Publications by authors named "Clement R"

680 Publications

Do Hospital or Surgeon Volume Affect Outcomes After Surgical Management of Tibial Shaft Fractures?

J Orthop Trauma 2020 May;34(5):263-270

Orthopaedic Surgery, University of North Carolina, Chapel Hill, NC.

Objectives: To determine whether hospital and surgeon volume are associated with outcomes after operative fixation of tibial shaft fractures.

Methods: Adults (≥18 year old) who underwent operative fixation of diaphyseal tibial fractures were identified in the New York Statewide Planning and Research Cooperative System data set from 2001 to 2015. Reoperation, nonunion, and other adverse event rates were compared across surgeon and hospital volume using multivariable Cox proportional hazards regression, adjusting for clinical and demographic factors. Low-volume providers (lowest 20%) were compared with high-volume providers (highest 20%). Low volume constituted <5 cases/year for hospitals and 1 case/year for surgeons. High volume constituted ≥40 cases/year for hospitals and ≥8 cases/year for surgeons.

Results: Nine thousand one hundred forty-seven patients were included. Relative to high-volume surgeons, low-volume surgeons experienced slightly higher rates of pneumonia [2% vs. 1%, hazard ratio (HR) 2.50, 95% confidence interval (CI) 1.38-4.53, P = 0.003], and respiratory failure (5% vs. 3%, HR 1.88, 95% CI 1.30-2.71, P = 0.001). Compared with high-volume hospitals, low-volume hospitals experienced slightly lower rates of compartment syndrome (1% vs. 3%, HR 0.45, 95% CI 0.24-0.85, P = 0.01) and fasciotomies (3% vs. 7%, HR 0.57, 95% CI 0.38-0.85, P = 0.005). The rates of all other reoperations and adverse events compared among hospitals and surgeons were not significantly different.

Conclusions: We did not detect a clinically meaningful volume-outcome relationship for either surgeons or hospitals despite the use of a robust database with rigorous statistical methodology. Of note, these findings should not be applied to rare complex injuries such as those with extensive bone loss or articular extension, which are not well represented by this study population. Therefore, we conclude that typical tibial shaft fracture, including open or closed injuries, can be safely managed in the vast majority of orthopaedic settings and that this care does not necessarily require transfer to a specialty centers. Future research into orthopaedic volume-outcome relationships could be strengthened by the use of functional outcomes (which would likely require well-organized multicenter prospective registries).

Level Of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
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http://dx.doi.org/10.1097/BOT.0000000000001680DOI Listing
May 2020

Comparison between two- and three-dimensional scoring of zebrafish response to psychoactive drugs: identifying when three-dimensional analysis is needed.

PeerJ 2019 16;7:e7893. Epub 2019 Oct 16.

Department of Mechanical and Aerospace Engineering, New York University, Tandon School of Engineering, Brooklyn, NY, USA.

Zebrafish () have recently emerged as a valuable laboratory species in the field of behavioral pharmacology, where they afford rapid and precise high-throughput drug screening. Although the behavioral repertoire of this species manifests along three-dimensional (3D), most of the efforts in behavioral pharmacology rely on two-dimensional (2D) projections acquired from a single overhead or front camera. We recently showed that, compared to a 3D scoring approach, 2D analyses could lead to inaccurate claims regarding individual and social behavior of drug-free experimental subjects. Here, we examined whether this conclusion extended to the field of behavioral pharmacology by phenotyping adult zebrafish, acutely exposed to citalopram (30, 50, and 100 mg/L) or ethanol (0.25%, 0.50%, and 1.00%), in the novel tank diving test over a 6-min experimental session. We observed that both compounds modulated the time course of general locomotion and anxiety-related profiles, the latter being represented by specific behaviors (erratic movements and freezing) and avoidance of anxiety-eliciting areas of the test tank (top half and distance from the side walls). We observed that 2D projections of 3D trajectories (ground truth data) may introduce a source of unwanted variation in zebrafish behavioral phenotyping. Predictably, both 2D views underestimate absolute levels of general locomotion. Additionally, while data obtained from a camera positioned on top of the experimental tank are similar to those obtained from a 3D reconstruction, 2D front view data yield false negative findings.
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http://dx.doi.org/10.7717/peerj.7893DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6800527PMC
October 2019

Design and development of a robotic predator as a stimulus in conditioned place aversion for the study of the effect of ethanol and citalopram in zebrafish.

Behav Brain Res 2020 01 12;378:112256. Epub 2019 Oct 12.

Department of Mechanical and Aerospace Engineering, New York University, Tandon School of Engineering, 6 MetroTech Center, Brooklyn, NY, 11201, USA; Department of Biomedical Engineering, New York University, Tandon School of Engineering, 6 MetroTech Center, Brooklyn, NY, 11201, USA. Electronic address:

Zebrafish are becoming a species of choice in psychopharmacology, laying a promising path to refined pharmacological manipulations and high-throughput behavioral phenotyping. The field of robotics has the potential to accelerate progress along this path, by offering unprecedented means for the design and development of accurate and reliable experimental stimuli. In this work, we demonstrate, for the first time, the integration of robotic predators in place conditioning experiments. We hypothesized zebrafish to be capable of forming a spatial association under a simulated predation risk. We repeatedly exposed experimental subjects to a robotic heron impacting the water surface and then evaluated their spatial avoidance within the experimental tank in a subsequent predator-free test session. To pharmacologically validate the paradigm, we tested zebrafish in drug-free conditions (control groups) or in response to three different concentrations of citalopram (30, 50, and 100 mg/L) and ethanol (0.25, 0.50, and 1.00%). Experimental data indicate that, when tested in the absence of the conditioning stimulus, zebrafish displayed a marked preference for the bottom of the test tank, that is, the farthest location from the simulated attacks by the robotic heron. This conditioned geotaxis was reduced by the administration of citalopram in a linear dose-response curve and ethanol at the low concentration. Ultimately, our data demonstrate that robotic stimuli may represent valid conditioning tools and, thereby, aid the field of zebrafish psychopharmacology.
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http://dx.doi.org/10.1016/j.bbr.2019.112256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6893136PMC
January 2020

Experimental validation of force inference in epithelia from cell to tissue scale.

