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The liver may react to different infectious and non- infectious agents, developing granulomatous lesions which characterize granulomatous hepatitis. Granulomas of the liver are circumscribed inflammatory lesions (size from 50 to 300 mm) composed of epithelioid cells, varied numbers of mononuclear cells and eosinophils and multinucleated giant cells. They represent a specialized cell-mediated immune response to a wide variety of etiological factors. A broad spectrum of microorganisms may trigger hepatic granulomas. M. tuberculosis is the more frequent agent (~ 44%). Granulomatous hepatitis is characterized by a febrile illness with systemic signs and symptoms such as fatigue, sweating, shivering, hepatomegaly and/or splenomegaly, abnormalities in serum liver tests (aminotransferase, alkaline phosphatase). Liver biopsy provides diagnostic information in approximately 15-30% of cases, identifying directly the microbial agent with special microbial stains and polymerase chain reaction or finding distinctive microscopic features, suggestive of specific microorganisms. In such cases appropriate therapy is possible. Unfortunately in one third of cases is impossible to reach aetiological diagnosis on histological criteria alone. In these cases a therapeutic attempt with steroids, effective in the idiopathic granulomatous hepatitis, may be useful.

This case-control study evaluated the real need for liver biopsy in subjects with persistently normal aminotransferase values over a long period by comparing the histological features of these subjects with those of patients with abnormal aminotransferase values. We considered as "Cases" all 32 consecutive anti-HCV/HCV-RNA positive subjects with at least eight normal serum ALT values during the last twelve months; for each "Case", we selected as a "Control" one anti-HCV/HCV-RNA positive patient with at least two abnormal serum ALT values during the last twelve months. The Cases and Controls were matched for age ( 5 years) and sex. In the Case group, 1 subject showed normal liver tissue, 18 minimal chronic hepatitis (CH) and 13 mild CH. In the Control group, 7 subjects showed minimal CH, 19 mild CH, 3 moderate CH, 1 severe CH and 2 cirrhosis. The subjects in the Control group showed a significantly higher HAI score (5.39+2.81) than those in the Case group (2.96+1.62, p0.001). The subjects in the Control group more frequently showed a fibrosis score greater than 1 (28.1%) compared to the Case group (9.4%; p0.05). Finally, steatosis was more frequent and more severe in the Control group than in the Case group (respectively, 78.1% vs 50%, p0.05; and 1.47+1.16 vs 0.6+0.71, p0.001). The HAI and fibrosis scores did not correlate with the ALT value, HCV genotype or HCV viral load in either the Case or Control group. Our findings showed that the subjects with a persistently normal serum ALT value had minimal or mild chronic hepatitis, thus demonstrating that a liver biopsy is not indicated for these subjects.

Lung cancer is a worldwide problem and in many countires it is the most lethal malignancy. Because relapse is frequent after resection of non small cell lung cancer, an urgent need exists to define prognostic factors which could help in choosing the best therapeutic approach. We performed immunohistochemistry on 60 formalin-fixed paraffin-embedded non small cell lung cancer specimens in order to evaluate the frequency of cyclin D1 overexpression, and to relate it to the degree of malignancy of these tumors and to the overall survival time of the patients. All specimens were positive for cyclin D1 immunostaining. We found cyclin D1 overexpression in 30 (50%) of our specimens, with no significant difference among the different histological types. Cyclin D1 overexpression correlates in a statistical manner with short-term patient survival. Mantel-Cox analysis of these data generated a significant P value = 0.003. The mean survival time and the five-year survival rate also differed statistically. We did not find any statistically significant correlation between cyclin D1 overexpression and histological grading, tumor stage or TNM status. We concluded that cyclin D1 overexpression in 30 patients is a frequent event in non small cell lung cancer pathogenesis and may have prognostic relevance.

The present report describes an unusual case (apparently the 10th in the world literature) of a type-A aortic dissection with full circumferential detachment of the ascending aortic intima and intussusception thereof into the aortic arch and descending aorta, partly occluding the arch vessels. Computed tomographic scanning and 2-dimensional echocardiography failed to detect an intimal flap and a false lumen in the ascending aorta. Aortic dissection was visualized by aortography. The ascending aorta was surgically repaired and the aortic valve resuspended. The pertinent literature is reviewed.

