In-office diagnostic arthroscopy for knee and shoulder intra-articular injuries its potential impact on cost savings in the United States

BACKGROUND: The purpose of this analysis was to determine whether in office diagnostic needle arthroscopy (Visionscope Imaging System [VSI]) can provide for improved diagnostic assessment and; more cost effective care. METHODS: Data on arthroscopy procedures in the US for deep seated pathology in the knee and shoulder were used (Calendar Year 2012). These procedures represent approximately 25-30% of all arthroscopic procedures performed annually. Sensitivities, specificities, positive predictive, and negative predictive values for MRI analysis of this deep seated pathology from systematic reviews and meta-analyses were used in assessing for false positive and false negative MRI findings. The costs of performing diagnostic and surgical arthroscopy procedures (using 2013 Medicare reimbursement amounts); costs associated with false negative findings; and the costs for treating associated complications arising from diagnostic and therapeutic arthroscopy procedures were then assessed. RESULTS: In patients presenting with medial meniscal pathology (ICD9CM diagnosis 836.0 over 540,000 procedures in CY 2012); use of the VSI system in place of MRI assessment (standard of care) resulted in a net cost savings to the system of $151 million. In patients presenting with rotator cuff pathology (ICD9CM 840.4 over 165,000 procedures in CY2012); use of VSI in place of MRI similarly saved$59 million. These savings were realized along with more appropriate care as; fewer patients were exposed to higher risk surgical arthroscopic procedures. CONCLUSIONS: The use of an in-office arthroscopy system can: possibly save the US healthcare system money; shorten the diagnostic odyssey for patients; potentially better prepare clinicians for arthroscopic surgery (when needed) and; eliminate unnecessary outpatient arthroscopy procedures, which commonly result in surgical intervention

A Synthetic Genetic Edge Detection Program

SummaryEdge detection is a signal processing algorithm common in artificial intelligence and image recognition programs. We have constructed a genetically encoded edge detection algorithm that programs an isogenic community of E. coli to sense an image of light, communicate to identify the light-dark edges, and visually present the result of the computation. The algorithm is implemented using multiple genetic circuits. An engineered light sensor enables cells to distinguish between light and dark regions. In the dark, cells produce a diffusible chemical signal that diffuses into light regions. Genetic logic gates are used so that only cells that sense light and the diffusible signal produce a positive output. A mathematical model constructed from first principles and parameterized with experimental measurements of the component circuits predicts the performance of the complete program. Quantitatively accurate models will facilitate the engineering of more complex biological behaviors and inform bottom-up studies of natural genetic regulatory networks

Non-neutralizing Antibodies May Contribute to Suppression of SIVmac239 Viremia in Indian Rhesus Macaques

The antiviral properties of broadly neutralizing antibodies against HIV are well-documented but no vaccine is currently able to elicit protective titers of these responses in primates. While current vaccine modalities can readily induce non-neutralizing antibodies against simian immunodeficiency virus (SIV) and HIV, the ability of these responses to restrict lentivirus transmission and replication remains controversial. Here, we investigated the antiviral properties of non-neutralizing antibodies in a group of Indian rhesus macaques (RMs) that were vaccinated with vif, rev, tat, nef, and env, as part of a previous study conducted by our group. These animals manifested rapid and durable control of viral replication to below detection limits shortly after SIVmac239 infection. Although these animals had no serological neutralizing activity against SIVmac239 prior to infection, their pre-challenge titers of Env-binding antibodies correlated with control of viral replication. To assess the contribution of anti-Env humoral immune responses to virologic control in two of these animals, we transiently depleted their circulating antibodies via extracorporeal plasma immunoadsorption and inhibition of IgG recycling through antibody-mediated blockade of the neonatal Fc receptor. These procedures reduced Ig serum concentrations by up to 80% and temporarily induced SIVmac239 replication in these animals. Next, we transferred purified total Ig from the rapid controllers into six vaccinated RMs one day before intrarectal challenge with SIVmac239. Although recipients of the hyperimmune anti-SIV Ig fraction were not protected from infection, their peak and chronic phase viral loads were significantly lower than those in concurrent unvaccinated control animals. Together, our results suggest that non-neutralizing Abs may play a role in the suppression of SIVmac239 viremia

The tropical rain belts with an annual cycle and a continent model intercomparison project: TRACMIP

This paper introduces the Tropical Rain belts with an Annual cycle and a Continent Model Intercomparison Project (TRACMIP). TRACMIP studies the dynamics of tropical rain belts and their response to past and future radiative forcings through simulations with 13 comprehensive and one simplified atmosphere models coupled to a slab ocean and driven by seasonally-varying insolation. Five idealised experiments, two with an aquaplanet setup and three with a setup with an idealized tropical continent, fill the space between prescribed-SST aquaplanet simulations and realistic simulations provided by CMIP5/6. The simulations reproduce key features of present-day climate and expected future climate change, including an annual-mean intertropical convergence zone (ITCZ) that is located north of the equator and Hadley cells and eddy-driven jets that are similar to present-day climate. Quadrupling CO2 leads to a northward ITCZ shift and preferential warming in Northern high-latitudes. The simulations show interesting CO2-induced changes in the seasonal excursion of the ITCZ and indicate a possible state-dependence of climate sensitivity. The inclusion of an idealized continent modulates both the control climate and the response to increased CO2; for example, it reduces the northward ITCZ shift associated with warming and, in some models, climate sensitivity. In response to eccentricity-driven orbital seasonal insolation changes, seasonal changes in oceanic rainfall are best characterized as a meridional dipole, while seasonal continental rainfall changes tend to be symmetric about the equator. This survey illustrates TRACMIP's potential to engender a deeper understanding of global and regional climate and to address questions on past and future climate

