Pulmonary outcomes following specialized respiratory management for acute cervical spinal cord injury: a retrospective analysis.

Study designRetrospective analysis.ObjectivesTo identify multivariate interactions of respiratory function that are sensitive to spinal cord injury level and pharmacological treatment to promote strategies that increase successful liberation from mechanical ventilation.SettingUnited States regional spinal cord injury (SCI) treatment center.MethodsRetrospective chart review of patients consecutively admitted to Santa Clara Valley Medical Center between May 2013 and December 2014 for ventilator weaning with C1-C5 American Spinal Injury Association Impairment Scale (AIS) A or B SCI, <3 months from injury and who had a tracheostomy in place. A nonlinear, categorical principal component analysis (NL-PCA) was performed to test the multivariate interaction of respiratory outcomes from patients (N=36) being weaned off ventilator support after acute SCI with (N=15) or without (N=21) theophylline treatment.ResultsIn total, 36 patients met inclusion criteria (2 C1, 5 C2, 11 C3, 14 C4 and 4 C5). The NL-PCA returned three independent components that accounted for 95% of the variance in the data set. Multivariate general linear models hypothesis tests revealed a significant syndromic interaction between theophylline treatment and SCI level (Wilks' Lambda, P=0.028, F (12,64)=2.116, η2=0.256, 1-β=0.838), with post hoc testing demonstrating a significant interaction on PC1, explained by a positive correlation between improved forced vital capacity and time it took to reach 16 h of ventilator-free breathing. Thirty-three patients (92%) achieved 16 h of ventilator-free breathing (VFB) and 30 patients (83%) achieved 24 h of VFB.ConclusionsWe suspect that some portion of the high success rate of ventilator weaning may be attributable to theophylline use in higher cervical SCI, in addition to our aggressive regimen of high volume ventilation, medication optimization and pulmonary toilet (positive pressure treatments and mechanical insufflation-exsufflation)

Representative bureaucracy: does female police leadership affect gender-based violence arrests?

Representative bureaucracy theory postulates that passive representation leads to active representation of minority groups. This article investigates the passive representation of female police officers at leadership levels and the active representation of women vis-a-vis gender-based violence arrest rates in the UK. Much of the extant research on representative bureaucracy is located at street level, with evidence showing that discretionary power of minority bureaucrats can lead to active representation. This article is focused on leadership levels of a public bureaucracy. The empirical research is based upon a panel dataset of female police officers as an independent variable and gender-based violence arrest rates as a dependent variable. The analysis reveals that there is little evidence of active representation of women by female police leadership

Magneto-optical coupling in whispering-gallery-mode resonators

We demonstrate that yttrium iron garnet microspheres support optical whispering gallery modes similar to those in non-magnetic dielectric materials. The direction of the ferromagnetic moment tunes both the resonant frequency via the Voigt effect as well as the degree of polarization rotation via the Faraday effect. An understanding of the magneto-optical coupling in whispering gallery modes, where the propagation direction rotates with respect to the magnetization, is fundamental to the emerging field of cavity optomagnonics.Engineering and Physical Sciences Research Council (Grant IDs: EP/M50693X/1, EP/L027151/1), European Research Council (Grant ID: 648613), Hitachi (research fellowship), Royal Society (University Research Fellowship), Winton programme for the Physics of SustainabilityThis is the author accepted manuscript. The final version is available from the American Physical Society via http://dx.doi.org/10.1103/PhysRevA.92.06384

Violent video games and morality: a meta-ethical approach

This paper considers what it is about violent video games that leads one reasonably minded person to declare "That is immoral" while another denies it. Three interpretations of video game content a re discussed: reductionist, narrow, and broad. It is argued that a broad interpretation is required for a moral objection to be justified. It is further argued that understanding the meaning of moral utterances – like "x is immoral" – is important to an understanding of why there is a lack of moral consensus when it comes to the content of violent video games. Constructive ecumenical expressivism is presented as a means of explaining what it is that we are doing when we make moral pronouncements and why, when it comes to video game content, differing moral attitudes abound. Constructive ecumenical expressivism is also presented as a means of illuminating what would be required for moral consensus to be achieved

Liver transplantation for type I and type IV glycogen storage disease

Progressive liver failure or hepatic complications of the primary disease led to orthotopic liver transplantation in eight children with glycogen storage disease over a 9-year period. One patient had glycogen storage disease (GSD) type I (von Gierke disease) and seven patients had type IV GSD (Andersen disease). As previously reported [19], a 16.5-year-old-girl with GSD type I was successfully treated in 1982 by orthotopic liver transplantation under cyclosporine and steroid immunosuppression. The metabolic consequences of the disease have been eliminated, the renal function and size have remained normal, and the patient has lived a normal young adult life. A late portal venous thrombosis was treated successfully with a distal splenorenal shunt. Orthotopic liver transplantation was performed in seven children with type N GSD who had progressive hepatic failure. Two patients died early from technical complications. The other five have no evidence of recurrent hepatic amylopectinosis after 1.1–5.8 postoperative years. They have had good physical and intellectual maturation. Amylopectin was found in many extrahepatic tissues prior to surgery, but cardiopathy and skeletal myopathy have not developed after transplantation. Postoperative heart biopsies from patients showed either minimal amylopectin deposits as long as 4.5 years following transplantation or a dramatic reduction in sequential biopsies from one patient who initially had dense myocardial deposits. Serious hepatic derangement is seen most commonly in types T and IV GSD. Liver transplantation cures the hepatic manifestations of both types. The extrahepatic deposition of abnormal glycogen appears not to be problematic in type I disease, and while potentially more threatening in type IV disease, may actually exhibit signs of regression after hepatic allografting

Absolute Humidity and the Seasonal Onset of Influenza in the Continental United States

Here, the authors demonstrate that variations of absolute humidity explain both the onset of wintertime influenza transmission and the overarching seasonality of this pathogen in temperate regions

Biogenesis of the inner membrane complex is dependent on vesicular transport by the alveolate specific GTPase Rab11B

Apicomplexan parasites belong to a recently recognised group of protozoa referred to as Alveolata. These protists contain membranous sacs (alveoli) beneath the plasma membrane, termed the Inner Membrane Complex (IMC) in the case of Apicomplexa. During parasite replication the IMC is formed de novo within the mother cell in a process described as internal budding. We hypothesized that an alveolate specific factor is involved in the specific transport of vesicles from the Golgi to the IMC and identified the small GTPase Rab11B as an alveolate specific Rab-GTPase that localises to the growing end of the IMC during replication of Toxoplasma gondii. Conditional interference with Rab11B function leads to a profound defect in IMC biogenesis, indicating that Rab11B is required for the transport of Golgi derived vesicles to the nascent IMC of the daughter cell. Curiously, a block in IMC biogenesis did not affect formation of sub-pellicular microtubules, indicating that IMC biogenesis and formation of sub-pellicular microtubules is not mechanistically linked. We propose a model where Rab11B specifically transports vesicles derived from the Golgi to the immature IMC of the growing daughter parasites

Antigenic Diversity, Transmission Mechanisms, and the Evolution of Pathogens

Pathogens have evolved diverse strategies to maximize their transmission fitness. Here we investigate these strategies for directly transmitted pathogens using mathematical models of disease pathogenesis and transmission, modeling fitness as a function of within- and between-host pathogen dynamics. The within-host model includes realistic constraints on pathogen replication via resource depletion and cross-immunity between pathogen strains. We find three distinct types of infection emerge as maxima in the fitness landscape, each characterized by particular within-host dynamics, host population contact network structure, and transmission mode. These three infection types are associated with distinct non-overlapping ranges of levels of antigenic diversity, and well-defined patterns of within-host dynamics and between-host transmissibility. Fitness, quantified by the basic reproduction number, also falls within distinct ranges for each infection type. Every type is optimal for certain contact structures over a range of contact rates. Sexually transmitted infections and childhood diseases are identified as exemplar types for low and high contact rates, respectively. This work generates a plausible mechanistic hypothesis for the observed tradeoff between pathogen transmissibility and antigenic diversity, and shows how different classes of pathogens arise evolutionarily as fitness optima for different contact network structures and host contact rates

The role of clathrin in post-golgi trafficking in toxoplasma gondii

Apicomplexan parasites are single eukaryotic cells with a highly polarised secretory system that contains unique secretory organelles (micronemes and rhoptries) that are required for host cell invasion. In contrast, the role of the endosomal system is poorly understood in these parasites. With many typical endocytic factors missing, we speculated that endocytosis depends exclusively on a clathrin-mediated mechanism. Intriguingly, in Toxoplasma gondii we were only able to observe the endogenous clathrin heavy chain 1 (CHC1) at the Golgi, but not at the parasite surface. For the functional characterisation of Toxoplasma gondii CHC1 we generated parasite mutants conditionally expressing the dominant negative clathrin Hub fragment and demonstrate that CHC1 is essential for vesicle formation at the trans-Golgi network. Consequently, the functional ablation of CHC1 results in Golgi aberrations, a block in the biogenesis of the unique secretory microneme and rhoptry organelles, and of the pellicle. However, we found no morphological evidence for clathrin mediating endocytosis in these parasites and speculate that they remodelled their vesicular trafficking system to adapt to an intracellular lifestyle