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Article: Mayo v. Prometheus: A Year Later.

Dorn, Brian R

ACS medicinal chemistry letters

2013 Volume 4, Issue 7, Page(s) 572–573

Abstract: Last year's U.S. Supreme Court decision in Mayo v. Prometheus regarding the patent eligibility of diagnostic method claims will probably have the most profound lasting effect of any recent court decision on the biopharmaceutical industry. The Mayo ... ...

Abstract	Last year's U.S. Supreme Court decision in Mayo v. Prometheus regarding the patent eligibility of diagnostic method claims will probably have the most profound lasting effect of any recent court decision on the biopharmaceutical industry. The Mayo decision changed the evaluation of patent eligibility of a method claim under 35 U.S.C. § 101. The new evaluation is a more difficult standard to clear and needs to be considered prior to filing a patent application.
Language	English
Publishing date	2013-06-27
Publishing country	United States
Document type	Journal Article
ISSN	1948-5875
ISSN	1948-5875
DOI	10.1021/ml400230u
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Article ; Online: Cardioverter-defibrillator reduces mortality risk in eligible ischemic and non-ischemic cardiomyopathy patients: Sub-analysis of the multi-center Improve SCA study.

Singh, Balbir / Hsieh, Yu-Cheng / Liu, Yen-Bin / Lin, Kuo-Hung / Joung, Boyoung / Rodriguez, Diego A / Chasnoits, Alexandr R / Huang, Dejia / Zhang, Shu / O'Brien, Janet E / Lexcen, Daniel R / Cerkvenik, Jeffrey / Van Dorn, Brian / Ching, Chi-Keong

Indian heart journal

2023 Volume 75, Issue 2, Page(s) 115–121

Abstract: Background & objective: Despite the burden of sudden cardiac arrest (SCA) worldwide, implantable cardioverter-defibrillators (ICDs) are underutilized, particularly in Asia, Latin America, Eastern Europe, the Middle East, and Africa. The Improve SCA ... ...

Abstract	Background & objective: Despite the burden of sudden cardiac arrest (SCA) worldwide, implantable cardioverter-defibrillators (ICDs) are underutilized, particularly in Asia, Latin America, Eastern Europe, the Middle East, and Africa. The Improve SCA trial demonstrated that primary prevention (PP) patients in these regions benefit from an ICD or a cardiac resynchronization therapy defibrillator (CRT-D). We aimed to compare the rate of device therapy and mortality among ischemic and non-ischemic cardiomyopathy (ICM and NICM) PP patients who met guideline indications for ICD therapy and had an ICD/CRT-D implanted. Methods: Improve SCA was a prospective, non-randomized, non-blinded multicenter trial that enrolled patients from the above-mentioned regions. All-cause mortality and device therapy were examined by cardiomyopathy (ICM vs NICM) and implantation status. Cox proportional hazards methods were used, adjusting for factors affecting mortality risk. Results: Of 1848 PP NICM patients, 1007 (54.5%) received ICD/CRT-D, while 303 of 581 (52.1%) PP ICM patients received an ICD/CRT-D. The all-cause mortality rate at 3 years for NICM patients with and without an ICD/CRT-D was 13.1% and 18.3%, respectively (HR 0.51, 95% CI 0.38-0.68, p < 0.001). Similarly, all-cause mortality at 3 years in ICM patients was 13.8% in those with a device and 19.9% in those without an ICD/CRT-D (HR 0.54, 95% CI 0.33-.0.88, p = 0.011). The time to first device therapy, time to first shock, and time to first antitachycardia pacing (ATP) therapy were not significantly different between groups (p ≥ 0.263). Conclusions: In this large data set of patients with a guideline-based PP ICD indication, defibrillator device implantation conferred a significant mortality benefit in both NICM and ICM patients. The rate of appropriate device therapy was also similar in both groups. Clinical trial registration: ClinicalTrials.gov ID: NCT02099721.
MeSH term(s)	Defibrillators, Implantable ; Cardiomyopathies/mortality ; Cardiomyopathies/therapy ; Humans ; India ; Male ; Female ; Middle Aged ; Aged ; Proportional Hazards Models ; Prospective Studies ; Death, Sudden, Cardiac/epidemiology ; Death, Sudden, Cardiac/prevention & control
Language	English
Publishing date	2023-02-02
Publishing country	India
Document type	Clinical Trial ; Journal Article ; Multicenter Study
ZDB-ID	604366-5
ISSN	2213-3763 ; 0019-4832
ISSN (online)	2213-3763
ISSN	0019-4832
DOI	10.1016/j.ihj.2023.01.010
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Article: Trpc6 Promotes Doxorubicin-Induced Cardiomyopathy in Male Mice With Pleiotropic Differences Between Males and Females.

