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Aims: Biomarker‐driven therapies have not been developed for infant medulloblastoma (iMB). We sought to robustly sub‐classify iMB, and proffer strategies for personalized, risk‐adapted therapies. Methods: We characterized the iMB molecular landscape, including second‐generation subtyping, and the associated retrospective clinical experience, using large independent discovery/validation cohorts (n = 387). Results: iMBGrp3 (42%) and iMBSHH (40%) subgroups predominated. iMBGrp3 harboured second‐generation subtypes II/III/IV. Subtype II strongly associated with large‐cell/anaplastic pathology (LCA; 23%) and MYC amplification (19%), defining a very‐high‐risk group (0% 10yr overall survival (OS)), which progressed rapidly on all therapies; novel approaches are urgently required. Subtype VII (predominant within iMBGrp4) and subtype IV tumours were standard risk (80% OS) using upfront CSI‐based therapies; randomized‐controlled trials of upfront radiation‐sparing and/or second‐line radiotherapy should be considered. Seventy‐five per cent of iMBSHH showed DN/MBEN histopathology in discovery and validation cohorts (P < 0.0001); central pathology review determined diagnosis of histological variants to WHO standards. In multivariable models, non‐DN/MBEN pathology was associated significantly with worse outcomes within iMBSHH. iMBSHH harboured two distinct subtypes (iMBSHH‐I/II). Within the discriminated favourable‐risk iMBSHH DN/MBEN patient group, iMBSHH‐II had significantly better progression‐free survival than iMBSHH‐I, offering opportunities for risk‐adapted stratification of upfront therapies. Both iMBSHH‐I and iMBSHH‐II showed notable rescue rates (56% combined post‐relapse survival), further supporting delay of irradiation. Survival models and risk factors described were reproducible in independent cohorts, strongly supporting their further investigation and development. Conclusions: Investigations of large, retrospective cohorts have enabled the comprehensive and robust characterization of molecular heterogeneity within iMB. Novel subtypes are clinically significant and subgroup‐dependent survival models highlight opportunities for biomarker‐directed therapies. [ABSTRACT FROM AUTHOR]

A 610-m-high portion of the South Wall of the Bingham Canyon open pit has experienced slow-moving slope deformations several times during spring melt until the movement was stabilized approximately 7 years ago. To develop and optimize life of mine slope designs, an understanding of the mechanism(s) and associated material strength parameters, was required. A back-analysis and calibration of the strength parameters for the salient rock mass and structural features was undertaken. The back-analysis consisted of understanding the conditions and trigger for the slope movement and adjusting strength parameters to match available monitoring data (time-domain reflectometer cables, inclinometers, interferometric radar data, etc.). The trigger for the movement was attributed to the spring high-perched water levels in the upper part of the wall. A FLAC3D model was built to back-analyze and capture the complex behavior of the slope during the high deformation period (August 2011). The back-analysis was consistent with the conceptual model and indicated that the slide was composed of mixed mechanisms, namely, a structurally controlled mechanism for the upper wall and a rock mass controlled mechanism for the lower wall (toe). The analysis supported by a converging FLAC3D model, were used to guide mining engineers in developing robust pit design in the South Wall. Today, the O-Slide instability is being fully managed by rigorous monitoring, implementation of a toe buttress, successful dewatering efforts, and unloading of the movement mass as another slice of mining advances down the South Wall. [ABSTRACT FROM AUTHOR]

Pandemic influenza A( H1 N1)pdm09 virus has retained its ability to infect swine whilst developing the ability to transmit effectively between humans, thus making the pig a valuable model for studying disease pathogenesis in both species. Lung lesions in pigs caused by infection with influenza A viruses vary in both their severity and distribution with individual lung lobes exhibiting lesions at different stages of infection pathogenic development and disease resolution. Consequently, investigating interactions between the virus and host and their implications for disease pathogenesis can be complicated. Studies were undertaken to investigate the discrete expression of pro- and anti-inflammatory mediators during lung lesion formation in pigs during infection with influenza A( H1 N1)pdm09 ( A/ Hamburg/05/09) virus. Laser capture microdissection was used to identify and select lung lobules containing lesions at different stages of development. Dissected samples were analysed using quantitative RT- PCR to assess pro- and anti-inflammatory cytokine m RNA transcripts. Differential expression of the immune mediators IL-8, IL-10 and IFN-γ was observed depending upon the lesion stage assessed. Upregulation of IFN-γ, IL-8 and IL-10 m RNA was observed in stage 2 lesions, whereas decreased m RNA expression was observed in stage 3 lesions, with IL-8 actively downregulated when compared with controls in both stage 3 and stage 4 lesions. This study highlighted the value of using laser capture microdissection to isolate specific tissue regions and investigate subtle differences in cytokine m RNA expression during lesion development in pigs infected with influenza A( H1 N1)pdm09. [ABSTRACT FROM AUTHOR]

