OBJECTIVE: To determine the pharmacokinetics of bromide in sheep after single intravenous (IV) and oral (PO) doses. PROCEDURE: Sixteen Merino sheep were randomly assigned to two treatment groups and ...given 120 mg/kg bromide, as sodium bromide IV or potassium bromide PO. Serum bromide concentrations were determined by colorimetric spectrophotometry. RESULTS: After IV administration the maximum concentration (Cₘₐₓ) was 822.11 ± 93.61 mg/L, volume of distribution (Vd) was 0.286 ± 0.031 L/kg and the clearance (Cl) was 0.836 ± 0.255 mL/h/kg. After PO administration the Cₘₐₓwas 453.86 ± 43.37 mg/L and the time of maximum concentration (Tₘₐₓ) was 108 ± 125 h. The terminal half‐life (t½) of bromide after IV and PO administration was 387.93 ± 115.35 h and 346.72 ± 94.05 h, respectively. The oral bioavailability (F) of bromide was 92%. No adverse reactions were noted in either treatment group during this study. The concentration versus time profiles exhibited secondary peaks, suggestive of gastrointestinal cyclic redistribution of the drug. CONCLUSIONS AND CLINICAL RELEVANCE: When administered PO, bromide in sheep has a long half‐life (t½) of approximately 14 days, with good bioavailability. Potassium bromide is a readily available, affordable salt with a long history of medical use as an anxiolytic, sedative and antiseizure therapy in other species. There are a number of husbandry activities and flock level neurological conditions, including perennial ryegrass toxicosis, in which bromide may have therapeutic or prophylactic application.
The Visual Physics Analysis (VISPA) software is a toolbox for accessing analysis software via the web. It is based on latest web technologies and provides a powerful extension mechanism that enables ...to interface a wide range of applications. It especially meets the demands of sophisticated experiment-specific use cases that focus on physics data analyses and typically require a high degree of interactivity. As an example, we developed a data inspector which is capable of browsing interactively through event content of several data formats, e.g., MiniAOD which is utilized by the CMS collaboration. Visual control of a chain of user analysis modules as well as visualization of user specific workflows support users in rather complex analyses at the level of ttH cross section measurements. The VISPA extension mechanism is also used to embed external web-based applications which benefit from dynamic allocation of user-defined computing resources via SSH. For example, by wrapping the JSROOT project, ROOT files located on any remote machine can be inspected directly through a VISPA server instance. We present the techniques of the extension mechanism and corresponding applications.
The U.S. territory of Guam attracts thousands of military and civilian divers annually and is home to the only recompression facility within a 5,000-km radius that accepts critically injured dive ...casualties. As recompression chambers are confined spaces and standard use of electrical cardioversion cannot be used, cardiac resuscitation at depth must deviate from advanced cardiovascular life support (ACLS) algorithms. Furthermore, many hyperbaric chambers that accept dive casualties are in remote locations, a situation that requires providers to approach cardiac resuscitation in a different way when compared to an in-hospital or ICU setting. This presents a challenge to trained medical and diving professionals. We present two contrasting vignettes of diving injuries initially responsive to appropriate treatment but then deteriorating during recompression therapy and ultimately requiring resuscitation at depth. Additionally, we explore the physiologic basis of resuscitation in a hyperbaric environment as it relates to the treatment of cardiac arrest at depth. This review critically examines the current guidelines in place for emergency cardiac resuscitation in a hyperbaric chamber followed by recommendations for the key steps in the sequence of care.
VISPA provides a graphical front-end to computing infrastructures giving its users all functionality needed for working conditions comparable to a personal computer. It is a framework that can be ...extended with custom applications to support individual needs, e.g. graphical interfaces for experiment-specific software. By design, VISPA serves as a multipurpose platform for many disciplines and experiments as demonstrated in the following different use-cases. A GUI to the analysis framework OFFLINE of the Pierre Auger collaboration, submission and monitoring of computing jobs, university teaching of hundreds of students, and outreach activity, especially in CERN's open data initiative. Serving heterogeneous user groups and applications gave us lots of experience. This helps us in maturing the system, i.e. improving the robustness and responsiveness, and the interplay of the components. Among the lessons learned are the choice of a file system, the implementation of websockets, efficient load balancing, and the fine-tuning of existing technologies like the RPC over SSH. We present in detail the improved server setup and report on the performance, the user acceptance and the realized applications of the system.
