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Purpose Evidence-based facts regarding spine abnormalities and back pain are needed in order to develop rehabilitation programs and prevent spine injuries in young skiers. The aim therefore is to identify MRI changes in the thoraco-lumbar spine and the lifetime prevalence of back pain, as well as the association between them, in young skiers compared to non-athletes. Methods Seventy-five young elite alpine and mogul skiers, age range 16–20 years, were compared with 27 non-athletic controls. All subjects underwent spinal MRI and answered back pain questionnaires. Results Fifty-six percent of skiers had at least one disc Pfirrmann grade ≥3 compared to 30% of controls (p = 0.027). Schmorl’s nodes (46%) and disc height reduction (37%) were significantly more prevalent in skiers compared to controls (0%) (p

Investigation of fatal cases of falls from height as well as jumps from height in suicidal ideation makes up an integral part of forensic practice. In Slovakia, a method of suicide by jumping from height is after hanging the second most chosen method of ending life. In about one third of the cases, the influence of addictive substances is determined. The basic mechanism of injury is a sudden deceleration of body movement when hitting a solid surface. Several factors influence the nature, localization, severity, and frequency of injuries. In most cases, there occur multiple injuries to the skeleton and internal organs caused by blunt objects. The authors demonstrate the case of an unusual mechanism of injury in a 55-year-old man who committed suicide by jumping from the seventh floor of a block of flats. A stepped fall from height resulted in the through knee amputation of both legs by hitting posterior thigh area and knee joints on the railing of the terrace of the block of flats on the ground floor level. The body was found in the basement. In contact with the railing, the mans trousers and pants were pulled off. The autopsy determined the immediate cause of death as polytrauma. Additional toxicological-chemical examination of blood and urine samples collected at autopsy revealed ethanol at the concentration within the extent of laboratory error, caffeine, and nicotine in toxicologically insignificant concentrations and traces of acetone. Motivation of mans suicide remains unknown.

The integrated interpretation of the airborne FALCON® Airborne Gravity Gradiometer (AGG) survey was designed to assist oil and gas producer Empire Oil and Gas in identifying target areas for hydrocarbon exploration in the Perth Basin. It was developed as a synthesis of the geological structure, tectonic evolution and principles of gravity and magnetic data behaviour. The survey identified areas containing large structural leads and trends as the target of future gas exploration activities, including infill 2D seismic acquisition. The prospectivity of some identified leads has been significantly increased by the gas discovery at wells Red Gully North-1 and Gingin-1, located in EP 389 in central Perth Basin.

SUMMARY This paper presents automatic 3D geophysical model generation based on equivalent pseudodepth slicing of the shape index of the equipotential surfaces derived from airborne gravity gradient data. The method is carried out in three steps. First, the pseudodepth slices of the vertical gravity gradient and the magnitude of the differential curvature components are generated. Second, the equivalent pseudodepth slices of the shape index are generated. Finally, 3D interpolation is carried out to obtain the final model. The method is applied to FALCON airborne gravity gradiometer data from the Glyde Basin, Northern Territory and compared to an independently interpreted, integrated 3D geological Earth model.

A 3D geological model for King Sound, in the offshore Canning Basin, Western Australia, was produced by interpretation of FALCON® high resolution airborne gravity gradiometry and magnetic data, aided by 2D gravity models, 2D seismic data and well logs. Pseudo-depth slices of the vertical gravity gradient (GDD) and magnetic data and interpreted seismic horizons were used to constrain the vertical distribution of sedimentary sequences, intrasedimentary intrusives and basement rocks. Basement depth was determined from the magnetic data using traditional profile-based automated magnetic depth estimation techniques with well control. The 3D model indicates an elevated, fault-bounded platform of Archaean to Proterozoic basement in the north. The platform is rimmed by Late Devonian and Early Carboniferous carbonate reefs and carbonate breccias and in the south, contemporaneous siliciclastic submarine fans and turbidite deposits occur in a deep marine environment. Density values derived from published literature and measured in wells at King Sound were assigned to units in the geological model. A forward model was calculated and compared to the observed GDD data. The assigned density values were then modified, within the expected range for each rock type, using property inversions until a good fit between the modelled and observed data was obtained. Models derived from potential field data can be beneficial for petroleum exploration in frontier basins worldwide, where only limited well and seismic data are available. The 3D geological model provides a good framework for use in designing future exploration programs in the area and it aids data visualisation and interpretation.