†† † . The flow over a double compression is investigated by means of schlieren visualization, quantitative infrared thermography and particle image velocimetry. While schlieren and infrared thermography are well-established measurement techniques for high-speed flows, PIV is far from common practice in the hypersonic flow regime. The implementation of PIV with nanometric particles and microsecond pulse separation allows the measurement of the instantaneous planar velocity field over a two-dimensional double compression ramp in a Mach 7 free stream produced with a Ludwieg tube facility. The wind tunnel free stream conditions are investigated as well as the tracer particle response to a shock wave. The PIV technique proves to be a valuable diagnostic tool returning quantitative information with relatively high spatial resolution. The investigated flow configuration is a 2D double compression ramp with a variable second ramp angle. Shock-shock interactions are found to be of Edney type VI or V for the lowest or highest ramp angle respectively. A single heat transfer peak is detected on the second ramp, associated to the type VI interaction, while the type V interaction shows a double heat transfer peak. Shock wave angles measured with PIV are in good agreement with theory and are consistent with schlieren visualization. Under adiabatic flow hypothesis the Mach number planar distribution can be inferred from the PIV data. Also in this case the results are in agreement with compressible flow theory. I. Introduction DVANCES in diagnostic techniques for hypersonic flows are driven by the need to extend the capabilities of ground-based flow investigations of re-entry vehicle aerodynamics. However, the objective of simulating reentry flow conditions with wind-tunnels can be only partly achieved. Even more critical is the issue of obtaining satisfactory and reliable measurements in the hypersonic regime. Among the limiting factors are the fact that the flow can be simulated over a very short time (typically milliseconds) requiring fast response measurement techniques. A relatively high data yield is desirable, given the cost of operation of hypersonic facilities. Moreover, the flow properties variation is extremely large as well as the range of flow scales due to the occurrence of shock waves and thin viscous layers associated to the high Reynolds number. In order to understand the origin of the aerodynamic heat loads on a re-entry vehicle it is necessary not only to diagnose the surface temperature of a windtunnel model but also to describe the flow around the model at the origin of the loads. Schlieren and shadowgraph techniques, together with interferometry are currently used as standard techniques for the visualization of high-speed flows 1 . InfraRed Thermography 2 showed to be a suitable technique for the measurement of transient heat loads. Particle Image Velocimetry offers the possibility to quantify the flow velocity field inside a thin plane during a relatively short time interval 3 and is therefore suited to describe not only the flow streamlines, but also compressible features such as shock waves and shear layers including flow unsteady effects and turbulence. The application of PIV in high-speed flows has been pioneered by Moraitis and Riethmuller 4 and Kompenhans and Hocker 5 . However the application of the digital version of the technique has been applied with success in supersonic flows only in the recent years 6,7,8 .The extension of PIV in the hypersonic regime involves that a number of critical issues are addressed, namely the selection of appropriate seeding particles, their dispersion in the flow and the measurement of particle image recordings with large spatial variation in particle image density. The present study proposes a challenging application of PIV to investigate the flow over a double compression ramp configuration in a Mach 7 flow produced with a Ludwieg tube facility 9 . The investigation aims first at the assessment of the PIV technique in the hypersonic limit where extreme compressibility effects are encountered in combination with important technical limitations (hypervelocity, short run time, hot-pressurized storage gas conditions). Technical issues such as the

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Background/aim: Mixed Cryoglobulinemia (MC) represents the most frequent extrahepatic manifestation of chronic Hepatitis C Virus (HCV) infection. Its pathogenic mechanisms involve HCV-induced chronic stimulation of B-lymphocytes. We aimed to investigate the relationship between serum levels of vitamin D (a regulator of immune response) and the presence of serum cryoglobulins in the setting of HCV infection. Patients and methods: We evaluated the serum concentration of 25(OH)vitamin D and cryoglobulins in 106 patients with chronic HCV infection. Results: Thirty patients (28.3%) showed the presence of serum cryoglobulins. For the cohort overall, the median serum 25(OH)vitamin D level was 10.95 ng/ml. Patients with serum cryoglobulins had significantly lower levels of 25(OH)vitamin D (5.61 ng/ml) than those without (13.65 ng/ml, p=0.029). At multivariate analysis, severe hypovitaminosis [i.e. 25(OH)vitamin D