Frontiers in cardiovascular medicine

2022 Volume 8, Page(s) 757784

Abstract: Background: ...

Abstract	Background:
Language	English
Publishing date	2022-01-13
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2781496-8
ISSN	2297-055X
ISSN	2297-055X
DOI	10.3389/fcvm.2021.757784
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Book ; Online: SoK

Brown, Michael D. / Meily, Adam / Fairservice, Brian / Sood, Akshay / Dorn, Jonathan / Kilmer, Eric / Eytchison, Ronald

A Broad Comparative Evaluation of Software Debloating Tools

2023

Abstract: Software debloating tools seek to improve the program security and performance by removing unnecessary code, called bloat. While many techniques have been proposed, several barriers to their adoption have emerged. Namely, debloating tools are highly ... ...

Abstract	Software debloating tools seek to improve the program security and performance by removing unnecessary code, called bloat. While many techniques have been proposed, several barriers to their adoption have emerged. Namely, debloating tools are highly specialized, making it difficult for adopters to find the right type of tool for their needs. This is further hindered by a lack of established metrics and comparative evaluations between tools. To close this gap, we surveyed of 10 years of debloating literature and several tools currently under commercial development to systematize the debloating ecosystem's knowledge. We then conducted a broad comparative evaluation of 10 debloating tools to determine their relative strengths and weaknesses. Our evaluation, conducted on a diverse set of 20 benchmark programs, measures tools across 16 performance, security, correctness, and usability metrics. Our evaluation surfaces several concerning findings that contradict the prevailing narrative in debloating literature. First, debloating tools lack the required maturity to be used on real-world software, evidenced by a slim 21% overall success rate for creating passable debloated versions of medium- and high-complexity benchmarks. Second, debloating tools struggle to produce sound and robust programs. Using our novel differential fuzzing tool, DIFFER, we discovered that only 13% of our debloating attempts produced a sound and robust debloated program. Finally, our results indicate that debloating tools typically do not improve the performance or security posture of debloated programs by a significant degree. We believe that our contributions in this paper will help potential adopters better understand the landscape of tools and will motivate future research and development of more capable debloating tools. To this end, we have made our benchmark set, data, and custom tools publicly available. Comment: 17 pages, 10 tables
Keywords	Computer Science - Software Engineering ; Computer Science - Cryptography and Security ; Computer Science - Programming Languages
Subject code	005
Publishing date	2023-12-20
Publishing country	us
Document type	Book ; Online
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Article ; Online: The mortality analysis of primary prevention patients receiving a cardiac resynchronization defibrillator (CRT-D) or implantable cardioverter-defibrillator (ICD) according to guideline indications in the improve SCA study.

Ching, Chi Keong / Hsieh, Yu-Cheng / Liu, Yen-Bing / Rodriguez, Diego A / Kim, Young-Hoon / Joung, Boyoung / Singh, Balbir / Huang, Dejia / Hussin, Azlan / Chasnoits, Alexandr R / O'Brien, Janet E / Cerkvenik, Jeffrey / Lexcen, Daniel / Van Dorn, Brian / Zhang, Shu

Journal of cardiovascular electrophysiology

2021 Volume 32, Issue 8, Page(s) 2285–2294

Abstract: Background: In primary prevention (PP) patients the utilization of implantable cardioverter-defibrillators (ICD) and cardiac resynchronization therapy-defibrillators (CRT-D) remains low in many geographies, despite the proven mortality benefit.: ... ...

