bluuebunny/crossref_metadata_2025 huggingface dataset:
Accuracy of the 15‐item geriatric depression scale (GDS‐15) in a community sample of the oldest old
Authors: de Craen Anton J. M. , Heeren T. J. , Gussekloo Jacobijn
Published: December 2002

Background

Cognitive impairment is common in the oldest old. This might influence the sensitivity and specificity of the 15‐item Geriatric Depression Scale (GDS‐15). Few studies, however, have included subjects older than 85 years to evaluate the GDS‐15 as a screening instrument for depression.

Objective

To assess the sensitivity and specificity of the GDS‐15 in a community sample of the oldest old.

Methods

Seventy‐nine subjects aged 85 and over were enrolled in the study. The GDS‐15 and the Mini‐Mental State Examination (MMSE) were administered by a trained interviewer. Within two days the Geriatric Mental State (GMS)/AGECAT, was administered to obtain a clinical diagnosis of depression.

Results

Eight subjects (10%) were diagnosed with clinical depression. At a cut‐off point of 3/4 the sensitivity and specificity of the GDS‐15 were 88% and 76% respectively. In the group with MMSE scores of 28 and higher sensitivity was unaffected at all cut‐off points while specificity increased. In the group with MMSE scores below 28 sensitivity was also unaffected at all cut‐off points while specificity decreased.

Conclusion

The GDS‐15 is a suitable instrument to diagnose depression in the general population of the oldest old. The optimal cut‐off point depends on its intended use. In subjects with cognitive impairment the accuracy should be investigated further. Copyright © 2002 John Wiley & Sons, Ltd.
The concept of effective length in hillslopes: assessing the influence of climate and topography on the contributing areas of catchments
Authors: Aryal Santosh K. , Mein Russell G. , O'Loughlin Emmett M.
Published: December 2002

This paper introduces a concept of ‘effective length’ in hillslopes to define the effective area influencing the runoff‐producing saturated zones of a hillslope or catchment. This effective area of a catchment usually is less than that given by its physical boundaries, particularly in regions where the total potential evaporation exceeds total rainfall on an annual basis. In this paper, expressions for effective lengths in hillslopes with different scale, shape and soil properties are derived for given climatic conditions. The influence of these variables on effective length is investigated. It is shown that, for a given rainfall frequency and soil parameters, the effective length changes with the planform geometry and profile shape of a hillslope; it is also a function of the ratio of available travel opportunity time to the hillslope's scale response time. The application of the concept to three natural catchments, subdivided into a number of simple hillslopes, is described. It is shown that, for these three test catchments and over 24 years of record, rarely would the entire catchment areas contribute to flow at the respective outlets. The implications of the concept of effective length for several land‐use practices, such as clearing for forest for greater water yield, and planting trees for salinity control, are discussed. Copyright © 2002 John Wiley & Sons, Ltd.
Surface glaciochemistry of Taylor Valley, southern Victoria Land, Antarctica and its relationship to stream chemistry
Authors: Berry Lyons W. , Welch Kathleen A. , Fountain Andrew G. , Dana Gayle L. , Vaughn Bruce H. , McKnight Diane M.
Published: December 2002

We have analysed a series of surface samples from the alpine glaciers of Taylor Valley, Southern Victoria Land, Antarctica for their geochemical composition. This was done to better establish the role of glaciochemical variation on the chemical composition of meltwater streams emanating from the glaciers. The chemistry of the snow and ice changes with proximity to the ocean and with elevation of the glacier surface. The aeolian transport of dry valley dust, as indicated by both chemical and particulate matter variations, is a major process affecting the overall glacier chemistry and the chemistry of the meltwaters. Streams originating on the western edges of the glaciers are more impacted by the aeolian input as they are in the direct path of the major regional wind direction. Our data strongly suggest that the variation in stream geochemistry in Taylor Valley is a result in part of the differences in chemical composition of glacier melt. Copyright © 2003 John Wiley & Sons, Ltd.
Separation of quantum and classical behavior in proton transfer reactions: Implications from studies of secondary kinetic isotope effects
Authors: Iftimie Radu , Schofield Jeremy
Published: December 2002

In this article the separability of the nuclear degrees of freedom system into mixed quantum and classical components is examined by looking at secondary kinetic isotope effects in a model proton transfer reaction. To explore this issue, the nature of secondary kinetic isotope effects is investigated by means of molecular mechanics and ab initio simulations of a model system in which intramolecular proton transfer occurs in a region whose chemical topology is similar to that of malonaldehyde. Isotope effects are calculated using importance sampling Monte Carlo techniques designed to improve the statistical efficiency of ab initio simulations within the framework of quantum centroid transition state theory. The ab initio results for kinetic isotope effects are contrasted with those obtained using two molecular mechanics potential energy functions. It is demonstrated that the calculated isotope effects are extremely sensitive to subtle features of the potential energy surface, which suggests that information from ab initio structure and energy calculations about configurations along the reaction path must be utilized in the construction of classical potentials to obtain accurate secondary kinetic isotope effect predictions. It is also demonstrated that quantum nuclear degrees of freedom of all secondary atoms that move significantly as a chemical reaction proceeds should be treated explicitly, as even secondary heavy‐atom tunneling effects could be significant. © 2002 Wiley Periodicals, Inc. Int J Quantum Chem, 2003
Conformational study of the vinylphosphonic acid and derivatives
Authors: Omar Salama , Gonzalez‐Jonte Raúl , de la Vega José Manuel Garciá
Published: December 2002

