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Reactivation of the varicella-zoster virus (VZV), which causes herpes zoster (HZ, synonym: shingles) in humans, can be a rare adverse reaction to vaccines. Recently, reports of cases after COVID-19 vaccination have arisen.The aim of this study was to assess whether the frequency of HZ is found to increase after COVID-19 vaccination in a large cohort, based on real-world data. As a hypothesis, the incidence of HZ was assumed to be significantly higher in subjects who received a COVID-19 vaccine (Cohort I) vs. unvaccinated individuals (Cohort II).The initial cohorts of 1 095 086 vaccinated and 16 966 018 unvaccinated patients were retrieved from the TriNetX database and were matched on age and gender in order to mitigate confounder bias.After matching, each cohort accounted for 1 095 086 patients. For the vaccinated group (Cohort I), 2204 subjects developed HZ within 60 days of COVID-19 vaccination, while among Cohort II, 1223 patients were diagnosed with HZ within 60 days after having visited the clinic for any other reason (i.e. not vaccination). The risk of developing shingles was calculated as 0.20% and 0.11% for cohort I and cohort II, respectively. The difference was statistically highly significant (P 0.0001; log-rank test). The risk ratio and odds ratio were 1.802 (95% confidence interval [CI] = 1.680; 1.932) and 1.804 (95% CI = 1.682; 1.934).Consistent with the hypothesis, a higher incidence of HZ was statistically detectable post-COVID-19 vaccine. Accordingly, the eruption of HZ may be a rare adverse drug reaction to COVID-19 vaccines. Even though the molecular basis of VZV reactivation remains murky, temporary compromising of VZV-specific T-cell-mediated immunity may play a mechanistic role in post-vaccination pathogenesis of HZ. Note that VZV reactivation is a well-established phenomenon both with infections and with other vaccines (i.e. this adverse event is not COVID-19-specific).

In this publication, the different metal transfer modes of a hot-wire GTAW process with indirect resistive preheating of the wire are presented. The hot-wire GTAW process is characterized by an additional preheating unit that is used to heat the wire before it reaches the melt pool. Thus, to preheat the wire, the contact between the melt pool and the wire is not necessary. In order to examine the metal transfer of the wire, deposition welds are analysed using a high-speed camera with a laser light source as well as a data acquisition unit. The presented results comprise the impact analysis of the GTAW current, the hot-wire current, the wire feeding rate, the wire feeding angle as well as the wire feeding direction. The observed metal transfer modes can be characterized as either a constant melting bridge (cmb) between the wire and the melt pool or a recurring melting bridge (rmb). The analysis also reveals that the influence of the process parameters and thus the metal transfer mode on the bead properties is only marginal.

Gas metal arc welding (GMAW) processes are used in a wide range of applications due to their high productivity and flexibility. Nevertheless, the supplied melting wire electrode leads to a coupling of material and heat input. Therefore, an increase of the melting rate correlates with an increase of the heat input by the arc at the same time. A possibility to separate material and heat input is to use an additional wire, which reduces penetration and worsens the wetting behaviour. Consequently, bead irregularities such as bonding defects or insufficient root weldings can occur. In the context of this article, a controlling system for a two-dimensional magnetic arc deflection is presented, which allows to influence arc position as well as material transfer. The analysed GMAW hot wire process is characterised by high melting rates while also realising a sufficient penetration depth and wetting behaviour.

The presented work deals with the development of a novel TIG hot-wire process for the additive manufacturing of metallic components, which, in contrast to previous arc processes, enables a significant increase in melting performance with simultaneously reduced heat input. This is achieved by means of an upstream resistance heating of the wire between two contact points within the hot wire feeding system. The torch, hot wire feeder and gas nozzle are designed in such a way that a constant bead geometry can be guaranteed regardless of the machining direction. On the one hand, this can improve the dimensional accuracy; on the other hand, an increase in productivity is achieved through a significant reduction of process times. Essential parts of the work include the simulation-supported development of the processing system, the design and implementation of an innovative process control system and the testing of the new technology.

Objectives: The aim of the study was to determine the frequency and natural history of infantile idiopathic cholestasis (IC) in a large, prospective, multicenter cohort of infants. Methods: We studied 94 cholestatic infants enrolled up to 6 months of age in the NIDDK ChiLDReN (Childhood Liver Disease Research Network) “PROBE” protocol with a final diagnosis of IC; they were followed up to 30 months of age. Results: Male sex (66/94; 70%), preterm birth (22/90 with data; 24% born at < 37 weeks’ gestational age), and low birth weight (25/89; 28% born at 1 mg/dL and/or ALT > 35 U/L; n = 7), and exited healthy (resolved disease per study site report but without documented biochemical resolution; n = 34). Biochemical resolution occurred at median of 9 months of age. GGT was

A new method for the measurement of two-dimensional heat flux profiles for GTAW processes is presented. The method is based on a least squares reconstruction algorithm for the inverse heat transfer problem for a steady-state temperature distribution in a specimen body. The temperature is measured with an experimental setup suited for the heat input of a welding process. The temperature distribution is then used to reconstruct the heat flux distribution on the specimen surface using a heat flux approach function. To calculate the temperature distribution ratio for the current approach heat flux profile, a numerical simulation model of the specimen is embedded in the reconstruction procedure. The residuum between the actual temperature distribution and the test function temperature is reduced using a least squares optimization step until convergence. The method is verified using a numerically calculated temperature distribution which is compared with a predefined heat flux profile. Moreover, the method is compared with a split-anode measurement for one-dimensional and two-dimensional reconstruction approaches. Measurements of a process with an inclined torch as well as a process with a magnetically deflected arc demonstrate the capability of the new method for the measurement of two-dimensionally resolved heat flux distributions of GTAW processes.

