Associations between WNT signaling pathway-related gene polymorphisms and risks of osteoporosis development in Chinese postmenopausal women: a case-control study.

BACKGROUND: The WNT signaling pathway is involved in the regulation of bone homeostasis, and the effect of WNT signaling pathway-related gene (WNT16 and LRP5) polymorphisms on osteoporosis risk among Chinese postmenopausal women is still unknown. Hence, we performed a case-control study to assess the association of WNT signaling pathway-related gene polymorphisms and osteoporosis risk. METHODS: A total of 1026 women (515 osteoporosis patients and 511 controls) of postmenopausal age who were randomly sampled from Xi'an 630 Hospital (Shaanxi Province, China) were involved in this study. Seven genetic polymorphisms in WNT16 (rs3779381, rs3801387, rs917727 and rs7776725) and LRP5 (rs2291467, rs11228240 and rs12272917) were selected and genotyped using the Agena MassARRAY iPLEX system. The association of the genetic polymorphisms and osteoporosis risk was assessed by odds ratios and 95% confidence intervals. The multifactor dimensionality reduction (MDR) method was conducted to analyze single nucleotide polymorphism (SNP)-SNP interaction. RESULTS: We found that LRP5 polymorphisms (rs2291467, rs11228240 and rs12272917) were significantly associated with a decreased risk of osteoporosis in homozygote, recessive and additive models (p < 0.05). Stratification analysis showed that LRP5 polymorphisms (rs2291467, rs11228240 and rs12272917) significantly decreased the osteoporosis risk in the subgroup of body mass index (BMI) ≤ 24 (p < 0.05) and that individuals carrying a heterozygote genotype of WNT16 polymorphisms (rs3779381, rs3801387, rs917727 and rs7776725) had a higher osteoporosis risk in the subgroup of BMI > 24 (p < 0.05). Two haplotypes (haplotype 1: rs3779381, rs3801387, rs917727 and rs7776725; haplotype 2: rs2291467 and rs11228240) were observed, yet only Trs2291467Trs11228240 and Crs2291467Crs11228240 had a strong association with a decreased risk of osteoporosis (p < 0.05). Additionally, MDR analysis revealed that LRP5 rs2291467 was the best model in single-locus MDR analysis. A seven-locus model including rs3779381-AG, rs7776725-TC, rs3801387-GA and rs917727-TC in WNT16 and rs11228240-CC, rs12272917-TC and rs2291467-CC in LRP5 was the best model in multiple-loci MDR analysis (p < 0.001). These two best models were the most significantly associated with osteoporosis risk. CONCLUSIONS: Our findings suggested that WNT16 and LRP5 genetic polymorphisms are associated with osteoporosis risk among Chinese postmenopausal women.

Improving early running-in wear characteristics for dental lithium disilicate glass-ceramics by ion-exchange.

OBJECTIVES: This study examined the effects of Li+→Na+ ion-exchange on the early wear performance of dental lithium disilicate (LD) glass-ceramics. METHODS: Specimens with different shapes were prepared using IPS e.max Press as the LD glass-ceramics. Ion-exchange was conducted by placing polished specimens in molten salt containing 25% NaNO3 and 75% KNO3 at 385 °C for 16 or 64 h. The ion-exchanged specimens were analyzed using X-ray diffraction (XRD) and energy-dispersive X-ray spectroscopy (EDS) to investigate the structure and the elemental distribution. Thereafter, the specimens were tested for flexural strength, Vickers hardness, and fracture resistance. A portion of the specimens were tested with a pin-on-disk tribometer with 10 N for 40 × 104 wear cycles in artificial saliva. Wear analysis of the specimens was performed using a 3D profilometer and analyzed with one-way analyses of variance and Tukey's post hoc pairwise comparisons. Worn surfaces were examined with scanning electron microscopy. RESULTS: The LD glass-ceramics exhibited strong time-dependent wear behavior, with typical running-in and steady wear stages. Ion-exchange treatments at 385 °C for 16 h and 64 h both enhanced the mechanical properties and decreased the wear rates of early running-in wear stage. The early wear performance of specimens treated with ion-exchange for long time (64 h) was improved significantly. CONCLUSION: A thicker ion-exchange layer may be obtained by processing ion-exchange for a long time. This protocol improves the early wear performance of the glass-ceramics effectively. CLINICAL SIGNIFICANCE: Dental restorations may fail prematurely due to excessive wear. It is important to improve the early wear performance of the glass-ceramics. Ion-exchange has the potential to strengthen dental LD glass-ceramics. Understanding the effect of ion-exchange on the early wear performance of glass-ceramics provides insight improving the early wear performance of these restorations.