The alkenyl phosphonics have become interesting compounds for the chemical industry. They have been used as drugs, polymer additives, flame retards, and metal extractants. The electronic structure of the smallest derivatives of this series of compounds, namely, vinylphosphonic acid (VPA), vinylphosphine oxide (VPO), and vinylphosphoryl dichloride (VPDC), are studied here. The nature of the phosphoryl bond was a subject of discussion because its electronic nature could be considered either as a resonance between a double bond and a single polarized bond or as a triple bond with different electronic possibilities. The electronic structure of VPA, VPO, and VPDC have been studied by density functional theory methods using a large basis set. Conformers “s‐cis,” “s‐cis‐gauche,” “s‐trans,” and “s‐trans‐gauche” and rotational barriers are determined for the internal rotational around the CP bond. © 2002 Wiley Periodicals, Inc. Int J Quantum Chem, 2003
Generalized spin density functional study of radical reactions
Authors: Yamanaka S. , Ohsaku T. , Yamaki D. , Yamaguchi K.
Published: December 2002

The generalized spin orbital (GSO) density functional theory (DFT) is applied to the radical reaction involving spin inversion. Along the ground‐state path for the cleavage of oxygen molecule, GSO–DFT solutions simulate the intercrossing change from triplet oxygen molecule to two triplet oxygen atoms through helical spin density wave, indicating the importance of GSO treatment of DFT. Numerical results are discussed in relation to the relativistic effects of the realistic oxidation reaction of other species, together with the near‐degeneracy effects discussed in relation to the multireference DFT. © 2002 Wiley Periodicals, Inc. Int J Quantum Chem, 2003
DFT study of ionization potentials for aza‐substituted aromatic rings
Authors: Barrio Laura , Catalán Javier , de Paz José L. G.
Published: December 2002

The ionization potentials of 20 azines and azanaphthalenes have been studied using Becke's three‐parameter exchange functional and the gradient‐corrected functional of Lee, Yang, and Paar (B3LYP) method with 6‐31G** basis set at optimized geometries. Vertical ionization potentials (IPV) have been calculated using Koopman's theorem (IPV = −εHOMO) and as the difference of single‐point energy calculations for the corresponding cation and for the neutral form (IPV = Ecation − Eneutral). From our theoretical results most of the first ionizations come from the nitrogen lone pair and not from the highest occupied π‐orbital. Good agreement is found with experimental results when IPV is calculated from unrestricted B3LYP calculations of the neutral and the cationic species. The first π‐ionization follows Koopman's theorem for all monocyclic and bi‐cyclic systems under study. The lone pair repulsion effect is acceptably described by the energy of the highest n‐orbital energy either for azines and azanaphthalenes. The annulation effect in the charged species is not reflected in the n–lone pair orbital energy of the neutral form and, consequently, it is not possible to find a fit that follows Koopman's theorem for lone pair orbital energies. © 2002 Wiley Periodicals, Inc. Int J Quantum Chem, 2003
DFT calculations of correlation energies for excited electronic states using MCSCF wave functions
Authors: San‐Fabián E. , Pastor‐Abia L.
Published: December 2002

A large set of correlation energy functionals has been applied, in a post‐SCF procedure, to incorporate the correlation energy of several excited atomic states using MCSCF wave functions. The results show that the application of standard density functionals does not consider the double count of the correlation energy obtained by the MCSCF wave function. However, the use of some dependence on the two‐body density matrix improves the results, with a partial account of this correlation energy balance. © 2002 Wiley Periodicals, Inc. Int J Quantum Chem, 2003
Ab initio study on elementary radical reactions in coke formation
Authors: Van Speybroeck V. , Van Neck D. , Waroquier M. , Wauters S. , Saeys M. , Marin G. B.
Published: December 2002

Ab initio calculations are presented on radical reactions that occur during the formation of coke in a thermal cracking unit. Kinetic parameters for the addition reaction of the ethylbenzene radical to ethene and the subsequent cyclization of the butylbenzene radical are calculated by means of Transition State Theory and Density Functional Theory. Special care is taken to correctly treat the internal rotations to predict accurate values of the preexponential factor. The influence of the local structure of the coke matrix on the kinetic parameters is tested by calculating kinetic parameters of clusters consisting of more than one benzene ring. © 2002 Wiley Periodicals, Inc. Int J Quantum Chem, 2003
An LMI approach to guaranteed cost control for uncertain linear neutral delay systems
Authors: Xu Shengyuan , Lam James , Yang Chengwu , Verriest Erik I.
Published: December 2002

This paper considers the problem of guaranteed cost control for uncertain neutral delay systems with a quadratic cost function. The system under consideration is subject to norm‐bounded time‐varying parametric uncertainty appearing in all the matrices of the state‐space model. The problem we address is the design of a state feedback controller such that the closed‐loop system is not only stable but also guarantees an adequate level of performance for all admissible uncertainties. A sufficient condition for the existence of guaranteed cost controllers is given in terms of a linear matrix inequality (LMI). When this condition is feasible, the desired state feedback controller gain matrices can be obtained via convex optimization. An illustrative example is provided to demonstrate the effectiveness of the proposed approach. Copyright © 2002 John Wiley & Sons, Ltd.
Reconstruction and Reorientation: Changing Disability Policies in the Netherlands and Norway
Authors: Drøpping Jon Anders , Hvinden Bjørn , van Oorschot Wim
Published: December 2002