A platform consisting of a multi-shock drive and an implosion backlighter has been developed for x-ray absorption fine structure (XAFS) measurements on materials compressed to multi-Mbar pressures. The experimental setup, target design, and backlighter characteristics are presented. Extended XAFS (EXAFS) measurements for various materials have been demonstrated. A quintuple-crystal design is described to enhance the efficiency of the x-ray spectrometer, enabling observation of very weak EXAFS signals in a single shot. [ABSTRACT FROM AUTHOR]

Measurements have been made of the in-flight dynamics of imploding capsules indirectly driven by laser energies of 1-1.7 MJ at the National Ignition Facility [Miller et al., Nucl. Fusion 44, 228 (2004)]. These experiments were part of the National Ignition Campaign [Landen et al., Phys. Plasmas 18, 051002 (2011)] to iteratively optimize the inputs required to achieve thermonuclear ignition in the laboratory. Using gated or streaked hard x-ray radiography, a suite of ablator performance parameters, including the time-resolved radius, velocity, mass, and thickness, have been determined throughout the acceleration history of surrogate gas-filled implosions. These measurements have been used to establish a dynamically consistent model of the ablative drive history and shell compressibility throughout the implosion trajectory. First results showed that the peak velocity of the original 1.3-MJ Ge-doped polymer (CH) point design using Au hohlraums reached only 75% of the required ignition velocity. Several capsule, hohlraum, and laser pulse changes were then implemented to improve this and other aspects of implosion performance and a dedicated effort was undertaken to test the sensitivity of the ablative drive to the rise time and length of the main laser pulse. Changing to Si rather than Ge-doped inner ablator layers and increasing the pulse length together raised peak velocity to 93% ± 5% of the ignition goal using a 1.5 MJ, 420 TW pulse. Further lengthening the pulse so that the laser remained on until the capsule reached 30% (rather than 60%-70%) of its initial radius, reduced the shell thickness and improved the final fuel ρR on companion shots with a cryogenic hydrogen fuel layer. Improved drive efficiency was observed using U rather than Au hohlraums, which was expected, and by slowing the rise time of laser pulse, which was not. The effect of changing the Si-dopant concentration and distribution, as well as the effect of using a larger initial shell thickness were also examined, both of which indicated that instabilities seeded at the ablation front are a significant source of hydrodynamic mix into the central hot spot. Additionally, a direct test of the surrogacy of cryogenic fuel layered versus gas-filled targets was performed. Together all these measurements have established the fundamental ablative-rocket relationship describing the dependence of implosion velocity on fractional ablator mass remaining. This curve shows a lower-than-expected ablator mass at a given velocity, making the capsule more susceptible to feedthrough of instabilities from the ablation front into the fuel and hot spot. This combination of low velocity and low ablator mass indicates that reaching ignition on the NIF will require >20 μm (∼10%) thicker targets and laser powers at or beyond facility limits. [ABSTRACT FROM AUTHOR]

The development of vaccines that prevent rabies has a long and distinguished history, with the earliest preceding modern understanding of viruses and the mechanisms of immune protection against disease. The correct application of inactivated tissue culture-derived vaccines is highly effective at preventing the development of rabies, and very few failures are recorded. Furthermore, oral and parenteral vaccination is possible for wildlife, companion animals and livestock, again using inactivated tissue culture-derived virus. However, rabies remains endemic in many regions of the world and causes thousands of human deaths annually. There also remain no means of prophylaxis for rabies once the virus enters the central nervous system (CNS). One reason for this is the poor immune response within the CNS to infection with rabies virus (RABV). New approaches to vaccination using modified rabies viruses that express components of the innate immune system are being applied to this problem. Preliminary reports suggest that direct inoculation of such viruses could trigger an effective anti-viral response and prevent a fatal outcome from RABV infection. [ABSTRACT FROM AUTHOR]

