A Diagnostic System Using Broad Categories With Clinicaly Relevant Specifiers: Lessons for ICD-10

A diagnostic system for ICD-11 is proposed which commences with broad reorganization and simplification of the current categories and the use of clinically relevant specifiers. Such changes have implications for the positioning of diagnostic groups and lead to a range of possibilities for improving terminology and the juxtaposition of individual conditions. The development of ICD-11 provides the first opportunity in almost two decades to improve the validity and reliability of the international classification system. Widespread change in broad categories and criteria cannot be justified by research that has emerged since the last revision. It would also be disruptive to clinical practice and might devalue past research work. However, the case for reorganization of the categories is stronger and has recently been made by an eminent international group of researchers (Andrews et al., 2009). A simpler, interlinked diagnostic system is proposed here which is likely to have fewer categories than its predecessor. There are major advantages of such a system for clinical practice and research and it could also produce much needed simplification for primary care (Gask et al., 2008) and the developing world (Wig, 1990; Kohn et al., 2004).

The conserved Helix C region in the superfamily of interferon-a/interleukin-10-related cytokines corresponds to a high-affinity binding site for the HSP70 chaperone DnaK.

HSP70 chaperones mediate protein folding by ATP-dependent interaction with short linear peptide segments that are exposed on unfolded proteins. The mode of action of the Escherichia coli homolog DnaK is representative of all HSP70 chaperones, including the endoplasmic reticulum variant BiP/GRP78. DnaK has been shown to be effective in assisting refolding of a wide variety of prokaryotic and eukaryotic proteins, including the -helical homodimeric secretory cytokine interferon- (IFN-). We screened solid-phase peptide libraries from human and mouse IFN- to identify DnaK-binding sites. Conserved DnaK-binding sites were identified in the N-terminal half of helix B and in the C-terminal half of helix C, both of which are located at the IFN- dimer interface. Soluble peptides derived from helices B and C bound DnaK with high affinity in competition assays. No DnaK-binding sites were found in the loops connecting the -helices. The helix C DnaK-binding site appears to be conserved in most members of the superfamily of interleukin (IL)-10-related cytokines that comprises, apart from IL-10 and IFN-, a series of recently discovered small secretory proteins, including IL-19, IL-20, IL-22/IL-TIF, IL-24/MDA-7 (melanoma differentiation-associated gene), IL-26/AK155, and a number of viral IL-10 homologs. These cytokines belong to a relatively small group of homodimeric proteins with highly interdigitated interfaces that exhibit the strongly hydrophobic character of the interior core of a single-chain folded domain. We propose that binding of DnaK to helix C in the superfamily of IL-10-related cytokines may constitute the hallmark of a novel conserved regulatory mechanism in which HSP70-like chaperones assist in the formation of a hydrophobic dimeric "folding" interface.

Prosodic Characteristics of Skilled Reading: Fluency and Expressiveness in 8- 10-year-old Readers

Statistical methods of describing prosody were used to study fluency, expressiveness and their relationship among 8-10-year-old readers. There were robust relationships between expressiveness and variables associated with pitch mobility; and between fluency and measures associated with temporal organization. Interactions indicated that the relationships were not simple. Differences between groups depended on sentence content and position. Some measures offer a basis for rules aimed at assigning individuals to skill categories. The effects suggest psychological hypotheses about the underlying mechanisms.

Search for 1-10 Hz modulations in coronal emission with SECIS during the August 11, 1999 eclipse

Results of the search of the periodic changes of the 530.3 nm line intensity emitted by selected structures of the solar corona in the frequency range 1-10 Hz are presented. A set of 12 728 images of the section of the solar corona extending from near the north pole to the south-west were taken simultaneously in the 530.3 nm ("green") line and white-light with the Solar Eclipse Coronal Imaging System (SECIS) during the 143-seconds- long totality of the 1999 August 11 solar eclipse observed in Shabla, Bulgaria. The time resolution of the collected data is better than 0.05 s and the pixel size is approximately 4 arcsec. Using classical Fourier spectral analysis tools, we investigated temporal changes of the local 530.3 nm coronal line brightness in the frequency range 1-10 Hz of thousands of points within the field of view. The various photometric and instrumental effects have been extensively considered. We did not find any indisputable, statistically significant evidence of periodicities in any of the investigated points (at significance level alpha = 0.05).