Publications by authors named "Mark Hermann"

11 Publications

  • Page 1 of 1

SPOT GRADE II: Clinical Validation of a New Method for Reproducibly Quantifying Surgical Wound Bleeding: Prospective, Multicenter, Multispecialty, Single-Arm Study.

Clin Appl Thromb Hemost 2020 Jan-Dec;26:1076029620936340

Biom'Up France, SAS, Saint-Priest, France.

The SPOT GRADE (SG), a Surface Bleeding Severity Scale, is a unique visual method for assessing bleeding severity based on quantitative determinations of blood flow. This study assessed the reliability of the SG scale in a clinical setting and collected initial data on the safety and efficacy of HEMOBLAST Bellows (HB), a hemostatic agent, in abdominal and orthopedic operations. Twenty-seven patients were enrolled across 3 centers and received the investigational device. Bleeding severity and hemostasis were independently assessed by 2 surgical investigators at baseline and at 3, 6, and 10 minutes after application of HB and compared for agreement. The mean paired κ statistic for assignment of SG scores was .7754. The mean paired κ statistics for determining eligibility for participation in the trial based on bleeding severity and the mean paired κ statistics determining the presence of hemostasis were .9301 and .9301, respectively. The proportion of patients achieving hemostasis within 3, 6, and 10 minutes of HB application were 50.0%, 79.2%, and 91.7%, respectively. There were no unanticipated adverse device effects and one possible serious adverse device effect, as determined by the Independent Data Monitoring Committee (IDMC). The reliability of the SG scale was validated in a clinical setting. Initial data on the safety and efficacy of HB in abdominal and orthopedic operations were collected, and there were no concerns raised by the investigators or the IDMC.
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http://dx.doi.org/10.1177/1076029620936340DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7383655PMC
July 2020

Injection laser system for Advanced Radiographic Capability using chirped pulse amplification on the National Ignition Facility.

Appl Opt 2019 Nov;58(31):8501-8510

We report on the design, performance, and qualification of the injection laser system designed to deliver joule-level chirped pulse beamlets arranged in dual rectangular beam formats into two main laser amplifier beamlines of the National Ignition Facility. The system is designed to meet the requirements of the Advanced Radiographic Capability upgrade with features that deliver performance, adjustability, and long-term reliability.
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http://dx.doi.org/10.1364/AO.58.008501DOI Listing
November 2019

The SPOT GRADE: A Clinically Validated, Quantitative Bleeding Severity Scale.

J Invest Surg 2019 Aug 14:1-2. Epub 2019 Aug 14.

c Department of Cardiovascular Surgery, Charité-Universitätsmedizin Berlin , Berlin , Germany.

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http://dx.doi.org/10.1080/08941939.2019.1651430DOI Listing
August 2019

Evaluation of the safety and efficacy of a new hemostatic powder using a quantitative surface bleeding severity scale.

J Card Surg 2019 Jan 10;34(1):50-62. Epub 2019 Jan 10.

Advanced Powder Investigators Group (APIG).

Aims Of The Study: The safety and efficacy of a hemostatic powder (HP) versus a control agent, absorbable gelatin sponge and thrombin (G + T), were assessed, using a validated, quantitative bleeding severity scale.

Methods: Subjects were randomized to receive HP (256 subjects) or G + T (132 subjects) for treatment of minimal, mild, or moderate bleeding at 20 investigational sites. The primary efficacy endpoint was non-inferiority of HP relative to G + T for success at achieving hemostasis within 6 minutes. Secondary endpoints in rank order included: superiority of HP relative to G + T in mean preparation time; non-inferiority of HP relative to G + T for achieving hemostasis within 3 min; superiority of HP relative to G + T for achieving hemostasis within 6 min; and superiority of HP relative to G + T for success for achieving hemostasis within 3 min.

Results: A total of 388 subjects were included in the primary efficacy analysis. At 6 min, hemostasis was achieved in 93.0% (238/256) of the HP group compared to 77.3% (102/132) of the G + T group (non-inferiority P < 0.0001, superiority P < 0.0001). All secondary endpoints were met. Complications were comparable between treatment groups.

Conclusions: HP had superior rates of hemostasis, shorter preparation time, and a similar safety profile compared to G + T in this prospective, randomized trial using quantitative bleeding severity criteria.
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http://dx.doi.org/10.1111/jocs.13982DOI Listing
January 2019

ISG15: In Sickness and in Health.

Trends Immunol 2017 02 22;38(2):79-93. Epub 2016 Nov 22.

