OKT3 and viral disease in pediatric liver transplant recipients

Seventy-four consecutive pediatric liver transplant recipients were reviewed to assess the effect of the monoclonal anti-T-lymphocyte antibody OKT3 on subsequent viral infection (9 patients were excluded due to postoperative demise during the 1st week). Twenty-two patients received OKT3 in addition to standard cyclosporine-prednisone immunosuppression for either steroid-resistant acute rejection (18) or to facilitate reduction of cyclosporine due to severe renal impairment (4). Invasive infections were diagnosed by histology or culture in tissue biopsies or bronchoalveolar lavage specimens. The overall incidence of viral infection was 58%, half of which was due to cytomegalovirus (CMV). Invasive viral disease was associated with increased mortality (37% vs. 3% p = 0.001). Viral-related deaths were due to CMV (5), disseminated adenovirus (3), disseminated enterovirus (1) and respiratory syncytial viral pneumonia (1). The use of OKT3 was associated with increased viral disease (59% vs. 33% p = 0.04) and invasive primary CMV disease (58% vs. 19% p = 0.04). Trends were observed toward increased overall viral infection (73% vs. 51% p = 0.08), primary CMV infection (58% vs. 25% p = 0.08) and overall mortality (27% vs. 9% p = 0.08) following OKT3 therapy. We conclude that pediatric liver transplant recipients who require OKT3 therapy may be at increased risk for invasive viral disease and especially invasive primary CMV disease

Delivering reform in English healthcare: an ideational perspective

A variety of perspectives has been put forward to understand reform across healthcare systems. Recently, some have called for these perspectives to give greater recognition to the role of ideational processes. The purpose of this article is to present an ideational approach to understanding the delivery of healthcare reform. It draws on a case of English healthcare reform – the Next Stage Review led by Lord Darzi – to show how the delivery of its reform proposals was associated with four ideational frames. These frames built on the idea of “progress” in responding to existing problems; the idea of “prevailing policy” in forming part of a bricolage of ideas within institutional contexts; the idea of “prescription” as top-down structural change at odds with local contexts; and the idea of “professional disputes” in challenging the notion of clinical engagement across professional groups. The article discusses the implications of these ideas in furthering our understanding of policy change, conflict and continuity across healthcare settings

Unified force law for granular impact cratering

Experiments on the low-speed impact of solid objects into granular media have been used both to mimic geophysical events and to probe the unusual nature of the granular state of matter. Observations have been interpreted in terms of conflicting stopping forces: product of powers of projectile depth and speed; linear in speed; constant, proportional to the initial impact speed; and proportional to depth. This is reminiscent of high-speed ballistics impact in the 19th and 20th centuries, when a plethora of empirical rules were proposed. To make progress, we developed a means to measure projectile dynamics with 100 nm and 20 us precision. For a 1-inch diameter steel sphere dropped from a wide range of heights into non-cohesive glass beads, we reproduce prior observations either as reasonable approximations or as limiting behaviours. Furthermore, we demonstrate that the interaction between projectile and medium can be decomposed into the sum of velocity-dependent inertial drag plus depth-dependent friction. Thus we achieve a unified description of low-speed impact phenomena and show that the complex response of granular materials to impact, while fundamentally different from that of liquids and solids, can be simply understood

An inhibitory pull-push circuit in frontal cortex.

Push-pull is a canonical computation of excitatory cortical circuits. By contrast, we identify a pull-push inhibitory circuit in frontal cortex that originates in vasoactive intestinal polypeptide (VIP)-expressing interneurons. During arousal, VIP cells rapidly and directly inhibit pyramidal neurons; VIP cells also indirectly excite these pyramidal neurons via parallel disinhibition. Thus, arousal exerts a feedback pull-push influence on excitatory neurons-an inversion of the canonical push-pull of feedforward input

