittle regime; this is essential in assessment of bedrock integrity for numerous geo-engineering applications, including groundwater management, transient or permanent CO2 storage and site investigations for permanent waste disposal. Investigations at Olkiluoto revealed that fluid flow along fractures is coupled with low normal tractions due to in-situ stresses and thus deviates from the generally accepted critically stressed fracture concept, where fluid flow is concentrated on fractures on the verge of failure. The difference is linked to the shallow conditions of Olkiluoto - due to the low differential stresses inherent at shallow depths, fracture activation and fluid flow is controlled by dilation due to low normal tractions. At deeper settings, however, fluid flow is controlled by fracture criticality caused by large differential stress, which drives shear deformation instead of dilation.

Noninvasive assessment of endothelial function and ST segment changes during exercise testing in coronary artery disease

Endothelial function (EF) plays an important role in the onset and clinical course of atherosclerosis, although its relationship with the presence and extent of coronary artery disease (CAD) has not been well defined. We evaluated EF and the ST segment response to an exercise test in patients with a broad spectrum of CAD defined by coronary angiography. Sixty-two patients submitted to diagnostic catheterization for the evaluation of chest pain or ischemia in a provocative test were divided into three groups according to the presence and severity of atherosclerotic lesions (AL): group 1: normal coronaries (N = 19); group 2: CAD with AL <70% (N = 17); group 3: CAD with AL ≥70% (N = 26). EF was evaluated by the percentage of flow-mediated dilatation (%FMD) in the brachial artery during reactive hyperemia induced by occlusion of the forearm with a pneumatic cuff for 5 min. Fifty-four patients were subjected to an exercise test. Gender and age were not significantly correlated with %FMD. EF was markedly reduced in both groups with CAD (76.5 and 73.1% vs 31.6% in group 1) and a higher frequency of ischemic alterations in the ST segment (70.8%) was observed in the group with obstructive CAD with AL ≥70% during the exercise test. Endothelial dysfunction was observed in patients with CAD, irrespective of the severity of injury. A significantly higher frequency of ischemic alterations in the ST segment was observed in the group with obstructive CAD. EF and exercise ECG differed among the three groups and may provide complementary information for the assessment of CAD.

The influence of high cable penetration in distribution networks on earth fault currents and the operation of relay protection.

Recent Storms in Nordic countries were a reason of long power outages in huge territories. After these disasters distribution networks' operators faced with a problem how to provide adequate quality of supply in such situation. The decision of utilization cable lines rather than overhead lines were made, which brings new features to distribution networks. The main idea of this work is a complex analysis of medium voltage distribution networks with long cable lines. High value of cable’s specific capacitance and length of lines determine such problems as: high values of earth fault currents, excessive amount of reactive power flow from distribution to transmission network, possibility of a high voltage level at the receiving end of cable feeders. However the core tasks was to estimate functional ability of the earth fault protection and the possibility to utilize simplified formulas for operating setting calculations in this network. In order to provide justify solution or evaluation of mentioned above problems corresponding calculations were made and in order to analyze behavior of relay protection principles PSCAD model of the examined network have been created. Evaluation of the voltage rise in the end of a cable line have educed absence of a dangerous increase in a voltage level, while excessive value of reactive power can be a reason of final penalty according to the Finish regulations. It was proved and calculated that for this networks compensation of earth fault currents should be implemented. In PSCAD models of the electrical grid with isolated neutral, central compensation and hybrid compensation were created. For the network with hybrid compensation methodology which allows to select number and rated power of distributed arc suppression coils have been offered. Based on the obtained results from experiments it was determined that in order to guarantee selective and reliable operation of the relay protection should be utilized hybrid compensation with connection of high-ohmic resistor. Directional and admittance based relay protection were tested under these conditions and advantageous of the novel protection were revealed. However, for electrical grids with extensive cabling necessity of a complex approach to the relay protection were explained and illustrated. Thus, in order to organize reliable earth fault protection is recommended to utilize both intermittent and conventional relay protection with operational settings calculated by the use of simplified formulas.