Implementation of evidence-based practice for benign paroxysmal positional vertigo: DIZZTINCT– A study protocol for an exploratory stepped-wedge randomized trial

Abstract Background Benign paroxysmal positional vertigo (BPPV) is the most common peripheral vestibular disorder, and accounts for 8% of individuals with moderate or severe dizziness. BPPV patients experience substantial inconveniences and disabilities during symptomatic periods. BPPV therapeutic processes – the Dix-Hallpike Test (DHT) and the Canalith Repositioning Maneuver (CRM) – have an evidence base that is at the clinical practice guideline level. The most commonly used CRM is the modified Epley maneuver. The DHT is the gold standard test for BPPV and the CRM is supported by numerous randomized controlled trials and systematic reviews. Despite this, BPPV care processes are underutilized. Methods/design This is a stepped-wedge, randomized clinical trial of a multi-faceted educational and care-process-based intervention designed to improve the guideline-concordant care of patients with BPPV presenting to the emergency department (ED) with dizziness. The unit of randomization and target of intervention is the hospital. After an initial observation period, the six hospitals will undergo the intervention in five waves (two closely integrated hospitals will be paired). The order will be randomized. The primary endpoint is measured at the individual patient level, and is the presence of documentation of either the Dix-Hallpike Test or CRM. The secondary endpoints are referral to a health care provider qualified to treat dizziness for CRM and 90-day stroke rates following an ED dizziness visit. Formative evaluations are also performed to monitor and identify potential and actual influences on the progress and effectiveness of the implementation efforts. Discussion If this study safely increases documentation of the DHT/CRM, this will be an important step in implementing the use of these evidenced-based processes of care. Positive results will support conducting larger-scale follow-up studies that assess patient outcomes. The data collection also enables evaluation of potential and actual influences on the progress and effectiveness of the implementation efforts. Trial registration ClinicalTrials.gov, ID: NCT02809599 . The record was first available to the public on 22 June 2016 prior to the enrollment of the first patients in October 2016.https://deepblue.lib.umich.edu/bitstream/2027.42/146751/1/13063_2018_Article_3099.pd

Detection of Gamma Rays of Up to 50 TeV From the Crab Nebula

Gamma rays with energies greater than 7 TeV from the Crab pulsar/nebula have been observed at large zenith angles, using the Imaging Atmospheric Technique from Woomera, South Australia. CANGAROO data taken in 1992, 1993 and 1995 indicate that the energy spectrum extends up to at least 50 TeV, without a change of the index of the power law spectrum. The observed differential spectrum is \noindent $(2.01\pm 0.36)\times 10^{-13}(E/{7 TeV})^{-2.53 \pm 0.18} TeV^{-1}cm^{-2}s^{-1}$ between 7 TeV and 50 TeV. There is no apparent cut-off. The spectrum for photon energies above $\sim$10 TeV allows the maximum particle acceleration energy to be inferred, and implies that this unpulsed emission does not originate near the light cylinder of the pulsar, but in the nebula where the magnetic field is not strong enough to allow pair creation from the TeV photons. The hard gamma-ray energy spectrum above 10 TeV also provides information about the varying role of seed photons for the inverse Compton process at these high energies, as well as a possible contribution of $\pi ^{\circ}$-gamma rays from proton collisions.Comment: 19 pages, 4 figures, LaTeX2.09 with AASTeX 4.0 maros, to appear in Astrophys. J. Let

First E region observations of mesoscale neutral wind interaction with auroral arcs

We report the first observations of E region neutral wind fields and their interaction with auroral arcs at mesoscale spatial resolution during geomagnetically quiet conditions at Mawson, Antarctica. This was achieved by using a scanning Doppler imager, which can observe thermospheric neutral line-of-sight winds and temperatures simultaneously over a wide field of view. In two cases, the background E region wind field was perpendicular to an auroral arc, which when it appeared caused the wind direction within ∼50 km of the arc to rotate parallel along the arc, reverting to the background flow direction when the arc disappeared. This was observed under both westward and eastward plasma convection. The wind rotations occurred within 7–16 min. In one case, as an auroral arc propagated from the horizon toward the local zenith, the background E region wind field became significantly weaker but remained unaffected where the arc had not passed through. We demonstrate through modeling that these effects cannot be explained by height changes in the emission layer. The most likely explanation seems to be the greatly enhanced ion drag associated with the increased plasma density and localized ionospheric electric field associated with auroral arcs. In all cases, the F region neutral wind appeared less affected by the auroral arc, although its presence is clear in the data

Acute hypoxemia and vascular function in healthy humans.