The energy modulation of 1.7-GeV electrons by femtosecond laser pulses was studied at the BESSY II “femtoslicing” source, a facility commissioned in 2004 for the purpose of producing sub-100 fs x-ray ...pulses. As a test case for future seeded free-electron lasers, the laser-electron interaction was investigated as function of various laser and electron beam parameters using different experimental methods.
A critical aspect of the opioid epidemic is its effect on the ability of opioid-dependent parents to care for their children. In this article we investigate the association between the rate of ...removals of children from their homes and the opioid prescription rate in Florida counties during 2012-15. We performed a panel data analysis of opioid prescriptions that also controlled for the prescription rates of benzodiazepines and stimulants and for other risk factors for child removal. We found that a one-standard-deviation increase in the opioid prescription rate was associated with a 32 percent increase in the removal rate for parental neglect. When we obtained subset samples by percentage of white residents, the estimated relationships were approximately twice as large in the counties with the highest concentration of whites than in the counties with the lowest. Policy makers should consider the opioid epidemic's effects on child welfare when determining the appropriate public health response.
Adaptive cellular immunity is initiated by antigen-specific interactions between T lymphocytes and dendritic cells (DCs). Plasmacytoid DCs (pDCs) support antiviral immunity by linking innate and ...adaptive immune responses. Here we examined pDC spatiotemporal dynamics during viral infection to uncover when, where, and how they exert their functions. We found that pDCs accumulated at sites of CD8+ T cell antigen-driven activation in a CCR5-dependent fashion. Furthermore, activated CD8+ T cells orchestrated the local recruitment of lymph node-resident XCR1 chemokine receptor-expressing DCs via secretion of the XCL1 chemokine. Functionally, this CD8+ T cell-mediated reorganization of the local DC network allowed for the interaction and cooperation of pDCs and XCR1+ DCs, thereby optimizing XCR1+ DC maturation and cross-presentation. These data support a model in which CD8+ T cells upon activation create their own optimal priming microenvironment by recruiting additional DC subsets to the site of initial antigen recognition.
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•CXCR3 and CCR5 selectively control intranodal pDC migration•CD8+ T cells instruct pDC recruitment via CCL3 and CCL4•CD8+ T cells directly recruit XCR1+ DCs via XCL1•Active colocalization of XCR1+ DCs and pDCs supports DC cooperativity
pDCs and XCR1+ dendritic cells are critical for the generation of antiviral CD8+ T cell responses. Brewitz and colleagues demonstrate that primed CD8+ T cells reorganize the intranodal dendritic cell network to optimize pDC and XCR1+ DC cooperativity and thereby enhance CD8+ T cell immunity.
An important effect of the current opioid epidemic is on children whose parents are unable to provide appropriate care. We employ quarterly, county-level data for California for 2009–2016 to study ...the relationship between foster care entries and opioid misuse by their parents. Our linear regression analysis includes both county and time fixed effects and controls related to child removal risk. We improve on the limited existing research in the area by analyzing higher frequency data, examining a proximal measure of opioid abuse, and allowing for differential associations by urbanicity. We found a positive association between the rate of child removals and the rate of residents who were cumulatively prescribed a high dose of opioids (>90 morphine milligram equivalents (MMEs) per day) during the quarter. A one standard deviation in this rate is associated with a roughly 9% increase in the overall removal rate. We further found that the association between removals and high MMEs is especially pronounced in rural areas and largely not existent in urban areas. Our results provide a more precise estimate of the relationship between the potential for opioid misuse and child welfare.
•Child welfare is an under-studied effect of opioid misuse.•We use quarterly, county-level data for California on child removals and opioid use.•We observe significant variation in opioid prescribing behavior across the state.•There is a positive association in rural counties adjacent to metropolitan areas.