The Netherlands and Norway are among the many countries that have faced serious challenges to the sustainability of their social security systems in recent years. In this article we examine the growth in benefit schemes related to illness and disability since they have been one source of particular concern in both countries. The Netherlands came to face more serious and persistent problems earlier than Norway in this policy area. Our analysis reveals significant differences with respect to the underlying assumptions in the social protection systems for the long-term sick and disabled as they were originally constructed in the 1960s. We identify a general emphasis on ‘integration’ in the Norwegian social policy discourse and legislation up until the late 1980s, whereas the Dutch legislation in the same period tended to focus on autonomy and individual ‘choice’. In the article we compare the reforms introduced in both countries to control the growth in sickness and disability schemes, by means of a common analytical and conceptual framework. ‘Incentives’ have occupied an increasingly prominent position in the policy discourse in both countries. While the Norwegian development may largely be seen as a return to and revival of partly forgotten, partly eroded assumptions behind the original social protection scheme, the Dutch policy shift amounts to a more fundamental reconstruction of the whole social security system.
Mapping Residents' Perceptions of Neighborhood Boundaries: A Methodological Note
Authors: Coulton Claudia J. , Korbin Jill , Chan Tsui , Su Marilyn
Published: December 2002

Neighborhood influences on children and youth are the subjects of increasing numbers of studies, but there is concern that these investigations may be biased, because they typically rely on census‐based units as proxies for neighborhoods. This pilot study tested several methods of defining neighborhood units based on maps drawn by residents, and compared the results with census definitions of neighborhoods. When residents' maps were used to create neighborhood boundary definitions, the resulting units covered different space and produced different social indicator values than did census‐defined units. Residents' agreement about their neighborhoods' boundaries differed among the neighborhoods studied. This pilot study suggests that discrepancies between researcher and resident‐defined neighborhoods are a possible source of bias in studies of neighborhood effects.
Inhibition of substrate synthesis as a strategy for glycolipid lysosomal storage disease therapy
Authors: Platt F. M. , Jeyakumar M. , Andersson U. , Priestman D. A. , Dwek R. A. , Butters T. D. , Cox T. M. , Lachmann R. H. , Hollak C. , Aerts J. M. F. G. , Van Weely S. , Hrebícek M. , Moyses C. , Gow I. , Elstein D. , Zimran A.
Published: December 2002

The glycosphingolipid (GSL) lysosomal storage diseases are caused by mutations in the genes encoding the glycohydrolases that catabolize GSLs within lysosomes. In these diseases the substrate for the defective enzyme accumulates in the lysosome and the stored GSL leads to cellular dysfunction and disease. The diseases frequently have a progressive neurodegenerative course. The therapeutic options for treating these diseases are relatively limited, and for the majority there are no effective therapies. The problem is further compounded by difficulties in delivering therapeutic agents to the brain. Most research effort to date has focused on strategies for augmenting enzyme levels to compensate for the underlying defect. These include bone marrow transplantation (BMT), enzyme replacement and gene therapy. An alternative strategy that we have been exploring is substrate deprivation. This approach aims to balance the rate of GSL synthesis with the impaired rate of GSL breakdown. The imino sugar N‐butyldeoxynojirimycin (NB‐DNJ) inhibits the first step in GSL biosynthesis and has been used to evaluate this approach. Studies in an asymptomatic mouse model of Tay–Sachs disease have shown that substrate deprivation prevents GSL storage in the CNS. In a severe neurodegenerative mouse model of Sandhoff disease, substrate deprivation delayed the onset of symptoms and disease progression and significantly increased life expectancy. Combining NB‐DNJ and BMT was found to be synergistic in the Sandhoff mouse model. A clinical trial in type I Gaucher disease has been undertaken and has shown beneficial effects. Efficacy was demonstrated on the basis of significant decreases in liver and spleen volumes, gradual but significant improvement in haematological parameters and disease activity markers, together with diminished GSL biosynthesis and storage as determined by independent biochemical assays. Further trials in type I Gaucher disease are in progress; studies are planned in patients with GSL storage in the CNS.
Building Collaborative Capacity in Community Coalitions: A Review and Integrative Framework
Authors: Foster-Fishman Pennie G. , Berkowitz Shelby L. , Lounsbury David W. , Jacobson Stephanie , Allen Nicole A.
Published: December 2002

This article presents the results of a qualitative analysis of 80 articles, chapters, and practitioners' guides focused on collaboration and coalition functioning. The purpose of this review was to develop an integrative framework that captures the core competencies and processes needed within collaborative bodies to facilitate their success. The resulting framework for building collaborative capacity is presented. Four critical levels of collaborative capacity—member capacity, relational capacity, organizational capacity, and programmatic capacity—are described and strategies for building each type are provided. The implications of this model for practitioners and scholars are discussed.
Spacer Length Dependence on the Efficiency of Dimeric Anionic Peptides in Gene Transfer by Glycosylated Polylysine/Plasmid Complexes
Authors: Freulon I. , Monsigny M. , Midoux P. , Mayer R.
Published: December 2002

