Summary Background The 2014 Zaire Ebola virus outbreak highlighted the need for a safe, effective vaccine with a rapid onset of protection. We report the safety and immunogenicity of the recombinant ...vesicular stomatitis virus-Zaire Ebola virus envelope glycoprotein vaccine (rVSV∆G-ZEBOV-GP) across a 6 log10 dose range in two sequential cohorts. Methods In this phase 1b double-blind, placebo-controlled, dose-response study we enrolled and randomly assigned healthy adults (aged 18–61 years) at eight study sites in the USA to receive a single injection of vaccine or placebo, administered by intramuscular injection. In cohort 1, participants were assigned to receive 3 × 103 , 3 × 104 , 3 × 105 , or 3 × 106 PFU doses of rVSV∆G-ZEBOV-GP or placebo. In cohort 2, participants were assigned to receive 3 × 106 , 9 × 106 , 2 × 107 , or 1 × 108 PFU doses of rVSV∆G-ZEBOV-GP or placebo. Participants were centrally allocated by the study statistician to vaccine groups or placebo through computer-generated randomisation lists. The primary safety outcome was incidence of adverse events within 14 days in the modified intention-to-treat population (all randomly assigned participants who received vaccine or placebo), and the primary outcome for immunogenicity was IgG ELISA antibody titres at day 28 in the per-protocol population. Surveillance was enhanced for arthritis and dermatitis through to day 56. This study is registered with ClinicalTrials.gov , number NCT02314923. Findings Between Dec 26, 2014, and June 8, 2015, 513 participants were enrolled and randomly assigned; one was not immunised because of unsuccessful phlebotomy. In cohort 1, 256 participants received vaccine (3 × 103 n=64, 3 × 104 n=64, 3 × 105 n=64, or 3 × 106 PFU n=64) and 74 received placebo. In cohort 2, 162 participants received vaccine (3 × 106 n=20, 9 × 106 n=47, 2 × 107 n=47, or 1 × 108 PFU n=48) and 20 received placebo. Most adverse events occurred in the first day after vaccination, and were mild to moderate in intensity, of a short duration, and more frequent at high vaccine doses (9 × 106 PFU and greater). At the 2 × 107 PFU dose (used in phase 3 trials), the most common local adverse events versus placebo within the first 14 days were arm pain (57·4% 27 of 47 vs 7·4% seven of 94) and local tenderness (59·6% 28 of 47 vs 8·5% eight of 94). The most common systemic adverse events at the 2 × 107 PFU dose versus placebo, occurring in the first 14 days, were headache (46·8% 22 of 47 vs 27·7% 26 of 94), fatigue (38·3% 18 of 47 vs 19·1% 18 of 94), myalgia (34·0% 16 of 47 vs 10·6% 10 of 94), subjective fever (29·8% 14 of 47 vs 2·1% two of 94), shivering or chills (27·7% 13 of 47 vs 7·4% seven of 94), sweats (23·4% 11 of 47 vs 3·2% three of 94), joint aches and pain (19·1% nine of 47 vs 7·4% seven of 94), objective fever (14·9% seven of 47 vs 1·1% one of 94), and joint tenderness or swelling (14·9% seven of 47 vs 2·1% two of 94). Self-limited, post-vaccination arthritis occurred in 4·5% (19 of 418) of vaccinees (median onset 12·0 days IQR 10–14; median duration 8·0 days 6–15) versus 3·2% (three of 94) of controls (median onset 15·0 days 6–20; median duration 47·0 days 37–339), with no apparent dose relationship. Post-vaccination dermatitis occurred in 5·7% (24 of 418) of vaccinees (median onset 9·0 days IQR 2–12; median duration 7·0 days 4–9) versus 3·2% (three of 94) of controls (median onset 5·0 days 3–53; median duration 33·0 days 5–370). A low-level, transient, dose-dependent viraemia occurred in concert with early reactogenicity. Antibody responses were observed in most participants by day 14. IgG and neutralising antibody titres were dose-related (p=0·0003 for IgG ELISA and p<0·0001 for the 60% plaque-reduction neutralisation test PRNT60 by linear trend). On day 28 at the 2 × 107 PFU dose, the geometric mean IgG ELISA endpoint titre was 1624 (95% CI 1146–2302) and seroconversion was 95·7% (95% CI 85·5–98·8); the geometric mean neutralising antibody titre by PRNT60 was 250 (176–355) and seroconversion was 95·7% (85·5–98·8). These robust immunological responses were sustained for 1 year. Interpretation rVSV∆G-ZEBOV-GP was well tolerated and stimulated a rapid onset of binding and neutralising antibodies, which were maintained through to day 360. The immunogenicity results support selection of the 2 × 107 PFU dose. Funding Biomedical Advanced Research and Development Authority, US Department of Health and Human Services.