Capacitor discharge welding primarily applies to projection welding. Components with ring projections up to 200 mm diameter can be welded with peak currents up to 1000 kA and welding times less than 10 ms. Weld nuggets are expected to occur, as the CD-Welding belongs to resistance welding. Although the required strength is given, welding nuggets in cross-sections cannot invariably be verified. According to recent researches, joining occurs without a welding nugget, but with metal vaporisation and linked activation of the surfaces. This process is called short-time welding with high thermal current density. The type of the welded joint depends on the heating properties in the weld zone. Different welding energies, electrode forces and welding times result in different welded joints. The process-specific advantages can be taken, and new application areas for CD welding can be developed by knowing the cause-and-effect relationships.

OBJECTIVES To advance our understanding of monogenic forms of intrahepatic cholestasis. METHODS Analyses included participants with pathogenic biallelic mutations in adenosine triphosphate (ATP)-binding cassette subfamily B member 11 (ABCB11) (bile salt export pump; BSEP) or adenosine triphosphatase (ATPase) phospholipid transporting 8B1 (ATP8B1) (familial intrahepatic cholestasis; FIC1), or those with monoallelic or biallelic mutations in adenosine triphosphate (ATP)-binding cassette subfamily B member 4 (ABCB4) (multidrug resistance; MDR3), prospectively enrolled in the Longitudinal Study of Genetic Causes of Intrahepatic Cholestasis (LOGIC; NCT00571272) between November 2007 and December 2013. Summary statistics were calculated to describe baseline demographics, history, anthropometrics, laboratory values, and mutation data. RESULTS Ninety-eight participants with FIC1 (n = 26), BSEP (n = 53, including 8 with biallelic truncating mutations [severe] and 10 with p.E297G or p.D482G [mild]), or MDR3 (n = 19, including four monoallelic) deficiency were analyzed. Thirty-five had a surgical interruption of the enterohepatic circulation (sEHC), including 10 who underwent liver transplant (LT) after sEHC. Onset of symptoms occurred by age 2 years in most with FIC1 and BSEP deficiency, but was later and more variable for MDR3. Pruritus was nearly universal in FIC1 and BSEP deficiency. In participants with native liver, failure to thrive was common in FIC1 deficiency, high ALT was common in BSEP deficiency, and thrombocytopenia was common in MDR3 deficiency. sEHC was successful after more than 1 year in 7 of 19 participants with FIC1 and BSEP deficiency. History of LT was most common in BSEP deficiency. Of 102 mutations identified, 43 were not previously reported. CONCLUSIONS In this cohort, BSEP deficiency appears to be correlated with a more severe disease course. Genotype-phenotype correlations in these diseases are not straightforward and will require the study of larger cohorts.

Osteopenia and bone fractures are significant causes of morbidity in children with cholestatic liver disease. Dual-energy X-ray absorptiometry (DXA) analysis was performed in children with intrahepatic cholestatic diseases who were enrolled in the Longitudinal Study of Genetic Causes of Intrahepatic Cholestasis in the Childhood Liver Disease Research Network. DXA was performed on participants aged >5 years (with native liver) diagnosed with bile acid synthetic disorder (BASD), alpha-1 antitrypsin deficiency (A1AT), chronic intrahepatic cholestasis (CIC), and Alagille syndrome (ALGS). Weight, height, and body mass index Z scores were lowest in CIC and ALGS. Total bilirubin (TB) and serum bile acids (SBA) were highest in ALGS. Bone mineral density (BMD) and bone mineral content (BMC) Z scores were significantly lower in CIC and ALGS than in BASD and A1AT (P < 0.001). After anthropometric adjustment, bone deficits persisted in CIC but were no longer noted in ALGS. In ALGS, height-adjusted and weight-adjusted subtotal BMD and BMC Z scores were negatively correlated with TB (P < 0.001) and SBA (P = 0.02). Mean height-adjusted and weight-adjusted subtotal BMC Z scores were lower in ALGS participants with a history of bone fractures. DXA measures did not correlate significantly with biliary diversion status. Conclusion: CIC patients had significant bone deficits that persisted after adjustment for height and weight and generally did not correlate with degree of cholestasis. In ALGS, low BMD and BMC reference Z scores were explained by poor growth. Anthropometrically adjusted DXA measures in ALGS correlate with markers of cholestasis and bone fracture history. Reduced bone density in this population is multifactorial and related to growth, degree of cholestasis, fracture vulnerability, and contribution of underlying genetic etiology.

Numerical investigations on the thermal efficiency in laser-assisted plasma arc welding (LAPAW) have been carried out by the combination of a magneto-hydrodynamic (MHD) arc model and a smoothed-particle-hydrodynamics (SPH) model of the weld pool. The comparison of the calculated weld seam cross-sections gained from numerical simulation as well as experimental examinations shows a good agreement. By the use of the weld pool model, the sensitivity of different influencing variables was investigated. The analysis clearly reveals the major influence of the central heat flux density on the penetration profile and on the thermal efficiency of the process. The higher the heat flux of the laser beam and the higher the constriction of the heat flux profile of the arc, the higher the thermal efficiency of the process.

In this paper, we present a numerical model for the calculation of weld pool dynamics and the resulting weld seam structure with regard to the arc forces. The model uses an incompressible smoothed particle hydrodynamics method and is suitable for three-dimensional calculations with a high spatial resolution at low computational costs. The model is applied to a GTAW process, where the arc forces as well as the arc heat input is modelled on the basis of known values from measurement and literature. The validity of the model is shown for different arc currents by comparison of the calculated penetration profile with measurements. Finally, the model is used to perform parameter studies on the influence of the arc pressure and the arc shear on the penetration profile. The parameter studies show the strong influences of the arc forces on the penetration depth.