The airborne TEMPEST electromagnetic (EM) and magnetic survey is a proven tool for mapping geological structure for exploration. This technique was applied at the Bulman project area in the McArthur Basin to identify the geological environment of stratabound carbonate-hosted Pb-Zn mineralisation. The Late Palaeoproterozoic to Early Mesoproterozoic sedimentary fill of the McArthur Basin in the Bulman project area consists of the Dook Creek and Limmen Formations. They are intruded by Early Mesoproterozoic dolerite sills and dykes. The location of the intrusive rocks was mapped using magnetic data while their depth was estimated from EM data. To find the top of the intrusives, depth to resistive basement was mapped using Conductivity Depth Images (CDIs) generated from the TEMPEST B-field Z-component data. Additionally, a voxel model was constructed from the CDIs to show the conductivity distribution in three dimensions. The conductivity pattern indicates that the dolomite sandstone and siltstone of the Dook Creek Formation are more conductive than the overlying coarse sandstone of the Limmen Formation. A disconformable boundary between the formations is shown as a distinct interface in the EM data. There is no marked conductivity contrast between intrusives and other rocks making up the resistive basement. As a result, the picked depth to resistive basement horizon corresponds to the bottom of a surface conductive unit that is interpreted to be the base of the Cenozoic unconsolidated deposits or part of the Dook Creek Formation. In places, the base of a sub-surface conductive zone is interpreted to be the top of the intrusives. The thickness of sediments above the resistive basement is variable, reaching up to 170 metres in the central - eastern part of the study area. Additionally, a 3D geological model has been constructed to image the distribution of the interpreted geological units and the tectonic pattern.

An interpretation of geologic structure at King Sound in the Canning Basin was completed using airborne gravity gradient, magnetic, and seismic data. During the Late Devonian and Mississippian periods, the elevated part of the basement in the north was rimmed by carbonate reefs and redeposited carbonate debris, whereas in the south, siliciclastic submarine fans and turbidites were deposited along the margin of the basement in a deep-marine environment. Three principal lithologic units were identified from the vertical gravity gradient (GDD) in the basin: (1) the Fairfield Group carbonates of high density are interpreted to be the source of prominent positive gravity anomalies; (2) forereef debris and carbonate clastics reworked from carbonates higher up the slope or from the carbonate platform are interpreted to be the source of medium-density responses; and (3) turbidites, debris flows, and associated clastic basinal sequences of low density are interpreted to be the source of prominent negative gravity anomalies. Depth slices of GDD indicate the channelized nature of turbidite flows. In the lower section of the basin, intrasedimentary intrusives were identified from magnetic, GDD, seismic, and well data. Depth to magnetic basement calculation indicates that the surface of the Archean to Paleoproterozoic basement ranges from 3200 to 130 m (10,499–427 ft) below sea level. The northwest- and northeast-oriented south-dipping faults cut the basement and propagate upward into the sediments. A three-dimensional geologic model constructed for King Sound satisfies all known geologic constraints and is consistent with the gravity, magnetic, seismic, and well data.

We apply equipotential surface curvatures to airborne gravity gradient data. The mean and differential curvature of the equipotential surface, the curvature of the gravity field line, the zero contour of the Gaussian curvature, and the shape index improve the understanding and geologic interpretation of gravity gradient data. Their use is illustrated in model data and applied to FALCON airborne gravity gradiometer data from the Canning Basin, Australia.

