Reference Values and Factors Associated With Renal Resistive Index in a Family-Based Population Study

Increased renal resistive index (RRI) has been recently associated with target organ damage and cardiovascular or renal outcomes in patients with hypertension and diabetes mellitus. However, reference values in the general population and information on familial aggregation are largely lacking. We determined the distribution of RRI, associated factors, and heritability in a population-based study. Families of European ancestry were randomly selected in 3 Swiss cities. Anthropometric parameters and cardiovascular risk factors were assessed. A renal Doppler ultrasound was performed, and RRI was measured in 3 segmental arteries of both kidneys. We used multilevel linear regression analysis to explore the factors associated with RRI, adjusting for center and family relationships. Sex-specific reference values for RRI were generated according to age. Heritability was estimated by variance components using the ASSOC program (SAGE software). Four hundred women (mean age±SD, 44.9±16.7 years) and 326 men (42.1±16.8 years) with normal renal ultrasound had mean RRI of 0.64±0.05 and 0.62±0.05, respectively (P<0.001). In multivariable analyses, RRI was positively associated with female sex, age, systolic blood pressure, and body mass index. We observed an inverse correlation with diastolic blood pressure and heart rate. Age had a nonlinear association with RRI. We found no independent association of RRI with diabetes mellitus, hypertension treatment, smoking, cholesterol levels, or estimated glomerular filtration rate. The adjusted heritability estimate was 42±8% (P<0.001). In a population-based sample with normal renal ultrasound, RRI normal values depend on sex, age, blood pressure, heart rate, and body mass index. The significant heritability of RRI suggests that genes influence this phenotype.

Parenting Pioneers and Parenting Teams: Strengthening Extended Family Ties in Family Support

Starting with the premise that extended family members often have great influence on family functioning, this article describes social work practice techniques for helping families utilize resources available in the extended family network. Two key concepts are presented: "parenting pioneers," who, while attempting newly learned parenting skills, may struggle with resistance from extended family members; and "parenting teams," in which the focal family is giving to or receiving from extended family members substantial family support. The article presents these practice techniques in the context of family support services, which are characterized as voluntary, preventive, developmental, and based in the concept of empowerment and the ecological perspective.

European Union Meets South Korea: Bureaucratic Interests, Exporter Discrimination and the Negotiations of Trade Agreements

Who in the European Union drives the process of pursuing bilateral trade negotiations? In contrast to societal explanations, this article develops a novel argument as to how the European Commission manages the process and uses its position in strategic ways to pursue its interests. Rooted in principal–agent theory, the article discusses agent preferences and theorizes the conditions under which the agent sets specific focal points and interacts strategically with principals and third parties. The argument is discussed with case study evidence drawn from the first trade agreement concluded and ratified since the EU Commission announced its new strategy in 2006: the EU–South Korea trade agreement

{\it Hox\/} genes and specification of regional identity in the axial skeleton: Analysis of the individual and combined mutant phenotypes of the paralogous group 4 murine {\it Hox\/} genes; {\it hoxa\/}-4, {\it hoxb\/}-4 and {\it hoxd\/}-4

The Hox gene products are transcription factors involved in specifying regional identity along the anteroposterior body axis. In Drosophila, where these genes are known as HOM-C (Homeotic-complex) genes and where they have been most extensively studied, they are expressed in restricted domains along the anteroposterior axis with different anterior limits. Genetic analysis of a large number of gain- and loss-of-function alleles of these genes has revealed that these genes are important in specifying segmental identity at their anterior limits of expression. Furthermore, there is a functional dominance of posterior genes over anterior genes, such that posterior genes can dominantly specify their developmental programs in spite of the expression of more anterior genes in the same segment. In the mouse, there are four clusters of HOM-C genes, called Hox genes. Thus, there may be up to four genes, called paralogs, that are more highly homologous to each other and to their Drosophila homolog than they are to the other mouse Hox genes. The single mutants for two paralogous genes, hoxa-4 and hoxd-4, presented in this dissertation, are similar to several other mouse Hox mutants in that they show partial, incompletely penetrant homeotic transformations of vertebrae at their anterior limit of expression. These mutants were then bred with hoxb-4 mutants (Ramirez-Solis, et al. 1993) to generate the three possible double mutant combinations as well as the triple mutant. The skeletal phenotypes of these group 4 Hox compound mutants displayed clear alterations in regional identity, such that a nearly complete transformation towards the morphology of the first cervical vertebra occurs. These results suggest a certain degree of functional redundancy among paralogous genes in specifying regional identity. Furthermore, there was a remarkable dose-dependent increase in the number of vertebrae transformed to a first cervical vertebra identity, including the second through the fifth cervical vertebrae in the triple mutant. Thus, these genes are required in a larger anteroposterior domain than is revealed by the single mutant phenotypes alone, such that multiple mutations in these genes result in transformations of vertebrae that are not at their anterior limit of expression. ^