To date, several numerical models predicting the properties of TIG-arcs are available. Recently, effort has been put into testing the reliability of these models for varying process parameters by means of comparing plasma temperatures and arc voltages against measured data. However, from an engineering point of view, the goal of these models is to predict the properties of weld beads. Therefore, the heat input into and the pressure applied onto the workpiece have to be predicted. This paper deals with the comparison of measured arc pressure data and the results of an approach which couples a simplified cathode sheath model with an LTE arc model.

Laser-based joining is a potential key manufacturing process for realizing metal plastic hybrids. Therefore, surface preparation is essential to achieve a mechanical form fit. A new approach for surface preparation is based on a tungsten inert gas (TIG) arc process with anodic polarity. This TIG structure was characterized compared to fiber laser manufactured structures in cw and pw mode. The comparison of different preparations was based on pure ultimate tensile strength tests on spot joints. Finally, a transfer to overlap joints was successfully carried out and characterized by tensile shear tests using fiber reinforced plastics.

Within the framework of the bilateral CORNET projects MeTexCom and MeTexCom2, new approaches were developed and tested to improve the adhesion strength of metal textile composites, with a focus on the targeted roughening of aluminum surfaces and the development of new acoustically insulating nonwovens. The metal textile composites were produced by melting thermoplastic components of the textile composites without a separately applied adhesive.For improved adhesion strength between metal and textile, roughness was generated on the metal surface by means of a novel arc treatment by an anodic polarized TIG process or a cw (continuous wave) fiber laser process. On the one hand, the goal was to produce uniformly rough, untercut surface structures in micro-and nanodimension by means of a highly dynamic arcing process. On the other hand, a similar approach was pursued with the cw laser method by using a single-mode as well as a multi-mode laser.

Gas metal arc welding (GMAW) processes are characterized by a high number of simultaneously running physical processes. The process capability is mainly determined by the properties of a metal vapour influenced arc and the material transfer. In recent years, experimental as well as numerical methods are being used increasingly in order to understand the complex interactions between the arc and material transfer. In this paper, we discuss the influence of metal vapour on GMAW processes in spray as well as pulsed material transfer mode. With respect to the high complexity of the process, experimental and numerical methods are combined in a targeted manner in order to obtain a high level of expressive capability with moderate numerical and experimental effort. The results illustrate the high influence of the changing vaporization rate not only on the arc properties but on the arc attachment at the filler wire. It could be shown, that in many cases the metal vapour concentration in the arc region has a greater influence on the arc properties and the material transfer than different shielding gas components like oxygen, hydrogen or helium.

In this paper, the suitability of different constructional concepts of gas trailing shields concerning the reduction of heat-tints is discussed. The evaluation of these concepts as well as the description of the main contamination mechanisms of gas trailing shields with atmospheric gases are performed for tungsten inert gas welding of stainless steel by a purposeful coupling of experimental as well as numerical methods. Furthermore, advantages and disadvantages of these design concepts are investigated regarding their constructional complexity, robustness against varying process parameters, and its feasible working distances. Finally, a modular concept is presented which allows the usage of the same constructional concept for a variety of different welding tasks.

The process capability of gas metal arc welding (GMAW) processes is mainly determined by the arc properties and the material transfer. In recent years, numerical methods are being used increasingly in order to understand the complex interactions between the arc and material transfer in gas metal arc welding. In this paper, we summarize a procedure to describe the interaction between an arc and a melting and vaporizing electrode. Thereafter, the presented numerical model is used to investigate the arc properties and the metal transfer for a pulsed GMAW process of mild steel in argon. The results of the numerical simulation are compared with OES measurements as well as high-speed images at different times in the pulse cycle and show excellent agreement. The results illustrate the high influence of the changing vaporization rate on the arc attachment at the wire electrode in the high current phase. It could be shown that a substantial part of the current does not participate in the constriction of the wire electrode via the resulting lorentz force which explains the nearly spatter-free droplet detachment in pulsed GMAW processes of mild steel in argon shielding gas.

Objectives Although screening for biliary atresia (BA) is associated with improved outcomes, no screening program currently exists in the United States. In this study, we explore the possibility of a screening strategy based on newborn direct or conjugated bilirubin (DB or CB) measurements. Our objective is to estimate testing's sensitivity and specificity for BA. Methods Two groups were examined retrospectively. For sensitivity calculations, a BA group consisting of infants born between January 2011 and December 2014, diagnosed with BA, and cared for at a pediatric gastroenterology referral center was examined. For specificity calculations, a non-BA group that comprised of infants born between June 2009 and August 2011 in a hospital with a policy of checking newborn bilirubin concentrations was studied. Results All 35 infants with newborn DB or CB measurements in the BA group had elevated concentrations, translating to a sensitivity of 100% (95% CI 87.7-100). In the non-BA group, 8936 of 9102 infants had DB concentrations within the laboratory's reference interval, translating to a specificity of 98.2% (95% CI 97.9-98.4). Three methods-calculating direct:total bilirubin ratios, using 99% reference intervals, and repeat testing-changed specificity to different degrees. Conclusions Newborn DB or CB measurements may have a high sensitivity and specificity for BA. Specificity can be further improved by using 99% reference intervals and/or repeat testing. Our findings can serve as the foundation for larger prospective studies, to determine whether newborn DB or CB measurements can be an effective screening strategy for BA.