Urinary complement proteins and risk of end-stage renal disease: quantitative urinary proteomics in patients with type 2 diabetes and biopsy-proven diabetic nephropathy.

PURPOSE: To investigate the association between urinary complement proteins and renal outcome in biopsy-proven diabetic nephropathy (DN). METHODS: Untargeted proteomic and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional analyses and targeted proteomic analysis using parallel reaction-monitoring (PRM)-mass spectrometry was performed to determine the abundance of urinary complement proteins in healthy controls, type 2 diabetes mellitus (T2DM) patients, and patients with T2DM and biopsy-proven DN. The abundance of each urinary complement protein was individually included in Cox proportional hazards models for predicting progression to end-stage renal disease (ESRD). RESULTS: Untargeted proteomic and functional analysis using the KEGG showed that differentially expressed urinary proteins were primarily associated with the complement and coagulation cascades. Subsequent urinary complement proteins quantification using PRM showed that urinary abundances of C3, C9, and complement factor H (CFAH) correlated negatively with annual estimated glomerular filtration rate (eGFR) decline, while urinary abundances of C5, decay-accelerating factor (DAF), and CD59 correlated positively with annual rate of eGFR decline. Furthermore, higher urinary abundance of CFAH and lower urinary abundance of DAF were independently associated with greater risk of progression to ESRD. Urinary abundance of CFAH and DAF had a larger area under the curve (AUC) than that of eGFR, proteinuria, or any pathological parameter. Moreover, the model that included CFAH or DAF had a larger AUC than that with only clinical or pathological parameters. CONCLUSION: Urinary abundance of complement proteins was significantly associated with ESRD in patients with T2DM and biopsy-proven DN, indicating that therapeutically targeting the complement pathway may alleviate progression of DN.

Committee machines-a universal method to deal with non-idealities in memristor-based neural networks.

Artificial neural networks are notoriously power- and time-consuming when implemented on conventional von Neumann computing systems. Consequently, recent years have seen an emergence of research in machine learning hardware that strives to bring memory and computing closer together. A popular approach is to realise artificial neural networks in hardware by implementing their synaptic weights using memristive devices. However, various device- and system-level non-idealities usually prevent these physical implementations from achieving high inference accuracy. We suggest applying a well-known concept in computer science-committee machines-in the context of memristor-based neural networks. Using simulations and experimental data from three different types of memristive devices, we show that committee machines employing ensemble averaging can successfully increase inference accuracy in physically implemented neural networks that suffer from faulty devices, device-to-device variability, random telegraph noise and line resistance. Importantly, we demonstrate that the accuracy can be improved even without increasing the total number of memristors.

Prognostic model for identifying candidates for hepatectomy among patients with hepatocellular carcinoma and hepatic vein invasion.

BACKGROUND: Hepatic vein tumour thrombus (HVTT) is a major determinant of survival outcomes for patients with hepatocellular carcinoma (HCC). An Eastern Hepatobiliary Surgery Hospital (EHBH)-HVTT model was established to predict the prognosis of patients with HCC and HVTT after liver resection, in order to identify optimal candidates for liver resection. METHODS: Patients with HCC and HVTT from 15 hospitals in China were included. The EHBH-HVTT model with contour plot was developed using a non-linear model in the training cohort, and subsequently validated in internal and external cohorts. RESULTS: Of 850 patients who met the inclusion criteria, there were 292 patients who had liver resection and 198 who did not in the training cohort, and 124 and 236 in the internal and external validation cohorts respectively. Contour plots for the EHBH-HVTT model were established to predict overall survival (OS) rates of patients visually, based on tumour diameter, number of tumours and portal vein tumour thrombus. This differentiated patients into low- and high-risk groups with distinct long-term prognoses in the liver resection cohort (median OS 34·7 versus 12·0 months; P < 0·001), internal validation cohort (32·8 versus 10·4 months; P = 0·002) and external validation cohort (15·2 versus 6·5 months; P = 0·006). On subgroup analysis, the model showed the same efficacy in differentiating patients with HVTT in peripheral and major hepatic veins, the inferior vena cava, or in patients with coexisting portal vein tumour thrombus. CONCLUSION: The EHBH-HVTT model was accurate in predicting prognosis in patients with HCC and HVTT after liver resection. It identified optimal candidates for liver resection among patients with HCC and HVTT, including tumour thrombus in the inferior vena cava, or coexisting portal vein tumour thrombus.