The limb-girdle muscular dystrophies are a group of disorders with wide genetic and clinical heterogeneity. Recently, mutations in the ANO5 gene, which encodes a putative calcium-activated chloride channel belonging to the Anoctamin family of proteins, were identified in five families with one of two previously identified disorders, limb-girdle muscular dystrophy 2L and non-dysferlin Miyoshi muscular dystrophy. We screened a candidate group of 64 patients from 59 British and German kindreds and found the truncating mutation, c.191dupA in exon 5 of ANO5 in 20 patients, homozygously in 15 and in compound heterozygosity with other ANO5 variants in the rest. An intragenic single nucleotide polymorphism and an extragenic microsatellite marker are in linkage disequilibrium with the mutation, suggesting a founder effect in the Northern European population. We have further defined the clinical phenotype of ANO5-associated muscular dystrophy. Patients show adult onset proximal lower limb weakness with highly raised serum creatine kinase values (average 4500 IU/l) and frequent muscle atrophy and asymmetry of muscle involvement. Onset varies from the early 20 s to 50 s and the weakness is generally slowly progressive, with most patients remaining ambulant for several decades. Distal presentation is much less common but a milder degree of distal lower limb weakness is often observed. Upper limb strength is only mildly affected and cardiac and respiratory function is normal. Females appear less frequently affected. In the North of England population we have identified eight patients with ANO5 mutations, suggesting a minimum prevalence of 0.27/100,000, twice as common as dysferlinopathy. We suggest that mutations in ANO5 represent a relatively common cause of adult onset muscular dystrophy with high serum creatine kinase and that mutation screening, particularly of the common mutation c.191dupA, should be an early step in the diagnostic algorithm of adult limb-girdle muscular dystrophy patients. [ABSTRACT FROM AUTHOR]

The velocity and remaining ablator mass of an imploding capsule are critical metrics for assessing the progress toward ignition of an inertially confined fusion experiment. These and other ablator rocket parameters have been measured using a single streaked x-ray radiograph. A regularization technique has been used to determine the ablator density profile ρ(r) at each time step; moments of ρ(r) then provide the areal density, average radius, and mass of the unablated, or remaining, ablator material, with the velocity determined from the time derivative of the average radius. The technique has been implemented on experiments at the OMEGA laser facility. [ABSTRACT FROM AUTHOR]

The velocity and remaining ablator mass of an imploding capsule are critical metrics for assessing the progress toward ignition of an inertially confined fusion experiment. These and other convergent ablator performance parameters have been measured using a single streaked x-ray radiograph. Traditional Abel inversion of such a radiograph is ill-posed since backlighter intensity profiles and x-ray attenuation by the ablated plasma are unknown. To address this we have developed a regularization technique which allows the ablator density profile ρ(r) and effective backlighter profile I0(y) at each time step to be uniquely determined subject to the constraints that ρ(r) is localized in radius space and I0(y) is delocalized in object space. Moments of ρ(r) then provide the time-resolved areal density, mass, and average radius (and thus velocity) of the remaining ablator material. These results are combined in the spherical rocket model to determine the ablation pressure and mass ablation rate during the implosion. The technique has been validated on simulated radiographs of implosions at the National Ignition Facility [Miller et al., Nucl. Fusion 44, 228 (2004)] and implemented on experiments at the OMEGA laser facility [Boehly et al., Opt. Commun. 133, 495 (1997)]. [ABSTRACT FROM AUTHOR]

The equation of state (EOS) of polystyrene and polypropylene were measured using laser-driven shock waves with pressures from 1 to 10 Mbar. Precision data resulting from the use of α-quartz as an impedance-matching (IM) standard tightly constrains the EOS of these hydrocarbons, even with the inclusion of systematic errors inherent to IM. The temperature at these high pressures was measured, which, combined with kinematic measurements, provide a complete shock EOS. Both hydrocarbons were observed to reach similar compressions and temperatures as a function of pressure. The materials were observed to transition from transparent insulators to reflecting conductors at pressures of 1 to 2 Mbar. [ABSTRACT FROM AUTHOR]