Abstract	Background: In primary prevention (PP) patients the utilization of implantable cardioverter-defibrillators (ICD) and cardiac resynchronization therapy-defibrillators (CRT-D) remains low in many geographies, despite the proven mortality benefit. Purpose: The objective of this analysis was to examine the mortality benefit in PP patients by guideline-indicated device type: ICD and CRT-D. Methods: Improve sudden cardiac arrest was a prospective, nonrandomized, nonblinded multicenter trial that enrolled patients from regions where ICD utilization is low. PP patient's CRT-D or ICD eligibility was based upon the 2008 ACC/AHA/HRS and 2006 ESC guidelines. Mortality was assessed according to guideline-indicated device type comparing implanted and nonimplanted patients. Cox proportional hazards methods were used, adjusting for known factors affecting mortality risk. Results: Among 2618 PP patients followed for a mean of 20.8 ± 10.8 months, 1073 were indicated for a CRT-D, and 1545 were indicated for an ICD. PP CRT-D-indicated patients who received CRT-D therapy had a 58% risk reduction in mortality compared with those without implant (adjusted hazard ratio [HR]: 0.42, 95% confidence interval [CI]: 0.28-0.61, p < .0001). PP patients with an ICD indication had a 43% risk reduction in mortality with an ICD implant compared with no implant (adjusted HR: 0.57, 95% CI: 0.41-0.81, p = .002). Conclusions: This analysis confirms the mortality benefit of adherence to guideline-indicated implantable defibrillation therapy for PP patients in geographies where ICD therapy was underutilized. These results affirm that medical practice should follow clinical guidelines when choosing therapy for PP patients who meet the respective defibrillator device implant indication.
MeSH term(s)	Cardiac Resynchronization Therapy ; Cardiac Resynchronization Therapy Devices ; Defibrillators, Implantable ; Heart Failure/diagnosis ; Heart Failure/therapy ; Humans ; Primary Prevention ; Prospective Studies ; Risk Factors ; Treatment Outcome
Language	English
Publishing date	2021-07-09
Publishing country	United States
Document type	Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't
ZDB-ID	1025989-2
ISSN	1540-8167 ; 1045-3873
ISSN (online)	1540-8167
ISSN	1045-3873
DOI	10.1111/jce.15149
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Zs.A 2863: Show issues

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Article ; Online: Endovascular treatment of cerebral sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia.

Weller, Johannes / Krzywicka, Katarzyna / van de Munckhof, Anita / Dorn, Franziska / Althaus, Katharina / Bode, Felix J / Bandettini di Poggio, Monica / Buck, Brian / Kleinig, Timothy / Cordonnier, Charlotte / Dizonno, Vanessa / Duan, Jiangang / Elkady, Ahmed / Chew, Beng Lim Alvin / Garcia-Esperon, Carlos / Field, Thalia S / Legault, Catherine / Morin Martin, Mar / Michalski, Dominik /

Pelz, Johann / Schoenenberger, Silvia / Nagel, Simon / Petruzzellis, Marco / Raposo, Nicolas / Skjelland, Mona / Zimatore, Domenico Sergio / Aaron, Sanjith / Sanchez van Kammen, Mayte / Aguiar de Sousa, Diana / Lindgren, Erik / Jood, Katarina / Scutelnic, Adrian / Heldner, Mirjam R / Poli, Sven / Arauz, Antonio / Conforto, Adriana B / Putaala, Jukka / Tatlisumak, Turgut / Arnold, Marcel / Coutinho, Jonathan M / Günther, Albrecht / Zimmermann, Julian / Ferro, José M

European stroke journal

2023 Volume 9, Issue 1, Page(s) 105–113

Abstract: Introduction: There is little data on the role of endovascular treatment (EVT) of cerebral venous sinus thrombosis (CVST) due to vaccine-induced immune thrombotic thrombocytopenia (VITT). Here, we describe clinical characteristics and outcomes of CVST- ... ...

Abstract	Introduction: There is little data on the role of endovascular treatment (EVT) of cerebral venous sinus thrombosis (CVST) due to vaccine-induced immune thrombotic thrombocytopenia (VITT). Here, we describe clinical characteristics and outcomes of CVST-VITT patients who were treated with EVT. Patients and methods: We report data from an international registry of patients who developed CVST within 28 days of SARS-CoV-2 vaccination, reported between 29 March 2021 and 6 March 2023. VITT was defined according to the Pavord criteria. Results: EVT was performed in 18/136 (13%) patients with CVST-VITT (92% aspiration and/or stent retrieval, 8% local thrombolysis). Most common indications were extensive thrombosis and clinical or radiological deterioration. Compared to non-EVT patients, those receiving EVT had a higher median thrombus load (4.5 vs 3). Following EVT, local blood flow was improved in 83% (10/12, 95% confidence interval [CI] 54-96). One (6%) asymptomatic sinus perforation occurred. Eight (44%) patients treated with EVT also underwent decompressive surgery. Mortality was 50% (9/18, 95% CI 29-71) and 88% (8/9, 95% CI 25-66) of surviving EVT patients achieved functional independence with a modified Rankin Scale score of 0-2 at follow-up. In multivariable analysis, EVT was not associated with increased mortality (adjusted odds ratio, 0.66, 95% CI 0.16-2.58). Discussion and conclusion: We describe the largest cohort of CVST-VITT patients receiving EVT. Half of the patients receiving EVT died during hospital admission, but most survivors achieved functional independence.
MeSH term(s)	Humans ; COVID-19 Vaccines/adverse effects ; Purpura, Thrombocytopenic, Idiopathic ; Thrombocytopenia/chemically induced ; Vaccines ; Sinus Thrombosis, Intracranial/etiology
Chemical Substances	COVID-19 Vaccines ; Vaccines
Language	English
Publishing date	2023-09-28
Publishing country	England
Document type	Journal Article
ZDB-ID	2851287-X
ISSN	2396-9881 ; 2396-9873
ISSN (online)	2396-9881
ISSN	2396-9873
DOI	10.1177/23969873231202363
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Article ; Online: "It's Not as Simple as Just Looking at One Chart": A Qualitative Study Exploring Clinician's Opinions on Various Visualisation Strategies to Represent Longitudinal Actigraphy Data.