ANTECEDENTES: La trombosis tumoral de la vena hepática (hepatic vein tumour thrombus, HVTT) es un determinante importante de los resultados de supervivencia en pacientes con carcinoma hepatocelular (hepatocellular carcinoma, HCC). Se desarrolló el modelo llamado Eastern Hepatobiliary Surgery Hospital (EHBH)-HVTT para predecir el pronóstico de los pacientes con HCC y HVTT después de la resección hepática (liver resection, LR), con el fin de identificar los candidatos óptimos para LR entre estos pacientes. MÉTODOS: Se incluyeron pacientes con HCC y HVTT de 15 hospitales en China. El modelo EHBH-HVTT con gráfico de contorno se desarrolló utilizando un modelo no lineal en la cohorte de entrenamiento, siendo posteriormente validado en cohortes internas y externas. RESULTADOS: De 850 pacientes que cumplieron con los criterios de inclusión, hubo 292 pacientes en el grupo LR y 198 pacientes en el grupo no LR en la cohorte de entrenamiento, y 124 y 236 en las cohortes de validación interna y externa. Los gráficos de contorno del modelo EHBH-HVTT se establecieron para predecir visualmente las tasas de supervivencia global (overall survival, OS) de los pacientes, en función del diámetro del tumor, número de tumores y del trombo tumoral de la vena porta (portal vein tumour thrombus, PVTT). Esto diferenciaba a los pacientes en los grupos de alto y bajo riesgo, con distinto pronóstico a largo plazo en las 3 cohortes (34,7 versus 12,0 meses, 32,8 versus 10,4 meses y 15,2 versus 6,5 meses, P < 0,001). En el análisis de subgrupos, el modelo mostró la misma eficacia en la diferenciación de pacientes con HVTT, con trombo tumoral en la vena cava inferior (inferior vena cava tumour thrombus, IVCTT) o en pacientes con PVTT coexistente. CONCLUSIÓN: El modelo EHBH-HVTT fue preciso para la predicción del pronóstico en pacientes con HCC y HVTT después de la LR. Identificó candidatos óptimos para LR en pacientes con HCC y HVTT, incluyendo IVCTT o PVTT coexistente.

Ti n+1C n MXenes with fully saturated and thermally stable Cl terminations.

MXenes are a rapidly growing family of 2D materials that exhibit a highly versatile structure and composition, allowing for significant tuning of the materials properties. These properties are, however, ultimately limited by the surface terminations, which are typically a mixture of species, including F and O that are inherent to the MXene processing. Other and robust terminations are lacking. Here, we apply high-resolution scanning transmission electron microscopy (STEM), corresponding image simulations and first-principles calculations to investigate the surface terminations on MXenes synthesized from MAX phases through Lewis acidic melts. The results show that atomic Cl terminates the synthesized MXenes, with mere residual presence of other termination species. Furthermore, in situ STEM-electron energy loss spectroscopy (EELS) heating experiments show that the Cl terminations are stable up to 750 °C. Thus, we present an attractive new termination that widely expands the MXenes' functionalization space and enables new applications.