Antigenic variation in Lyme disease spirochetes by segmental recombination of VMP-like sequence cassettes

Lyme disease is a multisystemic disorder caused by tick-borne infection of humans or other mammalian hosts with Borrelia burgdorferi. If untreated, the spirochetes can persist in the mammalian host for months or years. The mechanisms by which Lyme disease spirochetes evade the immune response have not been determined. In this study, we have identified and characterized an elaborate genetic system in the Lyme disease spirochete B. burgdorferi that promotes extensive antigenic variation of a 34-kDa surface-exposed lipoprotein, VlsE. A 28-kilobase linear plasmid of B. burgdorferi B31 (lp28-1) was found to contain a vmp-like sequence (vls) locus that closely resembles the variable major protein (vmp) system for antigenic variation of relapsing fever organisms. The presence of lp28-1 correlates with the high-infectivity phenotype in B. burgdorferi strains tested. Segments of the 15 non-expressed (silent) vls cassette sequences located upstream of vlsE are able to recombine into the centra vlsE cassette region during infection of C3H/HeN mice, resulting in antigenic variation of the expressed lipoprotein. When compared to parental VlsE, VlsE variants progressively accumulate sequence changes during the period of 4, 7, 14, 21, and 28 days post infection in C3H/HeN mice. However, no recombination was detected during the period of 28-day in vitro culture, suggesting in vivo induction of VlsE antigenic variation. Adaptive immune responses do not appear to play a significant role in this induction, since similar recombination events were also observed in immunodeficient SCID mice. The $5\sp\prime$ and $3\sp\prime$ noncassette regions of vlsE are apparently not subject to recombination and sequence variation. The structure and sequence of the silent vls cassette locus is preserved during the process of the VlsE antigenic variation, consistent with a nonreciprocal recombination mechanism. This combinatorial form of antigenic variation could potentially yield millions of VlsE variants in the mammalian host, and thereby contribute to immune evasion, long-term survival, and pathogenesis of B. burgdorferi. ^

The Protection and Promotion of Cultural Diversity in a Digital Networked Environment : Mapping Possible Advances to Coherence

The present paper is the result of a four-year-long project examining the concept and the policies of cultural diversity and the impact of digital media upon the regulatory environment where the goal of cultural diversity is to be achieved. The focus of the project was primarily on the international level and in particular on the World Trade Organization (WTO) and the United Nations Educational Scientific and Cultural Organization (UNESCO), which also epitomise the often framed as opposing pair of trade and culture. In the broad context of the project, we sought to pinpoint the essential elements of an international trade-and-culture conducive framework that can also overcome the existing fragmentation in the field of international law and move towards more coherent solutions. In a narrower context, we sketched some possible improvements to the WTO law that can make it more suitable to the digital networked environment and to the objective of diverse media that some states aspire. . Our key messages are: (1) Neither the WTO nor UNESCO currently offers appropriate solutions to the trade and culture predicament and allows for efficient protection and promotion of cultural diversity; (2) The trade and culture discourse is overly politicised and due to the related path dependencies, a number of feasible solutions appears presently blocked; (3) The digital networked environment has profoundly changed the ways cultural content is created, distributed, accessed and consumed, and may thus offer good reasons to reassess and readjust the present models of governance; (4) Access to information appears to be the most appropriate focus of the discussions with view to protecting and promoting cultural diversity in the new digital media setting, both in local and global contexts; (5) This new focal point demands also broadening and interconnecting the policy discussions, which should go beyond the narrow scope of audiovisual media services, but cautiously account for the developments at the network and applications levels, as well as in other domains, such as most notably intellectual property rights protection; (6) There are various ways in which the WTO can be made more conducive to cultural policy considerations and these include, among others, improved and updated services classifications; enhanced legal certainty with regard to digitally transferred goods and services; incorporation of rules on subsidies for services and on competition.