Amphiphilic anionic peptides have been used to enhance the efficiency of transfection by helping plasmids to escape from endosomes to the cytosol. It has been shown that efficiency of an eicosamers containing five glutamyl residues (E5), can be considerably enhanced either by transforming it into a dimer or by adding a tripeptide WYG in a C-terminal position (E5WYG). The dimerization of the peptide E5WYG leads to a more efficient tool when the dimerization device includes the tripeptide WYG unit and a longer spacer arm made of Gly-γAla-γAla residues, but to a 10-fold less efficient tool when the dimerization device includes a shorter spacer, a glycyl residue. Both dimers are taken up by the cells to a similar extent. Both dimers seem to be surrounded similarly as far as the environmental pH is concerned. In contrast, we found a correlation between the propensity of the peptides to adopt a helical structure at neutral pH and the gene transfer efficiency.
Enzyme therapy for Pompe disease with recombinant human α‐glucosidase from rabbit milk
Authors: Van den Hout J. M. P. , Reuser A. J. J. , de Klerk J. B. C. , Arts W. F. , Smeitink J. A. M. , Van der Ploeg A. T.
Published: December 2002

Pompe disease is a metabolic myopathy caused by deficiency of lysosomal acid α‐glucosidase. In this report we review the first 36 weeks of a clinical study on the safety and efficacy of enzyme therapy aimed at correcting the deficiency. Four patients with infantile Pompe disease were enrolled. They received recombinant human α‐glucosidase from transgenic rabbit milk. The product is generally well tolerated and reaches the primary target tissues. Normalization of α‐glucosidase activity in skeletal muscle was obtained and degradation of PAS‐positive material was seen in tissue sections. The clinical condition of all patients improved. The effect on heart was most significant, with an impressive reduction of the left ventricular mass index (LVMI). Motor function improved. The positive preliminary results stimulate continuation and extension of efforts towards the realization of enzyme therapy for Pompe disease.
Rare diseases and the assessment of intervention: What sorts of clinical trials can we use?
Authors: Wilcken B.
Published: December 2002

There is increasing emphasis on the importance of practising evidence‐based medicine. Randomized controlled trials are the standard way to assess the benefits of an intervention, and observational studies are not usually accorded much weight; the results are likely to be considered misleading. For rare diseases, there are great difficulties in obtaining adequate evidence for interventions or for the benefits of early diagnosis. This is because the disorders are not only very rare but also have variable expression, may have very long courses, and have incompletely known late effects; and surrogate end‐points often have to be used. Randomized controlled trials are usually impossible because of inadequate power, and because there are preconceived notions of the effects of treatments already in use. The adoption of the best possible design for observational trials, formation of a central registry of such trials, and a greater general appreciation of the problems that rare diseases pose will help in obtaining the best possible evidence for the effects of interventions.
Rickettsiaceae, Rickettsia-Like Endosymbionts, and the Origin of Mitochondria
Authors: Emelyanov Victor V.
Published: December 2002

Accumulating evolutionary data point to a monophyletic origin of mitochondria from the order Rickettsiales. This large group of obligate intracellular α-Proteobacteria includes the family Rickettsiaceae and several rickettsia-like endosymbionts (RLEs). Detailed phylogenetic analysis of small subunit (SSU) rRNA and chaperonin 60 (Cpn60) sequences testify to polyphyly of the Rickettsiales, and consistently indicate a sisterhood of Rickettsiaceae and mitochondria that excludes RLEs. Thus RLEs are considered as the nearest extant relatives of an extinct last common ancestor of mitochondria and rickettsiae. Phylogenetic inferences prompt the following assumptions. (1) Mitochondrial origin has been predisposed by the long-term endosymbiotic relationship between rickettsia-like bacteria and proto-eukaryotes, in which many endosymbiont genes have been lost while some indispensable genes have been transferred to the host genome. (2) The obligate dependence of rickettsiae upon a eukaryotic host rests on the import of proteins encoded by these transferred genes.The nature of a proto-eukaryotic cell still remains elusive. The divergence of Rickettsiaceae and mitochondria based on Cpn60, and the evolutionary history of two aminoacyl-tRNA synthetases favor the hypothesis that it was a chimera created by fusion of an archaebacterium and a eubacterium not long before an endosymbiotic event. These and other, mostly biochemical data suggest that all the mitochondrion-related organelles, i.e., both aerobically and anaerobically respiring mitochondria and hydrogenosomes, have originated from the same RLE, while hydrogenosomal energy metabolism may have a separate origin resulting from a eubacterial fusion partner.
Value‐Based Praxis in Community Psychology: Moving Toward Social Justice and Social Action
Authors: Prilleltensky Isaac
Published: December 2002