Keogh, Alison / Johnston, William / Ashton, Mitchell / Sett, Niladri / Mullan, Ronan / Donnelly, Seamas / Dorn, Jonas F / Calvo, Francesc / Mac Namee, Brian / Caulfield, Brian

Digital biomarkers

2020 Volume 4, Issue Suppl 1, Page(s) 87–99

Abstract: Background: Data derived from wearable activity trackers may provide important clinical insights into disease progression and response to intervention, but only if clinicians can interpret it in a meaningful manner. Longitudinal activity data can be ... ...

Abstract	Background: Data derived from wearable activity trackers may provide important clinical insights into disease progression and response to intervention, but only if clinicians can interpret it in a meaningful manner. Longitudinal activity data can be visually presented in multiple ways, but research has failed to explore how clinicians interact with and interpret these visualisations. In response, this study developed a variety of visualisations to understand whether alternative data presentation strategies can provide clinicians with meaningful insights into patient's physical activity patterns. Objective: To explore clinicians' opinions on different visualisations of actigraphy data. Methods: Four visualisations (stacked bar chart, clustered bar chart, linear heatmap and radial heatmap) were created using Matplotlib and Seaborn Python libraries. A focus group was conducted with 14 clinicians across 2 hospitals. Focus groups were audio-recorded, transcribed and analysed using inductive thematic analysis. Results: Three major themes were identified: (1) the importance of context, (2) interpreting the visualisations and (3) applying visualisations to clinical practice. Although clinicians saw the potential value in the visualisations, they expressed a need for further contextual information to gain clinical benefits from them. Allied health professionals preferred more granular, temporal information compared to doctors. Specifically, physiotherapists favoured heatmaps, whereas the remaining members of the team favoured stacked bar charts. Overall, heatmaps were considered more difficult to interpret. Conclusion: The current lack of contextual data provided by wearables hampers their use in clinical practice. Clinicians favour data presented in a familiar format and yet desire multi-faceted filtering. Future research should implement user-centred design processes to identify ways in which all clinical needs can be met, potentially using an interactive system that caters for multiple levels of granularity. Irrespective of how data is displayed, unless clinicians can apply it in a manner that best supports their role, the potential of this data cannot be fully realised.
Language	English
Publishing date	2020-11-26
Publishing country	Switzerland
Document type	Journal Article
ISSN	2504-110X
ISSN (online)	2504-110X
DOI	10.1159/000512044
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Article ; Online: A Thorough Examination of Morning Activity Patterns in Adults with Arthritis and Healthy Controls Using Actigraphy Data.

Keogh, Alison / Sett, Niladri / Donnelly, Seamas / Mullan, Ronan / Gheta, Diana / Maher-Donnelly, Martina / Illiano, Vittorio / Calvo, Francesc / Dorn, Jonas F / Mac Namee, Brian / Caulfield, Brian

Digital biomarkers

2020 Volume 4, Issue 3, Page(s) 78–88

Abstract: Background: Wearable sensors allow researchers to remotely capture digital health data, including physical activity, which may identify digital biomarkers to differentiate healthy and clinical cohorts. To date, research has focused on high-level data (e. ...