Comparative expression profile of microRNAs and piRNAs in three ruminant species testes using next-generation sequencing.

microRNA (miRNA) and piwi-interacting RNA (piRNA) are two classes small non-coding regulatory RNAs that play crucial roles in multiple biological processes such as spermatogenesis. However, there are no published studies on conjoint analysis of miRNA and piRNA profiles among cattle, yak and their interspecies (the dzo) using sequencing technology. Next-generation sequencing technology was used to profile miRNAs and piRNAs among those three ruminants to elucidate their functions. A total of 119, 14 and six differentially expressed miRNAs were obtained in cattle vs. dzo, cattle vs. yak and yak vs. dzo comparison groups, while there were 873, 1,065 and 1,158 differentially expressed piRNAs in those three comparison groups. The expression of three miRNAs was validated in the three ruminants, and the results suggested that the miRNA expression profiles data could represent actual miRNA expression levels. Moreover, the putative targets of differentially expressed miRNAs were predicted by their own genome, it is worth to note that both the cattle and yak genome were used for dzo, then the targets were subjected to GO enrichment and KEGG pathway analysis, revealing the likely roles for these differentially expressed miRNAs in spermatogenesis. In conclusion, this study provided a useful resource for further elucidation of the miRNAs and piRNAs regulatory roles in spermatogenesis. It may also facilitate the development of therapeutic strategies for dzo reproduction research.

Comparative study of the lattice Boltzmann models for Allen-Cahn and Cahn-Hilliard equations.

In this paper, a comparative study of the lattice Boltzmann (LB) models for the Allen-Cahn (A-C) and Cahn-Hilliard (C-H) equations is conducted. To this end, a new LB model for the A-C equation is first proposed, where the equilibrium distribution function and the source term distribution function are delicately designed to recover the A-C equation correctly. The gradient term in this model can be computed by the nonequilibrium part of the distribution function such that the collision process can be implemented locally. Then a detailed numerical study on several classical problems is performed to give a comparison between the present model for the A-C equation and the recently developed LB model [H. Liang et al., Phys. Rev. E 89, 053320 (2014)PLEEE81539-375510.1103/PhysRevE.89.053320] for the C-H equation in terms of tracking the interface of two-phase flow. The results show that the present LB model for the A-C equation is more accurate and more stable, and also has a second-order convergence rate in space, while the convergence rate of the previous LB model for the C-H equation is only about 1.5.

The neurotoxicity of iron, copper and cobalt in Parkinson's disease through ROS-mediated mechanisms.

Parkinson's disease (PD) is the second most common neurodegenerative disease with gradual loss of dopaminergic neurons. Despite extensive research in the past decades, the etiology of PD remains elusive. Nevertheless, multiple lines of evidence suggest that oxidative stress is one of the common causes in the pathogenesis of PD. It has also been suggested that heavy metal-associated oxidative stress may be implicated in the etiology and pathogenesis of PD. Here we review the roles of redox metals, including iron, copper and cobalt, in PD. Iron is a highly reactive element and deregulation of iron homeostasis is accompanied by concomitant oxidation processes in PD. Copper is a key metal in cell division process, and it has been shown to have an important role in neurodegenerative diseases such as PD. Cobalt induces the generation of reactive oxygen species (ROS) and DNA damage in brain tissues.

Lattice Boltzmann simulation of three-dimensional Rayleigh-Taylor instability.

In this paper, the three-dimensional (3D) Rayleigh-Taylor instability (RTI) with low Atwood number (A(t)=0.15) in a long square duct (12W × W × W) is studied by using a multiple-relaxation-time lattice Boltzmann (LB) multiphase model. The effect of the Reynolds number on the interfacial dynamics and bubble and spike amplitudes at late time is investigated in detail. The numerical results show that at sufficiently large Reynolds numbers, a sequence of stages in the 3D immiscible RTI can be observed, which includes the linear growth, terminal velocity growth, reacceleration, and chaotic development stages. At late stage, the RTI induces a very complicated topology structure of the interface, and an abundance of dissociative drops are also observed in the system. The bubble and spike velocities at late stage are unstable and their values have exceeded the predictions of the potential flow theory [V. N. Goncharov, Phys. Rev. Lett. 88, 134502 (2002)]. The acceleration of the bubble front is also measured and it is found that the normalized acceleration at late time fluctuates around a constant value of 0.16. When the Reynolds number is reduced to small values, some later stages cannot be reached sequentially. The interface becomes relatively smoothed and the bubble velocity at late time is approximate to a constant value, which coincides with the results of the extended Layzer model [S.-I. Sohn, Phys. Rev. E 80, 055302(R) (2009)] and the modified potential theory [R. Banerjee, L. Mandal, S. Roy, M. Khan, and M. R. Guptae, Phys. Plasmas 18, 022109 (2011)]. In our simulations, the Graphics Processing Unit (GPU) parallel computing is also used to relieve the massive computational cost.