The purpose of this paper is to articulate a rationale for value‐based praxis in community psychology. Although values need to promote personal, collective, and relational wellness at the same time, it is argued that community psychologists pay more attention to personal and relational wellness than to collective wellness. In order to address this imbalance it is important to promote the value of social justice. While praxis requires that we engage in a cycle of reflection, research, and social action, community psychologists devote more resources to the first two phases of praxis than to the last one. This paper offers a framework for deciding what values and what praxis considerations we should attend to and how we may advance social justice and social action in community psychology.
Innovation in HIV Prevention: Organizational and Intervention Characteristics Affecting Program Adoption
Authors: Miller Robin Lin
Published: December 2002

A multiple case study design was used to explore the organizational characteristics of community‐based organizations that provide HIV prevention programs and the criteria these organizations employ when judging the merits of externally‐developed HIV prevention programs. In‐depth interviews were conducted with organizational representatives of 38 randomly‐selected HIV prevention providers throughout Illinois. Results indicated that there were three main types of adopting organizations: adopters of entire programs, adopters of program components and practices, and adopters of common ideas. These three types of organizations were distinguished by their level of organizational commitment to HIV prevention, organizational resources, and level of organizational maturity. Narrative data from the interviews are used to describe the dimensions that underlie the organizations' program adoption criteria. The criteria of merit used by these organizations to evaluate prevention programs provide partial empirical support for existing theories of technology transfer. Implications for designing and disseminating HIV prevention programs are discussed.
Diadenosine Tetraphosphate-Gating of Recombinant Pancreatic ATP-Sensitive K+ Channels
Authors: Jovanovic Sofija , Jovanovic Aleksandar
Published: December 2002

Diadenosine tetraphosphate (Ap4A) has been recently discovered in the pancreatic γ cells where targets ATP-sensitive K+ (KATP) channels, depolarizes the cell membrane and induces insulin secretion. However, whether Ap4A inhibit pancreatic KATP channels by targeting protein channel complex itself was unknown. Therefore, we coexpressed pancreatic KATP channel subunits, Kir6.2 and SUR1, in COS-7 cells and examined the effect of Ap4A on the single channel behavior using the inside-out configuration of the patch-clamp technique. Ap4A inhibited channel opening in a concentration-dependent manner. Analysis of single channels demonstrated that Ap4A did not change intraburst kinetic behavior of KATP channels, but rather decreased burst duration and increased between-burst duration. It is concluded that Ap4A antagonizes KATP channel opening by targeting channel subunits themselves and by keeping channels longer in closed interburst states.
Membrane Fusion
Authors: Epand Richard M.
Published: December 2002

The fusion of biological membranes results in two bilayer-based membranes merging into a single membrane. In this process the lipids have to undergo considerable rearrangement. The nature of the intermediates that are formed during this rearrangement has been investigated. Certain fusion proteins facilitate this process. In many cases short segments of these fusion proteins have a particularly important role in accelerating the fusion process. Studies of the interaction of model peptides with membranes have allowed for increased understanding at the molecular level of the mechanism of the promotion of membrane fusion by fusion proteins. There is an increased appreciation of the roles of several independent segments of fusion proteins in promoting the fusion process.

Many of the studies of the fusion of biological membranes have been done with the fusion of enveloped viruses with other membranes. One reason for this is that the number of proteins involved in viral fusion is relatively simple, often requiring only a single protein. For many enveloped viruses, the structure of their fusion proteins has certain common elements, suggesting that they all promote fusion by an analogous mechanism. Some aspects of this mechanism also appears to be common to intracellular fusion, although several proteins are involved in that process which is more complex and regulated than is fusion.
Carrier detection and rapid newborn diagnostic test for the common Y393N maple syrup urine disease allele by PCR‐RFLP: Culturally permissible testing in the Mennonite community
Authors: Love‐Gregory L. D. , Dyer J. A. , Grasela J. , Hillman R. E. , Phillips C. L.
Published: December 2002

The turnaround time for diagnosis of maple syrup urine disease (MSUD) by classic serum amino acid analyses often requires 3–4 days. This is due to the need for branched‐chain amino acids (BCAA) to accumulate in the serum of the newborn before testing. The accumulation of BCAAs in infants with MSUD during this time increases the risk of the infant becoming clinically symptomatic. We have developed a noninvasive DNA‐based mismatch PCR‐RFLP assay for the Y393N BCKDHA allele (E1α gene of the branched chain α‐keto acid dehydrogenase complex), the primary cause of MSUD in Old Order Mennonite communities. The homozygosity and high frequency of this mutation in the Mennonite community and its prevalence in compound heterozygote non‐Mennonite MSUD patients is of significance. We describe carrier testing, present the results of nine newborns diagnostically evaluated for the Y393N BCKDHA allele, and demonstrate the efficacy of this PCR‐RFLP assay for determining clinical status within 24 h after birth. Analyses within the first 24h of life allow for immediate diagnosis and treatment of infants homozygous for the Y393N MSUD defect. This is a significant improvement over the time required by current serum amino acid analysis methods.
CASE REPORT: CblC/D defect combined with haemodynamically highly relevant VSD
Authors: Tomaske M. , Bosk A. , Heinemann M. K. , Sieverding L. , Baumgartner E. R. , Fowler B. , Trefz F. K.
Published: December 2002

