886 resultados para Skidmore, Stanley


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Many children are cared for on a full-time basis by relatives or adult friends, rather than their biological parents, and often in response to family crises. These kinship care arrangements have received increasing attention from the social science academy and social care professions. However, more information is needed on informal kinship care that is undertaken without official ratification by welfare agencies and often unsupported by the state. This article presents a comprehensive, narrative review of international, research literature on informal, kinship care to address this gap. Using systematic search and review protocols, it synthesises findings regarding: (i) the way that informal kinship care is defined and conceptualised; (ii) the needs of the carers and children; and (iii) ways of supporting this type of care. A number of prominent themes are highlighted including the lack of definitional clarity; the various adversities experienced by the families; and the requirement to understand the interface between formal and informal supports. Key messages are finally identified to inform the development of family friendly policies, interventions, and future research.

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ADAM17 (where ADAM is 'a disintegrin and metalloproteinase') can rapidly modulate cell-surface signalling events by the proteolytic release of soluble forms of proligands for cellular receptors. Many regulatory pathways affect the ADAM17 sheddase activity, but the mechanisms for the activation are still not clear. We have utilized a cell-based ADAM17 assay to show that thiol isomerases, specifically PDI (protein disulfide isomerase), could be responsible for maintaining ADAM17 in an inactive form. Down-regulation of thiol isomerases, by changes in the redox environment (for instance as elicited by phorbol ester modulation of mitochondrial reactive oxygen species) markedly enhanced ADAM17 activation. On the basis of ELISA binding studies with novel fragment antibodies against ADAM17 we propose that isomerization of the disulfide bonds in ADAM17, and the subsequent conformational changes, form the basis for the modulation of ADAM17 activity. The shuffling of disulfide bond patterns in ADAMs has been suggested by a number of recent adamalysin crystal structures, with distinct disulfide bond patterns altering the relative orientations of the domains. Such a mechanism is rapid and reversible, and the role of thiol isomerases should be investigated further as a potential factor in the redox regulation of ADAM17.

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Like humans, mice exhibit polymorphism in the N-acetylation of aromatic amines, many of which are toxic and/or carcinogenic. Mice have three N-acetyltransferase (Nat) genes, Nat1, Nat2 and Nat3, and Nat2 is known to be polymorphic. There is a dramatic difference in the acetylation of NAT2 substrates by blood from fast (C57BL/6J) compared with slow acetylator (A/J) mice. However, the acetylation of these substrates by liver cytosols from the two strains is very similar. In order to determine whether the expression of the NAT2 protein corresponded with the activities measured, a polyclonal antipeptide antisera was raised against the C-terminal decapeptide of NAT2 and characterized using recombinant murine NAT2 antigen. Enzyme-linked immunosorbent assays (ELISAs) demonstrated that the anti-NAT2 antiserum bound in a concentration-dependent fashion to recombinant NAT2. Immunochemical analysis of mouse liver cytosols from C57BL/6J or A/J livers indicated that the level of NAT2 protein expressed in the two strains was similar. Immunohistochemical staining of C57BL/6J liver with anti-NAT2 antiserum showed that NAT2 was expressed in hepatocytes throughout the liver although the intensity of staining in the perivenous (centrilobular) region was higher than that in the periportal region. NAT2 was also detected in epithelial cells in the lung, kidney, bladder, small intestine and skin as well as in erythrocytes and lymphocytes in the spleen and hair follicles and sebaceous glands in the skin. Characterization of the distribution of NAT2 will be of value in elucidating the role of polymorphic N-acetylation in protecting the organism from environmental insults as well as in endogenous metabolism.