Sci Rep 2019 10 10;9(1):14647. Epub 2019 Oct 10.

Aix Marseille Univ, CNRS, IBDM, Turing Center for Living Systems, Marseille, France.

Morphogenesis relies on the active generation of forces, and the transmission of these forces to surrounding cells and tissues. Hence measuring forces directly in developing embryos is an essential task to study the mechanics of development. Among the experimental techniques that have emerged to measure forces in epithelial tissues, force inference is particularly appealing. Indeed it only requires a snapshot of the tissue, as it relies on the topology and geometry of cell contacts, assuming that forces are balanced at each vertex. However, establishing force inference as a reliable technique requires thorough validation in multiple conditions. Here we performed systematic comparisons of force inference with laser ablation experiments in four epithelial tissues from two animals, the fruit fly and the quail. We show that force inference accurately predicts single junction tension, tension patterns in stereotyped groups of cells, and tissue-scale stress patterns, in wild type and mutant conditions. We emphasize its ability to capture the distribution of forces at different scales from a single image, which gives it a critical advantage over perturbative techniques such as laser ablation. Overall, our results demonstrate that force inference is a reliable and efficient method to quantify the mechanical state of epithelia during morphogenesis, especially at larger scales when inferred tensions and pressures are binned into a coarse-grained stress tensor.
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http://dx.doi.org/10.1038/s41598-019-50690-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6787039PMC
October 2019

Coopted temporal patterning governs cellular hierarchy, heterogeneity and metabolism in neuroblast tumors.

Elife 2019 09 30;8. Epub 2019 Sep 30.

Aix Marseille Univ, CNRS, IBDM, Equipe Labellisée LIGUE Contre le Cancer, Marseille, France.

It is still unclear what drives progression of childhood tumors. During larval development, asymmetrically-dividing neural stem cells, called neuroblasts, progress through an intrinsic temporal patterning program that ensures cessation of divisions before adulthood. We previously showed that temporal patterning also delineates an early developmental window during which neuroblasts are susceptible to tumor initiation (Narbonne-Reveau et al., 2016). Using single-cell transcriptomics, clonal analysis and numerical modeling, we now identify a network of twenty larval temporal patterning genes that are redeployed within neuroblast tumors to trigger a robust hierarchical division scheme that perpetuates growth while inducing predictable cell heterogeneity. Along the hierarchy, temporal patterning genes define a differentiation trajectory that regulates glucose metabolism genes to determine the proliferative properties of tumor cells. Thus, partial redeployment of the temporal patterning program encoded in the cell of origin may govern the hierarchy, heterogeneity and growth properties of neural tumors with a developmental origin.
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http://dx.doi.org/10.7554/eLife.50375DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6791719PMC
September 2019

Metagenomic deep sequencing reveals association of microbiome signature with functional biases in bovine mastitis.

Sci Rep 2019 09 19;9(1):13536. Epub 2019 Sep 19.

The Laboratory of Microbial Genetics and Bioinformatics, Department of Microbiology, University of Dhaka, Dhaka, 1000, Bangladesh.

Milk microbiomes significantly influence the pathophysiology of bovine mastitis. To assess the association between microbiome diversity and bovine mastitis, we compared the microbiome of clinical mastitis (CM, n = 14) and healthy (H, n = 7) milk samples through deep whole metagenome sequencing (WMS). A total of 483.38 million reads generated from both metagenomes were analyzed through PathoScope (PS) and MG-RAST (MR), and mapped to 380 bacterial, 56 archaeal, and 39 viral genomes. We observed distinct shifts and differences in abundance between the microbiome of CM and H milk in phyla Proteobacteria, Bacteroidetes, Firmicutes and Actinobacteria with an inclusion of 68.04% previously unreported and/or opportunistic strains in CM milk. PS identified 363 and 146 bacterial strains in CM and H milk samples respectively, and MR detected 356 and 251 bacterial genera respectively. Of the identified taxa, 29.51% of strains and 63.80% of genera were shared between both metagenomes. Additionally, 14 archaeal and 14 viral genera were found to be solely associated with CM. Functional annotation of metagenomic sequences identified several metabolic pathways related to bacterial colonization, proliferation, chemotaxis and invasion, immune-diseases, oxidative stress, regulation and cell signaling, phage and prophases, antibiotic and heavy metal resistance that might be associated with CM. Our WMS study provides conclusive data on milk microbiome diversity associated with bovine CM and its role in udder health.
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http://dx.doi.org/10.1038/s41598-019-49468-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6753130PMC
September 2019

Follicular regulatory T cells control humoral and allergic immunity by restraining early B cell responses.

Nat Immunol 2019 10 2;20(10):1360-1371. Epub 2019 Sep 2.

