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Profound
Terms modified by Profound Selected AbstractsLow Serum Biotinidase Activity in Children with Valproic Acid MonotherapyEPILEPSIA, Issue 10 2001K. H. Schulpis Summary: ,Purpose: Valproic acid (VPA) is an effective antiepileptic drug (AED), which is associated with dose-related adverse reactions such as skin rash, hair loss (alopecia), etc. Profound as well as partial biotinidase deficiency causes dermatologic manifestations similar these. Therefore, it was of interest to evaluate serum biotinidase activity in patients receiving VPA monotherapy. Methods: Seventy-five patients with seizures, mean age, 8.6 years (±1.9 years) were divided into three groups. Group A (n = 25) was treated with VPA 28.7 ± 8.5 mg/kg/24 h, group B (n = 25) with 41.6 ± 4.9 mg/kg/24 h, and group C with 54.5 ± 5.8 mg/kg/24 h. Their "trough" VPA serum levels were 40.9 ± 13.2, 86.25 ± 11.5, and 137 ± 14.5 ,g/ml, respectively. Fifty healthy children were the controls. Patients and controls underwent clinical and laboratory evaluations including liver function data, complete blood counts, NH3, and so on, after 45 days of VPA treatment. Biotinidase serum levels were evaluated fluorometrically. Results: Liver function data were found elevated in the groups B and C. On the contrary, biotinidase activity was significantly statistically lowered (p < 0.001) in groups B and C (1.22 ± 1.11, 0.97 ± 0.07 mmol/min/L respectively), as compared with controls (5.20 ± 0.90 mmol/min/L). Strong inverse correlations were observed between liver enzymes and VPA blood levels with the activity of the enzyme. Additionally, no inhibitory effect on biotinidase activity was found, when the enzyme was incubated in vitro with high (1.2 mM) concentrations of the drug. Skin lesions (seborrheic rash, alopecia) were improved in our patients after biotin (10 mg/day) supplementation. Conclusions: It is suggested that VPA impairs the liver mitochondrial function, resulting in a low biotinidase activity and or biotin deficiency. Biotin supplementation could restore some of the side effects of the drug. [source] Personal view: a potential novel treatment for fatigue complicating chronic liver disease , how should its efficacy be evaluated?ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 8 2006E. A. JONES Summary Profound fatigue is a clinically significant complication of chronic liver disease. A mechanism of fatigue in experimental animals and male athletes appears to be increased serotoninergic neurotransmission in the brain. Recently, attempts have been made to assess the efficacy of a serotonin antagonist, specifically the 5-HT3 receptor subtype antagonist, ondansetron, in ameliorating fatigue in patients with chronic liver disease. However, the results of a randomized controlled trial of ondansetron for fatigue in patients with primary biliary cirrhosis did not indicate that ondansetron was either effective or ineffective. The reasons for the uncertain outcome of the randomized controlled trial are not clear. One contributing factor may have been the use of subjective indices of fatigue as primary efficacy endpoints. There is a need to develop objective quantitative primary efficacy endpoints for use in trials of therapy for fatigue. Another contributing factor may relate to the conduct of a randomized controlled trial not invariably being the optimal approach to resolve a specific clinical issue, particularly when the application of statistical methods yields equivocal findings. When the results of a randomized controlled trial are indecisive, findings based on clinical judgement, medicine's most important asset, should be carefully evaluated. [source] DIFFICULT DISTINCTIONS: Refugee Law, Humanitarian Practice, and Political Identification in GazaCULTURAL ANTHROPOLOGY, Issue 1 2007ILANA FELDMAN In this article, I explore the intersection of humanitarian practice and refugee law in shaping categories of "refugee" and "citizen" in Gaza in the first years after 1948. I examine how humanitarian practice produced enduring distinctions within the Gazan population and provided a space in which ideas about Palestinian citizenship began to take shape. A key argument is that humanitarianism, despite commitments to political neutrality, often has profound and enduring political effects. In this case, humanitarian distinctions contributed to making the "refugee" a central figure in the Palestinian political landscape. I also consider how humanitarianism in Palestine was guided by the larger, emerging postwar refugee regime, even as Palestinians were formally excluded from some of its mechanisms. [source] Effects of severe dentoalveolar trauma on the quality-of-life of children and parentsDENTAL TRAUMATOLOGY, Issue 5 2009Teresa D. Berger Sample: A visual analogue scale (VAS) was used to assess the pain of injury and treatment for 27 individuals 8,20 years and their parents. The Child Oral Health Quality of Life (COHQoL) survey was used to assess the effects of dental injuries on the QoL of 23 children aged 8,14 and their parents. Results: Mean VAS scores revealed that all patients and parents perceived the pain of initial injury to be significantly greater than pain of splint removal (P , 0.05) and that pain decreased in a stepwise manner from injury through emergency treatment to splint removal. The COHQoL questionnaire demonstrated a profound and continuing effect on children and their parent's QoL following severe dental injury. The initial parental COHQoL score was significantly greater than the 12-month score (P , 0.05) in both 8,10 and 11-14- year-olds. The COHQoL results indicated a measurable reduction in the QoL of patients and parents was still present 12-months after the injuries. At the end of one-year children were still affected by the social and well-being aspects of the injury yet parents exclusively reported that one-year effects were limited to their children's oral symptoms and functional limitations. Conclusions: Severe dental injuries produce initial and ongoing pain. Detrimental effects on the QoL of both children and parents are still present at one-year and these long-term effects are different for children and parents. [source] DEWEYAN DARWINISM FOR THE TWENTY-FIRST CENTURY: TOWARD AN EDUCATIONAL METHOD FOR CRITICAL DEMOCRATIC ENGAGEMENT IN THE ERA OF THE INSTITUTE OF EDUCATION SCIENCESEDUCATIONAL THEORY, Issue 3 2008Deborah Seltzer-Kelly Early in the twentieth century, John Dewey also advocated for a vision of education guided by science, and more recent scholarship has validated many of his ideas. However, as Deborah Seltzer-Kelly argues in this essay, Dewey's vision of a scientifically based system of education was very different from that envisioned by the IES, and also very different from that implied by