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Background Italy has been the first Western country to be heavily affected by the spread of SARS-COV-2 infection and among the pioneers of the clinical management of pandemic. To improve the outcome, identification of patients at the highest risk seems mandatory. Objectives Aim of this study is to identify comorbidities and clinical conditions upon admission associated with in-hospital mortality in several COVID Centers in Campania Region (Italy). Methods COVOCA is a multicentre retrospective observational cohort study, which involved 18 COVID Centers throughout Campania Region, Italy. Data were collected from patients who completed their hospitalization between March-June 2020. The endpoint was in-hospital mortality, assessed either from data at discharge or death certificate, whilst all exposure variables were collected at hospital admission. Results Among 618 COVID-19 hospitalized patients included in the study, 143 in-hospital mortality events were recorded, with a cumulative incidence of about 23%. At multivariable logistic analysis, male sex (OR 2.63, 95%CI 1.42–4.90; p = 0.001), Chronic Liver Disease (OR 5.88, 95%CI 2.39–14.46; p Conclusion Mortality of patients hospitalized for COVID-19 appears strongly affected by both clinical conditions on admission and comorbidities. Originally, we observed a very poor outcome in subjects with a chronic liver disease, alongside with an increase of hepatic damage.

We present the spectral and timing analysis of the X-ray pulsar GRO J1744-28 during its 2014 outburst using data collected with the X-ray satellites Swift, INTEGRAL, Chandra, and XMM-Newton. We derived, by phase-connected timing analysis of the observed pulses, an updated set of the source ephemeris. We were also able to investigate the spin-up of the X-ray pulsar as a consequence of the accretion torque during the outburst. Relating the spin-up rate and the mass accretion rate as $\dot{\nu}\propto\dot{M}^{\beta}$, we fitted the pulse phase delays obtaining a value of $\beta=0.96(3)$. Combining the results from the source spin-up frequency derivative and the flux estimation, we constrained the source distance to be between 3.4-4.1 kpc, assuming a disc viscous parameter $\alpha$ to be in the range 0.1-1. Finally, we investigated the presence of a possible spin-down torque by adding a quadratic component to the pulse phase delay model. The marginal statistical improvement of the updated model does not allow us to firmly confirm the presence of this component., Comment: 12 pages, 5 figures. Accepted for publication in MNRAS

A new type of tracer is making its entry in the scenario of wind-tunnel measurements: helium-filled soap bubbles (HFSB). The present work discusses the main fluid-dynamic and optical properties of HFSB to evaluate their use for quantitative measurements in aerodynamic experiments.In the past three decades, particle image velocimetry (PIV) has become a standard measuring technique in experimental fluid mechanics. Advances in both hardware components and software analysis have allowed achieving many milestones in flow diagnostics, mainly time-resolved and instantaneous volumetric measurements. In particular, the extension to the third dimension in space, i.e. tomographic PIV and 3D particle tracking velocimetry (PTV), has been used to provide quantitative visualizations of the coherent structures occurring in various turbulent flows and have provided insight in the spatial organization of the turbulent motions at different scales. The extension of the aforementioned techniques towards industrial practice in wind tunnel testing requires the development of a more efficient approach in terms of scaling and versatility.The present dissertation tackles the upscaling of PIV experiments towards industrial wind tunnels with the use of HFSB as tracing particles. The reasons and motivations behind this choice are addressed in the first chapter and followed by a description of the state-of-the-art of PIV. The second chapter aims at familiarising the reader with the working principles of PIV, which will be later recalled when presenting the advances towards large-scale experiments. Information on the mechanical behaviour of tracer particles and on the underlying physics are discussed in the third chapter, where also the case of HFSB is examined for use during quantitative measurements in the low-speed flow regime.The problem of seeding in wind tunnels is discussed in chapter 4, where a system for the injection of HFSB in a large wind tunnel is presented. Here, the relationship between HFSB production rate and the resulting spatial concentration and dynamic spatial range (DSR) are discussed. Specific experiments that examine the tracing fidelity of sub-millimetre HFSB tracers are presented in chapter 5. The behaviour of HFSB is compared to micro-size droplets, yielding a characteristic response time in the range of 10 μs. The latter milestone opens up to the applicability of HFSB tracers for quantitative velocimetry in wind tunnel flows. In chapter 6, a specific case of interest is presented whereby HFSB tracers are used to measure the flow velocity within steady vortices such as those released at the tip of wings. A dedicated experiment shows that the neutrally or slightly buoyant HFSB return a rather homogeneous spatial concentration within the core of vortices, solving the long-standing issue encountered for small heavy tracers, such as fog droplets, that are systematically ejected from highly vortical regions.An analysis of the light scattering by HFSB was conducted with theoretical and experimental approaches, as described in chapter 7. The light intensity scattered by the HFSB is characterised by two source points: the glare points. The overall scattered light appears to be 104-105 times more intense with respect to the oil-based micro-size droplets. This information is used to retrieve the maximum size of the measurement volume for a given light source.Chapter 8 closes this dissertation presenting a survey of all the experiments that have been conducted during this PhD research. The scale of experiments varies from the more academic case of a circular cylinder up to the one of a ship model installed in one of the large industrial wind tunnels operated at the German-Dutch Wind Tunnels laboratories (DNW), going through the visualization and quantification of large structures in the rotor region of a vertical axis wind turbine (VAWT).