Human salmonellosis linked to contact with live poultry is an increasing public health concern. In 2012, eight unrelated outbreaks of human salmonellosis linked to live poultry contact resulted in ...517 illnesses. In July 2012, PulseNet, a national molecular surveillance network, reported a multistate cluster of a rare strain of Salmonella Braenderup infections which we investigated. We defined a case as infection with the outbreak strain, determined by pulsed-field gel electrophoresis, with illness onset from 25 July 2012–27 February 2013. Ill persons and mail-order hatchery (MOH) owners were interviewed using standardized questionnaires. Traceback and environmental investigations were conducted. We identified 48 cases in 24 states. Twenty-six (81%) of 32 ill persons reported live poultry contact in the week before illness; case-patients named 12 different MOHs from eight states. The investigation identified hatchery D as the ultimate poultry source. Sampling at hatchery D yielded the outbreak strain. Hatchery D improved sanitation procedures and pest control; subsequent sampling failed to yield Salmonella. This outbreak highlights the interconnectedness of humans, animals, and the environment and the importance of industry knowledge and involvement in solving complex outbreaks. Preventing these infections requires a ‘One Health’ approach that leverages expertise in human, animal, and environmental health.
Computed tomography of corpus luteal cysts Borders, Rebecca J; Breiman, Richard S; Yeh, Benjamin M ...
Journal of computer assisted tomography,
05/2004, Letnik:
28, Številka:
3
Journal Article
Recenzirano
To describe the computed tomography (CT) features of corpus luteal cysts.
We retrospectively identified 10 patients with a diagnosis of corpus luteal cysts established by ultrasound who had also ...undergone contemporaneous CT. A single attending radiologist, without knowledge of other clinical or radiologic findings, recorded the morphologic features of the cysts based on the CT images.
The corpus luteal cyst seen at sonography was visible at CT in all 10 patients. All cysts were unilocular, with a mean density of 25 HU (range, 12 to 45). The mean maximum axial cyst diameter was 2.2 cm (range, 1.4 to 2.9). The mean cyst wall thickness was 3 mm (range, 2 to 4). All cyst walls were crenulated. Cyst wall enhancement was hyperdense in 6 cases, isodense in 3 cases, and hypodense in 1 case. Free fluid was seen in 9 of 10 patients.
At CT, corpus luteal cysts are typically less than 3 cm in diameter and are characterized by a thick, crenulated, or hyperdense wall. Recognition of these CT findings should prevent misinterpretation or inappropriate management.
The purpose of this study is to identify the prevalence, location, and size of enlarged mediastinal lymph nodes in patients with chronic congestive heart failure and to correlate the presence of ...lymph node enlargement with cardiac ejection fraction.
Sixty-six consecutive, retrospectively identified patients underwent computer tomography (CT) imaging of the thorax as part of a routine work-up prior to cardiac transplantation from 1993 to 1996. CT images of 44 of these patients were independently examined by 3 radiologists for evidence of pulmonary edema, pleural effusions, and the presence, size, and location of lymph nodes >1 cm in short axis. Multigated acquisition (MUGA) scans were available for cardiac ejection fraction assessment in 38 of the 44 patients.
Twenty-nine (66%) patients had at least 1 mediastinal lymph node >1 cm. The mean ejection fraction was significantly less for patients with lymph node enlargement when compared with patients without lymph node enlargement (20% versus 35%; P < 0.01). Adenopathy was observed in 81% of patients with a calculated ejection fraction of <35%. No patient with an ejection fraction of >35% had lymph node enlargement. There was no correlation between pulmonary edema and the frequency of lymph node appearance. Sixty-three percent of the enlarged nodes were pretracheal, with a mean short axis diameter for all the enlarged nodes of 1.3 cm.
Enlarged mediastinal lymph nodes were observed in 81% of patients with a calculated ejection fraction of <35%, most commonly in the pretracheal group. The presence of the lymph nodes did not correlate with CT evidence of pulmonary edema.
After the Cold War, the US enjoyed such an uncontested or dominant superiority in every domain that the Department of Defense (DOD) could deploy forces when it wanted, assemble them where it wanted, ...and operate them as it wanted. Perhaps because of this history, combined with the objectives in the 2018 National Defense Strategy (NDS), DOD components have focused on the development of new offensive and lethal capabilities and concepts with the unstated assumption that, once developed, these capabilities would be available. Here, a scenario that will describe how these assumptions can adversely affect DOD force projection capabilities is offered.