Cardiovascular diseases belong to the most widespread illnesses in the developed countries. Therefore, the regenerative medicine and tissue modeling applications are highly interested in studying the ability of endothelial cells, derived from human stem cells, to form vascular networks. Several characteristics can be measured on images of these networks and hence describe the quality of the endothelial cells. With advances in the image processing, automatic analysis of these complex images becomes increasingly common. In this study, we introduce a new graph structure and additional constraints to the cellular Potts model, a framework commonly utilized in computational biology. Our extension allows to generate visually plausible synthetic image sequences of evolving fluorescently labeled vascular networks with ground truth data. Such generated datasets can be subsequently used for testing and validating methods employed for the analysis and measurement of the images of real vascular networks.

Athletes have a higher prevalence of LBP and spinal abnormalities on Magnetic Resonance Imaging (MRI) compared to non-athletes. The objective of this study was to investigate the amount of spinal MRI abnormalities and the lifetime prevalence of low back pain (LBP) in 16 young elite Mogul skiers compared to 28 non-athletes in the corresponding age in a cross-sectional design. LBP was assessed by a questionnaire consisting of a part regarding previous or present back pain, the Oswestry disability index, and the EuroQol questionnaire. MRI examinations from Th5 to sacrum were conducted to evaluate spinal pathologies. The Mogul skiers had significantly more MRI abnormalities (like disc degeneration) in mean (7.25 vs 3.78, P

Integrated interpretation through physical properties of rocks provides better approach towards understanding of geological set-up. High resolution heliborne time domain electromagnetic, magnetic and radiometric dataset acquired over Palaeo Proterozoic Bijawar Basin has been interpreted to enhance the geological understanding. The process involved knowledge driven analysis through correlation with geological units that outcrop and data driven analysis for extrapolation of information. Radiometric data in conjunction with spectral remote sensing data was used for generation of surface geology map. Spatial distribution of rock magnetization properties defines the subsurface extension of litho-structural elements and magnetic basement configuration. Electromagnetic data aided demarcation of resistive basement topography and various conductive layers. Radio-elemental distribution refines the unconformable contact shared by Bijawar Group with overlying and underlying group of rocks and also outlined the formational boundaries of arenaceous-argillaceous carbonate-volcano-sedimentary sequence. Subsurface extent of basic volcanics is much more than its surface manifestation and appears to extend well below the overlying Vindhyan Supergroup of rocks. The unconformable contact of Bijawar Group with underlying basement and overlying Vindhyan Supergroup is marked by distinct change in conductivity parameter and has been outlined in depth to resistive basement topography. Fault system and its manifestation over different litho-units indicate multiple tectonic episodes.

Geological interpretation from the Kaladgi Basin is based on integration of heliborne time domain electromagnetic (HELITEM), magnetic and gamma-ray spectrometry data with available geological mapping, ground exploration data, various published papers and spectral remote sensing data such as Landsat 7ETM+ and ASTER GDEM imagery. Electromagnetic (EM) data, magnetic, radiometric, Landsat TM and Aster datasets were used for delineation of surface and subsurface extent of geological units and structural elements and for better understanding of the overall structural pattern of the Kaladgi Basin, including distribution of its local depocentres, the resistive basement surface and the magnetic basement topography. The interpretation of the available data details the localisation of intrusive bodies, basaltic lava flows, mafic dykes, basement faults and major intrabasinal fault systems. Three dimensional grids (voxel models) of EM data were used for visualization in three dimensions.