Increased Intestinal Permeability Correlates with Sigmoid Mucosa alpha-Synuclein Staining and Endotoxin Exposure Markers in Early Parkinson's Disease

Parkinson's disease (PD) is the second most common neurodegenerative disorder of aging. The pathological hallmark of PD is neuronal inclusions termed Lewy bodies whose main component is alpha-synuclein protein. The finding of these Lewy bodies in the intestinal enteric nerves led to the hypothesis that the intestine might be an early site of PD disease in response to an environmental toxin or pathogen. One potential mechanism for environmental toxin(s) and proinflammatory luminal products to gain access to mucosal neuronal tissue and promote oxidative stress is compromised intestinal barrier integrity. However, the role of intestinal permeability in PD has never been tested. We hypothesized that PD subjects might exhibit increased intestinal permeability to proinflammatory bacterial products in the intestine. To test our hypothesis we evaluated intestinal permeability in subjects newly diagnosed with PD and compared their values to healthy subjects. In addition, we obtained intestinal biopsies from both groups and used immunohistochemistry to assess bacterial translocation, nitrotyrosine (oxidative stress), and alpha-synuclein. We also evaluated serum markers of endotoxin exposure including LPS binding protein (LBP). Our data show that our PD subjects exhibit significantly greater intestinal permeability (gut leakiness) than controls. In addition, this intestinal hyperpermeability significantly correlated with increased intestinal mucosa staining for E. coli bacteria, nitrotyrosine, and alpha-synuclein as well as serum LBP levels in PD subjects. These data represent not only the first demonstration of abnormal intestinal permeability in PD subjects but also the first correlation of increased intestinal permeability in PD with intestinal alpha-synuclein (the hallmark of PD), as well as staining for gram negative bacteria and tissue oxidative stress. Our study may thus shed new light on PD pathogenesis as well as provide a new method for earlier diagnosis of PD and suggests potential therapeutic targets in PD subjects.Clinicaltrials.gov NCT01155492

Pre-synaptic modulation of quadriceps arthrogenic muscle inhibition

Arthrogenic muscle inhibition (AMI) impedes rehabilitation following knee joint injury by preventing activation of the quadriceps. AMI has been attributed to neuronal reflex activity in which altered afferent input originating from the injured joint results in a diminished efferent motor drive to the quadriceps muscles. Beginning to understand the mechanisms responsible for muscle inhibition following joint injury is vital to control or eliminate this phenomenon. Therefore, the purpose of this investigation is to determine if quadriceps AMI is mediated by a presynaptic regulatory mechanism. Eight adults participated in two sessions: in one session their knee was injected with saline and in the other session it was not. The maximum Hoffmann reflex (H-reflex), M-wave, reflex activation history, plasma epinephrine, and norepinephrine were recorded at: baseline, post needle stick, post lidocaine, and 25 and 45 min post effusion. Measures for the control condition were matched to the effusion condition. The percent of the unconditioned reflex amplitude for reflex activation history and the maximum H-reflex were decreased at 25 and 45 min post effusion as compared to measures taken at baseline, post needle stick, and post lidocaine ( P 0.05). No differences were detected at any time interval for any measure during the control admission ( P >0.05). Quadriceps AMI elicited via an experimental knee joint effusion is, at least in part, mediated by a presynaptic mechanism.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46099/1/167_2004_Article_547.pd

Multi-campaign ship and aircraft observations of marine cloud condensation nuclei and droplet concentrations

In-situ marine cloud droplet number concentrations (CDNCs), cloud condensation nuclei (CCN), and CCN proxies, based on particle sizes and optical properties, are accumulated from seven field campaigns: ACTIVATE; NAAMES; CAMP2EX; ORACLES; SOCRATES; MARCUS; and CAPRICORN2. Each campaign involves aircraft measurements, ship-based measurements, or both. Measurements collected over the North and Central Atlantic, Indo-Pacific, and Southern Oceans, represent a range of clean to polluted conditions in various climate regimes. With the extensive range of environmental conditions sampled, this data collection is ideal for testing satellite remote detection methods of CDNC and CCN in marine environments. Remote measurement methods are vital to expanding the available data in these difficult-to-reach regions of the Earth and improving our understanding of aerosol-cloud interactions. The data collection includes particle composition and continental tracers to identify potential contributing CCN sources. Several of these campaigns include High Spectral Resolution Lidar (HSRL) and polarimetric imaging measurements and retrievals that will be the basis for the next generation of space-based remote sensors and, thus, can be utilized as satellite surrogates

Non-Standard Errors

In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty: Non-standard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for better reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants