Academic literature on the topic 'Published patent specifications'

Introduction: Tisagenlecleucel (CTL019, tisa-cel) was recently approved for treatment of relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL), high grade B cell lymphoma (r/r HGBCL), and transformed follicular lymphoma (r/r tFL) after second line therapy. Prior to tisa-cel release for commercial use in the United States (US), the final manufactured, patient-specific product must meet specific Lot Release Specifications including requirements that the product's dose contains 0.6 to 6.0 x 108 CAR-positive viable T cells and total cell viability is at least 80%. CAR T cell products that do not meet predetermined release specifications are considered "out of specification" (OOS) and may only be administered via an expanded access protocol or a single patient IND. To date, there are no prospectively reported data with regard to the reasons that commercially manufactured CTL019 products are OOS or clinical outcomes after infusion of OOS CTL019 products. Methods: We are participating in a prospective, managed access protocol to allow administration of CTL019 to patients (pts) with r/r aggressive B-cell lymphomas meeting the approved prescribing information who are intended for treatment with US commercial tisa-cel but have OOS products. Pts were provided product via this managed access program and consent was obtained from all pts enrolled. Pts were unable to receive commercially manufactured product due to failure of apheresis material to meet acceptance specifications, failure of final manufactured product to meet the commercial release specifications, or failure to meet other product specifications within the prescribing information (e.g., interferon gamma release testing). Response was assessed at 3 months post CTL019 infusion by 2014 Lugano Classification criteria applied to FDG-PET/CT imaging. Adverse events were defined by CTCAE and ASTCT criteria. Results: From 9/2018 to 7/2019, 16 pts were enrolled at our institution. Nine pts were diagnosed with r/r DLBCL, 5 pts had r/r HGBCL, and 2 pts had r/r tFL; 44% of all pts had "double-hit" lymphoma. Median age at CTL019 infusion was 68 years (range: 42-75 years); 7 pts (44%) were female. Twelve pts (75%) had advanced stage lymphoma at leukapheresis. Median prior therapies before leukapheresis was 3 (range: 2-5). Median ECOG performance status was 0 (range: 0-2). Median absolute lymphocyte count and CD3 count were 900/uL (range: 200-1300/uL) and 614/uL (range: 228-1343/uL), respectively. Median CTL019 dose was 1.3 x 108 CAR-positive viable T cells (range: 0.5 x 108 to 2.1 x 108). Median product viability was 78.4% (range: 70.8-87.4%). Thirteen of 16 pts (81%) were enrolled due to low viability products (viability < 80%). The median viability for pts enrolled due to low product viability was 78.0% (range: 70.8-79.8%). The remaining 3 pts' products did not meet release specifications due to T cell dose below 0.6 x 108 CAR-positive T cells (dose administered, 0.5 x 108; n=1), residual beads by microscopy (n=1), or IFN gamma release level above the upper range (>1000 fg/transduced cell; n=1). All pts with low viability products had CAR-positive T cell doses that were within the product dose specifications for tisa-cel (13 of 13 pts). Of 16 pts enrolled, 11 pts have at least 3 months follow-up; 3 pts were never treated due to progressive lymphoma and 2 pts have not had 3 month response assessments. Median follow-up is 3.4 months. There were 3 pts with CRS grades 1 or 2 by ASTCT criteria and no pts had neurotoxicity. Of 3 pts with CRS, one received a low dose of CTL019 (grade 2 CRS), one had higher levels of IFN gamma (grade 1 CRS), and one had low viability (grade 1 CRS). For all pts infused with OOS products, the 3-month overall response rate (ORR) was 64% including 6/11 (55%) CR and 1/11 (9%) PR. Progression-free survival (PFS) is 64% at 3 months (median not reached, 95%CI: 30-85%). For OOS products due to low viability, ORR was 4/8 (50%) CR and 4/8 (50%) PD; 3-month PFS was 50% (95%CI: 15-77%). Conclusions: We report the first experience with commercially produced CTL019 products that do not meet product release specifications, primarily due to low viability. Three-month ORRs appear similar to published tisa-cel outcomes for aggressive B-cell non-Hodgkin lymphomas. Our results suggest that other product release characteristics such as potency and replicative capacity should also be more carefully evaluated prior to establishing criteria for release. Disclosures Chong: Novartis: Consultancy; Merck: Research Funding; Tessa: Consultancy. Gerson:Abbvie: Consultancy; Seattle Genetics: Consultancy; Pharmacyclics: Consultancy. Landsburg:Takeda: Research Funding; Seattle Genetics: Speakers Bureau; Takeda: Research Funding; Triphase: Research Funding; Triphase: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Curis, INC: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Seattle Genetics: Speakers Bureau; Curis, INC: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Dwivedy Nasta:Debiopharm: Research Funding; Rafael: Research Funding; Millenium/Takeda: Research Funding; Roche: Research Funding; 47 (Forty Seven): Research Funding; Merck: Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria; Aileron: Research Funding; ATARA: Research Funding; Pharmacyclics: Research Funding. Svoboda:AstraZeneca: Consultancy; Celgene: Research Funding; Incyte: Research Funding; Pharmacyclics: Consultancy, Research Funding; Kyowa: Consultancy; Merck: Research Funding; BMS: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding. Porter:Glenmark Pharm: Membership on an entity's Board of Directors or advisory committees; Immunovative: Membership on an entity's Board of Directors or advisory committees; American Board of Internal Medicine: Membership on an entity's Board of Directors or advisory committees; Genentech: Employment; Wiley and Sons: Honoraria; Kite: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding; Incyte: Membership on an entity's Board of Directors or advisory committees. Barta:Merck: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding; Mundipharma: Honoraria; Celgene: Research Funding; Seattle Genetics: Honoraria, Research Funding; Bayer: Consultancy, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding; Mundipharma: Honoraria. Levine:Incysus: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Patents & Royalties, Research Funding; Novartis: Consultancy; CRC Oncology: Consultancy; Cure Genetics: Consultancy; Vycellix: Membership on an entity's Board of Directors or advisory committees; Brammer Bio: Membership on an entity's Board of Directors or advisory committees; Tmunity Therapeutics: Equity Ownership; Avectas: Membership on an entity's Board of Directors or advisory committees. June:Tmunity: Other: scientific founder, for which he has founders stock but no income, Patents & Royalties; Novartis: Research Funding. Schuster:Novartis: Other: a patent (with royalties paid to Novartis) on combination therapies of CAR and PD-1 inhibitors.; Novartis, Nordic Nanovector, and Pfizer: Membership on an entity's Board of Directors or advisory committees; Novartis, Celgene, Genentech, Merck, Pharmacyclics, Acerta, and Gilead: Other: Grants, Research Funding; Nordic Nanovector, Pfizer, AstraZeneca, Loxo Oncology, Acerta, and Celgene: Honoraria. OffLabel Disclosure: Out of specificity product release of tisagenlecleucel

A quick review of the specification sheets for new technologically intensive diagnostic ultrasound systems reveals a substantial number of fairly impressive operational performance claims. In at least one manufacturer's published material, the system specifications boasts of a dynamic range of 180 dB. To put that number in perspective, a device capable of 180 dB of dynamic range of resolution would be able to detect the flutter of a butterfly's wing in the middle of a thermonuclear explosion. How does one verify such an astounding performance claim using currently available ultrasound testing devices such as a tissue-mimicking phantom and what is the explicit clinical significance of such dynamic range? Additionally, while most of us were focused with amazement in leapfrog advances in system technology, diagnostic ultrasound transducers were also undergoing radical changes in array material composition and design. Most modern composite transducer specifications claim fractional bandwidths of 85%, and more and element counts as high as 2500. While the great technological strides made in ultrasound system design have been impressive, all of the computational and processing power of the 'all-digital' ultrasound device is singularly dependent on the output and input characteristics of the ultrasound transducer. Published data shows that the ultrasound transducer is subject to degradation in performance, as well as element failure, potentially leading to patient misdiagnosis or under-diagnosis. The need to regularly test transducers for performance variances will be explored within this paper. Additionally, the key areas of transducer performance as they relate to image and Doppler quality will be defined.

Abstract Accurate and consistent sequence variant interpretation is critical to the correct diagnosis and appropriate clinical management and counseling of patients with inherited genetic disorders. To minimize discrepancies in variant curation and classification among different clinical laboratories, the American College of Medical Genetics and Genomics (ACMG), along with the Association for Molecular Pathology (AMP), published standards and guidelines for the interpretation of sequence variants in 2015. Because the rules are not universally applicable to different genes or disorders, the Clinical Genome Resource (ClinGen) Platelet Disorder Expert Panel (PD-EP) has been tasked to make ACMG/AMP rule specifications for inherited platelet disorders. ITGA2B and ITGB3, the genes underlying autosomal recessive Glanzmann thrombasthenia (GT), were selected as the pilot genes for specification. Eight types of evidence covering clinical phenotype, functional data, and computational/population data were evaluated in the context of GT by the ClinGen PD-EP. The preliminary specifications were validated with 70 pilot ITGA2B/ITGB3 variants and further refined. In the final adapted criteria, gene- or disease-based specifications were made to 16 rules, including 7 with adjustable strength; no modification was made to 5 rules; and 7 rules were deemed not applicable to GT. Employing the GT-specific ACMG/AMP criteria to the pilot variants resulted in a reduction of variants classified with unknown significance from 29% to 20%. The overall concordance with the initial expert assertions was 71%. These adapted criteria will serve as guidelines for GT-related variant interpretation to increase specificity and consistency across laboratories and allow for better clinical integration of genetic knowledge into patient care.

Safety measure development has focused on inpatient care despite outpatient visits far outnumbering inpatient admissions. Some measures are clearly identified as outpatient safety measures when published, yet outcomes from quality improvement studies also may be useful measures. The authors conducted a systematic review of the literature to identify published articles detailing safety measures applicable to adult primary care. A total of 21 articles were identified, providing specifications for 182 safety measures. Each measure was classified into one of 6 outpatient safety dimensions: medication management, sentinel events, care coordination, procedures and treatment, laboratory testing and monitoring, and facility structures/resources. Compared to the multitude of available inpatient safety measures, the number of existing adult primary care measures is low. The measures identified by this systematic review may yield further insight into the breadth of safety events causing harm in primary care, while also identifying areas of patient safety in primary care that may be understudied.

PURPOSE Because of expanding interoperability requirements, structured patient data are increasingly available in electronic health records. Many oncology data elements (eg, staging, biomarkers, documentation of adverse events and cancer outcomes) remain challenging. The Minimal Common Oncology Data Elements (mCODE) project is a consensus data standard created to facilitate transmission of data of patients with cancer. METHODS In 2018, mCODE was developed through a work group convened by ASCO, including oncologists, informaticians, researchers, and experts in terminologies and standards. The mCODE specification is organized by 6 high-level domains: patient, laboratory/vital, disease, genomics, treatment, and outcome. In total, 23 mCODE profiles are composed of 90 data elements. RESULTS A conceptual model was published for public comment in January 2019 and, after additional refinement, the first public version of the mCODE (version 0.9.1) Fast Healthcare Interoperability Resources (FHIR) implementation guide (IG) was presented at the ASCO Annual Meeting in June 2019. The specification was approved for balloting by Health Level 7 International (HL7) in August 2019. mCODE passed the HL7 ballot in September 2019 with 86.5% approval. The mCODE IG authors worked with HL7 reviewers to resolve all negative comments, leading to a modest expansion in the number of data elements and tighter alignment with FHIR and other HL7 conventions. The mCODE version 1.0 FHIR IG Standard for Trial Use was formally published on March 18, 2020. CONCLUSION The mCODE project has the potential to offer tremendous benefits to cancer care delivery and research by creating an infrastructure to better share patient data. mCODE is available free from www.mCODEinitiative.org . Pilot implementations are underway, and a robust community of stakeholders has been assembled across the oncology ecosystem.