Endothelium-dependent flow mediated dilation (FMD) and endothelium-independent dilation (GTN) are impaired at high altitude (5050 m), and FMD is impaired following acute exposure (<60-minutes) to normobaric hypoxia equivalent to ∼5050 m (∼FI O2  = 0.11). Whether glyceryl trinitrate (GTN)-induced dilation is impaired acutely, and whether FMD is impaired during milder hypoxia is unknown. Therefore, we assessed brachial FMD at baseline and following 30-minutes of mild (74 ± 2 mmHg PET O₂) and moderate (50 ± 3 mmHg PET O₂) normobaric hypoxia (n = 12) or normoxia (time-control trial; n = 10). We also assessed GTN-dilaiton following the hypoxic FMD tests and in normoxia on a separate control day (n = 8). Compared to normoxic baseline, reduction during mild and moderate hypoxic exposure were evident in FMD (mild vs moderate: -1.2 ± 1.1% vs. -3.1 ± 1.7%; P = 0.01) and GTN-dilation (-2.1 ± 1.0 vs. -4.2 ± 2.0; P = 0.01); the decline in FMD and GTN-dilation were greater during moderate hypoxia (P < 0.01). When allometrically corrected for baseline diameter and FMD shear rate under the curve (SRAUC ), relative FMD was attenuated in both conditions (mild vs moderate: 0.6 ± 0.9% vs. 0.8 ± 0.7%; P ≤ 0.01). Following 30-minutes of normoxic time-control, FMD was reduced (-0.6 ± 0.3%; P = 0.02). In summary, there was a graded impairment in FMD during mild and moderate hypoxic exposure, which appears to be influenced by shear patterns and incremental declines in smooth muscle vasodilator capacity (impaired GTN-dilation). Our findings from the normoxic controls study, suggest the decline in FMD in acute hypoxia also appears to be influenced by 30-minutes of supine rest/inactivity. This article is protected by copyright. All rights reserved

Prolonged post-faint hypotension can be reversed by dynamic tension

A severe variant of vasovagal syncope, observed during tilt tests and blood donation has recently been termed “prolonged post-faint hypotension” (PPFH). A 49-year-old male with a life-long history of severe fainting attacks underwent head-up tilt for 20 min, and developed syncope 2 min after nitroglycerine spray. He was unconscious for 40 s and asystolic for 22 s. For the first 2 min of recovery, BP and HR remained low (65/45 mmHg and 40 beats/min) despite passive leg-raising. Blood pressure (and symptoms) only improved following active bilateral leg flexion and extension (“dynamic tension”). During PPFH, when vagal activity is extreme, patients may require central stimulation as well as correction of venous return

Diverse animal models to examine potential role(s) and mechanism of endocrine disrupting chemicals on the tumor progression and prevention: Do they have tumorigenic or anti-tumorigenic property?

Acting as hormone mimics or antagonists in the interaction with hormone receptors, endocrine disrupting chemicals (EDCs) have the potentials of disturbing the endocrine system in sex steroid hormone-controlled organs and tissues. These effects may lead to the disruption of major regulatory mechanisms, the onset of developmental disorders, and carcinogenesis. Especially, among diverse EDCs, xenoestrogens such as bisphenol A, dioxins, and di(2-ethylhexyl)phthalate, have been shown to activate estrogen receptors (ERs) and to modulate cellular functions induced by ERs. Furthermore, they appear to be closely related with carcinogenicity in estrogen-dependant cancers, including breast, ovary, and prostate cancers. In in vivo animal models, prenatal exposure to xenoestrogens changed the development of the mouse reproductive organs and increased the susceptibility to further carcinogenic exposure and tumor occurence in adults. Unlike EDCs, which are chemically synthesized, several phytoestrogens such as genistein and resveratrol showed chemopreventive effects on specific cancers by contending with ER binding and regulating normal ER action in target tissues of mice. These results support the notion that a diet containing high levels of phytoestrogens can have protective effects on estrogen-related diseases. In spite of the diverse evidences of EDCs and phytoestrogens on causation and prevention of estrogen-dependant cancers provided in this article, there are still disputable questions about the dose-response effect of EDCs or chemopreventive potentials of phytoestrogens. As a wide range of EDCs including phytoestrogens have been remarkably increasing in the environment with the rapid growth in our industrial society and more closely affecting human and wildlife, the potential risks of EDCs in endocrine disruption and carcinogenesis are important issues and needed to be verified in detail

DNA Encoding an HIV-1 Gag/Human Lysosome-Associated Membrane Protein-1 Chimera Elicits a Broad Cellular and Humoral Immune Response in Rhesus Macaques

