Pathologic changes in mice induced by subtilase cytotoxin, a potent new Escherichia coli AB(5) toxin that targets the endoplasmic reticulum

Subtilase cytotoxin (SubAB) is the prototype of a recently discovered AB₅ cytotoxin family produced by certain strains of Shiga toxigenic Escherichia coli (STEC). The catalytic A subunit is a highly specific subtilase-like serine protease that cleaves the endoplasmic reticulum chaperone BiP. The toxin is lethal for mice, but the pathology it induces is poorly understood. Here, we show that intraperitoneal injection of SubAB causes microangiopathic hemolytic anemia, thrombocytopenia, and renal impairment in mice-characteristics typical of Shiga toxin-induced hemolytic uremic syndrome. SubAB caused extensive microvascular thrombosis and other histologic damage in the brain, kidneys, and liver, as well as dramatic splenic atrophy. Peripheral blood leukocyte levels were increased at 24 h; there was also significant neutrophil infiltration in the liver, kidneys, and spleen and toxin-induced apoptosis at these sites. These findings raise the possibility that SubAB directly contributes to pathology in humans infected with strains of STEC that produce both Shiga toxin and SubAB.Hui Wang, James C. Paton, and Adrienne W. Pato

The abortion-crime link: evidence from England and Wales

We use panel data from 1983 to 1997 for the 42 police force areas in England and Wales to test the hypothesis that legalizing abortion contributes to lower crime rates. We provide an advance on previous work by focusing on the impact of possible endogeneity of effective abortion rates with respect to crime. Our use of U.K. data allows us to exploit regional differences in the provision of free abortions to identify abortion rates. When we use a similar model and estimation methodology, we are able to replicate the negative association between abortion rates and reported crime found by Donohue and Levitt for the U.S. However, when we allow for the potential endogeneity of effective abortion rates with respect to crime, we find no clear connection between the two.

Chandra X-Ray Spectroscopy Of The Very Early O Supergiant HD 93129A: Constraints On Wind Shocks And The Mass-Loss Rate

We present an analysis of both the resolved X-ray emission-line profiles and the broad-band X-ray spectrum of the O-2 If* star HD 93129A, measured with the Chandra High Energy Transmission Grating Spectrometer ( HETGS). This star is among the earliest and most massive stars in the Galaxy, and provides a test of the embedded wind-shock scenario in a very dense and powerful wind. A major new result is that continuum absorption by the dense wind is the primary cause of the hardness of the observed X-ray spectrum, while intrinsically hard emission from colliding wind shocks contributes less than 10 per cent of the X-ray flux. We find results consistent with the predictions of numerical simulations of the line-driving instability, including line broadening indicating an onset radius of X-ray emission of several tenths of R-*. Helium-like forbidden-to-intercombination line ratios are consistent with this onset radius, and inconsistent with being formed in a wind-collision interface with the star\u27s closest visual companion at a distance of 100 au. The broad-band X-ray spectrum is fitted with a dominant emission temperature of just kT = 0.6 keV along with significant wind absorption. The broad-band wind absorption and the line profiles provide two independent measurements of the wind mass-loss rate:. M = 5.2(-1.5)(+1.8) x 10(-6) and 6.8(-2.2)(+2.8) x 10(-6) M-circle dot yr(-1), respectively. This is the first consistent modelling of the X-ray line-profile shapes and broad-band X-ray spectral energy distribution in a massive star, and represents a reduction of a factor of 3-4 compared to the standard H alpha mass-loss rate that assumes a smooth wind

Enhancing scientific response in a crisis: evidence-based approaches from emergency management in New Zealand

Contemporary approaches to multi-organisational response planning for the management of complex volcanic crises assume that identifying the types of expertise needed provides the foundation for effective response. We discuss why this is only one aspect, and present the social, psychological and organizational issues that need to be accommodated to realize the full benefits of multi-agency collaboration. We discuss the need to consider how organizational culture, inter-agency trust, mental models, information management and communication and decision making competencies and processes, need to be understood and accommodated in crisis management planning and delivery. This paper discusses how these issues can be reconciled within superordinate (overarching) management structures designed to accommodate multi-agency response that incorporates decision-making inputs from both the response management team and the science advisors. We review the science advisory processes within New Zealand (NZ), and discuss lessons learnt from research into the inter-organisational response to historical eruptions and exercises in NZ. We argue that team development training is essential and review the different types of training and exercising techniques (including cross training, positional rotation, scenario planning, collaborative exercises, and simulations) which can be used to develop a coordinated capability in multiagency teams. We argue that to truly enhance the science response, science agencies must learn from the emergency management sector and embark on exercise and simulation programs within their own organisations, rather than solely participating as external players in emergency management exercises. We thus propose a science-led tiered exercise program, with example exercise scenarios, which can be used to enhance both the internal science response and the interagency response to a national or international event, and provide direction for the effective writing and conduct of these exercises

Undergraduate teaching in geriatric medicine: mapping the British Geriatrics Society undergraduate curriculum to Tomorrow's Doctors 2009

Introduction: in 2008, the British Geriatrics Society (BGS) developed the Recommended Undergraduate Curriculum in Geriatric Medicine. This was subsequently mapped to the second edition of Tomorrows' Doctors (TD2, 2003). Following the publication of the third edition of Tomorrow's Doctors in 2009 (TD3), the mapping exercise was repeated to verify the extent to which the updated General Medical Council recommendations supported teaching in ageing and geriatric medicine. Method: we analysed TD3 and identified 48 aspects of its general guidance that were relevant to the teaching of medicine for older people. We then mapped these to the 2009 BGS curriculum. Results: the BGS curriculum was supported in full by TD3. However, learning outcomes relating to the interpretation and conduct of research in TD3 had no corresponding outcomes in the BGS curriculum. Conclusion: the BGS curriculum for medical undergraduates continues to provide a specific and complete list of learning objectives, all of which could help to operationalise the general statements made in TD3 with relation to ageing and geriatric medicine. Learning outcomes in research in frail older patients have been added following this mapping exercise

How to increase earthquake and home fire preparedness: the fix-it intervention

Published, evaluated community intervention studies concerning natural hazard preparedness are rare. Most lack a rigorous methodology, thereby hampering the development of evidence-based interventions. This paper describes the rationale and methodology of a cross-cultural, longitudinal intervention study on earthquake and home fire preparedness, termed fix-it. The aim is to evaluate whether and how the intervention brings about behaviour change in the targeted communities in two coastal cities with high seismic risk: Seattle, USA and Izmir, Turkey. Participants are adult residents of these cities. The intervention group attends a 6-h workshop, which focuses on securing items in the household. The control group does not attend the workshop. All participants complete baseline and post-intervention, as well as 3- and 12-month follow-up assessments. The primary outcome measure is an observational measure of nine preparedness items for earthquake and fire in participants’ homes. This is evaluated alongside participants’ self-reports concerning their preparedness levels. Secondary outcomes are changes in levels of self-efficacy, perceived outcome, trust, corruption, empowerment, anxiety and social cohesion. Results from the first of the studies, conducted in Seattle in September 2015, indicate that while the fix-it intervention is effective, in the longer term, multi-hazard preparedness is increased by the mere act of going into people’s homes to observe their preparedness levels along with assessing self-reported preparedness and sociopsychological orientation towards natural hazards. This protocol and study aim to augment the empirical literature on natural hazard preparedness, informing national and international policy on delivery of evidence-based community interventions to promote multi-hazard preparedness in households

Gluelump Spectrum in the Bag Model

We explore the ordering of the lowest levels in a simple bag model of the ``gluelump'' of Michael and also discuss, again within the context of the bag model, the related problem of hybrid potentials in the limit of very small spacing between quark and anti-quark sources.Comment: 10 page