Abstract	Background: Wearable sensors allow researchers to remotely capture digital health data, including physical activity, which may identify digital biomarkers to differentiate healthy and clinical cohorts. To date, research has focused on high-level data (e.g., overall step counts) which may limit our insights to Objective: This study therefore aimed to use actigraphy data to thoroughly examine activity patterns during the first hours following waking in arthritis patients ( Methods: Participants wore an Actigraph GT9X Link for 28 days. Activity counts were analysed and compared over varying epochs, ranging from 15 min to 4 h, starting with waking in the morning. The sum, and a measure of rate of change of cumulative activity in the period immediately after waking (area under the curve [AUC]) for each time period, was calculated for each participant, each day, and individual and group means were calculated. Two-tailed independent Results: No differences were seen for summed activity counts across any time period studied. However, differences were noted in the AUC analysis for the discrete measures of relative activity. Specifically, within the first 15, 30, 45, and 60 min following waking, the AUC for activity counts was significantly higher in arthritis patients compared to controls, particularly at the 30 min period ( Conclusion: This study is the first to show that a detailed analysis of actigraphy variables could identify activity pattern changes associated with arthritis, where the high-level daily summaries did not. Results suggest discrete variables derived from raw data may be useful to help identify clinical cohorts and should be explored further to determine if they may be effective clinical biomarkers.
Language	English
Publishing date	2020-09-23
Publishing country	Switzerland
Document type	Journal Article
ISSN	2504-110X
ISSN (online)	2504-110X
DOI	10.1159/000509724
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Article ; Online: IT/QA and Regulatory Aspects of Digital Pathology: Results of the 8th ESTP International Workshop.

Toxicologic pathology

2022 Volume 50, Issue 6, Page(s) 793–807

Abstract: Digital toxicologic histopathology has been broadly adopted in preclinical compound development for informal consultation and peer review. There is now increased interest in implementing the technology for good laboratory practice-regulated study ... ...

Abstract	Digital toxicologic histopathology has been broadly adopted in preclinical compound development for informal consultation and peer review. There is now increased interest in implementing the technology for good laboratory practice-regulated study evaluations. However, the implementation is not straightforward because systems and work processes require qualification and validation, with consideration also given to security. As a result of the high-throughput, high-volume nature of safety evaluations, computer performance, ergonomics, efficiency, and integration with laboratory information management systems are further key considerations. The European Society of Toxicologic Pathology organized an international expert workshop with participation by toxicologic pathologists, quality assurance/regulatory experts, and information technology experts to discuss qualification and validation of digital histopathology systems in a good laboratory practice environment, and to share the resulting conclusions broadly in the toxicologic pathology community.
MeSH term(s)	Humans ; Laboratories ; Pathologists ; Pathology ; Peer Review
Language	English
Publishing date	2022-08-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	841009-4
ISSN	1533-1601 ; 0192-6233
ISSN (online)	1533-1601
ISSN	0192-6233
DOI	10.1177/01926233221113275
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Article: Bacterial interactions with the autophagic pathway.

Dorn, Brian R / Dunn, William A / Progulske-Fox, Ann

Cellular microbiology

2002 Volume 4, Issue 1, Page(s) 1–10

Abstract: Bacteria have evolved a variety of mechanisms to invade eukaryotic cells and survive intracellularly. Once inside, bacterial pathogens often modulate their phagosome to establish an intracellular niche for survival and replication. A subset of ... ...

Abstract	Bacteria have evolved a variety of mechanisms to invade eukaryotic cells and survive intracellularly. Once inside, bacterial pathogens often modulate their phagosome to establish an intracellular niche for survival and replication. A subset of intracellular pathogens, including Brucella abortus, Legionella pneumophila and Porphyromonas gingivalis, are diverted from the endosomal pathway to the auto-phagic pathway. Once within the autophagosome, each in some way presumably modifies this compartment to establish an environment necessary for its survival. Transit into autophagosomes represents an avenue by which to escape host defences. In this review, we examine the biochemical and morphological evidence for the survival of some bacterial pathogens by replicating within an autophagosome-like compartment.
MeSH term(s)	Autophagy ; Bacteria/growth & development ; Bacteria/pathogenicity ; Bacterial Physiological Phenomena ; Humans ; Models, Biological ; Phagosomes/microbiology ; Phagosomes/physiology ; Phagosomes/ultrastructure ; Porphyromonas gingivalis/physiology ; Porphyromonas gingivalis/ultrastructure
Language	English
Publishing date	2002-01-17
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1468320-9
ISSN	1462-5822 ; 1462-5814
ISSN (online)	1462-5822
ISSN	1462-5814
DOI	10.1046/j.1462-5822.2002.00164.x
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