An infant with combined methylmalonic aciduria and homocystinuria (cblC/D defect) presented with significant VSD. She underwent successful cardiac surgery at 53 days.
Effects of dietary cholesterol restriction in a feline model of Niemann–Pick type C disease
Authors: Somers K. L. , Brown D. E. , Fulton R. , Schultheiss P. C. , Hamar D. , Smith M. O. , Allison R. , Connally H. E. , Just C. , Mitchell T. W. , Wenger D. A. , Thrall M. A.
Published: December 2002

A feline model of Niemann–Pick disease type C (NPC) was employed to evaluate the effect of dietary cholesterol restriction on progression of disease. Two NPC‐affected treated cats were fed a cholesterol‐restricted diet beginning at 8 weeks of age; the cats remained on the diet for 150 and 270 days respectively. The study goal was to lower the amount of low density lipoprotein (LDL) available to cells, hypothetically reducing subsequent lysosomal accumulation of unesterified cholesterol and other lipids. Neurological progression of disease was not altered and dietary cholesterol restriction did not significantly decrease storage in NPC‐affected treated cats. One NPC‐affected treated cat had decreased serum alkaline phosphatase activity (ALP) and decreased serum cholesterol concentration. Liver lipid concentrations of unesterified cholesterol, cholesterol ester and phospholipids in NPC‐affected treated cats were similar to those seen in NPC‐affected untreated cats. Ganglioside concentrations in the NPC‐affected treated cats and NPC‐affected untreated cats were similar. Histological findings in liver sections from NPC‐affected treated cats showed a diffuse uniform microvacuolar pattern within hepatocytes and Kupffer cells, in contrast to a heterogeneous macro/microvacuolar pattern and prominent nodular fibrosis in NPC‐affected untreated cats. Similar differences in vacuolar patterns were seen in splenic macrophages. Although some hepatic parameters were modified, dietary cholesterol restriction did not appear to alter disease progression in NPC‐affected kittens.
Clinical course and biochemistry of sialuria
Authors: Enns G. M. , Seppala R. , Musci T. J. , Weisiger K. , Ferrell L. D. , Wenger D. A. , Gahl W. A. , Packman S.
Published: December 2002

Sialuria is a rare inborn error of metabolism in which excessive free sialic acid (N‐acetylneuraminic acid, NeuAc) is synthesized. A defect in the feedback inhibition of UDP‐N‐acetylglucosamine (UDP‐GlcNAc) 2‐epimerase by the end‐product of the sialic acid synthetic pathway, CMP‐NeuAc, is the mechanism underlying this overproduction. Recent evidence suggests that sialuria is an autosomal dominant disorder. Only five patients have been documented to have such an enzymatic defect. We report a longitudinal study of one of the original sialuria patients, to age 11 years. Although he has coarse features and massive hepatomegaly, he has shown normal growth and relatively normal development. Pulmonary function testing showed minimal small airway obstruction. At 11 years, he developed intermittent abdominal pain and transient transaminase elevation above his baseline. Sialuria should be considered in the differential diagnosis of a patient with a phenotype suggestive of a mucopolysaccharidosis or oligosaccharidosis in the absence of developmental regression or prominent dysostosis multiplex. We recommend close monitoring of liver and pulmonary function in sialuria patients.
On Markovian Master Equations II
Authors: Kossakowski Andrzej
Published: December 2002

The S-matrix formalism used for energy level shift calculations has been applied for the construction of Markovian master equations in all orders in the coupling constant.
The European Commission Proposal to Simplify Regulation 1408/71
Authors: Pennings Frans
Published: December 2002

On 21 December 1998, the European Commission published a Proposal for a new coordination regulation to replace Regulation 1408/71. The objective of the Proposal was to simplify the Regulation, which is often criticised for being very complicated. The new Proposal has been successful insofar as it is only one third of the size of Regulation 1408/71. However, this simplification has given rise to some politically sensitive propositions and it is around these that discussions of the proposal centre. Member States have not yet accepted the new text; it is expected to take at least a few years before agreement is reached. This paper presents a critical overview of the main parts of the Proposal.
A Truly European Type of Disability Struggle: Disability Policy in Denmark and the EU in the 1990s
Authors: Bengtsson Steen
Published: December 2002

Can one speak of a special European type of disability struggle? Today, European societies are characterised by corporatist structures. Boards and committees on which unions and employers organisations are represented are very powerful. This has become a model for other interest groups. In Denmark, a national organisation of disabled people quickly gained considerable political influence and later developed a corporatist structure. Denmark is considered to exemplify a genuinely European model which enables people with disabilities to influence policy and participate in society. The institutions that have been established (e.g. the Central Disability Council and the Centre of Equal Treatment) are an attempt to translate the ‘Social Model of Disability’ into social structures. Today, American influence has created pressure in Europe to enact equal rights legislation: the American way of empowering disabled people. Although equal rights legislation may be useful, it is argued that corporatist structures have the potential to achieve a much broader and deeper influence that can penetrate into all sectors of society.
Do Welfare States Reduce Poverty? A Critical Shortcoming in the Standard Analysis of the Anti-Poverty Effect of Welfare States
Authors: Kim Hwanjoon
Published: December 2002