Transplantation Research Center, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Follicular regulatory T (T) cells have specialized roles in modulating follicular helper T (T) cell activation of B cells. However, the precise role of T cells in controlling antibody responses to foreign antigens and autoantigens in vivo is still unclear due to a lack of specific tools. A T cell-deleter mouse was developed that selectively deletes T cells, facilitating temporal studies. T cells were found to regulate early, but not late, germinal center (GC) responses to control antigen-specific antibody and B cell memory. Deletion of T cells also resulted in increased self-reactive immunoglobulin (Ig) G and IgE. The increased IgE levels led us to interrogate the role of T cells in house dust mite models. T cells were found to control T13 cell-induced IgE. In vivo, loss of T cells increased house-dust-mite-specific IgE and lung inflammation. Thus, T cells control IgG and IgE responses to vaccines, allergens and autoantigens, and exert critical immunoregulatory functions before GC formation.
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http://dx.doi.org/10.1038/s41590-019-0472-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6754271PMC
October 2019

A Comparison of Individual Learning and Social Learning in Zebrafish Through an Ethorobotics Approach.

Front Robot AI 2019 14;6:71. Epub 2019 Aug 14.

Department of Mechanical and Aerospace Engineering, New York University, Tandon School of Engineering, Brooklyn, NY, United States.

Social learning is ubiquitous across the animal kingdom, where animals learn from group members about predators, foraging strategies, and so on. Despite its prevalence and adaptive benefits, our understanding of social learning is far from complete. Here, we study observational learning in zebrafish, a popular animal model in neuroscience. Toward fine control of experimental variables and high consistency across trials, we developed a novel robotics-based experimental test paradigm, in which a robotic replica demonstrated to live subjects the correct door to join a group of conspecifics. We performed two experimental conditions. In the individual training condition, subjects learned the correct door without the replica. In the social training condition, subjects observed the replica approaching both the incorrect door, to no effect, and the correct door, which would open after spending enough time close to it. During these observations, subjects could not actively follow the replica. Zebrafish increased their preference for the correct door over the course of 20 training sessions, but we failed to identify evidence of social learning, whereby we did not register significant differences in performance between the individual and social training conditions. These results suggest that zebrafish may not be able to learn a route by observation, although more research comparing robots to live demonstrators is needed to substantiate this claim.
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http://dx.doi.org/10.3389/frobt.2019.00071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7805697PMC
August 2019

Lung density measurement in postmortem computed tomography: a new tool to assess immediate neonatal breath in suspected neonaticides.

Int J Legal Med 2020 May 8;134(3):1159-1166. Epub 2019 Jul 8.

Forensic Medicine Department, Centre Hospitalier Universitaire de Nantes, 30 Boulevard Jean Monnet, 44000, Nantes, France.

Intro: Evidence of breath after birth is one of the main forensic issues in suspected neonaticide. Hydrostatic test (HT) and pathological examination are currently used to assess it, but they are not entirely reliable or immediately available.

Objective: To determine the performance of postmortem computed tomography (PMCT) to assess neonatal breath in suspected neonaticide, by comparing lung CT attenuation values between live birth and stillbirth cases, in correlation with HT and pathology.

Method: Cases of suspected neonaticides who underwent a PMCT and complete forensic autopsy with an HT were retrospectively selected from the databases of four French Forensic Medicine Departments. The diagnosis of vitality (i.e., stillbirth or live birth) was based on the pathological examination and/or a combination of arguments, including HT result. Lung density on CT was measured in Hounsfield units (HU) by ROIs drawn in both pulmonary parenchymas.

Results: Eleven patients were included, six live birth and five stillbirth cases. The result of HT was concordant with pathological examination when available (seven cases). Mean lung densities in live birth cases (- 173 HU [- 255; - 91 CI 95%]) were significantly lower than in stillbirth cases (40 HU [28; 52 CI 95%]) (p < 0.05), with a very high degree of interobserver reproducibility (ICC = 0.998 (CI 95% 0.991-0.999; p < 0.001).

Conclusion: PMCT and especially lung CT attenuation measurement is a reliable and easy-to-use method for assessing neonatal breath in suspected neonaticides.
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http://dx.doi.org/10.1007/s00414-019-02103-3DOI Listing
May 2020

Bacterial Respiratory Chain Diversity Reveals a Cytochrome Oxidase Reducing O at Low Overpotentials.

J Am Chem Soc 2019 07 5;141(28):11093-11102. Epub 2019 Jul 5.

Aix-Marseille Univ , CNRS, BIP UMR 7281, 31 Chemin Aiguier , CS 70071, 13402 Marseille Cedex 09 , France.

Cytochrome oxidases (COs) are the terminal enzymes in energy-converting chains of microorganisms, where they reduce oxygen into water. Their affinity for O makes them attractive biocatalysts for technological devices in which O concentration is limited, but the high overpotentials they display on electrodes severely limit their applicative use. Here, the CO of the acidophilic bacterium is studied on various carbon materials by direct protein electrochemistry and mediated one with redox mediators either diffusing or co-immobilized at the electrode surface. The entrapment of the CO in a network of hydrophobic carbon nanofibers permits a direct electrochemical communication between the enzyme and the electrode. We demonstrate that the CO displays a μM affinity for O and reduces O at exceptionally high electrode potentials in the range of +700 to +540 mV vs NHE over a pH range of 4-6. The kinetics of interactions between the enzyme and its physiological partners are fully quantified. Based on these results, an electron transfer pathway allowing O reduction in the acidic metabolic chain is proposed.
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http://dx.doi.org/10.1021/jacs.9b03268DOI Listing
July 2019

Ab initio computation for solid-state P NMR of inorganic phosphates: revisiting X-ray structures.

Phys Chem Chem Phys 2019 May;21(19):10070-10074

Materials Research Laboratory, University of California Santa Barbara, California 93106, USA.

The complete 31P NMR chemical shift tensors for 22 inorganic phosphates obtained from ab initio computation are found to correspond closely to experimentally obtained parameters. Further improvement was found when structures determined by diffraction were geometry optimized. Besides aiding in spectral assignment, the cases where correspondence is significantly improved upon geometry optimization point to the crystal structures requiring correction.
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http://dx.doi.org/10.1039/c9cp01420aDOI Listing
May 2019

A new widespread subclass of carbonic anhydrase in marine phytoplankton.