Nine years of experience with 2286 commercial synthesis allowed us to deliver comprehensive information on the quality of (18)F-FDG production. Semi-automated FDG production line using Cyclone 18/9 machine (IBA Belgium), TRACERLab MXFDG synthesiser (GE Health, USA) using alkalic hydrolysis, grade "A" isolator with dispensing robotic unit (Tema Sinergie, Italy), and automatic control system under GAMP5 (minus2, Slovakia) was assessed by TQM tools as highly reliable aseptic production line, fully compliant with Good Manufacturing Practice and just-in-time delivery of FDG radiopharmaceutical. Fluoride-18 is received in steady yield and of very high radioactive purity. Synthesis yields exhibited high variance connected probably with quality of disposable cassettes and chemicals sets. Most performance non-conformities within the manufacturing cycle occur at mechanical nodes of dispensing unit. The long-term monitoring of 2286 commercial synthesis indicated high reliability of automatic synthesizers. Shewhart chart and ANOVA analysis showed that minor non-compliances occurred were mostly caused by the declinations of less experienced staff from standard operation procedures, and also by quality of automatic cassettes. Only 15 syntheses were found unfinished and in 4 cases the product was out-of-specification of European Pharmacopoeia. Most vulnerable step of manufacturing was dispensing and filling in grade "A" isolator. Its cleanliness and sterility was fully controlled under the investigated period by applying hydrogen peroxide vapours (VHP). Our experience with quality assurance in the production of [(18)F]-fluorodeoxyglucose (FDG) at production facility of BIONT based on TRACERlab MXFDG production module can be used for bench-marking of the emerging manufacturing and automated manufacturing systems.

The aim of the present study was to evaluate digital tomosynthesis (DTS) in thoracic spine imaging, comparing the reproduction of anatomical structures with that achieved using digital radiography (DR). In a prospective visual grading study, 23 patients referred in 2014 for elective radiographic examination of the thoracic spine were examined using lateral DR and DTS. The DR image and the DTS section images were read in random order by four radiologists, evaluating the ability of the modalities to present a clear reproduction of nine specific relevant structures of the thoracic vertebrae 3, 6 and 9 (T3, T6 and T9). The data were analysed using visual grading characteristics (VGC) analysis. The VGC analysis revealed a statistically significant difference in favour of DTS for all evaluated structures, except for the anterior vertebral edges and lower end plate surfaces of T6 and T9 and the cancellous bone of T9. The difference was most striking in T3 and for posterior structures. For no structure in any vertebra was the reproduction rated significantly better for DR. In conclusion, DTS of the thoracic spine appears to be a promising alternative to DR, especially in areas where the problem of overlaying anatomy is accentuated, such as posterior and upper thoracic structures.

Introduction: The spino-pelvic complex in humans helps to maintain an upright posture, by balancing the spinal sagittal alignment with the hip joints and pelvic girdle. The extent of how the hip joint may influence the spino-pelvic alignment is not fully understood. Hip joint cam femoro-acetabular impingement is a common source of hip and groin disability in young athletes and has been linked to abnormal joint morphology from repetitive loading of the proximal femoral head abutting against the acetabulum. The aim of this study was to compare the radiological parameters of spino-pelvic sagittal alignment and spinal types according to Roussouly’s classification in relation to hip joint cam femoro-acetabular impingement. Methods: The sample group (n=102), mean age (17.7 ± 1.4) years, consisted of elite skiers (n=75) and nonathletes (n=27). Hip joints were examined for increased morphological cam deformity, (alpha angle greater than 55o) with Magnetic Resonance Imaging and standing lateral plain radiographs were taken for measurements of the spinopelvic sagittal alignment. Results: A significant difference was shown in a mixed population (skiers and non-athletes) for an increased Pelvic Tilt angle (13°, SD 10.2) in the presence of morphological hip joint cam deformity compared with participants without cam deformity (8.5°, SD 7.1, P=0.036). Type II Roussouly spines occurred more frequently in skiers in the presence of increased cam (67%) compared with no cam (33%), however, this was not significant (P=0.19). Secondary findings highlighted significant differences shown for the prevalence of cam in a mixed-population for gender; males 60% (n=26) shown to have significantly more cam deformity compared with females 22% (n=10, P=0.001). Similar for height, with taller participants being shown to have significantly more cam deformity >177cm (SD 7.6) compared with no cam deformity