A standard analysis of the anti-poverty effect of taxes and income transfers is to compare pre-tax-transfer poverty and post-tax-transfer poverty. A critical shortcoming of the standard approach is that it treats pre-tax-transfer poverty as given and ignores the potential effects of taxes and transfers on pre-tax-transfer poverty. Analysing cross-national variations, this study examines the potential endogeniety of pre-tax-transfer poverty. The results suggest that both the generosity and efficiency of the tax/transfer system may influence levels of pre-tax-transfer poverty. If this is true, the standard approach overestimates the anti-poverty effectiveness of generous and/or targeted welfare systems.
Introduction: Towards Convergence? Disability Policies in Europe
Authors: van Oorschot Wim , Hvinden Bjørn
Published: December 2002

Disability is one of the key areas of concern for social security. It represents one of the major risks for loss of income from work among people of working age and, historically, it belongs to the risks first covered by social insurance. All countries with encompassing income maintenance schemes have special provisions for people with disabilities, and the spending on these benefits usually amounts to a large proportion of total income maintenance expenditure. The administrative and legal procedures surrounding the assessment of claims for disability benefits are often complex and involve discretionary judgment. Assessments tend to rely on the input from different professional groups, such as physicians, psychologists, social workers, occupational therapists, and rehabilitation or employment counsellors. In the disability area there is also a close but rarely simple relationship between ‘cash’ and ‘care’. Participation in treatment, training and rehabilitation programmes, combined with suitable technical solutions and services provisions (transport, personal assistance etc.) are believed to diminish dependence on long-term financial support for disabled persons. At the same time, advances in medical diagnosis and treatment have also meant that more people are able to survive illnesses and injuries that would otherwise have been fatal.
Negative Social Dialogue versus Positive Social Dialogue
Authors: Lafoucriere Céline
Published: December 2002

This paper draws upon research exploring progress in achieving the ‘adaptability pillar’ of the 1997 European Employment Strategy. Using two national case studies, France and Belgium, it explores two highly different traditions and conceptions of social partnership, introducing ideas of ‘negative’ and ‘positive’ social dialogue, and arguing for the necessity of the latter for attaining significant progress. The paper highlights the value of such a typology as a useful analytical tool in the continuing development of social partnership and a healthy European Employment Strategy.

‘There is nothing more difficult to devise, where success is less assured and implementation more difficult to achieve, than the creation of a new system’ (Machiavelli, The Prince, 1563).
Coordination of Social Security: Developments in the Area of Posting
Authors: Van Zeben Maarten , Donders Peter
Published: December 2002

In this article we ask what has changed since 1995 with regard to the implementation of posting rules. In order to answer this question, the article examines a number of aspects of posting that relate primarily to the implementation of the rules: – administrative procedures and how they have been affected by the Fitzwilliam case; – the interpretation of Article 14 (2)(b); – the use of Article 17; – the position of self-employed persons following the Banks case.

Our considerations are based on the results of investigations by BMT consultants that were conducted in 1995 and 1996, and on a recently conducted survey of the Dutch competent institution for posting, the Sociale Verzekeringsbank. Finally, we look at what has changed and whether the challenge inherent in current mobility developments can be met using our present posting rules
Are there useful biochemical markers of disease activity in lysosomal storage diseases?
Authors: Winchester B.
Published: December 2002

The primary biochemical consequence of a defect in a gene encoding a functional component of the lysosomal system is disruption of the catabolism or processing of macromolecules in the lumen of the lysosome. Transport of the resulting digestion products through the lysosomal membrane may also be affected. This leads to the accumulation of specific metabolites within the lysosomes of affected cells. The nature of these storage products depends upon the functional protein affected and the cell type. The accumulation of storage products is progressive and leads to hypertrophy of the lysosomal system, the hallmark of lysosomal storage diseases (LSDs).Subsequent cell necrosis or, possibly, exocytosis results in the appearance in body fluids of the storage products and components of the lysosomes at much higher concentrations than seen in normal unaffected individuals. Measurement of these increased levels of metabolites and proteins provides disease‐specific and generic biochemical markers for LSDs. Secondary changes in metabolism and cellular function may also produce characteristic changes in the levels of metabolites or proteins, which can also be used as markers of the disease process. Although the rate of appearance of these biochemical markers in an individual will depend upon the underlying mutation in the gene and on other genetic and environmental factors, it provides a good indicator of the progression of the disease. As the novel forms of treatment being developed may reverse the hypertrophy of the lysosomal system, biochemical markers could also be used to monitor the reversal of pathology and the efficacy of treatment.
Phenotype variability in 130 adult patients with respiratory chain disorders
Authors: Finsterer J. , Jarius C. , Eichberger H. , Jaksch M.
Published: December 2002

