Association of hemoglobin Saint Etienne (alpha2beta295F8 His replaced by G1n) with hemoglobins A and F. Synthesis and subunit exchange in vitro

The unstable hemoglobin (Hb) Saint Etienne (alpha2beta295F8 His replaced by G1n) (betaSE) was found in the red blood cells of an 8-year-old boy. The composition of this hemoglobin was 26% Saint Etienne, 52% A, 3% A2 and 19% HbF. Studies of hemoglobin synthesis indicate: a) a balanced synthesis of alpha and non-alpha chains (alpha=betaA + betaSE + gamma), b) an increased pool of free alpha hemoglobin chains, and c) a rapid exchange of alpha chains between this pool and HbSE. The alpha chain pool resulted from the dissociation of HbSE and the greater instability of betaSE chains than alpha chains upon heating. Hemoglobin F is of the fetal type and is heterogeneously distributed among the red cells. Furthermore, two populations of red blood cells could be separated according to their i antigen content. Analysis of the hemoglobins revealed a heterogeneous distribution. Thus, F hemoglobin was preferentially associated with cells having low i antigen level, while Saint Etienne hemoglobin was increased in cells having a high i antigen level. HbF and HbSE were not present in the parents of the propositus. Study of the genetic markers confirmed the filiation. The parents were normal upon clinical and hematological examination; they exhibited a normal pattern and synthesis of hemoglobin. The Hb Saint Etienne case is compared with Hb Istanbul, which in spite of the same amino acid substitution is not associated with increased HbF level.     

Microstructure-Based Estimation of Strength and Ductility Distributions for $$\alpha +\beta $$ Titanium Alloys

Titanium alloys are processed to develop a wide range of microstructure configurations and therefore material properties. While these properties are typically measured experimentally, a framework for property prediction could greatly enhance alloy design and manufacturing. Here a microstructure-sensitive framework is presented for the prediction of strength and ductility as well as estimates of the bounds in variability for these properties. The framework explicitly considers distributions of microstructure via new approaches for instantiation of structure in synthetic samples. The parametric evaluation strategy, including the finite element simulation package FEpX, is used to create and test virtual polycrystalline samples to evaluate the variability bounds of mechanical properties in Ti-6Al-4V. Critical parameters for the property evaluation framework are provided by measurements of single crystal properties and advanced characterization of microstructure and slip system strengths in 2D and 3D. Property distributions for yield strength and ductility are presented, along with the validation and verification steps undertaken. Comparisons between strain localization and slip activity in virtual samples and in experimental grain-scale strain measurements are also discussed.

     

Exploring the biomechanics of walking and crowd “flow”

Crowd movement simulation models are generally based on aggregated speed and flow data collected more than 50 years ago. There appears to be no validated modelling capability to include the impact of recent and future changes in population demographics, resulting from an ageing population and increasing obesity rates. New analytical approaches and data gathering are required to successfully model crowd movement and safety for current and future generations. This study carried out (a) a review of the primary components of crowd movement, demographics and analytical techniques, (b) prototype experiments to investigate age-related aspects of space and potential points of contact and (c) a new predictive model for crowd flow analysis based on pedestrian biomechanics and anthropometric data. The model uses the physical space taken up by the biomechanical walking process and the spatial buffer between points of potential contact with other pedestrians to predict the speed of movement at different levels of congestion. The new analytical model was used to predict single file speeds (for people with different demographics in congested space), which compared well with published experimental data. The next steps for model development for wider “flows” and additional experiments to provide data sets for wider demographics are also proposed.     

Sequence analysis of the CCG polymorphic region adjacent to the CAG triplet repeat of the HD gene in normal and HD chromosomes

The CAG expansion responsible for Huntington's disease (HD) is followed by an adjacent polymorphic CCG repeat region which may interfere with a PCR based diagnosis. We have sequenced this region in 52 unrelated HD patients, from both normal and HD chromosomes. Fifty percent of the normal alleles were (CCG)7(CCT)2, 48% (CCG)10(CCT)2, and 2% (CCG)7(CCT)3. In contrast (CCG)7(CCT)2 was found in 85% of the HD alleles which represents significant linkage disequilibrium with the HD mutation.     

In-hospital malnutrition: indications of postoperative evolution

BACKGROUND: The question of the minimum number of Papanicolaou (Pap) smear slides that must be rescreened to draw statistically valid conclusions regarding the accuracy of screening often is raised. No method for generating answers in varying laboratory circumstances has achieved widespread application; standard statistical sample size calculations may represent such a resource. METHODS: A series of tables was constructed to display minimum required numbers of rescreens, with each table representing differing hypothetical laboratory circumstances. To use each table, assumptions must be specified in advance as to prevalence of abnormality, definition of error, baseline false-negative proportions (FNPs) of performance, and a degree of increase in FNPs that is considered a departure from baseline warranting concern, among others. RESULTS: The authors constructed four sample tables displaying minimum numbers of slides that must be rescreened in differing specified laboratory scenarios. Depending on assumed conditions and predetermined levels of satisfactory and unsatisfactory accuracy, the range of numbers is very broad (38-10,000). One example representing likely conditions indicates that 1040 slides must be reexamined; in another scenario, a sample size of 300 is sufficient. CONCLUSIONS: The minimum number of rescreened slides needed to draw statistically valid conclusions regarding Pap smear screening accuracy can be calculated using standard statistical methods. However, a number of assumptions must be detailed in advance. The authors offer this as a practical guide and a continuation of a general inquiry regarding Pap smear error rate measurement and display. The use of these tables raises at least as many questions as it answers, but still may represent a significant advance. Future efforts at further numeric characterization of aspects of Pap smear screening performance are warranted to enable rational decision making when performance is examined in the course of quality assurance, and during quality control and regulatory activities. [See editorial on pages 127-9, this issue.]