the progenitor of contemporary evolutionary thought, Donald Campbell. Seltzer-Kelly proposes a Deweyan Darwinist model of educational method as a genuinely scientific alternative to the scientism that pervades current official efforts to imbue education with science. The implications of this model are profound, highlighting the difference between education as preparation for consent to authoritarian structures and education as preparation for genuinely democratic participation. [source] Cold hardiness of diapausing and non-diapausing pupae of the European grapevine moth, Lobesia botranaENTOMOLOGIA EXPERIMENTALIS ET APPLICATA, Issue 2 2005Stefanos S. Andreadis Abstract Lobesia botrana (Denis & Schiffermüller) (Lepidoptera: Tortricidae) is a key pest of grapes in Europe. It overwinters as a pupa in the bark crevices of the plant. Supercooling point (SCP) and low temperature survival was investigated in the laboratory and was determined using a cool bath and a 1 °C min,1 cooling rate. Freezing was fatal both to diapausing and non-diapausing pupae. SCP was significantly lower in diapausing male (,24.8 °C) and female (,24.5 °C) pupae than in non-diapausing ones (,22.7 and ,22.5 °C, respectively). Sex had no influence on SCP both for diapausing and non-diapausing pupae. Supercooling was also not affected by acclimation. However, acclimation did improve survival of diapausing pupae at temperatures above the SCP. Survival increased as acclimation period increased and the influence was more profound at the lower temperatures examined. Diapausing pupae could withstand lower temperatures than non-diapausing ones and lethal temperature was significantly lower than for non-diapausing pupae. Freezing injury above the SCP has been well documented for both physiological stages of L. botrana pupae. Our findings suggest a diapause-related cold hardiness for L. botrana and given its cold hardiness ability, winter mortality due to low temperatures is not expected to occur, especially in southern Europe. [source] Effects of contaminated sediment on the epidermis of mummichog, Fundulus heteroclitusENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 11 2000Laurent C. Mézin Abstract Secretion of mucus by epidermal goblet cells protects fish against many biological, physical, and chemical insults encountered in the environment. This study monitored changes in hemoglobin concentration in epidermal mucus and in the density, diameter, and mucus quality of epidermal goblet cells in the mummichog, Fundulus heteroclitus, following exposure to creosote-contaminated sediment from the Elizabeth River, Virginia, USA. Fish were exposed for 13 d in flow-through aquaria to either uncontaminated (US) or contaminated (CS) sediments and were sampled periodically. The condition index was lower and the mortality rate and the occurrence of epidermal lesions were higher in CS-exposed fish than in US-exposed fish. Hemoglobin contents in epidermal mucus from the former group were significantly higher than from the latter. Significant reductions in both size and density of goblet cells in CS-exposed fish suggested a mucus secretion rate exceeding its production rate. Significant changes in mucin types between treatments did not occur until day 13 and are not believed to be directly related to the creosote present in the contaminated sediment. These results all indicate that exposure to creosote-contaminated sediment had a profound and deleterious effect on fish health. [source] Equine laminitis: Ultrastructural lesions detected in ponies following hyperinsulinaemiaEQUINE VETERINARY JOURNAL, Issue 7 2009A. R. NOURIAN Summary Reasons for performing study: Anatomical changes in the hoof lamellar tissue induced by prolonged hyperinsulinaemia have not been described previously. Analysis of the induced lesions may promote understanding of hyperinsulinaemic laminitis pathogenesis and produce clinical benefit. Objectives: To use light and transmission electron microscopy (TEM) to document hoof lamellar lesions in ponies clinically lame after prolonged hyperinsulinaemia. Methods: Nine clinically normal, mature ponies were allocated randomly to either a treatment group (n = 5) or control group (n = 4). The treatment group received insulin via a modified, prolonged euglycaemic hyperinsulinaemic clamp technique (EHCT) and were subjected to euthanasia when clinical signs of Obel grade II laminitis occurred. The control group was sham treated with an equivalent volume of 0.9% saline and killed at 72 h. Lamellar tissues of the right front feet were harvested and processed for TEM. Results: Lamellae from insulin treated ponies were attenuated and elongated with many epidermal basal cells (EBC) in mitosis. Unlike carbohydrate induced laminitis in horses there was no global separation at the lamellar dermal/epidermal interface among ponies. Sporadic EBC basement membrane (BM) separation was associated with the proximity of infiltrating leucocytes. In 2 ponies, the lamellar BM was thickened. The number of hemidesmosomes/,m of BM was decreased in all insulin treated ponies. Conclusions: Prolonged hyperinsulinaemia causes unique lamellar lesions normally characteristic of acute and chronic laminitis. Lamellar proliferation may be an insulin effect through its mitogenic pathway. Aberrant lamellar mitosis may lengthen and weaken the lamellar, distal phalanx attachment apparatus and contribute to the clinical signs that developed. Potential relevance: The study shows that insulin alone, in higher than normal circulating concentrations, induces profound, changes in lamellar anatomy. Medical control of insulin resistance and hyperinsulinaemia may ameliorate lesions and produce clinical benefit. [source] T-cell tolerance induced by repeated antigen stimulation: Selective loss of Foxp3, conventional CD4 T cells and induction of CD4 T-cell anergyEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 4 2009Lena Eroukhmanoff Abstract Repeated immunization of mice with bacterial superantigens induces extensive deletion and anergy of reactive CD4 T cells. Here we report that the in vitro proliferation anergy of CD4 T cells from TCR transgenic mice immunized three times with staphylococcal enterotoxin B (SEB) (3× SEB) is partially due to an increased frequency of Foxp3+ CD4 T cells. Importantly, reduced number of conventional CD25, Foxp3, cells, rather than conversion of such cells to Foxp3+ cells, was the cause of that increase and was also seen in mice repeatedly immunized with OVA (3× OVA) and OVA,peptide (OVAp) (3× OVAp). Cell-transfer experiments revealed profound but transient anergy of CD4 T cells isolated from 3× OVAp and 3× SEB mice. However, the in vivo anergy was CD4 T-cell autonomous and independent of Foxp3+ Treg. Finally, proliferation of transferred CD4 T cells was inhibited in