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Whole genome sequencing (WGS) technology holds great promise as a tool for the forensic epidemiology of bacterial pathogens. It is likely to be particularly useful for studying the transmission dynamics of an observed epidemic involving a largely unsampled 'reservoir' host, as for bovine tuberculosis (bTB) in British and Irish cattle and badgers. BTB is caused by Mycobacterium bovis, a member of the M. tuberculosis complex that also includes the aetiological agent for human TB. In this study, we identified a spatio-temporally linked group of 26 cattle and 4 badgers infected with the same Variable Number Tandem Repeat (VNTR) type of M. bovis. Single-nucleotide polymorphisms (SNPs) between sequences identified differences that were consistent with bacterial lineages being persistent on or near farms for several years, despite multiple clear whole herd tests in the interim. Comparing WGS data to mathematical models showed good correlations between genetic divergence and spatial distance, but poor correspondence to the network of cattle movements or within-herd contacts. Badger isolates showed between zero and four SNP differences from the nearest cattle isolate, providing evidence for recent transmissions between the two hosts. This is the first direct genetic evidence of M. bovis persistence on farms over multiple outbreaks with a continued, ongoing interaction with local badgers. However, despite unprecedented resolution, directionality of transmission cannot be inferred at this stage. Despite the often notoriously long timescales between time of infection and time of sampling for TB, our results suggest that WGS data alone can provide insights into TB epidemiology even where detailed contact data are not available, and that more extensive sampling and analysis will allow for quantification of the extent and direction of transmission between cattle and badgers. © 2012 Biek et al.

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Summary
Background
The ability to carry out a neurological examination and make an appropriate differential diagnosis is one of the mainstays of our final Bachelor of Medicine (MB) exam; however, with the introduction of objective structured clinical examinations (OSCEs) it has become impossible to arrange for adequate numbers of suitable real patients to participate in the exam.

Context
It is vital that newly qualified doctors can perform a basic neurological examination, interpret the physical signs and formulate a differential diagnosis.

It is vital that newly qualified doctors can perform a basic neurological examination

Innovation
Since 2010 we have introduced an objective structured video examination (OSVE) of a neurological examination of a real patient as part of our final MB OSCE exam. The students view clips of parts of the examination process. They answer questions on the signs that are demonstrated and formulate a differential diagnosis.

Implications
This type of station is logistically a lot easier to organise than a large number of real patients at different examination sites. The featured patients have clearly demonstrated signs and, as every student sees the same patient, are perfectly standardised. It is highly acceptable to examiners and performed well as an assessment tool. There are, however, certain drawbacks in that we are not examining the student's examination technique or their interaction with the patient. Also, certain signs, in particular the assessment of muscle tone and power, are more difficult for a student to estimate in this situation

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BACKGROUND: Ras signaling regulates a number of important processes in the heart, including cell growth and hypertrophy. Although it is known that defective Ras signaling is associated with Noonan, Costello, and other syndromes that are characterized by tumor formation and cardiac hypertrophy, little is known about factors that may control it. Here we investigate the role of Ras effector Ras-association domain family 1 isoform A (RASSF1A) in regulating myocardial hypertrophy.

METHODS AND RESULTS: A significant downregulation of RASSF1A expression was observed in hypertrophic mouse hearts, as well as in failing human hearts. To further investigate the role of RASSF1A in cardiac (patho)physiology, we used RASSF1A knock-out (RASSF1A(-)(/)(-)) mice and neonatal rat cardiomyocytes with adenoviral overexpression of RASSF1A. Ablation of RASSF1A in mice significantly enhanced the hypertrophic response to transverse aortic constriction (64.2% increase in heart weight/body weight ratio in RASSF1A(-)(/)(-) mice compared with 32.4% in wild type). Consistent with the in vivo data, overexpression of RASSF1A in cardiomyocytes markedly reduced the cellular hypertrophic response to phenylephrine stimulation. Analysis of molecular signaling events in isolated cardiomyocytes indicated that RASSF1A inhibited extracellular regulated kinase 1/2 activation, likely by blocking the binding of Raf1 to active Ras.

CONCLUSIONS: Our data establish RASSF1A as a novel inhibitor of cardiac hypertrophy by modulating the extracellular regulated kinase 1/2 pathway.

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Gold nanoparticle radiosensitization represents a novel technique in enhancement of ionising radiation dose and its effect on biological systems. Variation between theoretical predictions and experimental measurement is significant enough that the mechanism leading to an increase in cell killing and DNA damage is still not clear. We present the first experimental results that take into account both the measured biodistribution of gold nanoparticles at the cellular level and the range of the product electrons responsible for energy deposition. Combining synchrotron-generated monoenergetic X-rays, intracellular gold particle imaging and DNA damage assays, has enabled a DNA damage model to be generated that includes the production of intermediate electrons. We can therefore show for the first time good agreement between the prediction of biological outcomes from both the Local Effect Model and a DNA damage model with experimentally observed cell killing and DNA damage induction via the combination of X-rays and GNPs. However, the requirement of two distinct models as indicated by this mechanistic study, one for short-term DNA damage and another for cell survival, indicates that, at least for nanoparticle enhancement, it is not safe to equate the lethal lesions invoked in the local effect model with DNA damage events.