Lattice Boltzmann modeling of three-phase incompressible flows.

In this paper, based on multicomponent phase-field theory we intend to develop an efficient lattice Boltzmann (LB) model for simulating three-phase incompressible flows. In this model, two LB equations are used to capture the interfaces among three different fluids, and another LB equation is adopted to solve the flow field, where a new distribution function for the forcing term is delicately designed. Different from previous multiphase LB models, the interfacial force is not used in the computation of fluid velocity, which is more reasonable from the perspective of the multiscale analysis. As a result, the computation of fluid velocity can be much simpler. Through the Chapman-Enskog analysis, it is shown that the present model can recover exactly the physical formulations for the three-phase system. Numerical simulations of extensive examples including two circular interfaces, ternary spinodal decomposition, spreading of a liquid lens, and Kelvin-Helmholtz instability are conducted to test the model. It is found that the present model can capture accurate interfaces among three different fluids, which is attributed to its algebraical and dynamical consistency properties with the two-component model. Furthermore, the numerical results of three-phase flows agree well with the theoretical results or some available data, which demonstrates that the present LB model is a reliable and efficient method for simulating three-phase flow problems.

Paving the way for the synthesis of a series of divalent actinide complexes: a theoretical perspective.

Recently, the +2 formal oxidation state in soluble molecular complexes for lanthanides (La-Nd, Sm-Lu) and actinides (Th and U) has been discovered [W. J. Evans, et al., J. Am. Chem. Soc., 2011, 133, 15914; J. Am. Chem. Soc., 2012, 134, 8420; J. Am. Chem. Soc., 2013, 135, 13310; Chem. Sci., 2015, 6, 517]. To explore the nature of the bonding and stabilities of the low-valent actinide complexes, a series of divalent actinide species, [AnCp'3](-) (An[double bond, length as m-dash]Th-Am, Cp' = [η(5)-C5H4(SiMe3)](-)) have been investigated in THF solution using scalar relativistic density functional theory. The electronic structures and electron affinity properties were systematically studied to identify the interactions between the +2 actinide ions and Cp' ligands. The ground state electron configurations for the [AnCp'3](-) species are [ThCp'3](-) 6d(2), [PaCp'3](-) 5f(2)6d(1), [UCp'3](-) 5f(3)6d(1), [NpCp'3](-) 5f(5), [PuCp'3](-) 5f(6), and [AmCp'3](-) 5f(7), respectively, according to the MO analysis. The total bonding energy decreases from the Th- to the Am-complex and the electrostatic interactions mainly dominate the bonding between the actinide atom and ligands. The electron affinity analysis suggests that the reduction reaction of AnCp'3→ [AnCp'3](-) should become increasingly facile across the actinide series from Th to Am, in accord with the known An(iii/ii) reduction potentials. This work expands the knowledge on the low oxidation state chemistry of actinides, and further motivates and guides the synthesis of related low oxidation state compounds of 5f elements.

Genetic diversity and classification of Tibetan yak populations based on the mtDNA COIII gene.

To determine the level of genetic diversity and phylogenetic relationships among Tibetan yak populations, the mitochondrial DNA cytochrome c oxidase subunit 3 (COIII) genes of 378 yak individuals from 16 populations were analyzed in this study. The results showed that the length of cytochrome c oxidase subunit 3 gene sequences was 781 bp, with nucleotide frequencies of 29.2, 29.4, 26.1, and 15.2% for T, C, A, and G, respectively. A total of 26 haplotypes were identified, with 69 polymorphic sites, including 11 parsimony-informative sites and 58 single-nucleotide polymorphism sites. No deletions/insertions were found in sequence comparison, indicating that nucleotide mutation types were transitions and transversions. Haplotype and nucleotide diversities were 0.562 and 0.00138, respectively, indicating a high level of genetic diversity in Tibetan yak populations. Phylogenetic relationship analysis indicated that Tibetan yak populations are divided into 2 groups.