Since Ross proposed that there might be ‘diamonds in the sky’ in 1981 (ref. 1), the idea of significant quantities of pure carbon existing in giant planets such as Uranus and Neptune has gained both experimental and theoretical support. It is now accepted that the high-pressure, high-temperature behaviour of carbon is essential to predicting the evolution and structure of such planets. Still, one of the most defining of thermal properties for diamond, the melting temperature, has never been directly measured. This is perhaps understandable, given that diamond is thermodynamically unstable, converting to graphite before melting at ambient pressure, and tightly bonded, being the strongest bulk material known. Shock-compression experiments on diamond reported here reveal the melting temperature of carbon at pressures of 0.6–1.1 TPa (6–11 Mbar), and show that crystalline diamond can be stable deep inside giant planets such as Uranus and Neptune. The data indicate that diamond melts to a denser, metallic fluid—with the melting curve showing a negative Clapeyron slope—between 0.60 and 1.05 TPa, in good agreement with predictions of first-principles calculations. Temperature data at still higher pressures suggest diamond melts to a complex fluid state, which dissociates at shock pressures between 1.1 and 2.5 TPa (11–25 Mbar) as the temperatures increase above 50,000 K. [ABSTRACT FROM AUTHOR]

Drawing on interviews with parents of children with complex disabilities in several school systems in a US state, this paper examines how temporal units such as the school day and school year and practices organized around artifacts like clocks and calendars work as 'devices of temporal distanciation' to separate children with disabilities from other children and exclude their families from critical relations with schools. The paper focuses on two kinds of effects: the ways differentiated timetables separate children and the ways constructing school time in bounded, discrete units limits the ability of parents and children to make key elements of their lives visible to the school. [ABSTRACT FROM AUTHOR]

Macroscopic haematuria is a commonly seen condition in the emergency department (ED), which has a variety of causes. However, most importantly, macroscopic haematuria has a high diagnostic yield for urological malignancy. 30% of patients presenting with painless haematuria are found to have a malignancy. The majority of these patients can be managed in the outpatient setting. This review of current literature suggests a management pathway that can be used in the ED. A literature search was done using Medline, PubMed and Google. In men aged >60 years, the positive predictive value of macroscopic haematuria for urological malignancy is 22.1%, and in women of the same age it is 8.3%. In terms of the need for follow-up investigation, a single episode of haematuria is equally important as recurrent episodes. Baseline investigation in the ED includes full blood count, urea and electrolyte levels, midstream urine dipstick, β human chorionic gonadotrophin, and formal microscopy, culture and sensitivities. Treatment of macroscopic haematuria aims at RESP—Resuscitation, Ensuring, Safe and Prompt. Indications for admission include clot retention, cardiovascular instability, uncontrolled pain, sepsis, acute renal failure, coagulopathy, severe comorbidity, heavy haematuria or social restrictions. Discharged patients should drink plenty of clear fluids and return for further medical attention if the following occur: clot retention, worsening haematuria despite adequate fluid intake, uncontrolled pain or fever, or inability to cope at home. Follow-up by a urological team should be promptly arranged, ideally within the 2- week cancer referral target. [ABSTRACT FROM AUTHOR]

Background and aims: Cyclooxygenase 2 (COX-2) is upregulated in most colorectal cancers and is responsible for metabolism of the endogenous cannabinoid, anandamide, into prostaglandin-ethanolamides (PG-EAs). The aims of this study were to determine whether anandamide and PG-EAs induce cell death in colorectal carcinoma (CRC) cells, and whether high levels of COX-2 in CRC cells could be utilised for their specific targeting for cell death by anandamide. Methods: We determined the effect of anandamide on human CRC cell growth by measuring cell growth and cell death, whether this was dependent on COX-2 protein expression or enzyme activity, and the potential involvement of PG-EAs in induction of cell death. Results: Anandamide inhibited the growth of CRC cell lines HT29 and HCA7/C29 (moderate and high COX-2 expressors, respectively) but had little effect on the very low COX-2 expressing CRC cell line, SW480. Induction of cell death in HT29 and HCA7/C29 cell lines was partially rescued by the COX-2 selective inhibitor NS398. Cell death induced by anandamide was neither apoptosis nor necrosis. Furthermore, inhibition of fatty acid amide hydrolase potentiated the non-apoptotic cell death, indicating that anandamide induced cell death was mediated via metabolism of anandamide by COX-2, rather than its degradation into arachidonic acid and ethanolamine. Interestingly, both PGE2-EA and PGD2-EA induced classical apoptosis. Conclusions: These findings suggest anandamide may be a useful chemopreventive/therapeutic agent for colorectal cancer as it targets cells that are high expressors of COX-2, and may also be used in the eradication of tumour cells that have become resistant to apoptosis. [ABSTRACT FROM AUTHOR]