Dynamical systems theory can significantly contribute to the understanding and control of fluid flows. Fluid dynamical systems are governed by the Navier-Stokes equations, which are continuous in both time and space, resulting in a state space of infinite dimension. To incorporate tools from systems theory it has become common practise to approximate the infinite-dimensional system by a finite-dimensional lumped system. Current techniques for this reduction step are data driven and produce models which are sensitive to the simulation or experimental conditions. This dissertation proposes a rigorous and practical methodology for the derivation of accurate finite-dimensional approximations and output feedback controllers directly from the governing equations. The approach combines state-space discretisation of the linearised Navier-Stokes equations with balanced truncation to design experimentally feasible low-order controllers. The approximation techniques can be used to design any suitable linear controller. In this study the reduced-order controllers are designed within an H2 optimal control framework to account for external disturbances and measurement noise. Application is focused on control of laminar wall-bounded shear flows to delay the classical transition process initially governed by two-dimensional convective perturbations, to extend laminar flow and reduce skin friction drag. The controllers are successfully tested in the vertical wind tunnel at the TU Delft.

Boundary layer transition is a relevant phenomenon in many aerodynamic and aero-thermodynamic problems and has been extensively investigated from the past century till recent times. Among the factors affecting the transition process, surface roughness plays a key role. When a roughness element with sufficiently large height (h) compared to the boundary layer thickness (δ) is immersed in a laminar boundary layer, it will produce spanwise varying disturbances with the potential to accelerate the transition process. In the thesis, a fundamental study is carried out to understand the physical mechanism of isolated roughness element induced transition. Experiments are performed in incompressible flow regime covering both critical and supercritical conditions. Tomographic particle image velocimetry (PIV) is employed as the main experimental diagnostic technique, returning the three-dimensional velocity and vorticity field of the flow. The three-dimensional wake flow behaviour is firstly identified behind roughness element of micro-ramp geometry. The micro-ramp produces a pair of counter-rotating streamwise vortices in the wake, transporting low momentum fluid away from the wall by the central upwash motion, and sweeping the high momentum flow towards the near-wall region sideward. The shear layer around the central low-speed region is related to the growth of Kelvin-Helmholtz (K-H) instability. The active range of the primary vortices and the central low-speed region in the streamwise direction is associated to the selection of the dominant instability mechanism, which decreases with the increase of roughness-height based Reynolds number (Reh). The instantaneous flow field reveals that the earliest unstable structures featuring hairpin shape are caused by the K-H instability at the separated shear layer. The evolution of K-H vortices is strongly influenced by Reh. At Reh = 1170, the K-H vortices are lift up under the upwash motion effect of the quasi-streamwise vortices, following by paring, distortion and finally breakdown. The active region of K-H vortices is separated from the inception of turbulent wedge, where early stage transition occurs. When Reh decreases approaching the critical value, the K-H vortices progressed gradually until the overall shear layer is destabilized, indicating the correlation between K-H instability and transition. The POD analysis yields the symmetric (K-H) and asymmetric mode. The disturbance energy associated to the symmetric modes changes with Reh. At higher Reh, the disturbance energy of the symmetric modes quickly decays, having a comparable contribution as the asymmetric modes. When Reh < 1000, the symmetric modes produce a remarkably higher level of disturbance energy until the onset of transition, indicating its dominance. The effectiveness of roughness element on promoting transition is strongly influenced by its geometry. The bluff-front roughness elements induce horseshoe vortices due to upstream separation. The different rotation direction of these vortices compared to the micro-ramp leads to early inception of sideward growth of fluctuations, and more rapid transition process. While for the slender micro-ramp, significant longer distance is required to for the onset of transition.