Applications of structural concrete require use of reinforcement in one form or another. The known reinforcement concepts in additive concrete construction typically rely on conventional reinforcement approaches, which provide a solid basis for structural design, since existing guidelines and codes can be used. However, the use of conventional steel reinforcement poses serious limitations to the digitalization and automation of fabrication techniques. The article at hand presents two alternative approaches of reinforcing 3D-printed concrete structures: (1) additive manufacturing of steel reinforcement elements, (2) use of high-performance microfiber to achieve strain-hardening behavior of printed concrete. For both approaches materials and manufacturing techniques are briefly described followed by the results of mechanical testing and complimentary microscopic investigations. The printed steel bars showed similar mechanical performance in comparison to ordinary steel bars of the same cross-section area and comparable bond behavior to concrete too, as observed in pull-out experiments. The addition of 1% to 1.5% high-density polyethylene microfiber to fine-grained matrix enabled for printable strain-hardening cement-based composites (SHCC) with a tensile strain capacity of up to 3.2%.

Background & Aims Liver disease in Alagille syndrome is highly variable. Many of the patients presenting with severe cholestasis early in life improve spontaneously; 10–20%, however, have progressive disease. It is currently not possible to predict long-term hepatic outcomes in Alagille syndrome. This international, multicentre study was aimed at identifying early life predictors of liver disease outcome. Methods Retrospective clinical, laboratory and radiographic data from a cohort of 144 Alagille syndrome patients, whose long-term hepatic outcomes had been determined a priori based on previously published criteria, were collected. Results Sixty-seven patients had mild and 77 had severe hepatic outcome. Univariate analysis demonstrated that cholestasis and fibrosis on biopsy, as well as the presence of xanthomata were significantly different between the groups (P

OBJECTIVES α-1-Antitrypsin (A1AT) deficiency is a common genetic disease with an unpredictable and highly variable course. The Childhood Liver Disease Research and Education Network is a National Institutes of Health, multicenter, longitudinal consortium studying pediatric liver diseases, with the objective of prospectively defining natural history and identifying disease modifiers. METHODS Longitudinal, cohort study of A1AT patients' birth through 25 years diagnosed as having liver disease, type PIZZ or PISZ. Medical history, physical examination, laboratory, imaging, and standardized survey tool data were collected during the provision of standard of care. RESULTS In the present report of the cohort at baseline, 269 subjects were enrolled between November 2008 and October 2012 (208 with their native livers and 61 postliver transplant). Subjects with mild disease (native livers and no portal hypertension [PHT]) compared to severe disease (with PHT or postliver transplant) were not different in age at presentation. A total of 57% of subjects with mild disease and 76% with severe disease were jaundiced at presentation (P = 0.0024). A total of 29% of subjects with native livers had PHT, but age at diagnosis and growth were not different between the no-PHT and PHT groups (P > 0.05). Subjects with native livers and PHT were more likely to have elevated bilirubin, ALT, AST, INR, and GGTP than the no-PHT group (P <

To date, several numerical models representing the tungsten inert gas (TIG) arc are available. However, little has been done on testing the reliability of these models for parameter values differing from the ones used in the respective papers. This paper deals with the comparison of measured arc welding data provided by E. Siewert from Linde AG and the results of the two most common arc and cathode sheath models. These models make different degrees of simplification of the actual processes in the arc, especially the cathode sheath. Different shapes of the electrodes, different welding currents and shielding gases are taken into account as well as the resolution of the numerical grid on which the calculations are carried out. The findings of this paper are used to show when a simplified approach still leads to valid results and when more sophisticated models have to be used.

1. Yin Zhou, MD* 2. Paula Hertel, MD* 3. Jennifer Cu, MD* 1. *Texas Children's Hospital, Houston, TX A 14-year-old girl is referred to a liver clinic by her primary care physician (PCP) for large amounts of urine bilirubin on repeated urine dipstick analysis. She notes very mild abdominal pain that occurs occasionally after meals. She denies jaundice, bleeding, easy bruising, vomiting, diarrhea, or fevers. She visited her PCP in the previous month for labial cyst and urinary tract infection and was treated with cephalexin. Her urine dipstick at that time and during a subsequent visit showed large amounts of bilirubin. She uses amphetamine/dextroamphetamine salts and a methylphenidate patch for attention-deficit/hyperactivity disorder. She also takes etodolac (a nonsteroidal anti-inflammatory drug [NSAID]) for tendonitis and a vitamin B supplement. On physical examination, she appears comfortable. Her blood pressure is 102/66 mm Hg, her pulse is 93 beats/min, and she is afebrile. Her sclerae are anicteric. Her abdomen is not tender, and there …

To assess neurodevelopmental outcomes among participants with biliary atresia with their native liver at ages 12 months (group 1) and 24 months (group 2), and to evaluate variables predictive of neurodevelopmental impairment.Participants enrolled in a prospective, longitudinal, multicenter study underwent neurodevelopmental testing with either the Bayley Scales of Infant Development, 2nd edition, or Bayley Scales of Infant and Toddler Development, 3rd edition. Scores (normative mean = 100 ± 15) were categorized as ≥100, 85-99, and85 for χThere were 148 children who completed 217 Bayley Scales of Infant and Toddler Development, 3rd edition, examinations (group 1, n = 132; group 2, n = 85). Neurodevelopmental score distributions significantly shifted downward compared with test norms at 1 and 2 years of age. Multivariate analysis identified ascites (OR, 3.17; P = .01) and low length z-scores at time of testing (OR, 0.70; P .04) as risk factors for physical/motor impairment; low weight z-score (OR, 0.57; P = .001) and ascites (OR, 2.89; P = .01) for mental/cognitive/language impairment at 1 year of age. An unsuccessful hepatoportoenterostomy was predictive of both physical/motor (OR, 4.88; P .02) and mental/cognitive/language impairment (OR, 4.76; P = .02) at 2 years of age.Participants with biliary atresia surviving with native livers after hepatoportoenterostomy are at increased risk for neurodevelopmental delays at 12 and 24 months of age. Those with unsuccessful hepatoportoenterostomy are4 times more likely to have neurodevelopmental impairment compared with those with successful hepatoportoenterostomy. Growth delays and/or complications indicating advanced liver disease should alert clinicians to the risk for neurodevelopmental delays, and expedite appropriate interventions.Clinicaltrials.gov: NCT00061828 and NCT00294684.