ISME J 2019 08 25;13(8):2094-2106. Epub 2019 Apr 25.

Aix Marseille Univ, CNRS, BIP, UMR 7281, IMM, FR3479, 31 Chemin J. Aiguier, 13402, Marseille Cedex 20, France.

Most aquatic photoautotrophs depend on CO-concentrating mechanisms (CCMs) to maintain productivity at ambient concentrations of CO, and carbonic anhydrase (CA) plays a key role in these processes. Here we present different lines of evidence showing that the protein LCIP63, identified in the marine diatom Thalassiosira pseudonana, is a CA. However, sequence analysis showed that it has a low identity with any known CA and therefore belongs to a new subclass that we designate as iota-CA. Moreover, LCIP63 unusually prefers Mn to Zn as a cofactor, which is potentially of ecological relevance since Mn is more abundant than Zn in the ocean. LCIP63 is located in the chloroplast and only expressed at low concentrations of CO. When overexpressed using biolistic transformation, the rate of photosynthesis at limiting concentrations of dissolved inorganic carbon increased, confirming its role in the CCM. LCIP63 homologs are present in the five other sequenced diatoms and in other algae, bacteria, and archaea. Thus LCIP63 is phylogenetically widespread but overlooked. Analysis of the Tara Oceans database confirmed this and showed that LCIP63 is widely distributed in marine environments and is therefore likely to play an important role in global biogeochemical carbon cycling.
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http://dx.doi.org/10.1038/s41396-019-0426-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6776030PMC
August 2019

Disagreement in cardiac output measurements between fourth-generation FloTrac and critical care ultrasonography in patients with circulatory shock: a prospective observational study.

J Intensive Care 2019 11;7:21. Epub 2019 Apr 11.

2Department of Critical Care, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

Background: Cardiac output measurements may inform diagnosis and provide guidance of therapeutic interventions in patients with hemodynamic instability. The FloTrac™ algorithm uses uncalibrated arterial pressure waveform analysis to estimate cardiac output. Recently, a new version of the algorithm has been developed. The aim was to assess the agreement between FloTrac™ and routinely performed cardiac output measurements obtained by critical care ultrasonography in patients with circulatory shock.

Methods: A prospective observational study was performed in a tertiary hospital from June 2016 to January 2017. Adult critically ill patients with circulatory shock were eligible for inclusion. Cardiac output was measured simultaneously using FloTrac™ with a fourth-generation algorithm (CO) and critical care ultrasonography (CO). The strength of linear correlation of both methods was determined by the Pearson coefficient. Bland-Altman plot and four-quadrant plot were used to track agreement and trending ability.

Result: Eighty-nine paired cardiac output measurements were performed in 17 patients during their first 24 h of admittance. CO and CO had strong positive linear correlation (  = 0.60,  < 0.001). Bias of CO and CO was 0.2 L min (95% CI - 0.2 to 0.6) with limits of agreement of - 3.6 L min (95% CI - 4.3 to - 2.9) to 4.0 L min (95% CI 3.3 to 4.7). The percentage error was 65.6% (95% CI 53.2 to 77.3). Concordance rate was 64.4%.

Conclusions: In critically ill patients with circulatory shock, there was disagreement and clinically unacceptable trending ability between values of cardiac output obtained by uncalibrated arterial pressure waveform analysis and critical care ultrasonography.

Trial Registration: Clinicaltrials.gov, NCT02912624, registered on September 23, 2016.
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http://dx.doi.org/10.1186/s40560-019-0373-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6460822PMC
April 2019

Understanding the Impact of Mesh on Tank Overflow System Capacity.

J Am Water Works Assoc 2018 12 17;110(12):E44-E51. Epub 2018 Oct 17.

U.S. Environmental Protection Agency, Region 8.

A 2016 incident that resulted in damage to a water storage tank's roof motivated pilot-scale experiments to be conducted to determine the impact of mesh on tank overflow capacity. A clean mesh installed near the outlet of an overflow system did not reduce the capacity during the weir dominated flow regime. The impact of a mesh was found to be a reduction in the area available to flow, which was found to lower the achievable capacity through the system. Considering only the head loss or pressure drop associated with the mesh and not area reduction resulted in an overestimation of achievable capacity, which could lead to an undersized overflow system. The results and formulas presented will help water utilities ensure overflow systems with mesh are appropriately sized.
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http://dx.doi.org/10.1002/awwa.1162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6352912PMC
December 2018

FoxP3 and Ezh2 regulate Tfr cell suppressive function and transcriptional program.

J Exp Med 2019 03 31;216(3):605-620. Epub 2019 Jan 31.

Transplantation Research Center, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA

Follicular regulatory T (Tfr) cells are a regulatory T cell subset that controls antibody production by inhibiting T follicular helper (Tfh)-mediated help to B cells. Tfh and Tfr cells possess opposing functions suggesting unique programming. Here we elucidated the transcriptional program controlling Tfr suppressive function. We found that Tfr cells have a program for suppressive function fine-tuned by tissue microenvironment. The transcription factor FoxP3 and chromatin-modifying enzyme EZH2 are essential for this transcriptional program but regulate the program in distinct ways. FoxP3 modifies the Tfh program to induce a Tfr-like functional state, demonstrating that Tfr cells coopt the Tfh program for suppression. Importantly, we identified a Tfr cell population that loses the Tfr program to become "ex-Tfr" cells with altered functionality. These dysfunctional ex-Tfr cells may have roles in modulating pathogenic antibody responses. Taken together, our studies reveal mechanisms controlling the Tfr transcriptional program and how failure of these mechanisms leads to dysfunctional Tfr cells.
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http://dx.doi.org/10.1084/jem.20181134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6400538PMC
March 2019

Transdermal Delivery of Enfuvirtide in a Porcine Model Using a Low-Frequency, Low-Power Ultrasound Transducer Patch.