MXB 1659-298 is a transient neutron star Low-Mass X-ray binary system that shows eclipses with a periodicity of 7.1 hr. The source went to outburst in August 2015 after 14 years of quiescence. We investigate the orbital properties of this source with a baseline of 40 years obtained combining the eight eclipse arrival times present in literature with 51 eclipse arrival times collected during the last two outbursts. A quadratic ephemeris does not fit the delays associated with the eclipse arrival times and the addition of a sinusoidal term with a period of $2.31 \pm 0.02$ yr is required. We infer a binary orbital period of $P=7.1161099(3)$ hr and an orbital period derivative of $\dot{P}=-8.5(1.2) \times 10^{-12}$ s s$^{-1}$. We show that the large orbital period derivative can be explained with a highly non conservative mass transfer scenario in which more than 98\% of the mass provided by the companion star leaves the binary system. We predict an orbital period derivative value of $\dot{P}=-6(3) \times 10^{-12}$ s s$^{-1}$ and constrain the companion star mass between $\sim$0.3 and $ 0.9 \pm 0.3$ M$_{\odot}$. Assuming that the companion star is in thermal equilibrium the periodic modulation can be due to either a gravitational quadrupole coupling due to variations of the oblateness of the companion star or with the presence of a third body of mass M$_3 >21 $ Jovian masses., 10 pages, 6 figures. Accepted by MNRAS

A series of techniques is proposed for volumetric air flow measurements that are based upon the principles of particle image velocimetry (PIV). The proposed techniques fall in two categories; part 1 of this dissertation considers measurement data processing using constitutive laws and part 2 focuses on development of a coaxial volumetric flow measurement system that uses helium filled soap bubbles (HFSB) as tracer particles.In part 1, first a technique is proposed to measure instantaneous volumetric pressure using a low repetition rate tomographic PIV system. Instead of time-resolved measurement of the flow temporal evolution, which typically required for pressure-from-PIV procedures, the required temporal information is obtained by solution of the incompressible Navier-Stokes equations in vorticity-velocity formulation using the spatial information available from the instantaneous measurements. The reverse is proposed for cases where temporal resolution is more abundant, but spatial resolution is limited. The vorticity transport equation is leveraged to couple temporal information with instantaneous velocity data in the proposed VIC+ framework, in an attempt to obtain a dense velocity field at high spatial resolution. The governing principle is that by using the flow governing equations, the data ensemble used for interpolation is increased beyond instantaneous velocity measurements only. The technique is demonstrated to allow for measurement of vorticity and dissipation in a real-world experiment, which would otherwise be underestimated by more than 40% using the established tomographic PIV approach. The proposed VIC+ technique uses a data ensemble for dense velocity interpolation consisting of the instantaneous velocity and material derivative measurements obtained from Lagrangian particle tracking velocimetry. An extension of the VIC+ framework that uses a measurement time-segment instead of instantaneous data only is shown to potentially improve the measurement fidelity further, when a cost-effective three-dimensional implementation can be realized.An uncertainty quantification technique is proposed for future developments of such dense interpolation techniques. It is shown that the results from Lagrangian particle tracking measurements can be directly used for uncertainty quantification of dense interpolations and no independent measurement data is required.In part 2 of this dissertation, a technique is first proposed for large-scale volumetric pressure measurement. The method follows recent developments of large-scale measurements using HFSB tracer particles, in combination with Lagrangian particle tracking and ensemble bin-averaging. This allows for evaluation of accurate velocity statistics and in turn the time-averaged pressure field.The dissertation concludes with the proposal of the coaxial volumetric velocimeter (CVV). The CVV brings imaging and illumination together in a compact box, viewing and illuminating a measurement volume from a single viewing direction. The theoretical background that is derived shows that measurements in air using the CVV are only possible using tracer particles that scatter significantly more light than traditional micron sized tracer particles. Here, HFSB tracer particles are used. Due to the small solid angle of the imaging system, tracer particles need to be imaged over an extended number of snapshots to increase particle positional accuracy, making use of particle trajectory regularization. A prototype CVV has been realized, which is first used to confirm that the flow around a sphere is measured with acceptable correspondence to a potential flow solution. Second, in the case of the flow around a cyclist, the CVV is shown to allow for measurements near both concave and convex surfaces within one measurement volume. This allows for flow analysis using skin-friction lines. In addition, the compact nature of the CVV allows mounting on a robotic arm for time-averaged of a large and complex wind tunnel model. The full-scale measurement of the flow around Giro d’Italia cyclist Tom Dumoulin shown using the CVV is an example of the latter.