repeatedly immunized mice but inhibition was lost when transfer was delayed, despite the maintenance of elevated frequency of Foxp3+ cells. These data provide important implications for Foxp3+ cell-mediated tolerance in situations of repeated antigen exposure such as human persistent infections. [source] ARE PINNIPEDS FUNCTIONALLY DIFFERENT FROM FISSIPED CARNIVORES?EVOLUTION, Issue 3 2000THE IMPORTANCE OF PHYLOGENETIC COMPARATIVE ANALYSES Abstract., It is widely assumed that adaptations to an aquatic lifestyle are so profound as to produce only obvious differences between pinnipeds and the remaining, largely terrestrial carnivore species ("fissipeds"). Thus, comparative studies of the order Carnivora routinely examine these groups independently. This approach is invalid for two reasons. First, fissipeds are a paraphyletic assemblage, which raises the general issue of when it is appropriate to ignore monophyly as a criterion for inclusion in comparative studies. Second, the claim that most functional characters (beyond a few undoubted characteristic features) are different in pinnipeds and fissipeds has never been quantitatively examined, nor with phylogenetic comparative methods. We test for possible differences between these two groups in relation to 20 morphological, life-history, physiological, and ecological variables. Comparisons employed the method of independent contrasts based on a complete and dated species-level phylogeny of the extant Carnivora. Pinnipeds differ from fissipeds only through evolutionary grade shifts in a limited number of life-history traits: litter weight (vs. gestation length), birth weight, and age of eyes opening (both vs. size). Otherwise, pinnipeds display the same rate of evolution as phylogenetically equivalent fissiped taxa for all variables. Overall functional differences between pinnipeds and fissipeds appear to have been overstated and may be no greater than those among major fissiped groups. Recognition of this fact should lead to a more complete understanding of carnivore biology as a whole through more unified comparative tests. Comparative studies that do not include monophyletic groups for phylogenetically based comparative tests should be reconsidered. [source] The effect of water content on proton transport in polymer electrolyte membranesFUEL CELLS, Issue 3-4 2002P. Commer Abstract We investigate proton transport in a polymer electrolyte membrane using continuum theory and molecular dynamics (MD) computer simulations. Specifically our goal is to understand the possible molecular origin of the effect of water content on the activation energy (AE) and pre-exponential factor of proton conductivity, in comparison with experimental observations reported for Nafion, where a decrease of AE with increasing water content has been observed. We study proton diffusion in a single pore, using a slab-like model. We find that although the average proton diffusion coefficient is several times smaller in a narrow pore than in a wide water-rich pore, its AE is almost unaffected by the pore width. This contradicts an earlier proposed conjecture that the sizable Coulomb potential energy barriers near the lattice of immobile point-like SO3, groups increase the AE in a narrow pore. Here we show that these barriers become smeared out by thermal motion of SO3, groups and by the spatial charge distribution over their atoms. This effect strongly diminishes the variation of the AE with pore width, which is also found in MD simulations. The pre-exponential factor for the diffusion process, however, decreases, indicating a limited number of pathways for proton transfer and the freezing out of degrees of freedom that contribute to the effective frequency of transfer. Decreasing the pore size diminishes bulk-like water regions in the pore, with only less mobile surface water molecules remaining. This hampers proton transfer. The increase of AE takes place only if the thermal motion of the SO3, head groups freezes out simultaneously with decreasing water content, but the effect is not profound. The stronger effect observed experimentally may thus be associated with some other rate-determining consecutive process, concerned with polymer dynamics, such as opening and closing of connections (bridges) between aqueous domains in the membrane under low water content. [source] Impaired Pavlovian fear extinction is a common phenotype across genetic lineages of the 129 inbred mouse strainGENES, BRAIN AND BEHAVIOR, Issue 8 2009M. Camp Fear extinction is impaired in psychiatric disorders such as post-traumatic stress disorder and schizophrenia, which have a major genetic component. However, the genetic factors underlying individual variability in fear extinction remain to be determined. By comparing a panel of inbred mouse strains, we recently identified a strain, 129S1/SvImJ (129S1), that exhibits a profound and selective deficit in Pavlovian fear extinction, and associated abnormalities in functional activation of a key prefrontal-amygdala circuit, as compared with C57BL/6J. The first aim of the present study was to assess fear extinction across multiple 129 substrains representing the strain's four different genetic lineages (parental, steel, teratoma and contaminated). Results showed that 129P1/ReJ, 129P3/J, 129T2/SvEmsJ and 129X1/SvJ exhibited poor fear extinction, relative to C57BL/6J, while 129S1 showed evidence of fear incubation. On the basis of these results, the second aim was to further characterize the nature and specificity of the extinction phenotype in 129S1, as an exemplar of the 129 substrains. Results showed that the extinction deficit in 129S1 was neither the result of a failure to habituate to a sensitized fear response nor an artifact of a fear response to (unconditioned) tone per se. A stronger conditioning protocol (i.e. five × higher intensity shocks) produced an increase in fear expression in 129S1, relative to C57BL/6J, due to rapid rise in freezing during tone presentation. Taken together, these data show that impaired fear extinction is a phenotypic feature common across 129 substrains, and provide preliminary evidence that impaired fear extinction in 129S1 may reflect a pro-fear incubation-like process. [source] Genotypic and phenotypic classification of cancer: How should the impact of the two diagnostic approaches best be balanced?GENES, CHROMOSOMES AND CANCER, Issue 9 2010Petter Brandal Neoplastic tumors are traditionally named based on their differentiation (i.e., which normal cells and tissues they resemble) and bodily site. In recent years, knowledge about the genetic basis of tumorigenesis has grown rapidly, and the new information has in several instances been incorporated into the very definition of cancerous entities. The proper contribution of the diseases' phenotype and genotype to what they are called and how they are delineated from one another has rarely been subjected to explicit reasoning, however, nor is it often made clear whether existing naming practices are founded on ontological or utilitarian grounds. We look at several examples of how the new cytogenetic and molecular genetic understanding of tumorigenesis has impacted oncological nomenclature in a significant manner, but also at counterexamples where no similar change has taken place. In all likelihood, more and more neoplastic diseases will in the future be defined and named based on their pathogenesis rather than their phenotype, not least because effective and specific drug therapies directed against the molecular change at the very heart of oncogenesis will increasingly become available. The fact that this shift in emphasis is primarily guided by utilitarian considerations rather than any perception of acquired genetic changes as somehow being more ontologically "profound" or "important" in tumorigenesis, is as it should be; both the phenotype and the genotype of tumors are key parameters across most of oncology and are likely to be retained as the basis of coexisting disease classifications for as long as we can foresee. © 2010 Wiley-Liss, Inc. [source] Involvement of adenylate cyclase and tyrosine kinase signaling pathways in response of crayfish stretch receptor neuron and satellite glia cell to photodynamic treatmentGLIA, Issue 3 2005Anatoly Uzdensky Abstract Neuroglial interactions are most profound during development or damage of nerve tissue. We studied the responses of crayfish stretch receptor neurons (SRN) and satellite glial cells to photosensitization with sulfonated aluminum phthalocyanine Photosens. Although Photosens was localized mainly in the glial envelope, neurons were very sensitive to photodynamic treatment. Photosensitization gradually inhibited and then abolished neuron activity. Neuronal and glial nuclei shrank. Some neurons and glial cells lost the integrity of the plasma membrane and died through necrosis after the treatment. The nuclei of other glial cells but not neurons become fragmented, indicating apoptosis. The number of glial nuclei around neuron soma increased, probably indicating proliferation for enhanced neuron protection. Adenylate cyclase (AC) inhibition by MDL-12330A, or tyrosine kinase (TK) inhibition by genistein, shortened neuron lifetime, whereas AC activation by forskolin or protein tyrosine phosphatases (PTP) inhibition by sodium orthovanadate prolonged neuronal activity. Therefore, cAMP and phosphotyrosines produced by AC and TK, respectively, protected SRN against photoinactivation. AC inhibition reduced photodamage of the plasma membrane and subsequent necrosis in neuronal and glial cells. AC activation prevented apoptosis in photosensitized glial cells and stimulated glial proliferation. TK inhibition protected neurons but not glia against photoinduced membrane permeabilization and subsequent necrosis whereas PTP inhibition more strongly protected glial cells. Therefore, both signaling pathways involving cAMP and phosphotyrosines might contribute to the maintenance of neuronal activity and the integrity of the neuronal and glial plasma membranes. Adenylate cyclase but not phosphotyrosine signaling pathways modulated glial apoptosis and proliferation under photooxidative stress. © 2004 Wiley-Liss, Inc. [source] Impacts of extreme winter warming in the sub-Arctic: growing season responses of dwarf shrub heathlandGLOBAL CHANGE BIOLOGY, Issue 11 2008S. BOKHORST Abstract Climate change scenarios predict an increased frequency of extreme climatic events. In Arctic regions, one of the most profound of these are extreme and sudden winter warming events in which temperatures increase rapidly to above freezing, often causing snow melt across whole landscapes and exposure of ecosystems to warm temperatures. Following warming, vegetation and soils no longer insulated below snow are then exposed to rapidly returning extreme cold. Using a new experimental facility established in sub-Arctic dwarf shrub heathland in northern Sweden, we simulated an extreme winter warming event in the field and report findings on growth, phenology and reproduction during the subsequent growing season. A 1-week long extreme winter warming event was simulated in early March using infrared heating lamps run with or without soil warming cables. Both single short events delayed bud development of Vaccinium myrtillus by up to 3 weeks in the following spring (June) and reduced flower production by more than 80%: this also led to a near-complete elimination of berry production in mid-summer. Empetrum hermaphroditum also showed delayed bud development. In contrast, Vaccinium vitis-idaea showed no delay in bud development, but instead appeared to produce a greater number of actively growing vegetative buds within plots warmed by heating lamps only. Again, there was evidence of reduced flowering and berry production in this species. While bud break was delayed, growing season measurements of growth and photosynthesis did not reveal a differential response in the warmed plants for any of the species. These results demonstrate that a single, short, extreme winter warming event can have considerable impact on bud production, phenology and reproductive effort of dominant plant species within sub-Arctic dwarf shrub heathland. Furthermore, large interspecific differences in sensitivity are seen. These findings are of considerable concern, because they suggest that repeated events may potentially impact on the biodiversity and productivity of these systems should these extreme events increase in frequency as a result of global change. Although climate change may lengthen the growing season by earlier spring snow melt, there is a profound danger for these high-latitude ecosystems if extreme, short-lived warming in winter exposes plants to initial warm temperatures, but then extreme cold for the rest of the winter. Work is ongoing to determine the longer term and wider impacts of these events. [source] Southern African social movements at the 2007 Nairobi World Social ForumGLOBAL NETWORKS, Issue 1 2009MILES LARMER Abstract How relevant is the anti-globalization movement to the ideas and activities of social movements seeking to achieve economic justice and greater democratic accountability in southern Africa? Case study research in four southern African countries (Zimbabwe, Zambia, Malawi and Swaziland) indicates that, while aspects of the anti-globalization approach resonate with civil society and social movement actors (for example, an emphasis on mass participation and the internationalization of campaigning), the global social justice movement frequently displays the characteristics of globalization. These include: unaccountable decision-making; profound (yet largely unacknowledged) inequality of access to resources; and an imposed and uniform organizational form that fails to consider local conditions. The World Social Forum (WSF) held in Nairobi in January 2007 provided many southern African social movement actors with their first opportunity to participate in the global manifestation of the anti-globalization movement. The authors interviewed social movement activists across southern Africa before and during the Nairobi WSF about their experiences of the anti-globalization movement and the Social Forum. An assessment of the effectiveness of this participation leads to the conclusion that the WSF is severely limited in its capacity to provide an effective forum for these actors to express their grievances and aspirations. However, hosting national social forums, their precise form adapted to reflect widely varied conditions in southern African states that are affected by globalization in diverse ways, appears to provide an important new form of mobilization that draws on particular elements of anti-globalization praxis. [source] THE IMPACT OF THE UNIVERSAL DECLARATION OF HUMAN RIGHTS ON THE STUDY OF HISTORYHISTORY AND THEORY, Issue 1 2009ANTOON DE BAETS ABSTRACT There is perhaps no text with a broader impact on our lives than the 1948 Universal Declaration of Human Rights (UDHR). It is strange, therefore, that historians have paid so little attention to the UDHR. I argue that its potential impact on the study of history is profound. After asking whether the UDHR contains a general view of history, I address the consequences of the UDHR for the rights and duties of historians, and explain how it deals with their subjects of study. I demonstrate that the UDHR is a direct source of five important rights for historians: the rights to free expression and information, to meet and found associations, to intellectual property, to academic freedom, and to silence. It is also an indirect source of three duties for historians: the duties to produce expert knowledge about the past, to disseminate it, and to teach about it. I discuss the limits to, and conflicts among, these rights and duties. The UDHR also has an impact on historians' subjects of study: I argue that the UDHR applies to the living but not to the dead, and that, consequently, it is a compass for studying recent rather than remote historical injustice. Nevertheless, and although it is itself silent about historians' core duties to find and tell the truth, the UDHR firmly supports an emerging imprescriptible right to the truth, which in crucial respects is nothing less than a right to history. If the UDHR is a "Magna Carta of all men everywhere," it surely is one for all historians. [source] Pulpal status of human primary teeth with physiological root resorptionINTERNATIONAL JOURNAL OF PAEDIATRIC DENTISTRY, Issue 1 2009JOANA MONTEIRO Objective., The overall aim of this study was to determine whether any changes occur in the pulpal structure of human primary teeth in association with physiological root resorption. Methods., The experimental material comprised 64 sound primary molars, obtained from children requiring routine dental extractions under general anaesthesia. Pulp sections were processed for indirect immunofluorescence using combinations of: (i) protein gene product 9.5 (a general neuronal marker); (ii) leucocyte common antigen CD45 (a general immune cell marker); and (iii) Ulex europaeus I lectin (a marker of vascular endothelium). Image analysis was then used to determine the percentage area of staining for each label within both the pulp horn and mid-coronal region. Following measurement of the greatest degree of root resorption in each sample, teeth were subdivided into three groups: those with physiological resorption involving less than one-third, one-third to two-thirds, and more than two-thirds of their root length. Results., Wide variation was evident between different tooth samples with some resorbed teeth showing marked changes in pulpal histology. Decreased innervation density, increased immune cell accumulation, and increased vascularity were evident in some teeth with advanced root resorption. Analysis of pooled data, however, did not reveal any significant differences in mean percentage area of staining for any of these variables according to the three root resorption subgroups (P > 0.05, analysis of variance on transformed data). Conclusions., This investigation has revealed some changes in pulpal status of human primary teeth with physiological root resorption. These were not, however, as profound as one may have anticipated. It is therefore speculated that teeth could retain the potential for sensation, healing, and repair until advanced stages of root resorption. [source] Tales of resistance and other emancipatory functions of storytellingJOURNAL OF ADVANCED NURSING, Issue 11 2009Jane S. Grassley Abstract Title.,Tales of resistance and other emancipatory functions of storytelling. Aim., This paper is the report of a study to explore how the process of storytelling might facilitate women's emancipatory knowing, using examples from women's breastfeeding stories. Background., Storytelling, as an interactive process, can give women a way to explain pivotal life events, justify choices, examine reality and find meaning in experiences. Emancipatory functions of storytelling have been identified as contextual grounding, bonding with others, validating and affirming experiences, venting and catharsis, resisting oppression and educating others. Method., Secondary data analysis was conducted in 2008 on breastfeeding stories originally gathered from 13 women from 2002 to 2004 for a feminist hermeneutic study of maternal breastfeeding confidence. The stories were re-examined through the lens of the emancipatory functions of storytelling. Illustrations of contextual grounding, validating and affirming experiences, venting and catharsis and acts of resistance were found in the breastfeeding stories and presented as exemplars of emancipatory knowing. Findings., Women revealed the difficulties they encountered breastfeeding, transforming these experiences as they discovered their meaning. They described collisions that occurred when personal, familial, healthcare professionals' or cultural expectations differed from their experience. The stories suggested possible liberation from old ideologies about breastfeeding as women redefined the difficulties they encountered. Conclusion., Storytelling has potential as a simple, yet profound, and powerful emancipatory intervention which nurses can use to help women in their care make sense of and transform experiences of health and illness. Storytelling may have global implications for nursing practice and research. [source] Caring for Older Americans: The Future of Geriatric MedicineJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue S6 2005American Geriatrics Society Core Writing Group of the Task Force on the Future of Geriatric Medicine In response to the needs and demands of an aging population, geriatric medicine has grown rapidly during the past 3 decades. The discipline has defined its core values as well as the knowledge base and clinical skills needed to improve the health, functioning, and well-being of older persons and to provide appropriate palliative care. Geriatric medicine has developed new models of care, advanced the treatment of common geriatric conditions, and advocated for the health and health care of older persons. Nevertheless, at the beginning of the 21st century, the health care of older persons is at a crossroads. Despite the substantial progress that geriatric medicine has made, much more remains to be done to meet the healthcare needs of our aging population. The clinical, educational, and research approaches of the 20th century are unable to keep pace and require major revisions. Maintaining the status quo will mean falling further and further behind. The healthcare delivery and financing systems need fundamental redesign to improve quality and eliminate waste. The American Geriatrics Society (AGS) Task Force on the Future of Geriatric Medicine has identified five goals aimed at optimizing the health of older persons: ,,To ensure that every older person receives high-quality, patient-centered health care ,,To expand the geriatrics knowledge base ,,To increase the number of healthcare professionals who employ the principles of geriatric medicine in caring for older persons ,,To recruit physicians and other healthcare professionals into careers in geriatric medicine ,,To unite professional and lay groups in the effort to influence public policy to continually improve the health and health care of seniors Geriatric medicine cannot accomplish these goals alone. Accordingly, the Task Force has articulated a set of recommendations primarily aimed at the government, organizations, agencies, foundations, and other partners whose collaboration will be essential in accomplishing these goals. The vision described in this document and the accompanying recommendations are only the broad outline of an agenda for the future. Geriatric medicine, through its professional organizations and its partners, will need to mobilize resources to identify and implement the specific steps that will make the vision a reality. Doing so will require broad participation, consensus building, creativity, and perseverance. The consequences of inaction will be profound. The combination of a burgeoning number of older persons and an inadequately prepared, poorly organized physician workforce is a recipe for expensive, fragmented health care that does not meet the needs of our older population. By virtue of their unique skills and advocacy for the health of older persons, geriatricians can be key leaders of change to achieve the goals of geriatric medicine and optimize the health of our aging population. Nevertheless, the goals of geriatric medicine will be accomplished only if geriatricians and their partners work in a system that is designed to provide high-quality, efficient care and recognizes the value of geriatrics. [source] Remote Weaponry: The Ethical ImplicationsJOURNAL OF APPLIED PHILOSOPHY, Issue 2 2008SUZY KILLMISTER abstract The nature of warfare is changing. Increasingly, developments in military technology are removing soldiers from the battlefield, enabling war to be waged from afar. Bombs can be dropped from unmanned drones flying above the range of retaliation. Missiles can be launched, at minimal cost, from ships 200 miles to sea. Micro Air Vehicles, or ,WASPS', will soon be able to lethally attack enemy soldiers. Though still in the developmental stage, progress is rapidly being made towards autonomous weaponry capable of selecting, pursuing, and destroying targets without the necessity for human instruction. These developments have a profound , and as yet under-analysed , impact on just war theory. I argue that a state under attack from remote weaponry is unable to respond in the traditional, just war sanctioned, method of targeting combatants on the battlefield. This restriction of options potentially creates a situation whereby a state is either coerced into surrender, or it must transgress civilian immunity. Just war theory in conditions of remote warfare therefore either serves the interests of the technologically advanced by demanding the surrender of targeted states, or else it becomes redundant. [source] The Assessment of Basic Learning Abilities Test for Persons with Intellectual Disability: A Valuable Clinical ToolJOURNAL OF APPLIED RESEARCH IN INTELLECTUAL DISABILITIES, Issue 5 2007Tricia Vause The Assessment of Basic Learning Abilities (ABLA) test requires a tester to attempt to teach to a person, using standard prompting and reinforcement procedures, six tasks that are hierarchically ordered in difficulty. Performance on the test provides valuable information for teachers and rehabilitation workers to match the difficulty of training tasks with the learning ability of persons with profound, severe and moderate intellectual disabilities. This paper summarizes the characteristics of the test, outlines the testing procedures, and reviews supporting data and practical guidelines for clinicians. [source] ORIGINAL ARTICLE: Towards an understanding of the Holocene distribution of Fagus sylvatica L.JOURNAL OF BIOGEOGRAPHY, Issue 1 2007Thomas Giesecke Abstract Aim, Understanding the driving forces and mechanisms of changes in past plant distribution and abundance will help assess the biological consequences of future climate change scenarios. The aim of this paper is to investigate whether modelled patterns of climate parameters 6000 years ago can account for the European distribution of Fagus sylvatica at that time. Consideration is also given to the role of non-climatic parameters as driving forces of the Holocene spread and population expansion of F. sylvatica. Location, Europe. Methods, European distributions were simulated using a physiologically-based bioclimatic model (STASH) driven by three different atmospheric general circulation model (AGCM) outputs for 6000 years ago. Results, The three simulations generally showed F. sylvatica to have potentially been as widespread 6000 years ago as it is today, which gives a profound mismatch with pollen-based reconstructions of the F. sylvatica distribution at that time. The results indicate that drier conditions during the growing season 6000 years ago could have caused a restriction of the range in the south. Poorer growth conditions with consequently reduced competitive ability were