To evaluate the efficacy of nontransplant surgery for pediatric cholestasis, 58 clinically diagnosed children, including 20 with Alagille syndrome (ALGS), 16 with familial intrahepatic cholestasis-1 (FIC1), 18 with bile salt export pump (BSEP) disease, and 4 others with low γ-glutamyl transpeptidase disease (levels100 U/L), were identified across 14 Childhood Liver Disease Research Network (ChiLDReN) centers. Data were collected retrospectively from individuals who collectively had 39 partial external biliary diversions (PEBDs), 11 ileal exclusions (IEs), and seven gallbladder-to-colon (GBC) diversions. Serum total bilirubin decreased after PEBD in FIC1 (8.1 ± 4.0 vs. 2.9 ± 4.1 mg/dL, preoperatively vs. 12-24 months postoperatively, respectively; P = 0.02), but not in ALGS or BSEP. Total serum cholesterol decreased after PEBD in ALGS patients (695 ± 465 vs. 457 ± 319 mg/dL, preoperatively vs. 12-24 months postoperatively, respectively; P = 0.0001). Alanine aminotransferase levels increased in ALGS after PEBD (182 ± 70 vs. 260 ± 73 IU/L, preoperatively vs. 24 months; P = 0.03), but not in FIC1 or BSEP. ALGS, FIC1, and BSEP patients experienced less severely scored pruritus after PEBD (ALGS, 100% vs. 9% severe; FIC1, 64% vs. 10%; BSEP, 50% vs. 20%, preoperatively vs.24 months postoperatively, respectively; P0.001). ALGS patients experienced a trend toward greater freedom from xanthomata after PEBD. There was a trend toward decreased pruritus in FIC1 after IE and GBC. Vitamin K supplementation increased in ALGS after PEBD (33% vs. 77%; P = 0.03). Overall, there were 15 major complications after surgery. Twelve patients (3 ALGS, 3 FIC1, and 6 BSEP) subsequently underwent liver transplantation.This was a multicenter analysis of nontransplant surgical approaches to intrahepatic cholestasis. Approaches vary, are well tolerated, and generally, although not uniformly, result in improvement of pruritus and cholestasis. (Hepatology 2017;65:1645-1654).

Fat-soluble vitamin (FSV) deficiency is a well-recognized consequence of cholestatic liver disease and reduced intestinal intraluminal bile acid. We hypothesized that serum bile acid (SBA) would predict biochemical FSV deficiency better than serum total bilirubin (TB) level in infants with biliary atresia.Infants enrolled in the Trial of Corticosteroid Therapy in Infants with Biliary Atresia after hepatoportoenterostomy were the subjects of this investigation. Infants received standardized FSV supplementation and monitoring of TB, SBA, and vitamin levels at 1, 3, and 6 months. A logistic regression model was used with the binary indicator variable insufficient/sufficient as the outcome variable. Linear and nonparametric correlations were made between specific vitamin measurement levels and either TB or SBA.The degree of correlation for any particular vitamin at a specific time point was higher with TB than with SBA (higher for TB in 31 circumstances vs 3 circumstances for SBA). Receiver operating characteristic curve shows that TB performed better than SBA (area under the curve 0.998 vs 0.821). Including both TB and SBA did not perform better than TB alone (area under the curve 0.998).We found that TB was a better predictor of FSV deficiency than SBA in infants with biliary atresia. The role of SBA as a surrogate marker of FSV deficiency in other cholestatic liver diseases, such as progressive familial intrahepatic cholestasis, α-1-antitrypsin deficiency, and Alagille syndrome in which the pathophysiology is dominated by intrahepatic cholestasis, warrants further study.

a b s t r a c t Biliary atresia is a neonatal cholangiopathy of unknown etiology that results in obliteration of bile ducts and is the primary indication for liver transplant in children. A murine model of BA, which involves infecting newborn mice with rhesus rotavirus (RRV) and leads to development of an obstructive cholan- giopathy, has provided a model to assess measures to prevent and treat BA. We used this mouse model of RRV-induced BA to determine if passive immunization of pups using maternal immunization (injection of dams with non-replicating rotavirus (RV) virus-like particles (VLPs) or live RRV) or injection of pups with RV immune serum would protect these RRV-infected neonates from developing BA (measured using cholestasis). Parenteral immunization of mouse dams with two formulations of VLPs (containing viral proteins 2/6 or 2/6/7) resulted in a significant increase in serum RV antibody, and pups born to these immunized dams were protected from developing cholestasis following neonatal infection with RRV. Serum RV-specific antibody with titers of ≥400-800 in dams significantly protected pups from develop- ing cholestasis, and a significant trend of increasing protection with high titers was observed (p < 0.0001). Cholestatic pups had lower levels of RV serum antibody and higher serum (p < 0.01) and liver (p < 0.05) RV antigen compared to healthy pups. Passive transfer of low-titer (1600; p < 0.05) or high-titer (25,600; p < 0.01) RV immune serum to neonatal pups prior to RRV infection also protected them from developing cholestasis. Together, these findings indicate that passively acquired, neutralizing or non-neutralizing RV serum antibody attenuates viral replication and protects pups against disease in the RRV BA model. Early reduction of viral load by clearance with RV-specific antibody is likely a critical determinant of disease in this model.