Previous studies of HIV-1 p55Gag immunization of mice have demonstrated the usefulness of targeting antigens to the cellular compartment containing the major histocompatibility complex type II (MHC II) complex molecules by use of a DNA antigen formulation encoding Gag as a chimera with the mouse lysosome-associated membrane protein (mLAMP/gag). In the present study, we have analyzed the magnitude and breadth of Gag-specific T-lymphocyte and antibody responses elicited in Rhesus macaques after immunization with DNA encoding a human LAMP/gag (hLAMP/gag) chimera. ELISPOT analyses indicated that the average Gag-specific IFN-γ response elicited by the hLAMP/gag chimera was detectable after only two or three naked DNA immunizations in all five immunized macaques and reached an average of 1000 spot-forming cells (SFC)/10(6) PBMCs. High IFN-γ ELISPOT responses were detected in CD8(+)-depleted cells, indicating that CD4(+) T-cells play a major role in these responses. The T-cell responses of four of the macaques were also tested by use of ELISPOT to 12 overlapping 15-amino acids (aa) peptide pools containing ten peptides each, encompassing the complete Gag protein sequence. The two Mamu 08 immunized macaques responded to eight and twelve of the pools, the Mamu B01 to six, and the other macaque to five pools indicating that the hLAMP/gag DNA antigen formulation elicits a broad T-cell response against Gag. Additionally, there was a strong HIV-1-specific IgG response. The IgG antibody titers increased after each DNA injection, indicating a strong amnestic B-cell response, and were highly elevated in all the macaques after three immunizations. Moreover, the serum of each macaque recognized 13 of the 49 peptides of a 20-aa peptide library covering the complete Gag amino acid sequence. In addition, HIV-1-specific IgA antibodies were present in the plasma and external secretions, including nasal washes. These data support the findings of increased immunogenicity of genetic vaccines encoded as LAMP chimeras, including the response to DNA vaccines by non-human primates

Using derivative logic to speculate on the future of the social investment market

This article pries open the black box of the social impact bond (SIB), the novel financial instrument at the heart of social investment. We discover that concrete information is currently limited and our method is thus more speculative. We address the obfuscation of the nomenclature of the instrument and explore the mechanics of SIBs to suggest that they are not simple bonds but rather also bear properties akin to those associated with derivative contracts. We speculate on possible developments of the market in these bonds by considering the history of some previous financial innovations, namely, collateralized debt obligations (CDOs) underpinned by microfinance loans and the short-lived policy analysis market. Our discussion leads us to reevaluate Goodhart’s law and the ways in which it operates in relation to SIBs. We conclude by suggesting that SIBs' inherent indifference to the underlying state of the world renders them ultimately unlikely to delivery improvements in public services

Physiological aspects of the determination of comprehensive arterial inflows in the lower abdomen assessed by Doppler ultrasound

Non-invasive measurement of splanchnic hemodynamics has been utilized in the clinical setting for diagnosis of gastro-intestinal disease, and for determining reserve blood flow (BF) distribution. However, previous studies that measured BF in a "single vessel with small size volume", such as the superior mesenteric and coeliac arteries, were concerned solely with the target organ in the gastrointestinal area, and therefore evaluation of alterations in these single arterial BFs under various states was sometimes limited to "small blood volumes", even though there was a relatively large change in flow. BF in the lower abdomen (BFAb) is potentially a useful indicator of the influence of comprehensive BF redistribution in cardiovascular and hepato-gastrointestinal disease, in the postprandial period, and in relation to physical exercise. BFAb can be determined theoretically using Doppler ultrasound by subtracting BF in the bilateral proximal femoral arteries (FAs) from BF in the upper abdominal aorta (Ao) above the coeliac trunk. Prior to acceptance of this method of determining a true BFAb value, it is necessary to obtain validated normal physiological data that represent the hemodynamic relationship between the three arteries. In determining BFAb, relative reliability was acceptably high (range in intra-class correlation coefficient: 0.85-0.97) for three arterial hemodynamic parameters (blood velocity, vessel diameter, and BF) in three repeated measurements obtained over three different days. Bland-Altman analysis of the three repeated measurements revealed that day-to-day physiological variation (potentially including measurement error) was within the acceptable minimum range (95% of confidence interval), calculated as the difference in hemodynamics between two measurements. Mean BF (ml/min) was 2951 ± 767 in Ao, 316 ± 97 in left FA, 313 ± 83 in right FA, and 2323 ± 703 in BFAb, which is in agreement with a previous study that measured the sum of BF in the major part of the coeliac, mesenteric, and renal arteries. This review presents the methodological concept that underlies BFAb, and aspects of its day-to-day relative reliability in terms of the hemodynamics of the three target arteries, relationship with body surface area, respiratory effects, and potential clinical usefulness and application, in relation to data previously reported in original dedicated research