Background The purpose of the present study is to compare the radiological parameters of the spino-pelvic sagittal alignment in young elite skiers and non-athletes of a similar age. Methods The sample group (n = 102) consisted of elite Alpine and Mogul skiers (n = 75) and a non-athletic population (n = 27), mean age for both groups was 17.7 (±1.4) years (skiers mean age 18.3 SD 1.1 and controls 16.4 SD 0.6). Radiological measurements of the spino-pelvic sagittal alignment were examined from plain radiographs taken in the long-standing position. Results There were no significant differences reported in the pelvic parameters between both groups. A difference was reported in the sagittal vertebral axis between skiers (8.0 cm SD 46.0) and the control group (−2.0 cm SD 39.0), which may be of clinical significance, in spite of being statistically non-significant. Type I spinal curves according to Roussouly were shown to be more prevalent in the skiers (18.2 %) compared with the control group (0.0 %) and were statistically significant (p = 0.03). Conclusion Elite young skiers are shown to have a more prevalent type I spine and a different spino-pelvic sagittal alignment compared to a healthy non-sporting population of a similar age.

In the work we analyze three cases of unusual dyadic deaths when the perpetrator of homicide committed suicide shortly after the murder. In the first case a man stabbed his girlfriend with a knife and subsequently committed a car crash suicide. In the second case an apparent simultaneous hanging of a married couple turned out to be homicide-suicide act. In the last case a man shot his ex-wife while she was on a walk with their dog and in a short time turned the gun against himself.

Validation of the Debrunner Kyphometer as a clinical non-radiological method for investigating spinal sagittal alignment was compared with standing lateral radiographs. The sample group (n=102) consisted of elite Alpine skiers (n=75) and a non-athletic population (n=27), mean age 17.7 (±1.4) years. Non-radiological and radiological measurements of the spinal sagittal kyphosis and lordosis range of motion were carried out in the erect standing position. Thoracic kyphosis measurements comparing the Debrunner Kyphometer with a radiological standard, showed a good level of agreement and a statistical significance (ICC 0.67, 95% CI: 0.26 to 0.83, p

The Logar Ophiolite Complex (LOC) is located 30 km south of Kabul, Afghanistan, and extends over approximately 2000 km2. It comprises a lower lherzolitic-dunitic-harzburgitic-gabbro ultramafic-mafic unit that passes upwards into a dolerite dyke complex, basaltic pillow lavas and an uppermost sequence of volcaniclastic- and terrigenous-dominated sedimentary units. The ophiolite represents an obducted remnant of intra-Tethyan basin oceanic crust, thrust onto a platform-style cover component of the Kabul Terrane during the Himalayan orogeny. Platinum group minerals have been detected for the first time in chromitites and ultramafic units from the LOC. Two distinct types of chromitites and ultramafic lithologies with different origins have also been identified in this study. The first type is a low Cr, PGE-poor chromitite interpreted to have been produced in a mid ocean ridge (MOR) environment. The second type is a high Cr, relatively PGE-rich dunite and peridotite from a boninitic magma produced in a supra-subduction zone (SSZ) setting. Platinum group element (PGE) abundances in these chromitites average 12 ppb and 26 ppb for PtzPdzRh for the dunite and peridotite. Chondrite-normalised PGE patterns have two distinct trends: (a) the MOR rocks have a positive Ru anomaly with a negative Pt anomaly and a generally negative slope; and (b) the SSZ rocks show weak positive Ru and Pt anomalies and a positive slope. It is concluded that the negative sloping pattern is typical of PGE in most ophiolites elsewhere. In contrast, the positively sloping pattern is more unusual and may indicate PGE remobilisation and enrichment.

Legal framework for expert witnesses in the continental legal system differs from that of common law in many aspects. The position of an expert witness in continental legal system is more formalized and the processual rights and duties of an expert witness differs from rights and duties of witness in general. As of 1st September 2004 the Act No. 417/2002 Coll. on Expert Witnesses, Translators and Interpreters became effective in the Slovak Republic. The Act repealed expert witnesses legislation that originated from 1967 which is still effective in the Czech Republic. The authors present a short overview of the Act.