The plasma–metal inert gas (MIG) process is characterized by a variety of process parameters. Numerical simulation can be used to investigate the influence of these process parameters and thus helps to improve the properties of the weld. In this paper we discuss a procedure to describe the plasma–MIG process by coupling numerical models of the arc and the droplet detachment with a three-dimensional model for the plasma–MIG weld pool. Using the magnetohydrodynamic (MHD) arc model, the effects of process parameters on the arc pressure profile and the energy input profile on the workpiece can be analyzed. The volume-of-fluid (VoF)–MHD model of the droplet detachment describes the properties of the resulting droplet in terms of its size, temperature and speed. In the three-dimensional VoF model of the weld pool, the influences of the arc and the droplet are simplified by source terms in the mass, momentum and energy equations. Due to these simplifications in the physical complexity, the process and the seam shape can be described with reasonable computational effort.

This paper presents extensive investigations about the influence of He-additions to argon TIG-arc properties. Results of diagnostic methods, numerical simulations and welding trials are combined to improve the comprehension about the mode of action of gas mixtures. Additionally, selected results of the investigation with H2- and N2-additions are summarized. The investigations show that all gas additions cause an increase of the heat input into the workpiece. However, the stagnation pressure depends on the gas composition: He-additions result in a decrease of the stagnation pressure which depends on the arc length, whereas H2-and N2-additions increase the pressure. By a systematic choice of the gas mixture the weld depth and also the maximum feed speed can be influenced.

Current numerical models of gas metal arc welding (GMAW) attempt to combine a magnetohydrodynamic (MHD) model of the arc and a volume-of-fluid (VoF) model of metal transfer. But in these models vaporization of metal is neglected and the arc region is assumed to be composed of pure argon, as it is common practice for models of gas tungsten arc welding (GTAW). These models predict temperatures over 20 000 K and a temperature distribution similar to GTAW arcs. However, recent spectroscopic temperature measurements in GMAW arcs have demonstrated much lower arc temperatures. In contrast to GTAW arcs, they found a central local minimum of the radial temperature distribution. The paper presents a GMAW arc model that considers metal vapour and which is in very good agreement with experimentally observed temperatures. Furthermore, the model is able to predict the local central minimum in the radial temperature and the radial electric current density distributions for the first time. The axially symmetric model of the welding torch, the workpiece, the wire and the arc (fluid domain) implements MHD as well as turbulent mixing and thermal demixing of metal vapour in argon. The mass fraction of iron vapour obtained from the simulation shows an accumulation in the arc core and another accumulation on the fringes of the arc at 2 000 to 5 000 K. The demixing effects lead to very low concentrations of iron between these two regions. Sensitive analyses demonstrate the influence of the transport and radiation properties of metal vapour, the welding current and the evaporation rate.

Current numerical models of gas metal arc welding (GMAW) are trying to combine magnetohydrodynamics (MHD) models of the arc and volume of fluid (VoF) models of metal transfer. They neglect vaporization and assume an argon atmosphere for the arc region, as it is common practice for models of gas tungsten arc welding. These models predict temperatures above 20 000 K and a temperature distribution similar to tungsten inert gas (TIG) arcs. However, current spectroscopic temperature measurements in GMAW arcs demonstrate much lower arc temperatures. In contrast to TIG arcs they found a central local minimum of the radial temperature distribution. The paper presents a GMAW arc model that considers metal vapour and which is in a very good agreement with experimentally observed temperatures. Furthermore, the model is able to predict the local central minimum in the radial temperature and the radial electric current density distributions for the first time. The axially symmetric model of the welding torch, the work piece, the wire and the arc (fluid domain) implements MHD as well as turbulent mixing and thermal demixing of metal vapour in argon. The mass fraction of iron vapour obtained from the simulation shows an accumulation in the arc core and another accumulation on the fringes of the arc at 2000 to 5000 K. The demixing effects lead to very low concentrations of iron between these two regions. Sensitive analyses demonstrate the influence of the transport and radiation properties of metal vapour, and the evaporation rate relative to the wire feed. Finally the model predictions are compared with the measuring results of Zielinska et al.