Despite continuously improving diagnostic facilities, respiratory chain disorders (RCDs) are easily overlooked or misdiagnosed. We thus studied phenotype variability and the diagnostic pootential of clinical and laboratory investigations in patients with RCD. We retrospectively evaluated clinical and laboratory investigations in 130 patients with RCD: 63 women and 67 men, aged 17–87 years, diagnosed between January 1992 and December 1999. mtDNA mutations were found in 20 patients; a respiratory chain defect but no mutation in 4; an abnormal lactate stress test but no mutation or biochemical defect in 66; and ragged‐red fibres or reduced oxidative enzyme staining but no mutation, biochemical defect or abnormal lactate stress test in 40 patients. The most frequent initial manifestation of RCD were limb weakness, muscle pain and sensory disturbances. The most frequent clinical findings at diagnosis were muscle pain, fatiguability, limb weakness, reduced tendon reflexes and muscle wasting, irrespective of the diagnostic evidence. Mean age at onset, disease duration and time until diagnosis were 39, 14 and 13 years, respectively, without sex differences. The family history was positive in 29% of the patients. Hyperlipidaemia was found in 45%, hyper‐CK‐aemia in 42%, short stature in 33%, thyroid dysfunction in 17%, diabetes in 12%, and epilepsy in 8% of the patients. Laboratory investigations that prove useful to support the diagnosis of RCD are muscle biopsy, electromyography, lactate stress testing, echocardiography and mtDNA analysis. Systems most often involved in RCDs were the PNS, CNS, endocrine system and heart. The diagnosis of RCD requires awareness of the great phenotypic heterogeneity and an individualized, integral, multidisciplinary approach.
Cardiac manifestations in Fabry disease
Authors: Linhart A. , Lubanda J.‐C. , Palecek T. , Bultas J. , Karetová D. , Ledvinová J. , Elleder M. , Aschermann M.
Published: December 2002

Fabry disease is an X‐linked recessive genetic disorder of glycosphingolipid metabolism, due to deficiency of the lysosomal enzymeα‐galactosidase A. The disease is characterized by the progressive intracellular lysosomal accumulation of neutral glycosphingolipids throughout the body, including the cardiovascular system.

It has been reported that cardiac involvement could be the sole manifestation of the disease in some patients. Myocardial abnormalities are characterized mainly by left ventricular (LV) wall thickening without significant cavity dilatation, the most frequent abnormal structural pattern being concentric LV hypertrophy (LVH). In some patients the disease mimics a typical hypertrophic obstructive cardiomyopathy. According to our experience, systolic function is largely preserved in a large majority of affected individuals. In contrast, mild to moderate impairment of diastolic filling is a relatively common finding, representing probably the most important cause of dyspnoea in patients with Fabry disease. However, in a relatively large population of affected patients, severe diastolic dysfunction, typical of restrictive cardiomyopathy, was not found. Valvular structural abnormalities are frequent due to valvular infiltration. In several patients, hypertrophy of papillary muscles and/or systolic anterior motion of the mitral leaflets associated with LV outflow obstruction may aggravate the mitral valve dysfunction. We did not confirm the previously reported high prevalence of mitral valve prolapse. Valvular regurgitation seems to be relatively frequent but mostly non‐significant. Electrocardiographic changes in Fabry disease are multiple and include at rioventricular (AV) conduction abnormalities (abbreviation of the P‐R interval or AV blocks), signs of LVH and repolarization abnormalities. Our observations suggest that conduction defects and repolarization changes are present predominantly in subjects with LV structural abnormalities. Cardiac symptoms inpatients with Fabry disease include shortness of breath on effort (related to LV diastolic dysfunction), vasospastic and/or exertional angina pectoris (due to LVH, endothelial dysfunction and/or fixed coronary artery stenosis) and syncope (related to AV blocks or LV outflow obstruction). The extent of cardiac involvement, in particular LV mass assessment, could represent an ideal surrogate endpoint for evaluating the efficacy of specific therapies.
Delayed lysosomal metabolism of lipids in mucolipidosis type IV fibroblasts after LDL‐receptor‐mediated endocytosis
Authors: Jansen S. M. , Groener J. E. M. , Bax W. , Poorthuis B. J. H. M.
Published: December 2002

We specifically probed the low‐density lipoprotein‐receptor‐dependent endosomal/lysosomal pathway of lipid degradation in control and mucolipidosis type IV fibroblasts using either [choline‐methyl‐14C]sphingo‐myelin in complex with apolipoprotein E, or cholesteryl [14C]oleate‐labelled low‐density lipoprotein as a substrate. Mucolipidosis type IV fibroblasts metabolized [14C]sphingomyelin and cholesteryl [14C]oleate significantly more slowly than controls and fibroblasts from patients with Hurler disease or Niemann–Pick disease type C. So far, no lysosomal enzyme deficiency has been reported for mucolipidosis type IV. Rather, the defect in mucolipidosis type IV cells has recently been suggested to be related to intracellular trafficking. Our results suggest that the defect in mucolipidosis type IV also affects the low‐density lipoprotein‐receptor‐mediated endocytosis pathway.
The Role of Life Stress and Social Support in the Adjustment of Sexually Victimized Pregnant and Parenting Minority Adolescents
Authors: Osborne Lori N. , Rhodes Jean E.
Published: December 2002

Associations among sexual victimization and the psychosocial functioning of African American and Latina pregnant and parenting adolescents were examined. Forty‐seven (17.7%) of the 265 participants reported histories of sexual victimization, most of which was unwanted sexual intercourse. The victimized adolescents reported higher levels of depression, anxiety, and life stress and, although the two groups reported no differences in their levels of social support, support was found to be differentially related to depression and anxiety in the two groups. In particular, victims derived benefits from social support at low levels of stress, but social support provided no protection against depression and anxiety at average or high levels of stress. For nonvictims, social support provided no benefits at low levels of stress, but protected against depression and anxiety at moderate levels of stress and against depression at high levels of stress. Implications of these findings for research, theory, and intervention are discussed.