Department of Microbiology, Icahn School of Medicine at Mount Sinai, NY, NY 10029, USA; Department of Pediatrics, Icahn School of Medicine at Mount Sinai, NY, NY 10029, USA; The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, NY, NY 10029, USA. Electronic address:

ISG15 is a type I interferon (IFN)-inducible gene encoding a protein with pleiotropic functions, acting both as a soluble molecule and as a protein modifier. Surprisingly, and despite the antiviral functions of ISG15 described in mice, humans born with inactivating mutations of ISG15 do not present with any overt viral phenotype, but are highly susceptible to environmental mycobacteria and have autoinflammatory disease presentations. In vitro, ISG15 deficiency also leads to persistently high levels of type I IFN-stimulated gene expression and to increased resistance to all viruses tested to date. This suggests that ISG15 deficiency increases antiviral responses in humans, in stark contrast to expectations based on mouse experiments. We discuss here the roles of each of the forms of ISG15 in health and disease, as well as the differences between species.
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http://dx.doi.org/10.1016/j.it.2016.11.001DOI Listing
February 2017

Human USP18 deficiency underlies type 1 interferonopathy leading to severe pseudo-TORCH syndrome.

J Exp Med 2016 06 20;213(7):1163-74. Epub 2016 Jun 20.

Department of Clinical Genetics, Erasmus University Medical Center, 3015 CE Rotterdam, the Netherlands

Pseudo-TORCH syndrome (PTS) is characterized by microcephaly, enlarged ventricles, cerebral calcification, and, occasionally, by systemic features at birth resembling the sequelae of congenital infection but in the absence of an infectious agent. Genetic defects resulting in activation of type 1 interferon (IFN) responses have been documented to cause Aicardi-Goutières syndrome, which is a cause of PTS. Ubiquitin-specific peptidase 18 (USP18) is a key negative regulator of type I IFN signaling. In this study, we identified loss-of-function recessive mutations of USP18 in five PTS patients from two unrelated families. Ex vivo brain autopsy material demonstrated innate immune inflammation with calcification and polymicrogyria. In vitro, patient fibroblasts displayed severely enhanced IFN-induced inflammation, which was completely rescued by lentiviral transduction of USP18. These findings add USP18 deficiency to the list of genetic disorders collectively termed type I interferonopathies. Moreover, USP18 deficiency represents the first genetic disorder of PTS caused by dysregulation of the response to type I IFNs. Therapeutically, this places USP18 as a promising target not only for genetic but also acquired IFN-mediated CNS disorders.
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http://dx.doi.org/10.1084/jem.20151529DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4925017PMC
June 2016

ISG15 deficiency and increased viral resistance in humans but not mice.

Nat Commun 2016 05 19;7:11496. Epub 2016 May 19.

Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York 10029, USA.

ISG15 is an interferon (IFN)-α/β-induced ubiquitin-like protein. It exists as a free molecule, intracellularly and extracellularly, and conjugated to target proteins. Studies in mice have demonstrated a role for Isg15 in antiviral immunity. By contrast, human ISG15 was shown to have critical immune functions, but not in antiviral immunity. Namely, free extracellular ISG15 is crucial in IFN-γ-dependent antimycobacterial immunity, while free intracellular ISG15 is crucial for USP18-mediated downregulation of IFN-α/β signalling. Here we describe ISG15-deficient patients who display no enhanced susceptibility to viruses in vivo, in stark contrast to Isg15-deficient mice. Furthermore, fibroblasts derived from ISG15-deficient patients display enhanced antiviral protection, and expression of ISG15 attenuates viral resistance to WT control levels. The species-specific gain-of-function in antiviral immunity observed in ISG15 deficiency is explained by the requirement of ISG15 to sustain USP18 levels in humans, a mechanism not operating in mice.
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http://dx.doi.org/10.1038/ncomms11496DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4873964PMC
May 2016

A randomized clinical trial to evaluate two doses of an intra-articular injection of LMWF-5A in adults with pain due to osteoarthritis of the knee.

PLoS One 2014 3;9(2):e87910. Epub 2014 Feb 3.

Ampio Pharmaceuticals, Inc., Greenwood Village, Colorado, United States of America.

Objective: The Low Molecular Weight Fraction of 5% human serum Albumin (LMWF-5A) is being investigated as a treatment for knee pain from osteoarthritis.

Methods: This was a multicenter randomized, vehicle-controlled, double-blind, parallel study designed to evaluate the safety and efficacy of two doses of an intra-articular injection of LMWF-5A. Patients with symptomatic knee osteoarthritis were randomized 1∶1∶1∶1 to receive a single 4 mL or 10 mL intra-articular knee injection of either LMWF-5A or vehicle control (saline). The primary efficacy endpoint was the difference between treatment groups in the Western Ontario and McMaster Universities (WOMAC) pain change from baseline over 12 weeks. Safety was examined as the incidence and severity of adverse events (AEs).