In tropical mountainous regions of South East Asia, intensive cultivation of annual crops on steep slopes makes the area prone to erosion resulting in decreasing soil fertility. Sediment deposition in the valleys, however, can enhance soil fertility, depending on the quality of the sediments, and influence crop productivity. The aim of the study was to assess (i) the spatio-temporal variation in grain yield along two rice terrace cascades in the uplands of northern Viet Nam, (ii) possible linkage of sediment deposition with the observed variation in grain yield, and (iii) whether spatial variation in soil water or nitrogen availability influenced the obtained yields masking the effect of inherent soil fertility using carbon isotope ( 13 C) discrimination and 15 N natural abundance techniques. In order to evaluate the impact of seasonal conditions, fertilizer use and sediment quality on rice performance, 15 N and 13 C stable isotope compositions of rice leaves and grains taken after harvest were examined and combined with soil fertility information and rice performance using multivariate statistics. The observed grain yields for the non-fertilized fields, averaged over both cascades, accounted for 4.0 ± 1.4 Mg ha −1 and 6.6 ± 2.5 Mg ha −1 in the spring and summer crop, respectively, while for the fertilized fields, grain yields of 6.5 ± 2.1 Mg ha −1 and 6.9 ± 2.1 Mg ha −1 were obtained. In general, the spatial variation of rice grain yield was strongly and significantly linked to sediment induced soil fertility and textural changes, such as soil organic carbon ( r 0.34/0.77 for Cascades 1 and 2, respectively) and sand fraction ( r −0.88/−0.34). However, the observed seasonal alteration in topsoil quality, due to sediment deposition over two cropping cycles, was not sufficient to fully account for spatial variability in rice productivity. Spatial variability in soil water availability, assessed through 13 C discrimination, was mainly present in the spring crop and was linearly related to the distance from the irrigation channel, and overshadowed in Cascade 2 the expected yield trends based on sediment deposition. Although δ 15 N signatures in plants indicated sufficient N uptake, grain yields were not found to be always significantly influenced by fertilizer application. These results showed the importance of integrating sediment enrichment in paddy fields within soil fertility analysis. Furthermore, where the effect of inherent soil fertility on rice productivity is masked by soil water or nitrogen availability, the use of 13 C and 15 N stable isotopes and its integration with conventional techniques showed potential to enhance the understanding of the influence of erosion – sedimentation and nutrient fluxes on crop productivity, at toposequence level.

Objective To investigate the impact of corticosteroid therapy on the growth of participants in the Steroids in Biliary Atresia Randomized Trial (START) conducted through the Childhood Liver Disease Research Network. The primary analysis in START indicated that steroids did not have a beneficial effect on drainage in a cohort of infants with biliary atresia. We hypothesized that steroids would have a detrimental effect on growth in these infants. Study design A total of 140 infants were enrolled in START, with 70 randomized to each treatment arm: steroid and placebo. Length, weight, and head circumference were obtained at baseline and follow-up visits to 24 months of age. Results Patients treated with steroids had significantly lower length and head circumference z scores during the first 3 months post-hepatoportoenterostomy (HPE), and significantly lower weight until 12 months. Growth trajectories in the steroid and placebo arms differed significantly for length (P Conclusions Steroid therapy following HPE in patients with biliary atresia is associated with impaired length, weight, and head circumference growth trajectories for at least 6 months post-HPE, especially impacting infants with successful bile drainage. Trial registration ClinicalTrials.gov : NCT00294684 .

Live pentavalent human-bovine reassortant rotavirus vaccine is recommended in the United States for routine immunization of infants. We describe three infants, two with failure to thrive, who had dehydration and diarrhea within 1 month after their first or second rotavirus immunization and subsequently received a diagnosis of severe combined immunodeficiency. Rotavirus was detected, by means of reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay, in stool specimens obtained from all three infants, and gene-sequence analysis revealed the presence of vaccine rotavirus. These infections raise concerns regarding the safety of rotavirus vaccine in severely immunocompromised patients.

Mutations in TJP2 (also named ZO-2), encoding tight-junction protein 2 (TJP2), cause an autosomal-recessive form of progressive intrahepatic cholestasis.1 Association of TJP2 deficiency with hepatocellular carcinoma (HCC) in childhood has not been recognized.

Metabolic studies utilizing stable isotope tracer in humans have typically used intravenous tracer infusions and venous blood sampling. These studies explore subcutaneous infusion of isotope and "finger stick" capillary blood sampling to measure glucose turnover. Five subjects received simultaneous 8-h infusions of glucose labeled with isotope: [1-(13)C]glucose subcutaneously and [6,6-(2)H(2)]glucose intravenously. At regular intervals, venous and finger stick blood specimens were obtained. Finger stick blood was applied to filter paper. Substrate and isotopic steady state was reached after 7.0 h with both routes of infusion. The isotopic enrichments of finger stick and venous specimens did not differ significantly for the subcutaneously infused [1-(13)C]glucose (p = 0.33 and p = 0.23, respectively) but the finger stick [6,6-(2)H(2)]glucose enrichment was slightly higher (p0.03) than that of the venous sample. Using [6,6-(2)H(2)]glucose infusion and venous plasma sampling as the reference method, the [1-(13)C]glucose gave estimates of glucose R(a) that were 13% (plasma) and 17% (finger stick) lower (p0.001 and p0.02, respectively). This difference could be attributed to recycling of (13)C label. In conclusion, subcutaneous infusion and finger stick specimen collection onto filter paper represent a potential method of conducting in vivo studies of substrate metabolism outside of a hospital-based research unit.

Within this review, we describe a home-built pulsed electron paramagnetic resonance (EPR) spectrometer operating at 180 GHz as well as the incorporation of two double resonance techniques, electron nuclear double resonance (ENDOR) and pulsed electron double resonance (PELDOR), along with first applications. Hahn-echo decays on a TEMPO/polystyrene sample are presented, demonstrating that the observation of anisotropic librational motions is possible in a very precise manner at high magnetic fields. Bisdiphenylene-phenyl-allyl is used as a model system to illustrate the performance of the setup for 1H-ENDOR using the Mims as well as the Davies sequence. Furthermore, first 1H-Mims and Davies ENDOR spectra on a biological sample, the wild-type Ras*Mn2+*GDP protein, are reported. The capability of the 180-GHz PELDOR setup is demonstrated using the three-pulse ELDOR sequence on the protein ribonucleotide reductase (RNR) subunit R2 from Escherichia coli, which contains two tyrosyl radicals at a 33 angstroms distance. At 180 GHz, orientation selectivity is observed and the modulation frequency is found to be in good agreement with theoretical predictions.