A FALCON® AGG and magnetic survey in the Glyde Sub-basin aims to define the structural pattern to identify unconventional hydrocarbon plays. The survey area consists of variable thick fluvial and lacustrine to shallow marginal marine carbonate-siliciclastic sequences and lesser volcanic rocks. The dominant tectonic feature identified on the AGG data is the Emu Fault Zone: a major structure of the central-southern part of the McArthur Basin. Seismic and surface geology suggest its overall sub-vertical strike-slip nature with positive flower structure geometry. In the north, a regional size pop-up structure, reverse, transpressional and strike-slip faults, and abundant synclines and anticlines identified in the AGG data indicate sinistral transpression. In the south, a transtensional segment of the Emu Fault Zone formed several regularly oriented, fault controlled depocentres. A geological cross-section across the Glyde Sub-basin supported by gravity modelling indicates a system of inverted transtensional faults. Offsets and bifurcations are common, forming local-scale transtensional or transpressional areas. The relationship between dolomitic carbonaceous siltstone, fault-related hydrothermal dolomite (HTD), and the tectonic pattern strongly suggests that the Emu Fault Zone controlled fluid migration and fault-related HTD deposition. Brecciated HTD reservoirs are best developed where a combination of strike-slip movement and extension allowed dolomitising and porosity-generating fluids to migrate along fracture networks, especially in transtensional pull-apart structures, and along the principal faults bounding elevated parts of the basement. This is consistent with the results of the Glyde–1 ST1 exploration well, which drilled 122 m of gas charged dolomitic breccia.

As of 1st January 2003 the Law No. 417/2002 Coll. on the Usage of Deoxyribonucleotic Acid Analysis for the Identification of Persons became effective in the Slovak Republic. The Law sets the conditions to take samples due to carry out the forensic DNA analysis, laid down regulations for laboratories approved to perform DNA analysis and at the same time establishes national database of DNA profiles. The author presents short overview of the Law.

Venous wall weakness is supposed to be the most probable reason of primary varicosis. There are conflicting findings in literature about its structural changes. NO is potent vasodilatator due to the smooth muscle relaxation. It is synthesized by nitric oxide synthase (NOS). There are 3 known isoforms of NOS: nNOS (neuronal NOS), iNOS (inducible NOS), eNOS (endothelial NOS).10 varicose vein and 10 control vein samples were processed by standard light microscopy method. Sections were then processed by standard immuno-histochemic technique using rabbit polyclonal antibodies against all 3 NOS isoforms: iNOS, eNOS (SantaCruz, USA), nNOS (BioScience, USA). Antibodies expression was evaluated semiquantitatively and then proved morphometricaly by 2D image analysis (ImageJ 1.34n, National Institute of Health, USA). Total area of NOS isoforms expressions was determined by color analysis and color digital substraction.Histomorphological and semi quantitative evaluation of NOS isoforms showed discontinuous and significantly lower expression of all 3 NOS isoforms in tunica media of varicose veins compared with control group, where the expression of all 3 NOS isoforms was continuous. For the statistical analysis unpaired t-test was used.Our results suppose lower NO levels in varicose vein wall, deducing that varicose vasodilatation is due to other mechanism, although the stage of chronic venous disease of varicose vein samples was undetermined. Our results are in contradiction with previously published results of Howlader et al., who observed raised total NO levels in patients with severe stages of chronic venous disease(Tab. 2, Fig. 13, Ref. 18).

Recreational and technical diving in the past twenty years have become extraordinary popular. Until then diving was a priority of police, army and scientists. Today more and more enthusiasts are exposed to abnormally high surrounding pressure. To the severest of all risks associated with diving, decompression sickness is the greatest threat. Even the most advanced scientific approaches yet did not reveal the complex mechanisms of decompression sickness formation. The majority of experiments use a live model for decompression sickness studies. This is associated with high fatality rate. The new approach of this scientific study is in the use of an in vitro working media as a means of visualization of gas bubbles due to decompression. The aim of this study is to bring above new approaches in in vitro gas bubble formation during decompression. Main goals are: development of in vitro inert gas bubble visualization and evaluation techniques after a real decompression dive with air a as the diving gas and EANx50 as a decompression gas. We selected cell cultures derived from human fibroblasts B-HEF-2 and cell cultures of mice N2A neuroblasts. We used two decompression profiles. "Explosive" decompression profile with a linear compression to overpressure of 50 bar with an rapid decompression to atmospheric pressure (1 bar). In simulation of a realistic decompression profile we used compressed air as a mean for compression and isocompression breathing gas and an EANx50 blend as a decompression breathing gas. This dive was planned with the use of a VPM-B decompression profile by V-Planner software v.3.62. Our latest experiments show that DNA fragmentation and apoptosis is activated during decompression shock. Use of culture cells can be of great value in further studies of decompression changes in the cellular and subcellular level.