Neuropathology and pathogenesis of HIV encephalopathies

The nervous system is frequently affected in patients with the acquired immune deficiency syndrome (AIDS). In addition to opportunistic CNS infections and cerebral lymphomas, approx. 20% of the patients develop HIV-associated encephalopathies. Two major histopathological manifestations are observed. HIV leukoencephalopathy (progressive diffuse leukoencephalopathy) is characterized by a diffuse loss of myelin in the deep white matter of the cerebral and cerebellar hemispheres, with scattered multinucleated giant cells and microglia but scarce or absent inflammatory reaction. HIV encephalitis (multinucleated giant cell encephalitis) is associated with accumulations of multinucleated giant cells, inflammatory reaction and often focal necroses. In some patients, both patterns may overlap. In order to identify the HIV genome in the CNS, brain tissue from 27 patients was analyzed for the presence of HIV gag sequences using the polymerase chain reaction (PCR) and primers encoding a 109 base pair segment of the gag gene. Amplification of HIV gag succeeded in all 5 patients with clinical and histopathological evidence for HIV encephalopathy but was negative in the 20 AIDS patients with opportunistic bacterial, parasitic and/or viral infections or with cerebral lymphomas. These results strongly suggest that the evolution of histopathologically recognizable HIV-encephalopathies closely correlates with the presence and/or tissue concentration of HIV. Since there were no cases with amplified HIV DNA in the absence of HIV-associated tissue lesions, we conclude that harboring and replication of HIV in the CNS rapidly causes corresponding clinical and morphological changes of HIV-associated encephalopathies. In two children with severe HIV encephalomyelitis, large amounts of HIV gag and env transcripts were detected in affected areas of the brain and spinal cord by in situ hybridization.(ABSTRACT TRUNCATED AT 250 WORDS)

HIV encephalopathy: incidence, definition and pathogenesis. Results of a Swiss collaborative study

The incidence of HIV encephalopathies was determined in an ongoing consecutive autopsy study. Among 345 patients who died from AIDS in Switzerland during 1981-1990, 68 (19%) showed morphological evidence of HIV encephalopathy. Two major histopathological manifestations were observed. Progressive diffuse leukoencephalopathy (PDL) was present in 33 cases and is characterized by a diffuse loss of myelin staining in the deep white matter of the cerebral and cerebellar hemispheres, with scattered multinucleated giant cells but little or no inflammatory reaction. Multinucleated giant cell encephalitis (MGCE) was diagnosed in 32 cases; it's hallmarks are accumulations of multinucleated giant cells with prominent inflammatory reaction and focal necroses. In 3 patients both types of lesions overlapped. Brain tissue from 27 patients was analyzed for the presence of HIV gag sequences using the polymerase chain reaction (PCR) with primers encoding a 109 base pair segment of the viral gene. Amplification succeeded in all patients with clinical and histopathological evidence for HIV encephalopathy but was absent in AIDS patients with opportunistic bacterial, parasitic and/or viral infections. Potential mechanisms by which HIV exerts it's adverse effects on the human CNS are discussed.

Reversible cerebral vasoconstriction syndrome and cervical artery dissection in 20 patients

OBJECTIVES To describe clinical-radiologic characteristics in a prospective series of patients having both confirmed reversible cerebral vasoconstriction syndrome (RCVS) and cervical artery dissection (CeAD). METHODS From January 2004 to December 2011, from our prospective cohorts of RCVS and CeAD, we studied patients with both conditions. RESULTS Of 173 RCVS cases and 285 CeAD cases, 20 patients (18 women, 2 men; mean age 41 years) had both RCVS and CeAD. Main associated conditions were migraine (12/20) and postpartum (5/18). Clinical features included severe headache in all patients, neck pain in 15, focal neurologic deficit in 9, and seizures in 4. Pain was the only symptom in 10 patients. All patients had multifocal cerebral vasoconstriction. There were brain lesions in 12 patients, cortical subarachnoid hemorrhage in 11, posterior reversible encephalopathy syndrome in 4, intracerebral hemorrhage in 3, and infarcts in 4. CeAD involved one artery in 13 patients and multiple arteries in 7. CeAD mostly affected vertebral arteries (25 of 30 CeAD). Only one vertebral CeAD was associated with a related symptomatic infarct. At 3 months, 18 patients had fully recovered, all patients showed reversal of cerebral vasoconstriction, and 21 dissected arteries had normalized, whereas 9 arteries showed residual stenosis (7) and/or aneurysm (3). CONCLUSION The association of RCVS and CeAD was found in 12% of our patients with RCVS and 7% of our patients with CeAD. Underlying mechanisms are unknown. In practice, our results point to the need for a systematic study of both cervical and intracranial arteries in the 2 conditions.

Standing waves as an explanation for generic stationary correlation patterns in noninvasive EEG of focal onset seizures.