Ultrasound Med Biol 2019 02 21;45(2):513-525. Epub 2018 Dec 21.

Actuated Medical, Inc., Bellefonte, Pennsylvania, USA.

Ultrasound-mediated transdermal delivery is a promising parenteral administration method for large-molecule or unstable medications. This study evaluated skin health and systemic delivery when administering enfuvirtide, an injectable anti-retroviral medication, over a 1-mo period in a porcine model using a low-frequency cymbal transducer. Three groups received twice-daily treatments: (i) enfuvirtide injection control (n = 12); (ii) saline ultrasound control (n = 6); and (iii) enfuvirtide ultrasound treatment (n = 13). Ultrasound parameters were as follows: 30-min exposure, 90 mW/cm², 24-26 kHz and 15% duty cycle. No statistical difference in trans-epidermal water loss, a measure of skin health and function, was seen between ultrasound-treated and control skin sites for either saline (p = 0.50) or enfuvirtide (p = 0.29) groups. Average trough plasma concentrations of enfuvirtide were 0.6 ± 0.2 and 2.8 ± 0.8 μg/mL for ultrasound and injection, respectively. Tolerability and efficacy results indicate that chronic, low-frequency ultrasound exposure can be a practical means for transdermal delivery of medications such as enfuvirtide.
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http://dx.doi.org/10.1016/j.ultrasmedbio.2018.10.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6476176PMC
February 2019

Probing Cell Mechanics with Bead-Free Optical Tweezers in the Drosophila Embryo.

J Vis Exp 2018 11 2(141). Epub 2018 Nov 2.

CNRS, Institut de Biologie du Développement de Marseille, Aix-Marseille Université;

Morphogenesis requires coordination between genetic patterning and mechanical forces to robustly shape the cells and tissues. Hence, a challenge to understand morphogenetic processes is to directly measure cellular forces and mechanical properties in vivo during embryogenesis. Here, we present a setup of optical tweezers coupled to a light sheet microscope, which allows to directly apply forces on cell-cell contacts of the early Drosophila embryo, while imaging at a speed of several frames per second. This technique has the advantage that it does not require the injection of beads into the embryo, usually used as intermediate probes on which optical forces are exerted. We detail step by step the implementation of the setup, and propose tools to extract mechanical information from the experiments. By monitoring the displacements of cell-cell contacts in real time, one can perform tension measurements and investigate cell contacts' rheology.
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http://dx.doi.org/10.3791/57900DOI Listing
November 2018

Orthopedics in the Age of Accountable Care Organizations and Population Health: From Profit-Center to Cost-Center.

Am J Orthop (Belle Mead NJ) 2018 Sep;47(9)

Department of Orthopedic Surgery, Children's Hospital of New Orleans and Louisiana State University Health Sciences Center, New Orleans, LA.

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http://dx.doi.org/10.12788/ajo.2018.0073DOI Listing
September 2018

Influence of cytochrome charge and potential on the cathodic current of electroactive artificial biofilms.

Bioelectrochemistry 2018 Dec 22;124:185-194. Epub 2018 Jul 22.

Université de Lorraine, CNRS, LCPME, F-54000 Nancy, France. Electronic address:

An electroactive artificial biofilm has been optimized for the cathodic reduction of fumarate by Shewanella oneidensis. The system is based on the self-assembly of multi-walled carbon nanotubes with bacterial cells in the presence of a c-type cytochrome. The aggregates are then deposited on an electrode to form the electroactive artificial biofilm. Six c-type cytochromes have been studied, from bovine heart or Desulfuromonas and Desulfuvibrio strains. The isoelectric point of the cytochrome controls the self-assembly process that occurs only with positively-charged cytochromes. The redox potential of the cytochrome is critical for electron transfer reactions with membrane cytochromes of the Mtr pathway. Optimal results have been obtained with c from Desulfovibrio vulgaris Hildenborough having an isoelectric point of 10.2 and redox potentials of the four hemes ranging between -290 and -375 mV vs SHE. A current density of 170 μA cm could be achieved in the presence of 50 mM fumarate. The stability of the electrochemical response was evaluated, showing a regular decrease of the current within 13 h, possibly due to the inactivation or leaching of loosely-bound cytochromes from the biofilm.
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http://dx.doi.org/10.1016/j.bioelechem.2018.07.015DOI Listing
December 2018

The Tagging Procedure of Visible Implant Elastomers Influences Zebrafish Individual and Social Behavior.

Zebrafish 2018 10 2;15(5):433-444. Epub 2018 Aug 2.

1 Department of Mechanical and Aerospace Engineering, New York University Tandon School of Engineering , Brooklyn, New York.

One commonly used method to preserve individual identity in the study of social behavior of zebrafish is through silicone-based visible implant elastomers (VIEs), which represent a safe and durable tagging procedure. While the effects of VIE tagging on welfare and general health have been addressed in detail, whether this procedure influences social behavior remains unclear. In this study, we compared individual and group behaviors exhibited by shoals composed of three individuals: two nontagged and one (focal subject) that was either nontagged (control condition) or sham-, purple-, blue-, or yellow tagged. Traditional behavioral parameters of activity, shoaling, and schooling (speed, polarization, and interindividual distances), along with an information-theoretic measure of social interaction (transfer entropy), were used to study the effect of tagging. Our findings indicate that tagging procedure per se significantly increased individual speed of the tagged subjects and of the group. The tagging procedure also altered the level of interaction between individuals, measured by transfer entropy. Conversely, tagging procedure did not influence shoaling and schooling tendencies. These findings suggest that VIE tagging may elicit some level of stress, which may affect some behavioral responses more than others. We recommend use of alternative methods such as multitracking systems when possible.
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http://dx.doi.org/10.1089/zeb.2018.1616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6198762PMC
October 2018

Perioperative goal-directed therapy: A systematic review without meta-analysis.