modelled for large parts of France. Main conclusions, Consideration of the entire European range of F. sylvatica showed that no single driving force could account for the observed distributional limits 6000 years ago, or the pattern of spread during the Holocene. Climatic factors, particularly drought during the growing season, are the likely major determinants of the potential range. Climatic factors are regionally moderated by competition, disturbance effects and the intrinsically slow rate of population increase of F. sylvatica. Dynamic vegetation modelling is needed to account for potentially important competitive interactions and their relationship with changing climate. We identify uncertainties in the climate and pollen data, as well as the bioclimatic model, which suggest that the current study does not identify whether or not climate determined the distribution of F. sylvatica 6000 years ago. Pollen data are better suited for comparison with relative abundance gradients rather than absolute distributional limits. These uncertainties from a study of the past, where we have information about plant distribution and abundance, argue for extreme caution in making forecasts for the future using equilibrium models. [source] In vitro biostability evaluation of polyurethane composites in acidic, basic, oxidative, and neutral solutionsJOURNAL OF BIOMEDICAL MATERIALS RESEARCH, Issue 2 2008SuPing Lyu Abstract New and improved properties can often be achieved by compounding two or more different but compatible materials. But, can failure possibility also be increased by such a compounding strategy? In this article, we compared the in vitro biostability of composites with that of the pure polymer. We tested three model composites in oxidative, acidic, basic, and neutral solutions. We found that oxidation degradation was much more profound in the composites than in the corresponding pure polymer. This degradation seemed to be an intrinsic property of composite materials. We also observed the well documented interfacial debonding between filler and matrix and its effects on the mechanical reinforcement of the hydrated composites. The improvements in acid and base resistance were also observed. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2008 [source] A Single-Dose Placebo-Controlled Study of AMG 162, a Fully Human Monoclonal Antibody to RANKL, in Postmenopausal WomenJOURNAL OF BONE AND MINERAL RESEARCH, Issue 7 2004Pirow J Bekker Abstract The safety and bone antiresorptive effect of a single subcutaneous dose of AMG 162, a human monoclonal antibody to RANKL, was investigated in 49 postmenopausal women. AMG 162 is a potent antiresorptive agent for diseases such as osteoporosis. Introduction: RANKL is an essential osteoclastic differentiation and activation factor. Materials and Methods: The bone antiresorptive activity and safety of AMG 162, a fully human monoclonal antibody to RANKL, were evaluated in postmenopausal women in this randomized, double-blind, placebo-controlled, single-dose, dose escalation study. Six cohorts of eight to nine women were randomly assigned to receive a single subcutaneous injection of either AMG 162 or placebo (3:1 ratio). AMG 162 doses were 0.01, 0.03, 0.1, 0.3, 1.0, and 3.0 mg/kg. Subjects were followed up to 6 months in all cohorts and 9 months in the three highest dose cohorts. Second morning void urinary N-telopeptide/creatinine (NTX; Osteomark), serum NTX, and serum bone-specific alkaline phosphatase (BALP, Ostase) were assessed as bone turnover markers. Results and Conclusions: Forty-nine women were enrolled. A single subcutaneous dose of AMG 162 resulted in a dose-dependent, rapid (within 12 h), profound (up to 84%), and sustained (up to 6 months) decrease in urinary NTX. At 6 months, there was a mean change from baseline of ,81% in the 3.0 mg/kg AMG 162 group compared with ,10% in the placebo group; serum NTX changes were ,56% and 2%, respectively. BALP levels did not decrease remarkably until after 1 month, indicating that the effect of AMG 162 is primarily antiresorptive. Intact parathyroid hormone (PTH) levels increased up to ,3-fold after 4 days in the 3.0 mg/kg dose group, but returned toward baseline with follow-up. Albumin-adjusted serum calcium did not decrease >10% on average in any group, and no subject had values below 2 mmol/liter. AMG 162 was well tolerated. No related serious adverse events occurred. No clinically meaningful laboratory changes, other than those described above, were observed. In summary, a single subcutaneous dose of AMG 162 resulted in a dose-dependent rapid and sustained decrease from baseline in bone turnover and could be an effective and convenient treatment for osteoporosis. [source] Experience with over 1000 Implanted Ventricular Assist DevicesJOURNAL OF CARDIAC SURGERY, Issue 3 2008Evgenij V. Potapov M.D. We present our experience since 1987. Subjects and Methods: Between July 1987 and December 2006, 1026 VADs were implanted in 970 patients. Most of them were men (81.9%). The indications were: cardiomyopathy (n = 708), postcardiotomy heart failure (n = 173), acute myocardial infarction (n = 36), acute graft failure (n = 45), a VAD problem (n = 6), and others (n = 2). Mean age was 46.1 (range 3 days to 78) years. In 50.5% of the patients the VAD implanted was left ventricular, in 47.9% biventricular, and in 1.5% right ventricular. There were 14 different types of VAD. A total artificial heart was implanted in 14 patients. Results: Survival analysis showed higher early mortality (p < 0.05) in the postcardiotomy group (50.9%) than in patients with preoperative profound cardiogenic shock (31.1%) and patients with preoperative end-stage heart failure without severe shock (28.9%). A total of 270 patients were successfully bridged to heart transplantation (HTx). There were no significant differences in long-term survival after HTx among patients with and without previous VAD. In 76 patients the device could be explanted after myocardial recovery. In 72 patients the aim of implantation was permanent support. During the study period 114 patients were discharged home. Currently, 54 patients are on a device. Conclusions: VAD implantation may lead to recovery from secondary organ failure. Patients should be considered for VAD implantation before profound, possibly irreversible, cardiogenic shock occurs. In patients with postcardiotomy heart failure, a more efficient algorithm should be developed to improve survival. With increased experience, more VAD patients can participate in out-patient programs. [source] Sequence-specific potentiation of topoisomerase II inhibitors by the histone deacetylase inhibitor suberoylanilide hydroxamic acidJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 2 2004Douglas C. Marchion Abstract Acetylation of histones leads to