Discrete Nondeterministic Modeling of the Fas Pathway

Abstract: Computer modeling of molecular signaling cascades can provide useful insight into the underlying complexities of biological systems. We present a refined approach for the discrete modeling of protein interactions within the environment of a single cell. The technique we offer utilizes the Membrane Systems paradigm which, due to its hierarchical structure, lends itself readily to mimic the behavior of cells. Since our approach is nondeterministic and discrete, it provides an interesting contrast to the standard deterministic ordinary differential equations techniques. We argue that our approach may outperform ordinary differential equations when modeling systems with relatively low numbers of molecules – a frequent occurrence in cellular signaling cascades. Refinements over our previous modeling efforts include the addition of nondeterminism for handling reaction competition over limited reactants, increased efficiency in the storing and sorting of reaction waiting times, and modifications of the model reactions. Results of our discrete simulation of the type I and type II Fas-mediated apoptotic signaling cascade are illustrated and compared with two approaches: one based on ordinary differential equations and another based on the well-known Gillespie algorithm

Chemoreception and neuroplasticity in respiratory circuits

The respiratory central pattern generator must respond to chemosensory cues to maintain oxygen (O2) and carbon dioxide (CO2) homeostasis in the blood and tissues. To do this, sensorial cells located in the periphery and central nervous system monitor the arterial partial pressure of O2 and CO2 and initiate respiratory and autonomic reflex adjustments in conditions of hypoxia and hypercapnia. In conditions of chronic intermittent hypoxia (CIH), repeated peripheral chemoreceptor input mediated by the nucleus of the solitary tract induces plastic changes in respiratory circuits that alter baseline respiratory and sympathetic motor outputs and result in chemoreflex sensitization, active expiration, and arterial hypertension. Herein, we explored the hypothesis that the CIH-induced neuroplasticity primarily consists of increased excitability of pre-inspiratory/inspiratory neurons in the pre-Bötzinger complex. To evaluate this hypothesis and elucidate neural mechanisms for the emergence of active expiration and sympathetic overactivity in CIH-treated animals, we extended a previously developed computational model of the brainstem respiratory-sympathetic network to reproduce experimental data on peripheral and central chemoreflexes post-CIH. The model incorporated neuronal connections between the 2nd-order NTS neurons and peripheral chemoreceptors afferents, the respiratory pattern generator, and sympathetic neurons in the rostral ventrolateral medulla in order to capture key features of sympathetic and respiratory responses to peripheral chemoreflex stimulation. Our model identifies the potential neuronal groups recruited during peripheral chemoreflex stimulation that may be required for the development of inspiratory, expiratory and sympathetic reflex responses. Moreover, our model predicts that pre-inspiratory neurons in the pre-Bötzinger complex experience plasticity of channel expression due to excessive excitation during peripheral chemoreflex. Simulations also show that, due to positive interactions between pre-inspiratory neurons in the pre-Bötzinger complex and expiratory neurons in the retrotrapezoid nucleus, increased excitability of the former may lead to the emergence of the active expiratory pattern at normal CO2 levels found after CIH exposure. We conclude that neuronal type specific neuroplasticity in the pre-Bötzinger complex induced by repetitive episodes of peripheral chemoreceptor activation by hypoxia may contribute to the development of sympathetic over-activity and hypertension

Tree scattering amplitudes of the spin-4/3 fractional superstring I: the untwisted sectors

Scattering amplitudes of the spin-4/3 fractional superstring are shown to satisfy spurious state decoupling and cyclic symmetry (duality) at tree-level in the string perturbation expansion. This fractional superstring is characterized by the spin-4/3 fractional superconformal algebra---a parafermionic algebra studied by Zamolodchikov and Fateev involving chiral spin-4/3 currents on the world-sheet in addition to the stress-energy tensor. Examples of tree scattering amplitudes are calculated in an explicit c=5 representation of this fractional superconformal algebra realized in terms of free bosons on the string world-sheet. The target space of this model is three-dimensional flat Minkowski space-time with a level-2 Kac-Moody so(2,1) internal symmetry, and has bosons and fermions in its spectrum. Its closed string version contains a graviton in its spectrum. Tree-level unitarity (i.e., the no-ghost theorem for space-time bosonic physical states) can be shown for this model. Since the critical central charge of the spin-4/3 fractional superstring theory is 10, this c=5 representation cannot be consistent at the string loop level. The existence of a critical fractional superstring containing a four-dimensional space-time remains an open question.Comment: 42 pages, 4 figures, latex, IASSNS-HEP-93/57, CLNS-92/117