Results: A total of 329 patients were randomized and received treatment. LMWF-5A resulted in a significant decrease in pain at 12 weeks compared to vehicle control (-0.93 vs -0.72; estimated difference from control: -0.25, p = 0.004); an injection volume effect was not observed (p = 0.64). The effect of LMWF-5A on pain was even more pronounced in patients with severe knee OA (Kellgren Lawrence Grade IV): the estimated difference from control was -0.42 (p = 0.02). Adverse events were generally mild and were similar in patients who received vehicle control (47%) and LMWF-5A (41%).

Conclusions: This clinical trial demonstrated that LMWF-5A is safe and effective at providing relief for the pain of moderate to severe OA of the knee over 12 weeks when administered by intra-articular injection into the knee.

Trial Registration: ClinicalTrials.gov NCT01839331.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0087910PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3912151PMC
October 2014

Mutations in the gene PRRT2 cause paroxysmal kinesigenic dyskinesia with infantile convulsions.

Cell Rep 2012 Jan 15;1(1):2-12. Epub 2011 Dec 15.

Department of Neurology, UCSF, San Francisco, CA 94158, USA.

Paroxysmal kinesigenic dyskinesia with infantile convulsions (PKD/IC) is an episodic movement disorder with autosomal-dominant inheritance and high penetrance, but the causative genetic mutation is unknown. We have now identified four truncating mutations involving the gene PRRT2 in the vast majority (24/25) of well-characterized families with PKD/IC. PRRT2 truncating mutations were also detected in 28 of 78 additional families. PRRT2 encodes a proline-rich transmembrane protein of unknown function that has been reported to interact with the t-SNARE, SNAP25. PRRT2 localizes to axons but not to dendritic processes in primary neuronal culture, and mutants associated with PKD/IC lead to dramatically reduced PRRT2 levels, leading ultimately to neuronal hyperexcitability that manifests in vivo as PKD/IC.
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http://dx.doi.org/10.1016/j.celrep.2011.11.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3334308PMC
January 2012

Detecting and resolving position-dependent temperature effects in real-time quantitative polymerase chain reaction.

Anal Biochem 2011 Dec 27;419(2):161-7. Epub 2011 Aug 27.

Division of Human Genetics, Departments of Pediatrics and Clinical Research, Inselspital, University of Bern, 3010 Bern, Switzerland.

Real-time quantitative polymerase chain reaction (qPCR) depends on precise temperature control of the sample during cycling. In the current study, we investigated how temperature variation in plate-based qPCR instruments influences qPCR results. Temperature variation was measured by amplicon melting analysis as a convenient means to assess well-to-well differences. Multiple technical replicates of several SYBR Green I-based qPCR assays allowed correlation of relative well temperature to quantification cycle. We found that inadequate template denaturation results in an inverse correlation and requires increasing the denaturation temperature, adding a DNA destabilizing agent, or pretreating with a restriction enzyme. In contrast, inadequate primer annealing results in a direct correlation and requires lowering the annealing temperature. Significant correlations were found in 18 of 25 assays. The critical nature of temperature-dependent effects was shown in a blinded study of 29 patients for the diagnosis of Prader-Willy and Angelman syndromes, where eight diagnoses were incorrect unless temperature-dependent effects were controlled. A method to detect temperature-dependent effects by pairwise comparisons of replicates in routine experiments is presented and applied. Systematic temperature errors in qPCR instruments can be recognized and their effects eliminated when high precision is required in quantitative genetic diagnostics and critical complementary DNA analyses.
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http://dx.doi.org/10.1016/j.ab.2011.08.041DOI Listing
December 2011

Measurement of the repeatability of the prompt flashlamp-induced wavefront aberration on beamlines at the National Ignition Facility.

Appl Opt 2011 Aug;50(22):4382-8

Lawrence Livermore National Laboratory, Livermore, California 94550, USA.

We have undertaken a measurement campaign to determine the repeatability of the prompt flashlamp-induced wavefront aberration on beamlines at the National Ignition Facility (NIF) and determine the extent to which shot-to-shot variations in this aberration may degrade the performance of a proposed adaptive optics system for the short-pulse Advanced Radiographic Capability beamline on NIF. In this paper we will describe the unique NIF configuration that was required to make this measurement, present the results of the experiment, and discuss the implications of these results for the adaptive optics system design.
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http://dx.doi.org/10.1364/AO.50.004382DOI Listing
August 2011