The Hugoniot of quartz has been measured using laser-driven shock waves with pressures from 2 to 15 Mbars. Within this pressure range silica transforms from a liquid near melt into a dense plasma. Results are in good agreement with previous studies in part of this range performed using explosive- and nuclear-driven shocks indicating the absence of time-dependent effects for time scales between several hundred picoseconds and several hundred microseconds. These data combined with earlier data at lower pressures clearly show the increasing compressibility of silica as it transitions from solid to liquid to dense plasma regimes. [ABSTRACT FROM AUTHOR]

Modern measurement techniques such as aerial laser scanning allow for rapid determination of the spatial variation of sea surface elevation. Wave fields obtained from such data show spatial inhomogeneity associated with the presence of wave groups. A method based on two-dimensional directional wavelet analysis is described by which such inhomogeneity can be characterized in the spatial and wavenumber domains. The directional wavelet method has been applied to aerial laser scanning measurements of nearshore wave conditions off the east coast of New Zealand’s South Island. A high level of spatial variability was observed, with evidence of ensembles of wave-group envelopes of quasi-Gaussian form. These envelopes occur, with variations in spatial location, across a range of wavelet scales and directions. [ABSTRACT FROM AUTHOR]

The death ligand TRAIL (Apo2L) has potential for cancer therapy, since tumour cells are thought to be more sensitive than normal cells. We investigated whether sensitivity to TRAIL increases during the adenoma to carcinoma transition of colorectal carcinogenesis. Under the same culture conditions, we compared the extent of TRAIL-induced apoptosis in four premalignant adenoma and three carcinoma cell lines. Although TRAIL induced some apoptosis in adenoma cultures, the carcinoma cell lines were significantly more sensitive (P<0.001). This finding was recapitulated in an in vitro model of tumour progression in which conversion of the adenoma cell line AA/C1 to a tumorigenic phenotype was associated with increased TRAIL sensitivity (P<0.001). Increased TRAIL sensitivity during colorectal carcinogenesis has been previously attributed to changes in the balance between TRAIL receptors TRAIL-R1 and -R2 and "decoy" receptors TRAIL-R3 and -R4 during malignant progression. To address this, cell surface receptor expression was measured by flow cytometry. In summary, during colorectal carcinogenesis, there is a marked increase in sensitivity to TRAIL-induced apoptosis associated with progression from benign to malignant tumour that could be exploited for colon cancer therapy, but alterations in cell surface TRAIL receptor expression may not be the primary reason for this change. [ABSTRACT FROM AUTHOR]

Focuses on cultural activities in the Mexican-American border region, particularly the cities of San Diego, California and Tijuana, Mexico. Redefinition of citizenship; Insights from Donna Haraway's essay "A Cyborg Manifesto"; Rejection of the distinction between bourgeois and proletarian.

