Reference enthalpy method developed from solutions of the boundary-layer equations

A simple average of local enthalpy over the velocity profile is proposed as the proper definition of reference enthalpy for the purpose of quasi-one-dimensional treatment of compressible boundary layers. Use of Van Driest's nearly exact solutions of the laminar boundary-layer equations shows that this definition produces Eckert's reference enthalpy formulation for the special case of an adiabatic wall. For surfaces other than adiabatic, either Eckert's form should be replaced by that of Young and Janssen, or the coefficient in Eckert's viscous heating term should be slightly modified. A similar analysis was conducted for turbulent flows using Whitfield and High's simplified solutions of the turbulent boundary-layer equations. Dorrance's derivation of reference quantities is also addressed. This work provides a theoretical basis for the empirical reference enthalpy formulas of Eckert and others and supplies practical expressions for the reference enthalpy of both laminar and turbulent compressible boundary layers

DNS study of a pipe flow following a step increase in flow rate

Direct numerical simulation (DNS) is conducted to study the transient flow in a pipe following a near-step increase of flow rate from an initial turbulent flow. The results are compared with those of the transient flow in a channel reported in He and Seddighi (2013). It is shown that the flow again exhibits a laminar–turbulent transition, similar to that in a channel. The behaviours of the flow in a pipe and a channel are the same in the near-wall region, but there are significant differences in the centre of the flow. The correlation between the critical Reynolds number and free stream turbulence previously established for a channel flow has been shown to be applicable to the pipe flow. The responses of turbulent viscosity, vorticity Reynolds number, and budget terms are analysed. Some significant differences have been found to exist between the developments of the vorticity Reynolds number in the pipe and channel flows

Low copy numbers of complement C4 and C4A deficiency are risk factors for myositis, its subgroups and autoantibodies

Background Idiopathic inflammatory myopathies (IIM) are a group of autoimmune diseases characterised by myositis-related autoantibodies plus infiltration of leucocytes into muscles and/or the skin, leading to the destruction of blood vessels and muscle fibres, chronic weakness and fatigue. While complement-mediated destruction of capillary endothelia is implicated in paediatric and adult dermatomyositis, the complex diversity of complement C4 in IIM pathology was unknown. Methods We elucidated the gene copy number (GCN) variations of total C4, C4A and C4B, long and short genes in 1644 Caucasian patients with IIM, plus 3526 matched healthy controls using real-time PCR or Southern blot analyses. Plasma complement levels were determined by single radial immunodiffusion. Results The large study populations helped establish the distribution patterns of various C4 GCN groups. Low GCNs of C4T (C4T=2+3) and C4A deficiency (C4A=0+1) were strongly correlated with increased risk of IIM with OR equalled to 2.58 (2.28-2.91), p=5.0×10 -53 for C4T, and 2.82 (2.48-3.21), p=7.0×10 -57 for C4A deficiency. Contingency and regression analyses showed that among patients with C4A deficiency, the presence of HLA-DR3 became insignificant as a risk factor in IIM except for inclusion body myositis (IBM), by which 98.2% had HLA-DR3 with an OR of 11.02 (1.44-84.4). Intragroup analyses of patients with IIM for C4 protein levels and IIM-related autoantibodies showed that those with anti-Jo-1 or with anti-PM/Scl had significantly lower C4 plasma concentrations than those without these autoantibodies. Conclusions C4A deficiency is relevant in dermatomyositis, HLA-DRB1∗03 is important in IBM and both C4A deficiency and HLA-DRB1∗03 contribute interactively to risk of polymyositis

Коррекция двигательных и поведенческих функций в лечении и реабилитации больных шизотипическим расстройством

На основании особенностей невербального поведения больных шизотипическим расстройством разработаны поведенческие методы, применение которых в их комплексной терапии позволяет добиться более полной редукции психопатологической симптоматики.Behavioral methods were worked out basing of the peculiarities of non−verbal behavior of the patients with schizotypical disorders. The use of the methods in complex therapy allows to achieve more complete reduction in psychopathological signs

Myosin binding protein C: implications for signal-transduction

Myosin binding protein C (MYBPC) is a crucial component of the sarcomere and an important regulator of muscle function. While mutations in different myosin binding protein C (MYBPC) genes are well known causes of various human diseases, such as hypertrophic (HCM) and dilated (DCM) forms of cardiomyopathy as well as skeletal muscular disorders, the underlying molecular mechanisms remain not well understood. A variety of MYBPC3 (cardiac isoform) mutations have been studied in great detail and several corresponding genetically altered mouse models have been generated. Most MYBPC3 mutations may cause haploinsufficiency and with it they may cause a primary increase in calcium sensitivity which is potentially able to explain major features observed in HCM patients such as the hypercontractile phenotype and the well known secondary effects such as myofibrillar disarray, fibrosis, myocardial hypertrophy and remodelling including arrhythmogenesis. However the presence of poison peptides in some cases cannot be fully excluded and most probably other mechanisms are also at play. Here we shall discuss MYBPC interacting proteins and possible pathways linked to cardiomyopathy and heart failure

Interaction between a normal shock wave and a turbulent boundary layer at high transonic speeds. Part I: Pressure distribution