Acta Anaesthesiol Scand 2018 11 6;62(10):1340-1355. Epub 2018 Jul 6.

Department of Critical Care, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

Background: Perioperative goal-directed therapy aims to optimise haemodynamics by titrating fluids, vasopressors and/or inotropes to predefined haemodynamic targets. Perioperative goal-directed therapy is a complex intervention composed of several independent component interventions. Trials on perioperative goal-directed therapy show conflicting results. We aimed to conduct a systematic review and meta-analysis to investigate the benefits and harms of perioperative goal-directed therapy.

Methods: PubMED, EMBASE, Web of Science and Cochrane Library were searched. Trials were included if they had a perioperative goal-directed therapy protocol. The primary outcome was all-cause mortality. The first secondary outcome was serious adverse events excluding mortality. Risk of bias was assessed, and GRADE was used to evaluate quality of evidence.

Results: One hundred and twelve randomised trials were included of which one trial (1%) had low risk of bias. Included trials varied in patients: types of surgery which was expected due to inclusion criteria; in intervention and comparison: timing of intervention, monitoring devices, haemodynamic variables, target values, use of fluids, vasopressors and/or inotropes as well as combinations of these within protocols; and in outcome: mortality was reported in 87 trials (78%). Due to substantial clinical heterogeneity also within the various types of surgery a meta-analysis of data, including subgroup analyses, as defined in our protocol was considered inappropriate.

Conclusion: Clinical heterogeneity in patients, interventions and outcomes in perioperative goal-directed therapy trials is too large to perform meta-analysis on all trials. Future trials and meta-analyses highly depend on universally agreed definitions on aspects beyond type of surgery of the complex intervention and its evaluation.
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http://dx.doi.org/10.1111/aas.13212DOI Listing
November 2018

Electron transfer in an acidophilic bacterium: interaction between a diheme cytochrome and a cupredoxin.

Chem Sci 2018 Jun 1;9(21):4879-4891. Epub 2018 May 1.

Aix Marseille Univ , CNRS , IMM , BIP , UMR 7281 , 31 Chemin Aiguier , 13009 Marseille , France . Email: ; Email:

, a chemolithoautotrophic Gram-negative bacterium, has a remarkable ability to obtain energy from ferrous iron oxidation at pH 2. Several metalloproteins have been described as being involved in this respiratory chain coupling iron oxidation with oxygen reduction. However, their properties and physiological functions remain largely unknown, preventing a clear understanding of the global mechanism. In this work, we focus on two metalloproteins of this respiratory pathway, a diheme cytochrome c (Cyt c) and a green copper protein (AcoP) of unknown function. We first demonstrate the formation of a complex between these two purified proteins, which allows homogeneous intermolecular electron-transfer in solution. We then mimic the physiological interaction between the two partners by replacing one at a time with electrodes displaying different chemical functionalities. From the electrochemical behavior of individual proteins, we show that, while electron transfer on AcoP requires weak electrostatic interaction, electron transfer on Cyt c tolerates different charge and hydrophobicity conditions, suggesting a pivotal role of this protein in the metabolic chain. The electrochemical study of the proteins incubated together demonstrates an intermolecular electron transfer involving the protein complex, in which AcoP is reduced through the high potential heme of Cyt c. Modelling of the electrochemical signals at different scan rates allows us to estimate the rate constant of this intermolecular electron transfer in the range of a few s. Possible routes for electron transfer in the acidophilic bacterium are deduced.
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http://dx.doi.org/10.1039/c8sc01615aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5982212PMC
June 2018

Are Medicare's "Comprehensive Care for Joint Replacement" Bundled Payments Stratifying Risk Adequately?

J Arthroplasty 2018 09 19;33(9):2722-2727. Epub 2018 Apr 19.

Department of Orthopaedics, University of North Carolina Health Care, Durham, North Carolina.

Background: Bundled payments are meant to reduce costs and improve quality of care. Without adequate risk adjustment, bundling may be inequitable to providers and restrict access for certain patients. This study examines patient factors that could improve risk stratification for the Comprehensive Care for Joint Replacement (CJR) bundled-payment program.

Methods: Ninety-five thousand twenty-four patients meeting the CJR criteria were retrospectively reviewed using administrative Medicare data. Multivariable regression was used to identify associations between patient factors and traditional (fee-for-service) Medicare reimbursement over the bundle period.

Results: Average reimbursement was $18,786 ± $12,386. Older age, male gender, cases performed for hip fractures, and most comorbidities were associated with higher reimbursement (P < .05), except dementia (lower reimbursement; P < .01). Stratification incorporating these factors displayed greater accuracy than the current CJR risk adjustment methods (R = 0.23 vs 0.17).

Conclusion: More robust risk stratification could provide more equitable reimbursement in the CJR program.

Level Of Evidence: Large database analysis; Level III.
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http://dx.doi.org/10.1016/j.arth.2018.04.006DOI Listing
September 2018

Spontaneous Healing of a Bucket-Handle Posterior Labral Detachment After Hip Dislocation in a Five-Year-Old Child: A Case Report.