We report on the timing analysis of the 2015 outburst of the intermittent accreting millisecond X-ray pulsar SAX J1748.9-2021 observed on March 4 by the X-ray satellite XMM-Newton. By phase-connecting the time of arrivals of the observed pulses, we derived the best-fit orbital solution for the 2015 outburst. We investigated the energy pulse profile dependence finding that the pulse fractional amplitude increases with energy while no significant time lags are detected. Moreover, we investigated the previous outbursts from this source, finding previously undetected pulsations in some intervals during the 2010 outburst of the source. Comparing the updated set of orbital parameters, in particular the value of the time of passage from the ascending node, with the orbital solutions reported from the previous outbursts, we estimated for the first time the orbital period derivative corresponding with $\dot{P}_{orb}=(1.1\pm0.3)\times 10^{-10}$ s/s. We note that this value is significant at 3.5 sigma confidence level, because of significant fluctuations with respect to the parabolic trend and more observations are needed in order to confirm the finding. Assuming the reliability of the result, we suggest that the large value of the orbital-period derivative can be explained as a result of an highly non-conservative mass transfer driven by emission of gravitational waves, which implies the ejection of matter from a region close to the inner Lagrangian point. We also discuss possible alternative explanations., Comment: Accepted for publication in MNRAS; 11 pages, 9 figures, 2 tables

The liver histology of 68 consecutive anti-HCV/HCV-RNA positive chronic hepatitis patients who were HBsAg/anti-HBs negative, anti-HBc positive (Case bC group) was compared with that of 68 anti-HCV/HCV-RNA positive chronic hepatitis patients who were HBsAg/anti-HBc negative (control C group). The patients were pair-matched by age (+/-5 years), sex, and risk factors for the acquisition of parenteral infection. Case bC group showed a significantly higher mean fibrosis score (2.3 +/- 1.1) than control C group (1.5 +/- 1.1, P

The correlation between the length of viremia as detected by reverse transcriptase-polymerase chain reaction (RT-PCR) and the clinical course of hepatitis A virus (HAV) infection was studied. Sixty-six consecutive patients with acute hepatitis A who were admitted to hospital in two infectious disease units in southern Italy were enrolled: 57 had a self-limited course of the disease (typical course), 4 a prolonged course, and 5 relapsing hepatitis. Plasma HAV RNA was sought by RT-PCR, using primers made at 5′-NTR of HAV, designed to amplify a 273-bp fragment and detected by 2% agarose gel and by hybridization with a specific biotinylated probe. In four patients with prolonged acute hepatitis A, the plasma HAV RNA, which was positive on the day of admission to hospital, was found to be negative from day 62, 46, 84, and 105, respectively, after the onset of the symptoms. In patients with relapsing hepatitis, HAV viremia paralleled the clinical and biochemical course of disease. In all patients with a typical self-limiting course, clearance of plasma HAV RNA was observed within 20 days of the onset of symptoms. In most patients, plasma HAV viremia became undetectable before the normalization of serum aminotransferases, underlining the importance of the immune reaction in the pathogenesis of acute hepatitis A. The data also suggest that the detection of plasma HAV RNA after 20 days of illness may predict a prolonged course of the disease, but relapsing hepatitis remains unpredictable on the basis of plasma HAV determination. J. Med. Virol. 71:1–6, 2003. © 2003 Wiley-Liss, Inc.