Cerebral electrical activity is highly nonstationary because the brain reacts to ever changing external stimuli and continuously monitors internal control circuits. However, a large amount of energy is spent to maintain remarkably stationary activity patterns and functional inter-relations between different brain regions. Here we examine linear EEG correlations in the peri-ictal transition of focal onset seizures, which are typically understood to be manifestations of dramatically changing inter-relations. Contrary to expectations we find stable correlation patterns with a high similarity across different patients and different frequency bands. This skeleton of spatial correlations may be interpreted as a signature of standing waves of electrical brain activity constituting a dynamical ground state. Such a state could promote the formation of spatiotemporal neuronal assemblies and may be important for the integration of information stemming from different local circuits of the functional brain network.

Germanic Mythology in Music: Cultural Memory and Conflict within the Framework of Modern Globalization

The multi-layered enactment of a national past in music has been strongly intertwined with the usage of mythological elements. Having often been compiled as a coherent narrative during the emergence of the European nation-states (like the Finnish Kalevala), the mythological material has often been perceived as a form of historical truth and national justification. This focal role is also apparent in various music genres ranging from folk revival to metal in post-1989 Europe. Within the globalized context, however, local-national interpretations can collide with earlier nationalist appropriations. This complex and sometimes politically conflicting situation becomes particularly evident with groups falling back on symbols and narrations that had previously been employed by Nazi-Germany. While Nazi-Germany had, among others, tried replace the Christmas tradition with elements and songs from Germanic (and other) mythological sources, modern Neo-Nazi music groups often employ central mythological names (like Odin or Tyr) and iconic elements (like Vikings and warriors) in song lyrics and CD cover designs. However, while many covers and lyrics are legally forbidden in Germany, Scandinavian and Baltic groups (like the Faroese Viking metal group Tyr and the Latvian pagan metal band Skyforger) employ similar elements of Norse mythology, which are often combined with traditional material. Discussing selected case studies, this paper highlights central discursive points of colliding historical-national associations and individual interpretations of the mythological elements in musical contexts. How far can the material be disassociated from the earlier historical political usage and instrumentalization? Is this necessary ? And how can the specific global-local conflict points be approached by a theoretical framework ?

Focal hemodynamic patterns of status epilepticus detected by susceptibility weighted imaging (SWI).

OBJECTIVE To investigate pathological findings in the susceptibility weighted imaging (SWI) of patients experiencing convulsive (CSE) or non-convulsive status epilepticus (NCSE) with focal hyperperfusion in the acute setting. METHODS Twelve patients (six with NCSE confirmed by electroencephalogram (EEG) and six patients with CSE with seizure event clinically diagnosed) underwent MRI in this acute setting (mean time between onset of symptoms and MRI was 3 h 8 min), including SWI, dynamic susceptibility contrast MR imaging (DSC) and diffusion-weighted imaging (DWI). MRI sequences were retrospectively evaluated and compared with EEG findings (10/12 patients), and clinical symptoms. RESULTS Twelve out of 12 (100 %) patients showed a focal parenchymal area with pseudo-narrowed cortical veins on SWI, associated with focal hyperperfused areas (increased cerebral blood flow (CBF) and mean transit time (MTT) shortening), and cortical DWI restriction in 6/12 patients (50 %). Additionally, these areas were associated with ictal or postical EEG patterns in 8/10 patients (80 %). Most frequent acute clinical findings were aphasia and/or hemiparesis in eight patients, and all of them showed pseudo-narrowed veins in those parenchymal areas responsible for these symptoms. CONCLUSION In this study series with CSE and NCSE patients, SWI showed focally pseudo-narrowed cortical veins in hyperperfused and ictal parenchymal areas. Therefore, SWI might have the potential to identify an ictal region in CSE/NCSE. KEY POINTS • The focal ictal brain regions show hyperperfusion in DSC MR-perfusion imaging. • SWI shows focally diminished cortical veins in hyperperfused ictal regions. • SWI has the potential to identify a focal ictal region in CSE/NCSE.

Dynamics of governance and control in inter-organizational software development

In recent years, development of information systems (IS) has rapidly changed towards increasing division of labor between firms. Two trends are emerging. First, client companies increasingly outsource software development to external service providers. Second, the formerly oligopolistic enterprise application software industry has started to disintegrate into focal partnership networks – so called platform ecosystems. Despite the increasing prominence of IS outsourcing and platform ecosystems, many of these inter-organizational partnerships fail to achieve expected benefits. Ineffective governance and control frequently plays a pivotal role in producing these failures. While designing effective governance and control mechanisms is always challenging, inter-organizational software development projects are often business-critical and exhibit additional dynamics and uncertainty. As a consequence governance and control have to be adapted over time. The three research projects included in this book provide a better understanding of how and why governance and control can be effectively adapted over time. The implications for successful management of inter-organizational software development projects are highly relevant for theory and practice.