JBJS Case Connect 2018 Apr-Jun;8(2):e28

Department of Orthopaedics, University of North Carolina School of Medicine, Chapel Hill, North Carolina.

Case: We report the case of a 5-year-old girl who sustained a traumatic hip dislocation and a spontaneous reduction that was complicated by nonconcentric reduction and a large bucket-handle labral detachment. This injury was managed, via an anterior approach, with capsulotomy and reduction of the large interposed labral tear with an attached osteochondral fragment from the posterior aspect of the acetabulum. No additional surgical treatment was employed for the labral tear.

Conclusion: The patient ultimately demonstrated radiographic healing and an asymptomatic, clinically stable hip. This case illustrates the spontaneous healing of a large posterior labral detachment in a young pediatric patient with a good outcome at 2.5 years after injury.
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http://dx.doi.org/10.2106/JBJS.CC.17.00133DOI Listing
November 2019

Should All Orthopaedists Perform Hemiarthroplasty for Femoral Neck Fractures? A Volume-Outcome Analysis.

J Orthop Trauma 2018 07;32(7):354-360

Orthopaedic Surgery, University of North Carolina, Chapel Hill, NC.

Objectives: To determine whether very low surgeon and hospital hip arthroplasty volumes are associated with unfavorable outcomes after hemiarthroplasty for femoral neck fractures.

Methods: Patients ≥60 years of age and who underwent hemiarthroplasty for femoral neck fracture were identified in the New York Statewide Planning and Research Cooperative System data from 2001 to 2015. Incidence of inpatient mortality and postoperative complications were compared across both surgeon and hospital volume using multivariable Cox proportional hazards regression, adjusting for clinical and demographic factors.

Results: Fifty eight thousand eight hundred fourteen patients were included. Low surgeon volume (1 case/year) was associated with increased complications [hazard ratio (HR) 1.35, 95% CI, 1.26-1.44, P < 0.0001), including dislocations (HR 1.31 95% CI, 1.04-1.65, P = 0.02) and several medical complications (P = 0.003) compared with surgeons performing at least 2 hip arthroplasties/year. Low hospital volume (<20 cases/year) was associated with increased complications (HR 1.11, 95% CI, 1.02-1.20, P = 0.02), including deep infections (HR 1.39, 95% CI, 1.02-1.89, P = 0.04) and certain medical complications (P = 0.02) compared with centers performing at least 50 hip arthroplasties/year. Hospital and surgeon volume were not associated with inpatient mortality (P = 0.98) or reoperations (P = 0.40).

Conclusions: Providers who rarely perform hemiarthroplasty for femoral neck fractures should defer these cases to surgeons and hospitals who regularly perform hip arthroplasty. Additional research is needed to further characterize the thresholds for "low volume" and to determine whether there is additional benefit afforded by high-volume surgeons and hospitals (or if it is adequate that providers performing hemiarthroplasty maintain volumes above relatively low thresholds as identified here).

Level Of Evidence: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.
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http://dx.doi.org/10.1097/BOT.0000000000001176DOI Listing
July 2018

Reversible Mn/Mn double redox in lithium-excess cathode materials.

Nature 2018 04 11;556(7700):185-190. Epub 2018 Apr 11.

Department of Materials Science and Engineering, University of California, Berkeley, CA, USA.

There is an urgent need for low-cost, resource-friendly, high-energy-density cathode materials for lithium-ion batteries to satisfy the rapidly increasing need for electrical energy storage. To replace the nickel and cobalt, which are limited resources and are associated with safety problems, in current lithium-ion batteries, high-capacity cathodes based on manganese would be particularly desirable owing to the low cost and high abundance of the metal, and the intrinsic stability of the Mn oxidation state. Here we present a strategy of combining high-valent cations and the partial substitution of fluorine for oxygen in a disordered-rocksalt structure to incorporate the reversible Mn/Mn double redox couple into lithium-excess cathode materials. The lithium-rich cathodes thus produced have high capacity and energy density. The use of the Mn/Mn redox reduces oxygen redox activity, thereby stabilizing the materials, and opens up new opportunities for the design of high-performance manganese-rich cathodes for advanced lithium-ion batteries.
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http://dx.doi.org/10.1038/s41586-018-0015-4DOI Listing
April 2018

Refining Risk Adjustment for the Proposed CMS Surgical Hip and Femur Fracture Treatment Bundled Payment Program.

J Bone Joint Surg Am 2018 Feb;100(4):269-277

UNC Health Care, Chapel Hill, North Carolina.

Background: The U.S. Centers for Medicare & Medicaid Services (CMS) has been considering the implementation of a mandatory bundled payment program, the Surgical Hip and Femur Fracture Treatment (SHFFT) model. However, bundled payments without appropriate risk adjustment may be inequitable to providers and may restrict access to care for certain patients. The SHFFT proposal includes adjustment using the Diagnosis-Related Group (DRG) and geographic location. The goal of the current study was to identify and quantify patient factors that could improve risk adjustment for SHFFT bundled payments.

Methods: We retrospectively reviewed a 5% random sample of Medicare data from 2008 to 2012. A total of 27,898 patients were identified who met SHFFT inclusion criteria (DRG 480, 481, and 482). Reimbursement was determined for each patient over the bundle period (the surgical hospitalization and 90 days of post-discharge care). Multivariable regression was performed to test demographic factors, comorbidities, geographic location, and specific surgical procedures for associations with reimbursement.