Sand volumes and cross-shore sand transport within a swath of beach and shoreface at Mangawhai, Northland, New Zealand were monitored during six weeks of swell and storm waves in order to capture any significant sand exchanges between the beach and inner shelf. The main data-collection involved repeat surveys of sand levels over 16 profiles, evenly spaced along 500 m of shore and extending from dune-toe to 10-11 m depth. The upper beach was surveyed with Emery poles while a sea-sled was used for the shoreface. The sea-sled was equipped with tilt-sensors and a wheel so that the surveyed bed profile could be adjusted for mast-tilt and bedform effects. The spatial distribution of cross-shore sand fluxes was derived by integrating the sand level changes between consecutive surveys. Reference rods in the shoreface were used to verify the sled data and to identify depth of bed disturbance. An instrumented tripod was used to measure near-bed wave-orbital and steady-current velocities and sand concentrations and to compute sand fluxes at several points on the shoreface. Results showed that during a swell-dominated accretionary phase, onshore sand fluxes were associated with shoreward migrating bars in the swash zone and on the upper beachface but were negligible on the shoreface. With waves generated by an extra-tropical cyclone, offshore fluxes peaked over the outer bar as it was translated seaward but appeared to pinch-out at about 8 m depth, as predicted from wave climate statistics by HALLERMEIER'S (1981) model. This average pattern was confused at individual profiles by longshore gradients in sand transport associated with rip-channels, rhythmic topography, and non-uniform beach drainage. When averaged over the whole study swath, the differences in sand volume between surveys were small (1-4 m³m[sup -1]) and consistent with measurement error, suggesting that the beach-shoreface was essentially a closed system, with no significant sand exchange with offshore... [ABSTRACT FROM AUTHOR]

Fast protons >=1 MeV have been observed on the 60-beam, 30 kJ OMEGA laser [T. R. Boehly et al., Opt. Commun. 133, 495 (1997)] at an intensity I=10[sup 15] W/cm[sup 2] and a wavelength λ=0.35 μm. These energies are more than 5 times greater than those observed on previous, single-beam experiments at the same Iλ[sup 2]. The total energy in the proton spectrum above 0.2 MeV is ∼0.1% of the laser energy. Some of the proton spectra display intense, regular lines which may be related to ion acoustic perturbations in the expanding plasma. © 2001 American Institute of Physics. [ABSTRACT FROM AUTHOR]

The basis for a time-of-flight neutron spectrometer for inertial confinement fusion (ICF) experiments using recoils from a shaped scattering foil is presented. It is shown that the number of elastic recoils can be substantially increased by utilizing a large scattering foil in the shape of an ellipsoid, with the curvature of the ellipsoid being determined by the mass of the recoil particle. This shape allows the time-of-flight dispersion — present originally in the neutrons — to be maintained in the recoils despite the large foil area. The feasibility of using this design on current ICF experiments is discussed. © 2001 American Institute of Physics. [ABSTRACT FROM AUTHOR]

Discusses the design and fabrication of an electronic charged particle spectrometer to measure the energy spectra of charged particles from targets on the Omega Upgrade. Design of the magnet; Charge coupled devices; Energy resolution; Operating yield; Signal-to-noise; CR-39 track detectors.

Investigates competing congressional and presidential roles in making and articulating the United States' foreign policy. Reviews on rival Supreme Court decisions on the respective roles of the president and Congress, following the Iran-contra affair; Interpretations of both cases of constitutional meaning.

Examines sand wave development of an initially flat bottom under steady unidirectional flow on the basis of laboratory measurements. Change of sand wavelength and wave height; Combination of relationships into a double scaling form; Generation of initial bed waves.

The article focuses on two models of foreign-policy making, the bureaucratic politics model and the royal court model. These are helpful in explaining the U.S. arms sales to Iran in 1985 end in 1986. The bureaucratic politics model is particularly useful in clarifying both positions taken by leaders of the foreign policy bureaucracy to arms sales proposals and the behavior of these officials as sales were implemented.

A streaked radiography diagnostic has been proposed as a technique to determine the ablator mass remaining in an inertial confinement fusion ignition capsule at peak velocity. This instrument, the “HXRI-5,” has been designed to fit within a National Ignition Facility Diagnostic Instrument Manipulator. The HXRI-5 will be built at Sandia National Laboratories (SNL), and initial testing will be done at the SNL Z-Beamlet Facility. In this paper, we will describe the National Ignition Campaign requirements for this diagnostic, the instrument design, and the planned test experiments. [ABSTRACT FROM AUTHOR]

Discusses the results of experiments on the use of charged-coupled devices (CCD) for charged-particle spectroscopy on OMEGA and NOVA lasers. Description of the charged-particle device; Tests of back-illuminated CCD; Signal and noise.

Cardiac 3D printing is mainly performed from magnetic resonance imaging (MRI) and computed tomography (CT) 3D datasets, though anatomic detail of atrioventricular (AV) valves may be limited. 3D echo provides excellent visualization of AV valves. Thus, we tested the feasibility and accuracy of 3D printing from 3D echo in this pilot series of subjects with congenital heart disease (CHD), with a focus on valve anatomy. Five subjects with CHD were identified. 3D echo data were converted to 3D printable files and printed in collaboration with 3D Systems Healthcare (Golden, Colorado). A novel technique for valve modeling was utilized using commercially available software. Two readers (KM, SA) independently measured valve structures from 3D models and compared to source echo images. 3D printing was feasible for all cases. Table 1 shows measurements comparing 2D echo to 3D models. Bland Altman analysis showed close agreement and no significant bias between 2D and digital 3D models (mean difference 0.0, 95% CI 1.1 to − 1.1) or 2D vs printed 3D models, though with wider limits of agreement (mean difference − 0.3, 95% CI 1.9 to − 2.6). Accuracy of 3D models compared to 2D was within < 0.5 mm. This pilot study shows 3D echo datasets can be used to reliably print AV and semilunar valve structures in CHD. The 3D models are highly accurate compared to the source echo images. This is a novel and value-added technique that adds incremental information on cardiac anatomy over current methods. [ABSTRACT FROM AUTHOR]

A method for producing quantitative estimates of systematic uncertainties generated in the analysis of impedance-match shock-wave data is described. Central to the method is an analytic representation of the principal Hugoniot of the standard which incorporates a description of data-dependent uncertainties of the principal Hugoniot and model-dependent uncertainties of the off-Hugoniot states. Expressions for the sound speed and Grüneisen coefficient along the principal Hugoniot are also derived with uncertainties. An accurate impedance-match shock-wave equation of state for Al to shock pressure of 3 TPa is given and is used to estimate the systematic uncertainties of several previously published experimental results. [ABSTRACT FROM AUTHOR]

Abstract We analyse recent morphological evolution of braiding rivers of disparate regions of the Earth to develop and address the hypothesis that braiding of rivers tends to be reduced by human presence and related activities. Firstly, through a large-scale literature survey we observe generalised paths of bed degradation, channel narrowing and shift towards single-thread configuration in braided reaches due to multiple anthropogenic stressors. Secondly, we select three rivers from different geographic contexts characterised by complementary anthropic stressors for a detailed analysis (the lower Waitaki River in New Zealand, the middle Piave River in Italy and the lower Dunajec River in Poland) which shows that these rivers have undergone very similar trajectories of morphological change. In previous works, these morphodynamic changes have been related to the alteration of the fundamental physical processes of braided rivers, due to anthropogenic changes in constraints and controls. Here, a closer analysis of these alterations shows that analogous morphological evolutionary trajectories can result from very different paths of causation, i.e., from different management causes and different alteration of physical processes. Through the use of pattern predictors we analyse observed morphological trajectories and potential for recovery. We highlight the role of different geographic contexts as sources of constraints and drivers to the river evolution, with reference both to the physical and human environment, showing that the observed similar trajectories are the product of different local conditions and characteristics. These observations have implications for river management and restorations. [ABSTRACT FROM AUTHOR]

Recessive mutations in the ANO5 gene cause a spectrum of phenotypes ranging from isolated hyperCKaemia to limb girdle muscular dystrophy (LGMD2L), characterized by adult onset proximal lower limb muscular weakness and raised CK values. The recurrent exon 5 mutation (c.191dupA) has been found in most of the British and German patients so far reported. We performed molecular analysis of the ANO5 gene in a large cohort of undiagnosed patients with clinical suspicion of anoctaminopathy. We identified two pathogenic mutations in 42/205 unrelated patients (21%), while a single change only was found in further 14 patients. Fifteen pathogenic changes were novel. The founder c.191dupA mutation represents 61% of mutated alleles but is confirmed to be less prevalent in non-Northern European populations. Retrospective clinical analysis of patients with 2 mutations corroborates previous finding such as the male predominance and absence of major cardiac or respiratory involvement, as well as very mild late onset cases of both sexes and isolated hyperCKaemia only. Our results also confirm anoctaminopathy as one of the most common adult muscular dystrophies in Northern Europe, with a prevalence of about 20–25% in undiagnosed patients. [Copyright &y& Elsevier]