Mucopolysaccharidosis type II (MPS II or Hunter syndrome) is a rare X-linked disorder caused by deficient activity of the lysosomal enzyme, iduronate-2-sulfatase (IDS). Phenotypic expression of MPS II in female patients rarely occurs and may be the result of (i) structural abnormalities of the X chromosome, (ii) homozygosity for disease-causing mutations, or (iii) skewed X-chromosome inactivation, in which the normal IDS allele is preferentially inactivated and the abnormal IDS allele is active. We report here on a female patient with clinical MPS II manifestations, deficiency of IDS enzyme activity and a de novo balanced reciprocal X;9 translocation. As our patient has a skewed XCI pattern, but neither genomic IDS mutations nor abnormal IDS transcripts were detected, we speculate about the possible role of the chromosomal rearrangement in reducing the IDS translation efficiency.

Particle Image Velocimetry (PIV) is a well-established technique for the measurement of the flow velocity in a two or three-dimensional domain. As in any other technique, PIV data is affected by measurement errors, defined as the difference between the measured velocity and its actual value, which is unknown. Aim of uncertainty quantification is estimating an interval that contains the (unknown) actual error magnitude with a certain probability. The present work introduces a novel methodology for the uncertainty quantification of PIV data. The method relies upon the concept of image matching: the PIV recordings are matched based on the measured velocity field. The positional disparity between paired particle images is then computed to retrieve the measurement uncertainty. Both the numerical assessment via Monte Carlo simulations and the experimental assessment show that the image matching approach allows estimating the measurement uncertainty in good agreement with the actual error value. Furthermore, advanced methodologies for time-resolved image and data analysis are investigated. Those methodologies include: the enhancement of the image quality via a temporal filter applied to the PIV images; a multi-frame processing algorithm (pyramid correlation) that improves precision and robustness of PIV measurements; a post processing approach based on the solution of the Navier-Stokes equations for estimating the velocity field in regions where no experimental data is available.

We present a timing analysis of the 2015 outburst of the accreting millisecond X-ray pulsar SAX J1808.4-3658, using non-simultaneous XMM-Newton and NuStar observations. We estimate the pulsar spin frequency and update the system orbital solution. Combining the average spin frequency from the previous observed, we confirm the long-term spin down at an average rate $\dot{\nu}_{\text{SD}}=1.5(2)\times 10^{-15}$ Hz s$^{-1}$. We also discuss possible corrections to the spin down rate accounting for mass accretion onto the compact object when the system is X-ray active. Finally, combining the updated ephemerides with those of the previous outbursts, we find a long-term orbital evolution compatible with a binary expansion at a mean rate $\dot{P}_{orb}=3.6(4)\times 10^{-12}$ s s$^{-1}$, in agreement with previously reported values. This fast evolution is incompatible with an evolution driven by angular momentum losses caused by gravitational radiation under the hypothesis of conservative mass transfer. We discuss the observed orbital expansion in terms of non-conservative mass transfer and gravitational quadrupole coupling mechanism. We find that the latter can explain, under certain conditions, small fluctuations (of the order of few seconds) of the orbital period around a global parabolic trend. At the same time, a non-conservative mass transfer is required to explain the observed fast orbital evolution, which likely reflects ejection of a large fraction of mass from the inner Lagrangian point caused by the irradiation of the donor by the magneto-dipole rotator during quiescence (radio-ejection model). This strong outflow may power tidal dissipation in the companion star and be responsible of the gravitational quadrupole change oscillations., Comment: 16 pages, 8 figures. Accepted for publication in MNRAS