Results: The average reimbursement was $23,632 ± $17,587. On average, reimbursements for male patients were $1,213 higher than for female patients (p < 0.01). Younger age was also associated with higher payments; e.g., reimbursement for those ≥85 years of age averaged $2,282 ± $389 less than for those aged 65 to 69 (p < 0.01). Most comorbidities were associated with higher reimbursement, but dementia was associated with lower payments, by an average of $2,354 ± $243 (p < 0.01). Twenty-two procedure codes are included in the bundle, and patients with the 3 most common codes accounted for 98% of the cases, with average reimbursement ranging from $22,527 to $24,033. Less common procedures varied by >$20,000 in average reimbursement (p < 0.01). DRGs also showed significant differences in reimbursement (p < 0.01); e.g., DRG 480 was reimbursed by an average of $10,421 ± $543 more than DRG 482. Payments varied significantly by state (p ≤ 0.01). Risk adjustment incorporating specific comorbidities demonstrated better performance than with use of DRG alone (r = 0.22 versus 0.15).

Conclusions: Our results suggest that the proposed SHFFT bundled payment model should use more robust risk-adjustment methods to ensure that providers are reimbursed fairly and that patients retain access to care. At a minimum, payments should be adjusted for age, comorbidities, demographic factors, geographic location, and surgical procedure.
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http://dx.doi.org/10.2106/JBJS.17.00327DOI Listing
February 2018

An inconclusive study comparing the effect of concrete and abstract descriptions of belief-inconsistent information.

PLoS One 2018 15;13(2):e0189570. Epub 2018 Feb 15.

School of Psychology, University of Ottawa, Ottawa, Ontario, Canada.

Linguistic bias is the differential use of linguistic abstraction (as defined by the Linguistic Category Model) to describe the same behaviour for members of different groups. Essentially, it is the tendency to use concrete language for belief-inconsistent behaviours and abstract language for belief-consistent behaviours. Having found that linguistic bias is produced without intention or awareness in many contexts, researchers argue that linguistic bias reflects, reinforces, and transmits pre-existing beliefs, thus playing a role in belief maintenance. Based on the Linguistic Category Model, this assumes that concrete descriptions reduce the impact of belief-inconsistent behaviours while abstract descriptions maximize the impact of belief-consistent behaviours. However, a key study by Geschke, Sassenberg, Ruhrmann, and Sommer [2007] found that concrete descriptions of belief-inconsistent behaviours actually had a greater impact than abstract descriptions, a finding that does not fit easily within the linguistic bias paradigm. Abstract descriptions (e.g. the elderly woman is athletic) are, by definition, more open to interpretation than concrete descriptions (e.g. the elderly woman works out regularly). It is thus possible that abstract descriptions are (1) perceived as having less evidentiary strength than concrete descriptions, and (2) understood in context (i.e. athletic for an elderly woman). In this study, the design of Geschke et al. [2007] was modified to address this possibility. We expected that the differences in the impact of concrete and abstract descriptions would be reduced or reversed, but instead we found that differences were largely absent. This study did not support the findings of Geschke et al. [2007] or the linguistic bias paradigm. We encourage further attempts to understand the strong effect of concrete descriptions for belief-inconsistent behaviour.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0189570PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5813903PMC
March 2018

Acute hand injury splinting - the good, the bad and the ugly.

Ann R Coll Surg Engl 2018 Feb 28;100(2):92-96. Epub 2017 Nov 28.

Department of Orthopaedic Hand Surgery, Morriston Hospital , Swansea , UK.

Injuries to the hand comprise 20% of all emergency department attendances, with an estimated annual treatment cost of over £100 million in the UK. The initial assessment and management of hand injuries is usually undertaken by junior staff, many of whom have little or no training or experience in splinting hand fractures. In the Department of Orthopaedic Hand Surgery, Morriston Hospital, we regularly observe patients presenting to the specialist hand fracture clinics having had initial management that shows no appreciation for the treatment objectives or the safe positions for splinting. This article aims to provide guidance for frontline staff on the management of hand fractures, with particular emphasis on the appropriate nonoperative care to avoid any unnecessary morbidity.
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http://dx.doi.org/10.1308/rcsann.2017.0195DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5838697PMC
February 2018

Acute and repetitive fronto-cerebellar tDCS stimulation improves mood in non-depressed participants.

Exp Brain Res 2018 01 2;236(1):83-97. Epub 2017 Nov 2.

CHEMRI, Center for Health and Environmental Management Research and Innovation, School of Management, Swansea University, Swansea, UK.

Transcranial direct current stimulation (tDCS) is a non-invasive form of brain stimulation, which allows for selective inhibition or excitation of neural structures. It has demonstrated some efficacy in the treatment of mood disorders. However, these studies have predominately focused on stimulation of the prefrontal cortex (PFC). The cerebellum has an increasingly recognized role in emotional control, affective state, and some psychopathologies. As such, tDCS research into mood modulation needs to expand beyond conventional PFC-focused paradigms. Using a contralateral stimulation electrode placement [anodal left dorsolateral(dl)PFC, cathodal right cerebellum], and a single-blind, repeated-measures design, we initially assessed changes in the mood of healthy participants in response to acute stimulation (n = 44) and three repeated stimulations delivered second-daily (n = 21). In a second experiment, we separately investigated the influence of reversed polarity upon these same measures, in response to acute stimulation (n = 23) and repeated stimulation (n = 11). We observed a systematic elevation of mood in both active conditions following single and repeated tDCS, the latter of which displayed a progressive elevation of mood from baseline. No mood change was noted in response to either single or repeated stimulation in the sham condition. Frontocerebellar tDCS stimulation advantageously influences mood in healthy participants, with an accumulative and potentiated effect following successive stimulations. The possibility that frontocerebellar stimulation may provide a novel therapeutic adjunctive or pre-emptive intervention in stress-related disorders and mood-related psychopathologies should be considered.
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http://dx.doi.org/10.1007/s00221-017-5109-yDOI Listing
January 2018
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