conformational changes of DNA. We have previously shown that the histone deacetylase (HDAC) inhibitor, suberoylanilide hydroxamic acid (SAHA), induced cell cycle arrest, differentiation, and apoptosis. In addition to their antitumor effects as single agents, HDAC inhibitors may cause conformational changes in the chromatin, rendering the DNA more vulnerable to DNA damaging agents. We examined the effects of SAHA on cell death induced by topo II inhibitors in breast cancer cell lines. Topo II inhibitors stabilize the topo II,DNA complex, resulting in DNA damage. Treatment of cells with SAHA promoted chromatin decondensation associated with increased nuclear concentration and DNA binding of the topo II inhibitor and subsequent potentiation of DNA damage. While SAHA-induced histone hyperacetylation occurred as early as 4 h, chromatin decondensation was most profound at 48 h. SAHA-induced potentiation of topo II inhibitors was sequence-specific. Pre-exposure of cells to SAHA for 48 h was synergistic, whereas shorter pre-exposure periods abrogated synergy and exposure of cells to SAHA after the topo II inhibitor resulted in antagonistic effects. Synergy was not observed in cells with depleted topo II levels. These effects were not limited to specific types of topo II inhibitors. We propose that SAHA significantly potentiates the DNA damage induced by topo II inhibitors; however, synergy is dependent on the sequence of drug administration and the expression of the target. These findings may impact the clinical development of combining HDAC inhibitors with DNA damaging agents. © 2004 Wiley-Liss, Inc. [source] Children's and young people's experiences of chronic renal disease: a review of the literature, methodological commentary and an alternative proposalJOURNAL OF CLINICAL NURSING, Issue 6 2006Philip Darbyshire MN Aim., The aims of this paper were to review and critique existing research literature on children's and young people's experiences of chronic renal disease and to propose alternative approaches that may be more fruitful in addressing existing research shortcomings. Background., Chronic renal disease, which results in approximately 1·6,4 new cases per year per million population in the 0,15 years age group, is a serious illness that causes severe and irreversible reduction in kidney function. Despite modern medical advances, its significance and implications for the lives of the children and young people concerned are profound. Method., Salient literature for this review was obtained using the major health and social science electronic databases such as Medline, CINAHL, Psyclit and Sociofile. Manual searching of relevant books, journals and ,grey literature', combined with the genealogy approach, extended and strengthened the search. Conclusions., Research in this area focuses mainly on two areas, namely psychological adjustment and adaptation to end-stage renal disease. This research is grounded within a framework of empirical psychology that values objectivity, measurement and quantification. This predominantly psychometric approach is critiqued for simplifying the complex experience of end-stage renal disease and for pathologizing children and young people with this disease. We identify a significant gap in the research literature, namely the lack of research that takes into account these children's and young peoples'own perspectives of their experiences. Relevance to clinical practice., Chronic renal disease has a significant impact on children's and young people's lives. Understanding the experiences of these children is important for the provision of effective healthcare. Conducting child-centred qualitative research in this area would allow us to explore vital questions of meaning, perception and understanding. If health and social care organizations claim to provide ,consumer-focused' services, it behoves us to develop first a clearer understanding of the lives and experiences of children and families who seek our help and to use this knowledge and understanding to plan and provide more grounded and responsive services. [source] Foreign investment: Impact on China's economyJOURNAL OF CORPORATE ACCOUNTING & FINANCE, Issue 6 2010Roger Y. W. Tang Foreign direct investment (FDI) has been a key driver of economic growth, globalization of business, and the expansion of international trade. And in today's age of the Internet and globalization, the impact of FDI and foreign-invested enterprises (FIEs) on a hosting country's economy will be more profound than it was in the twentieth century. Given all that, what roles are FIEs playing in the economy of the world's most populous country-China? And what are the implications for investors? © 2010 Wiley Periodicals, Inc. [source] Preliminary evaluation of a scale to assess cognitive function in adults with Down's syndrome: the Prudhoe Cognitive Function TestJOURNAL OF INTELLECTUAL DISABILITY RESEARCH, Issue 3 2003D. W. K. Kay Abstract Background In the clinical diagnosis of dementia in Down's syndrome (DS), it may be difficult to distinguish between cognitive deterioration and the various degrees of pre-existing intellectual disability (ID). Serial measurements of both cognitive function and behaviour are required. The aim of the present study was to evaluate the performance of non-demented adults with DS on a subject-directed instrument, the Prudhoe Cognitive Function Test (PCFT), preliminary to its serial use in a prospective study. Methods From 1985 to 1986, 85 non-demented hospitalized adults with DS were interviewed using the PCFT. The Adaptive Behavior Scale (ABS) was administered to the carers. The subjects' levels of ID (graded from mild through moderate, severe and profound to untestable) were based on their scores on the Stanford,Binet Intelligence Scale, as reported in the medical records, and the relationship between level of disability and performance on the PCFT and ABS, and their respective domains, was examined. Results Both scales produced a wide range of scores and the correlation between them was highly significant. Both scales correlated highly significantly with the degree of ID, but more subjects with high levels (i.e. profound to untestable) of disability obtained very low or zero scores on the PCFT and its domains than on the ABS. Conclusions The PCFT provides a reliable quantitative measure of cognitive function in subjects with DS, and could be a useful adjunct to the diagnosis of dementia in prospective studies. However, the almost uniformly low scores obtained by those with high levels of ID suggests that its power to detect cognitive decline will be limited to those who are less disabled, while the ABS may be more useful than the PCFT in detecting deterioration in people with profound ID. [source] | ||||||||||||||||||||||||||||||||||||||||||||||