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This study describes an investigation into the characteristics, needs and experiences of kinship foster carers in Northern Ireland. By adopting a mixed-methods approach with 54 carers, a number of salient themes was captured. The respondents were predominantly grandparents who experienced a significant incidence of health-related issues. The cohort also endured high levels of stress, particularly at the beginning stage of the foster placement. Consequently, their need for practical, emotional and respite support was most evident. In terms of the children for whom they cared, many required help at school, and some presented with challenging emotions and behaviours. Overall, these findings emphasised the importance of relationship-based social work and demonstration of accurate empathy to the carer.

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Embedding a double barrier resonant tunnelling diode (RTD) in a unipolar InGaAlAs optical waveguide gives rise to a very low driving voltage electroabsorption modulator (EAM) at optical wavelengths around 1550 nm. The presence of the RTD within the waveguide core introduces high non- linearity and negative di erential resistance in the current±voltage (I±V) characteristic of the waveguide. This makes the electric ®eld distribution across the waveguide core strongly dependent on the bias voltage: when the current decreases from the peak to the valley, there is an increase of the electric ®eld across the depleted core. The electric ®eld enhancement in the core-depleted layer causes the Franz±Keldysh absorption band-edge to red shift, which is responsible for the electroabsorption e ect. High-frequency ac signals as low as 100mV can induce electric ®eld high-speed switching, producing substantial light modulation (up to 15 dB) at photon energies slightly lower than the waveguide core band-gap energy. The key di erence between this device and conventional p-i-n EAMs is that the tunnelling characteristics of the RTD are employed to switch the electric ®eld across the core-depleted region; the RTD- EAM has in essence an integrated electronic ampli®er and, therefore, requires considerably less switching power.

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The basic mechanism underlying electric field switching produced by a resonant tunneling diode (RTD) is analyzed and the theory compared with experimental results; agreement to within 12% is achieved. The electroabsorption modulator (EAM) device potential of this effect is explored in an optical waveguide configuration. It is shown that a RTD-EAM can provide significant absorption coefficient change, via the Franz– Keldysh effect, at appropriate optical communication wavelengths around 1550 nm and can achieve up to 28-dB optical modulation in a 200- m active length device. The advantage of the RTD-EAM over the conventional reverse-biased p–n junction EAM, is that the RTD-EAM has, in essence, an integrated electronic amplifier and, therefore, requires considerably less switching power.

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La recherche porte sur les changements que le journalisme a subis au fil du temps, et particulièrement sur les mutations de toutes sortes que connaît le journalisme sportif entre 1955 et 2006. Elle a pour objectif la mise en évidence des ressemblances et des dissemblances des pages sportives des deux époques étudiées et s'inscrit ainsi dans la lignée des recherches sur les changements paradigmatiques du journalisme, dont les théories ont été proposées par Colette Brin, Jean Charron et Jean de Bonville (1996, 2002, 2004). Le corpus est constitué des pages sportives du quotidien québécois La Presse de 1955 et de 2006. La date des deux journaux a été choisie en fonction d'un événement de référence, le match final de la Coupe Stanley, respectivement le 15 mars 1955 et le 20 juin 2006. Les méthodes retenues, une analyse de contenu et une analyse de textes, visent essentiellement à permettre l'atteinte de notre objectif principal, à savoir une étude comparative des pages sportives de 1955 et de 2006. Trois hypothèses ont été posées. La première, postulant l'existence de différences marquées entre 1955 et 2006, a été confirmée, puisque de nombreuses dissemblances ont été observées, particulièrement en ce qui a trait à l'aspect visuel des deux journaux et à la nature impressionniste du langage. La seconde hypothèse, liée à l'existence présumée d'une relation différente ente le journaliste et le lecteur, a également été largement confirmée. La troisième hypothèse, selon laquelle certains éléments caractéristiques du journalisme de communication allaient jaillir de l'analyse interprétative, a été partiellement confirmée. Les mises en garde de plusieurs chercheurs ainsi que les limites d'une telle recherche ne nous permettent pas d'affirmer l'existence effective du journalisme de communication, mais plutôt de faire ressortir certains points qui montrent que le journalisme contemporain semble aller dans la direction de la communication plutôt que celle de l'information.