Asymptotic solutions are derived for the pressure distribution in the interaction of a weak normal shock wave with a turbulent boundary layer. The undisturbed boundary layer is characterized by the law of the wall and the law of the wake for compressible flow. In the limiting case considered, for ‘high’ transonic speeds, the sonic line is very close to the wall. Comparisons with experiment are shown, with corrections included for the effect of longitudinal wall curvature and for the boundary-layer displacement effect in a circular pipe. Asymptotische Lösungen für den Druckverlauf bei der Wechselwirkung zwischen einem schwachen normalen Stoss und einer turbulente Grenzschicht werden hergeleitet. Das Wandgesetz und Geschwindigkeitsdefekt-Gesetz für kompressible Strömung kennzeichnen die ungestörte Grenzschicht. Der Grenzfall hoher transsonischen Strömung, in dem die Schallinie in der Nähe der Wand liegt, wird untersucht. Die theoretischen Ergebnisse werden mit Experimenten verglichen. Dabei wird die Wandkrümmung und im Fall der Rohrströmung die Verdrängungsdicke berücksichtigt.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43384/1/33_2005_Article_BF01590748.pd

Variants in ADRB1 and CYP2C9: Association with Response to Atenolol and Losartan in Marfan Syndrome

Objective: To test whether variants in ADRB1 and CYP2C9 genes identify subgroups of individuals with differential response to treatment for Marfan syndrome through analysis of data from a large, randomized trial. Study design: In a subset of 250 white, non-Hispanic participants with Marfan syndrome in a prior randomized trial of atenolol vs losartan, the common variants rs1801252 and rs1801253 in ADRB1 and rs1799853 and rs1057910 in CYP2C9 were analyzed. The primary outcome was baseline-adjusted annual rate of change in the maximum aortic root diameter z-score over 3 years, assessed using mixed effects models. Results: Among 122 atenolol-assigned participants, the 70 with rs1801253 CC genotype had greater rate of improvement in aortic root z-score compared with 52 participants with CG or GG genotypes (Time × Genotype interaction P = .005, mean annual z-score change ± SE -0.20 ± 0.03 vs -0.09 ± 0.03). Among participants with the CC genotype in both treatment arms, those assigned to atenolol had greater rate of improvement compared with the 71 of the 121 assigned to losartan (interaction P = .002; -0.20 ± 0.02 vs -0.07 ± 0.02; P < .001). There were no differences in atenolol response by rs1801252 genotype or in losartan response by CYP2C9 metabolizer status. Conclusions: In this exploratory study, ADRB1-rs1801253 was associated with atenolol response in children and young adults with Marfan syndrome. If these findings are confirmed in future studies, ADRB1 genotyping has the potential to guide therapy by identifying those who are likely to have greater therapeutic response to atenolol than losartan

Establishing the value of genomics in medicine: the IGNITE Pragmatic Trials Network.

PURPOSE: A critical gap in the adoption of genomic medicine into medical practice is the need for the rigorous evaluation of the utility of genomic medicine interventions. METHODS: The Implementing Genomics in Practice Pragmatic Trials Network (IGNITE PTN) was formed in 2018 to measure the clinical utility and cost-effectiveness of genomic medicine interventions, to assess approaches for real-world application of genomic medicine in diverse clinical settings, and to produce generalizable knowledge on clinical trials using genomic interventions. Five clinical sites and a coordinating center evaluated trial proposals and developed working groups to enable their implementation. RESULTS: Two pragmatic clinical trials (PCTs) have been initiated, one evaluating genetic risk APOL1 variants in African Americans in the management of their hypertension, and the other to evaluate the use of pharmacogenetic testing for medications to manage acute and chronic pain as well as depression. CONCLUSION: IGNITE PTN is a network that carries out PCTs in genomic medicine; it is focused on diversity and inclusion of underrepresented minority trial participants; it uses electronic health records and clinical decision support to deliver the interventions. IGNITE PTN will develop the evidence to support (or oppose) the adoption of genomic medicine interventions by patients, providers, and payers

Opportunity for Genotype-Guided Prescribing Among Adult Patients in 11 US Health Systems.

The value of utilizing a multigene pharmacogenetic panel to tailor pharmacotherapy is contingent on the prevalence of prescribed medications with an actionable pharmacogenetic association. The Clinical Pharmacogenetics Implementation Consortium (CPIC) has categorized over 35 gene-drug pairs as "level A," for which there is sufficiently strong evidence to recommend that genetic information be used to guide drug prescribing. The opportunity to use genetic information to tailor pharmacotherapy among adult patients was determined by elucidating the exposure to CPIC level A drugs among 11 Implementing Genomics In Practice Network (IGNITE)-affiliated health systems across the US. Inpatient and/or outpatient electronic-prescribing data were collected between January 1, 2011 and December 31, 2016 for patients ≥ 18 years of age who had at least one medical encounter that was eligible for drug prescribing in a calendar year. A median of ~ 7.2 million adult patients was available for assessment of drug prescribing per year. From 2011 to 2016, the annual estimated prevalence of exposure to at least one CPIC level A drug prescribed to unique patients ranged between 15,719 (95% confidence interval (CI): 15,658-15,781) in 2011 to 17,335 (CI: 17,283-17,386) in 2016 per 100,000 patients. The estimated annual exposure to at least 2 drugs was above 7,200 per 100,000 patients in most years of the study, reaching an apex of 7,660 (CI: 7,632-7,687) per 100,000 patients in 2014. An estimated 4,748 per 100,000 prescribing events were potentially eligible for a genotype-guided intervention. Results from this study show that a significant portion of adults treated at medical institutions across the United States is exposed to medications for which genetic information, if available, should be used to guide prescribing