Effects of corn and soybean meal types on rumen fermentation, nitrogen metabolism and productivity in dairy cows.

Twelve multiparous Holstein dairy cows in mid-lactation were selected for a replicated 4×4 Latin square design with a 2 ×2 factorial arrangement to investigate the effects of corn and soybean meal (SBM) types on rumen fermentation, N metabolism and lactation performance in dairy cows. Two types of corn (dry ground [DGC] and steam-flaked corn [SFC]) and two types of SBM (solvent-extracted and heat-treated SBM) with different ruminal degradation rates and extents were used to formulate four diets with the same basal ingredients. Each period lasted for 21 days, including 14 d for adaptation and 7 d for sample collection. Cows receiving SFC had a lower dry matter (DM) and total N intake than those fed DGC. However, the milk yield and milk protein yield were not influenced by the corn type, resulting in higher feed and N utilization efficiency in SFC-fed cows than those receiving DGC. Ruminal acetate concentrations was greater and total volatile fatty acids concentrations tended to be greater for cows receiving DGC relative to cows fed SFC, but milk fat content was not influenced by corn type. The SFC-fed cows had lower ruminal ammonia-N, less urea N in their blood and milk, and lower fecal N excretion than those on DGC. Compared with solvent-extracted SBM-fed cows, cows receiving heat-treated SBM had lower microbial protein yield in the rumen, but similar total tract apparent nutrient digestibility, N metabolism measurements, and productivity. Excessive supply of metabolizable protein in all diets may have caused the lack of difference in lactation performance between SBM types. Results of the present study indicated that increasing the energy degradability in the rumen could improve feed efficiency, and reduce environmental pollution.

Phase-field-based multiple-relaxation-time lattice Boltzmann model for incompressible multiphase flows.

In this paper, a phase-field-based multiple-relaxation-time lattice Boltzmann (LB) model is proposed for incompressible multiphase flow systems. In this model, one distribution function is used to solve the Chan-Hilliard equation and the other is adopted to solve the Navier-Stokes equations. Unlike previous phase-field-based LB models, a proper source term is incorporated in the interfacial evolution equation such that the Chan-Hilliard equation can be derived exactly and also a pressure distribution is designed to recover the correct hydrodynamic equations. Furthermore, the pressure and velocity fields can be calculated explicitly. A series of numerical tests, including Zalesak's disk rotation, a single vortex, a deformation field, and a static droplet, have been performed to test the accuracy and stability of the present model. The results show that, compared with the previous models, the present model is more stable and achieves an overall improvement in the accuracy of the capturing interface. In addition, compared to the single-relaxation-time LB model, the present model can effectively reduce the spurious velocity and fluctuation of the kinetic energy. Finally, as an application, the Rayleigh-Taylor instability at high Reynolds numbers is investigated.

Importing, caring, breeding, genotyping, and phenotyping a genetic mouse in a Chinese university.

The genetic manipulation of the laboratory mouse has been well developed and generated more and more mouse lines for biomedical research. To advance our science exploration, it is necessary to share genetically modified mouse lines with collaborators between institutions, even in different countries. The transfer process is complicated. Significant paperwork and coordination are required, concerning animal welfare, intellectual property rights, colony health status, and biohazard. Here, we provide a practical example of importing a transgenic mice line, Dynamin 1 knockout mice, from Yale University in the USA to Perking University in China for studying cell secretion. This example including the length of time that required for paper work, mice quarantine at the receiving institution, and expansion of the mouse line for experiments. The procedure described in this paper for delivery live transgenic mice from USA to China may serve a simple reference for transferring mouse lines between other countries too.

Unilateral mydriasis as the primary sign of neurosyphilis.