As of 1st January 2006, new criminal law consisting of the Act No. 300/2004 Coll. (Penal Code) and the Act No. 301/2005 Coll. (Criminal Procedure Code) became effective in the Slovak Republic. These two acts replaced Criminal Law originating from 1961. The author analyses impact and changes introduced with new Criminal Procedure Code in the regulation of expert witness in general and expert witness testimony.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access. Nearly three-quarters of the 143 genetic signals associated with platelet and erythrocyte phenotypes identified by meta-analyses of genome-wide association (GWA) studies are located at non-protein-coding regions. Here, we assessed the role of candidate regulatory variants associated with cell type-restricted, closely related hematological quantitative traits in biologically relevant hematopoietic cell types. We used formaldehyde-assisted isolation of regulatory elements followed by next-generation sequencing (FAIRE-seq) to map regions of open chromatin in three primary human blood cells of the myeloid lineage. In the precursors of platelets and erythrocytes, as well as in monocytes, we found that open chromatin signatures reflect the corresponding hematopoietic lineages of the studied cell types and associate with the cell type-specific gene expression patterns. Dependent on their signal strength, open chromatin regions showed correlation with promoter and enhancer histone marks, distance to the transcription start site, and ontology classes of nearby genes. Cell type-restricted regions of open chromatin were enriched in sequence variants associated with hematological indices. The majority (63.6%) of such candidate functional variants at platelet quantitative trait loci (QTLs) coincided with binding sites of five transcription factors key in regulating megakaryopoiesis. We experimentally tested 13 candidate regulatory variants at 10 platelet QTLs and found that 10 (76.9%) affected protein binding, suggesting that this is a frequent mechanism by which regulatory variants influence quantitative trait levels. Our findings demonstrate that combining large-scale GWA data with open chromatin profiles of relevant cell types can be a powerful means of dissecting the genetic architecture of closely related quantitative traits. Marie-Curie Initial Training Network NETSIM British Heart Foundation RG/09/12/28096 National Institutes for Health RP-PG-0310-1002 Wellcome Trust 098051 info:eu-repo/grantAgreement/EC/FP7/282510