Homicide and geographic access to gun dealers in the United States

<p>Abstract</p> <p>Background</p> <p>Firearms are the most commonly used weapon to commit homicide in the U.S. Virtually all firearms enter the public marketplace through a federal firearms licensee (FFL): a store or individual licensed by the federal government to sell firearms. Whether FFLs contribute to gun-related homicide in areas where they are located, in which case FFLs may be a homicide risk factor that can be modified, is not known.</p> <p>Methods</p> <p>Annual county-level data (1993–1999) on gun homicide rates and rates of FFLs per capita were analyzed using negative binomial regression controlling for socio-demographic characteristics. Models were run to evaluate whether the relation between rates of FFLs and rates of gun homicide varied over the study period and across counties according to their level of urbanism (defined by four groupings, as below). Also, rates of FFLs were compared against FS/S – which is the proportion of suicides committed by firearm and is thought to be a good proxy for firearm availability in a region – to help evaluate how well the FFL variable is serving as a way to proxy firearm availability in each of the county types of interest.</p> <p>Results</p> <p>In major cities, gun homicide rates were higher where FFLs were more prevalent (rate ratio [RR] = 1.70, 95% CI 1.03–2.81). This association increased (p < 0.01) from 1993 (RR = 1.69) to 1999 (RR = 12.72), due likely to federal reforms that eliminated low-volume dealers, making FFL prevalence a more accurate exposure measure over time. No association was found in small towns. In other cities and in suburbs, gun homicide rates were significantly lower where FFLs were more prevalent, with associations that did not change over the years of the study period. FFL prevalence was correlated strongly (positively) with FS/S in major cities only, suggesting that the findings for how FFL prevalence relates to gun homicide may be valid for the findings pertaining to major cities but not to counties of other types.</p> <p>Conclusion</p> <p>Modification of FFLs through federal, state, and local regulation may be a feasible intervention to reduce gun homicide in major cities.</p

Interdisciplinary research: putting the methods under the microscope

BACKGROUND: While the desirability of interdisciplinary inquiry has been widely acknowledged, indeed has become 'the mantra of science policy', the methods of interdisciplinary collaboration are opaque to outsiders and generally remain undescribed. DISCUSSION: Many have analysed interdisciplinarity, especially in relation to the creation of new disciplines and institutions. These analyses are briefly outlined. Still, there currently persists a silence about the methods of interdisciplinary collaboration itself, and the core of this paper proposes a template for such methods. SUMMARY: Breaking this silence – by making the methods of interdisciplinary projects transparent – could further invigorate interdisciplinary research

Correlates of comorbid anxiety and externalizing disorders in childhood obsessive compulsive disorder

The present study examines the influence of diagnostic comorbidity on the demographic, psychiatric, and functional status of youth with a primary diagnosis of obsessive compulsive disorder (OCD). Two hundred and fifteen children (ages 5–17) referred to a university-based OCD specialty clinic were compared based on DSM-IV diagnostic profile: OCD without comorbid anxiety or externalizing disorder, OCD plus anxiety disorder, and OCD plus externalizing disorder. No age or gender differences were found across groups. Higher OCD severity was found for the OCD + ANX group, while the OCD + EXT group reported greater functional impairment than the other two groups. Lower family cohesion was reported by the OCD + EXT group compared to the OCD group and the OCD + ANX group reported higher family conflict compared to the OCD + EXT group. The OCD + ANX group had significantly lower rates of tic disorders while rates of depressive disorders did not differ among the three groups. The presence of comorbid anxiety and externalizing psychopathology are associated with greater symptom severity and functional and family impairment and underscores the importance of a better understanding of the relationship of OCD characteristics and associated disorders. Results and clinical implications are further discussed

The not-so-barren ranges

© Thesis Eleven Pty, Ltd., SAGE Publications. This is an impressionistic and informal essay written near the end of a novelist's Australia Research Council funded research project: 'Developing narratives from language and stories indigenous to the south coast of Western Australia', and informed by how that research project morphed into an emphasis on revitalization of Noongar language, and the attempt to restore connections between a particular Creation Story and landscape in an area regarded as 'massacre territory'. A sympathetic reader might think of the topic as 'The Wirlomin Noongar Language and Stories Project meets The Barren Ranges'