Syphilis can mimic most ocular disorders, and there is no characteristic to distinguish ocular syphilis from other eye diseases. We report a rare case of a 41-year-old man who presented with an Adie's-like pupil as the only feature of neurosyphilis. The patient met the criteria for the diagnosis of neurosyphilis by the finding of positive cerebrospinal fluid-Venereal Disease Research Laboratory (CSF-VDRL) and CSF-Treponema pallidum particle agglutination tests. The patient was then treated with 2 g intravenous ceftriaxone per day for 15 days because of penicillin allergy. Nine months after anti-syphilitic treatment alone, the diameter of the patient's left pupil reduced from 10 to 5 mm. The CSF-VDRL test was negative. It is highly recommended that any patients with ocular disease that does not respond to the routine treatment should undergo syphilis evaluation to avoid misdiagnosis.

Phase-field-based lattice Boltzmann model for axisymmetric multiphase flows.

In this paper, a phase-field-based lattice Boltzmann (LB) model is proposed for axisymmetric multiphase flows. Modified equilibrium distribution functions and some source terms are properly added into the evolution equations such that multiphase flows in the axisymmetric coordinate system can be described. Different from previous axisymmetric LB multiphase models, the added source terms that arise from the axisymmetric effect contain no additional gradients, and therefore the present model is much simpler. Furthermore, through the Chapmann-Enskog analysis, the axisymmetric Chan-Hilliard equation and Navier-Stokes equations can be exactly derived from the present model. The model is also able to deal with flows with density contrast. A variety of numerical experiments, including planar and curve interfaces, an elongation field, a static droplet, a droplet oscillation, breakup of a liquid thread, and dripping of a liquid droplet under gravity, have been conducted to test the proposed model. It is found that the present model can capture accurate interface and the numerical results of multiphase flows also agree well with the analytical solutions and/or available experimental data.

Cardiac involvement and treatment-related mortality after non-myeloablative haemopoietic stem-cell transplantation with unselected autologous peripheral blood for patients with systemic sclerosis: a retrospective analysis.

BACKGROUND: Autologous haemopoietic stem-cell transplantation (HSCT) benefits patients with systemic sclerosis but has been associated with significant treatment-related mortality and failure to improve diffusion capacity of carbon monoxide (DLCO). We aimed to assess efficacy of HSCT and use of rigorous cardiac screening in this group. METHODS: We assessed patients with diffuse systemic sclerosis or limited systemic sclerosis and interstitial lung disease who were treated with HSCT as part of a study or on a compassionate basis at Northwestern University (Chicago, IL, USA) or the University of São Paulo (Ribeirão Preto, Brazil). Unselected peripheral blood stem cells were harvested with cyclophosphamide (2 g/m(2)) and filgrastim. The transplant regimen was a non-myeloablative regimen of cyclophosphamide (200 mg/kg) and rabbit anti-thymocyte globulin (rATG; 4·5-6·5 mg/kg). We followed patients up to 5 years for overall survival, relapse-free survival, modified Rodnan skin score, and pulmonary function tests. FINDINGS: Five (6%) of 90 patients died from treatment-related causes. Despite standard guidelines that recommend echocardiogram for screening before transplantation, four treatment-related deaths occurred because of cardiovascular complications (one constrictive pericarditis, two right heart failures without underlying infection, and one heart failure during mobilisation), and one death was secondary to sepsis without documented underlying heart disease. Kaplan-Meier analysis showed survival was 78% at 5 years (after eight relapse-related deaths) and relapse-free survival was 70% at 5 years. Compared with baseline, we noted improvements after HSCT in modified Rodnan skin scores at 1 year (58 patients; p<0·0001), 2 years (42 patients; p<0·0001), and 3 years (27 patients; p<0·0001) and forced vital capacity at 1 year (58 patients; p=0·009), 2 years (40 patients; p=0·02), and 3 years (28 patients; p=0·004), but total lung capacity and DLCO were not improved significantly after HSCT. Overall mean DLCO was significantly improved in patients with normal baseline echocardiograms (p=0·005) or electrocardiographs (p=0·05). INTERPRETATION: Autologous HSCT with a non-myeloablative regimen of cyclophosphamide and rATG with a non-selected autograft results in sustained improvement in skin thickness and forced vital capacity. DLCO is affected by baseline cardiac function. Guidelines for cardiac screening of patients with systemic sclerosis to assess treatment-related risk from pulmonary artery hypertension, primary cardiac involvement, or pericardial disease should be reconsidered and updated. FUNDING: None.