Barban N, Jansen R, de Vlaming R, Vaez A, Mandemakers JJ, Tropf FC, Shen X, Wilson JF, Chasman DI, Nolte IM, Tragante V, van der Laan SW, Perry JR, Kong A; BIOS Consortium, Ahluwalia TS, Albrecht E, Yerges-Armstrong L, Atzmon G, Auro K, Ayers K, Bakshi A, Ben-Avraham D, Berger K, Bergman A, Bertram L, Bielak LF, Bjornsdottir G, Bonder MJ, Broer L, Bui M, Barbieri C, Cavadino A, Chavarro JE, Turman C, Concas MP, Cordell HJ, Davies G, Eibich P, Eriksson N, Esko T, Eriksson J, Falahi F, Felix JF, Fontana MA, Franke L, Gandin I, Gaskins AJ, Gieger C, Gunderson EP, Guo X, Hayward C, He C, Hofer E, Huang H, Joshi PK, Kanoni S, Karlsson R, Kiechl S, Kifley A, Kluttig A, Kraft P, Lagou V, Lecoeur C, Lahti J, Li-Gao R, Lind PA, Liu T, Makalic E, Mamasoula C, Matteson L, Mbarek H, McArdle PF, McMahon G, Meddens SF, Mihailov E, Miller M, Missmer SA, Monnereau C, van der Most PJ, Myhre R, Nalls MA, Nutile T, Kalafati IP, Porcu E, Prokopenko I, Rajan KB, Rich-Edwards J, Rietveld CA, Robino A, Rose LM, Rueedi R, Ryan KA, Saba Y, Schmidt D, Smith JA, Stolk L, Streeten E, Tönjes A, Thorleifsson G, Ulivi S, Wedenoja J, Wellmann J, Willeit P, Yao J, Yengo L, Zhao JH, Zhao W, Zhernakova DV, Amin N, Andrews H, Balkau B, Barzilai N, Bergmann S, Biino G, Bisgaard H, Bønnelykke K, Boomsma DI, Buring JE, Campbell H, Cappellani S, Ciullo M, Cox SR, Cucca F, Toniolo D, Davey-Smith G, Deary IJ, Dedoussis G, Deloukas P, van Duijn CM, de Geus EJ, Eriksson JG, Evans DA, Faul JD, Sala CF, Froguel P, Gasparini P, Girotto G, Grabe HJ, Greiser KH, Groenen PJ, de Haan HG, Haerting J, Harris TB, Heath AC, Heikkilä K, Hofman A, Homuth G, Holliday EG, Hopper J, Hyppönen E, Jacobsson B, Jaddoe VW, Johannesson M, Jugessur A, Kähönen M, Kajantie E, Kardia SL, Keavney B, Kolcic I, Koponen P, Kovacs P, Kronenberg F, Kutalik Z, La Bianca M, Lachance G, Iacono WG, Lai S, Lehtimäki T, Liewald DC; LifeLines Cohort Study, Lindgren CM, Liu Y, Luben R, Lucht M, Luoto R, Magnus P, Magnusson PK, Martin NG, McGue M, McQuillan R, Medland SE, Meisinger C, Mellström D, Metspalu A, Traglia M, Milani L, Mitchell P, Montgomery GW, Mook-Kanamori D, de Mutsert R, Nohr EA, Ohlsson C, Olsen J, Ong KK, Paternoster L, Pattie A, Penninx BW, Perola M, Peyser PA, Pirastu M, Polasek O, Power C, Kaprio J, Raffel LJ, Räikkönen K, Raitakari O, Ridker PM, Ring SM, Roll K, Rudan I, Ruggiero D, Rujescu D, Salomaa V, Schlessinger D, Schmidt H, Schmidt R, Schupf N, Smit J, Sorice R, Spector TD, Starr JM, Stöckl D, Strauch K, Stumvoll M, Swertz MA, Thorsteinsdottir U, Thurik AR, Timpson NJ, Tung JY, Uitterlinden AG, Vaccargiu S, Viikari J, Vitart V, Völzke H, Vollenweider P, Vuckovic D, Waage J, Wagner GG, Wang JJ, Wareham NJ, Weir DR, Willemsen G, Willeit J, Wright AF, Zondervan KT, Stefansson K, Krueger RF, Lee JJ, Benjamin DJ, Cesarini D, Koellinger PD, den Hoed M, Snieder H, Mills MC.

Platelets are the second most abundant cell type in blood and are essential for maintaining haemostasis. Their count and volume are tightly controlled within narrow physiological ranges, but there is only limited understanding of the molecular processes controlling both traits. Here we carried out a high-powered meta-analysis of genome-wide association studies (GWAS) in up to 66,867 individuals of European ancestry, followed by extensive biological and functional assessment. We identified 68 genomic loci reliably associated with platelet count and volume mapping to established and putative novel regulators of megakaryopoiesis and platelet formation. These genes show megakaryocyte-specific gene expression patterns and extensive network connectivity. Using gene silencing in Danio rerio and Drosophila melanogaster, we identified 11 of the genes as novel regulators of blood cell formation. Taken together, our findings advance understanding of novel gene functions controlling fate-determining events during megakaryopoiesis and platelet formation, providing a new example of successful translation of GWAS to function. © 2011 Macmillan Publishers Limited. All rights reserved.