Kobrynski et al. [1] showed gastrointestinal complaints in children can be an early sign of primary immunodeficiency disease (PIDD). Rotavirus infection associated with PIDD can be life-threatening. Rotavirus is a leading cause of childhood gastrointestinal disease worldwide [2]. Most rotavirus disease is caused by 5 G types (G1-G4 and G9) and 3 P types (P1A[8], P1B[4], and P2A[6]) [2]. Two live oral rotavirus vaccines, RotaTeq® (5 different human-bovine reassortant rotavirus strains; Merck and Co, Whitehouse Station, NJ) and Rotarix® (1 human rotavirus strain; GlaxoSmithKline, Rixensart, Belgium) are recommended for routine immunization of US infants [2]. Disease caused by emerging worldwide rotavirus type, G9P[8] may be prevented by both vaccines although this strain is not included in either vaccine. Severe combined immunodeficiency (SCID) is characterized by lack of T cells and life-threatening infections [3]. Treatment of viral infections prior to hematopoietic stem cell transplantation (HSCT) with intravenous immunoglobulin (IVIG) and antivirals has been attempted, but persistence of viral disease has been reported [3–8]. We report a 7 month-old male infant with SCID who had persistent, nonvaccine-associated rotavirus gastroenteritis and viremia despite oral and IVIG administration. T-cell engraftment following HSCT possibly helped by oral and IVIG was necessary to eliminate rotavirus infection. The full-term, formula-fed infant received RotaTeq at 2 and 4 months of age. The patient developed chronic intermittent diarrhea at 2 months of age and was hospitalized at 7 months of age with respiratory distress, diarrhea, and failure to thrive. A peripheral white blood cell count was 16,140 cells/μl with 59% neutrophils, 17% lymphocytes (absolute lymphocyte count=2743cells/μl [normal range 3,900–9,000]), 7% monocytes, and 13% eosinophils. Bronchoscopy aspirate revealed Pneumocystis jiroveci. Stool for rotavirus was positive by electron microscopy (EM). Immunoglobulins were very low including IgG 77 mg/dL (normal range 184–974 mg/dL), IgA

Objectives To assess health-related quality of life (HRQOL) in children with Alagille syndrome (ALGS) in comparison with healthy and other liver disease cohorts, and to identify determinants of HRQOL in patients with ALGS. Study design Within the Childhood Liver Disease Research Network prospective study of cholestasis, Pediatric Quality of Life Inventory (PedsQL) questionnaires were administered to 70 children with ALGS, 95 children with alpha-1-antitrypsin deficiency (A1ATD), and 49 children with other causes of chronic intrahepatic cholestasis (IHC) aged 5-18 years. Parent proxy PedsQL scores were recorded for children aged 2-18 years (98 ALGS, 123 A1ATD, and 68 IHC). Results Mean ages and total bilirubin (mg/dL) were ALGS 9.4 years; 4.4, A1ATD 9.5 years; 0.7, and IHC 10.3 years; 2.9. ALGS child PedsQL scores were lower than in healthy children and children with A1ATD (mean 73 vs 83; P = .001). Children with ALGS and IHC were similar, except in physical scores (73 vs 79; P = .05). Parents of children with ALGS perceived their children to have worse HRQOL than A1ATD ( P ≤ .001) and marginally lower compared with IHC. Univariate analysis revealed ALGS child-reported scores were positively associated with better growth and inversely with total bilirubin. Growth failure, elevated international normalized ratio, and an intracardiac defect were predictive of poor parental scores ( P ≤ .05). In multivariate analysis, only weight z-score remained significant for child- and parent-reported scores. Conclusions HRQOL is impaired in children with ALGS compared with healthy and children with A1ATD, similar to children with IHC and is associated with growth failure, which is a potentially treatable cause of impaired HRQOL.

Membrane filtration systems can handle varying wastewaters with simple and robust operation. However, current low permeate flux rates attributed to solids accumulation at the membrane surface limit more widespread technology use. This work seeks a better understanding of flux performance relative to solids concentration and transmembrane pressure coupled with potential flux enhancements. Enhancements revolve around disturbing solids accumulation at the membrane surface by physical cleaning or periodic flow reversal. Results indicate both rotary and tubular membranes produce consistent particle-free, low-turbidity permeate at varying levels of feed solids concentrations. Rotary membranes may produce only slightly greater permeate flux rates than tubular membranes at low feed solids concentration, but the difference increases drastically as feed solids concentration increases. Rotary membrane systems can concentrate wastewaters to greater than 40% solids, but the greater the feed solids, the less ad...

Progressive familial intrahepatic cholestasis (PFIC) type 2 results from a mutation in the bile salt exporter pump, impeding bile acid transport. Patients usually present with jaundice, pruritus, growth failure, and fat soluble vitamin deficiencies. We present two patients diagnosed with PFIC type 2 due to severe coagulopathy and bleeding without jaundice.

Ornithine transcarbamylase (OTC) deficiency is the most common urea cycle defect. Thromboembolic complications have not heretofore been linked with this diagnosis. We describe four patients with neonatal-onset OTC deficiency who developed vascular thromboses. One patient had arterial thrombosis; the rest developed venous thromboses. Multiple pro-thrombotic risk factors were identified. Low plasma arginine levels were observed in all patients at the time of thrombosis. Arginine deficiency and the resultant nitric oxide insufficiency may contribute to thrombotic risk. Careful normalization of plasma arginine and citrulline levels and increased surveillance for thrombotic complications should be considered in patients with OTC deficiency.