The control of cryogenic temperatures is usually accomplished by a passive stage, exploiting the combined effect of a thermal mass connected to a thermal resistance; by an active control, often of a ...PID type, based on the combination of a dedicated sensor, a heater and a controller; or by a combination of the two. Such a system typically uses a controlled stage that is isolated from the source of the fluctuations by a thermal isolator. Controlled insertion of heat into this stage counters the temperature fluctuations reaching the stage. Inherent to this type of system is the insertion of heat into the controlled stage that eventually reaches the cold end of the cooler, reducing the net heat lift available. The larger the thermal isolation, the smaller the reduction of the net heat lift, but with the attendant increase in the interface temperature. Any scheme that can reduce the penalty associated with the loss of heat lift or the temperature offset would be attractive in terms of cooler performance. If the cooler system has a recuperative heat exchanger between the coldest heat sink and a higher temperature precooler, a different approach can be used. In this paper we describe a novel control approach capable of passively damping low frequency fluctuations, requiring minimal reduction of cooler heat lift and minimal temperature increase of the cold end interface. This alternative scheme is based on the idea of controlling the temperature of a section of the recuperative heat exchanger between the coldest precooler and the cold end of the cooler and it has been tested on a 20 K hydrogen sorption JT cooler.
A system has been implemented for measurement of red blood cell velocity in microvessels by using an optical Doppler technique. Ronchi rulings are used to stimulate a differential grating to ...translate red blood cell movement to light intensity variations. These variations are sensed by two photodiodes coupled in a resistive subtraction mode. The nonelectronic subtraction allows high transimpedance gains (2 X 10(9) V/I) while noise is held to a minimum (4.5 mv RMS in a 5-kHz bandwidth). To derive average velocity the average frequency determination of the amplified signal is performed with a thresholding frequency-to-voltage functional block. The velocimeter provides the typical performance features of an optical Doppler system, including high-frequency response, without the need for the complications of the laser Doppler technique or the requirement of custom micro-prism gratings. The device represents a cost-effective approach to intravital work, and offers significant improvements in performance over standard techniques.
Quantitative dual-energy radiographic absorptiometry (DRA) and dual-photon absorptiometry (DPA) were compared to determine the best means of assessing bone density. Both methods were used to evaluate ...the lumbar spine in 107 women (aged 35-84 years mean, 64 years) referred for evaluation of osteoporosis risk. High correlation was documented between measurements derived by the two techniques, with a .95 linear regression coefficient for the total spine density measurement. Age-related regression equations were similar in slope but manifested different intercepts. Bone mineral density values derived with DRA were consistently lower than those obtained with DPA (conversion equation: DPA density = 1.067 X DRA density + 0.163). Besides the inherent imperfections of each system, it was found that inaccurate identification of intervertebral spaces on the low-resolution DPA images introduced errors in patient data. DRA may replace DPA as the dedicated projectional densitometric procedure of choice for technical reasons, but at present a conversion equation must be used to compare DRA data to DPA data.
The production of ecdysteroid molting hormones by crustacean Y-organs is negatively regulated by a neuropeptide, molt-inhibiting hormone. It is generally agreed that molt-inhibiting hormone is ...produced and released by the eyestalk neuroendocrine system. In the present study, immunocytochemical methods were used to detect molt-inhibiting hormone immunoreactive neurons in eyestalk ganglia of the blue crab,
Callinectes sapidus. The primary antiserum used was generated against molt-inhibiting hormone of the green shore crab,
Carcinus maenas. A preliminary Western blot analysis indicated the antiserum binds molt-inhibiting hormone of
Callinectes sapidus. Using confocal and conventional immunofluorescence microscopy, molt-inhibiting hormone immunoreactivity was visualized in whole mounts and thin sections of
Callinectes sapidus eyestalk ganglia. Immunoreactivity was detected in 15–25 neurosecretory cell bodies in the medulla terminalis X-organ, their associated axons and collateral branches, and their axon terminals in the neurohemal sinus gland. The cellular organization of molt-inhibiting hormone immunoreactive neurons in blue crabs is generally similar to that reported for other crab species. The combined results suggest the cellular structure of the molt-inhibiting hormone neuroendocrine system is highly conserved among brachyurans.
Peripheral resistance was examined in the microcirculation of the rat cremaster muscle using a network-conserved parameter, power dissipation. Previous studies of peripheral resistance used ...network-sensitive parameters, and their interpretation is limited by tacit assumptions about the structure of the peripheral vasculature. Power dissipation is directly linked to the resistive process, providing a measure of resistance based on the actual hemodynamics of the network. The dissipation parameter was quantified with the usual vascular parameters of velocity and vessel segment length; 991 segment lengths were measured in 12 normotensive Wistar-Kyoto rats and 16 spontaneously hypertensive rats. Arterial power dissipation was significantly elevated over a wide range of vessel segments; blood flow ranged from 0.08 to 80 nl/sec. Since the largest vessels showed the greatest power dissipation, the organ resistance elevation seen in hypertension in the cremaster apparently is mediated by the larger vessels in the high flow range. Vessel segment length and number of dissipative vessels were unchanged. The increase in power dissipation was due to a network-averaged reduction in mean vessel diameter. Power dissipation also increased significantly in the fastest flowing venous microvessels (greater than 25 nl/sec), also due to a reduction in vessel segment diameter.
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