Ullrich Congenital Muscular Dystrophy (UCMD) and Bethlem Myopathy (BM) are muscle disorders within the spectrum of Collagen VI-related myopathies. These disorders are associated with mutations in the Collagen VI genes (COL6A1, COL6A2 and COL6A3), which are components of extracellular matrix (ECM). Several UCMD and BM phenotypes have been reported with no mutations in Collagen VIA genes, indicating genetic heterogeneity in these disorders. We investigated a consanguineous Saudi Arabian family with a UCMD-like phenotype but without mutations in the COL6A genes. By a combined approach of autozygosity analysis, exome sequencing and sanger sequencing we were able to identify an indel in exon 1 of the ALG2 (Asparagine-linked glycosylation 2) gene; c.283–296delGGGGACTGGCTGCc.283–293insAGTCCCCGGC p.73–76delGDWLinsSPR. ALG2 encodes mannosyltransferase of the N-glycosylation pathway. Due to the recently discovered role of N-glycosylation pathway genes in congenital myasthenia syndrome (CMS) (1) two patients from the family underwent electromyography repetitive nerve stimulation, which revealed a potential neuromuscular junction defect. Due to the fact that the phenotype of the family showed a mix of UCMD and CMS-like features, and that proper N-glycosylation is essential for secretion of collagens to extracellular matrix (ECM) (3), we aimed to investigate collagen VI assembly and secretion in the context of deficient Alg2. Collagen VI was assayed in ALG2 mutant patient dermal fibroblast cells and shRNA knock down cells by immunofluorescence and western blotting to determine whether the pathomechanism of ALG2 mutation was dependent or independent of collagen VI which in turn would allow for insight into whether these neuromuscular phenotypes could form part of the wider spectrum of congenital disorders of glycosylation due to impaired N-linked glycosylation. [Copyright &y& Elsevier]

River managers currently have difficulty predicting the combined effects of changes in flow regime and nutrients on periphyton biomass. Biomass accumulation is known to be promoted by increasing nutrients, light and temperature, and its loss has been related to invertebrate grazing and hydrological disturbance. However, biomass predictors that are reliable across a range of rivers have proven elusive. One possible contributing reason is that disturbance thresholds used in predictive models are typically linked to flow metrics, whereas the mechanisms for periphyton removal (current drag, abrasion and molar action by mobile sediment) relate more directly to hydraulic and geomorphic conditions., We explored this possibility by relating periphyton removal events to hydraulic thresholds for sediment entrainment in 18 gravel- to boulder-bed river reaches at which periphyton cover and nutrient concentrations had been regularly monitored. We converted observed threshold discharges for periphyton removal into shear stress thresholds using hydraulic models., Our results demonstrate that: (i) abrasion by finer fractions of the bed material (2-16 mm) was the dominant physical mechanism removing periphyton; (ii) the frequency of mobility of this fine bed material was the dominant control on periphyton abundance and (iii) growth-promoting variables, such as nutrient concentrations, tended to only become important to periphyton abundance when the frequency of sediment movement was low., These findings highlight the importance of geomorphic differences between sites and explain why a single flow metric may be a poor predictor of periphyton abundance across geomorphically different rivers. Our analysis suggests that partitioning sites based on frequency of sediment mobility (either sand or the D50) could improve predictability of sites at which there is potential for nuisance levels of periphyton to develop. [ABSTRACT FROM AUTHOR]

A technique for comparing simulation results directly with radiograph data from backlit capsule implosion experiments will be discussed. Forward Abel transforms are applied to the kappa*rho profiles of the simulation. These provide the transmission ratio (optical depth) profiles of the simulation. Gaussian and top hat blurs are applied to the simulated transmission ratio profiles in order to account for the motion blurring and imaging slit resolution of the experimental measurement. Comparisons between the simulated transmission ratios and the radiograph data lineouts are iterated until a reasonable backlighter profile is obtained. This backlighter profile is combined with the blurred, simulated transmission ratios to obtain simulated intensity profiles that can be directly compared with the radiograph data. Examples will be shown from recent convergent ablation (backlit implosion) experiments at the NIF. [ABSTRACT FROM AUTHOR]