The process of automatic evaluation of a structured C++ program has the first and foremost requirement of specifying the developed structural C++ program in a standard, generalized and unified format. This generalized and standard representation of the program needs to incorporate the specification in terms of semantics as per the language features used and also the contextual binding in regards of the program definition as perceived and desired by the subject expert. Hence an inter - lingua which can represent the semantic and contextual knowledge of the developed structured C++ program will be the first and foremost requirement towards the process of automated assessment and grading of a structured C++ program.The work presented here is published for patent at Patent Office Branch, Mumbai, India with the reference number E-12/215/2021/MUM and application number 202121000796.

Abstract Stability of a measurand in a specimen is a function of the property variation over time in specific storage conditions, which can be expressed as a stability equation, and is usually simplified to stability limits (SLs). Stability studies show differences or even inconsistent results due to the lack of standardized experimental designs and heterogeneity of the chosen specifications. Although guidelines for the validation of sample collection tubes have been published recently, the measurand stability evaluation is not addressed. This document provides an easy guideline for the development of a stability test protocol based on a two-step process. A preliminary test is proposed to evaluate the stability under laboratory habitual conditions. The loss of stability is assessed by comparing measurement values of two samples obtained from the same patient and analyzed at different time points. One of them is analyzed under optimal conditions (basal sample). The other is stored under specific stability conditions for a time set by the laboratory (test sample). Differences are expressed using percentage deviation (PD%) to facilitate comparison with specifications. When the preliminary test demonstrates instability, a comprehensive test is proposed in order to define the stability equation and to specify SLs. Several samples are collected from a set of patients. The basal sample is analyzed under optimal conditions, whereas analysis of test samples is delayed at time intervals. For each patient PD% is calculated as the difference between measurements for every test sample and its basal one and represented in a coordinate graph versus time.

Bioethics is currently witnessing unprecedented debate over the moral and legal norms governing the conduct of clinical research. At the center of this debate is the duty of care in clinical research, and its most widely accepted specification, clinical equipoise. In recent work, we have argued that equipoise and cognate concepts central to the ethics of clinical research have been left unnecessarily vulnerable to criticism. We have suggested that the vulnerability lies in the conspicuous absence of an articulated foundation in moral and legal theory of the physician-researcher's duty of care to the patient-subject. We have repeatedly suggested that the requisite foundation is in the ethics of trust and the law of fiduciaries.Curiously, despite the absence of a published thorough exposition of our position, some have preemptively criticized our suggestion that the relationship between physician-researcher and patient-subject is fiduciary. Others have offered their own accounts of the implications of fiduciary law for the relationship.

Virtual Reality (VR) can play a key role in automotive marketing research, lowering costs and shortening the time to launch a new product. However, few VR applications support automotive customers’ experiences during the early stages of product design. This study aims to identify and characterize into attributes the challenges and opportunities for the application of Virtual Reality in car clinics through a systematic review of the literature and patents. We searched PatentScout, ScienceDirect, Springer, and IEEEXplore for studies published between the databases’ inception and July 2020. Of the 77,383 patents and 336,785 articles identified, 72 and 13 were eligible, respectively. We discovered that patents are strongly concentrated by a few inventors, that the United States has the most records, and that the most prevalent applications relate to devices for automatically reading responders’ emotions in virtual environments. The articles revealed sixteen categories of challenges and opportunities: cost, location to customers, flexibility in interactions, model transportation, depth perception, haptic perception, motion, movement perception/physical collision, color and texture, sound feedback, product interaction/manipulation, visual–spatial, graphic quality, intuitiveness, cybersecurity, and cybersickness. Virtual Reality may be used for automotive marketing research but key factors such as hardware and software specification, stimulus quality, and survey objectives must be considered.

Background: Concerns have been raised over poor standards of hospital cleanliness and insufficient time for staff to clean reusable communal patient care equipment. These items may then act as vectors for the transmission of nosocomial pathogens between hospital patients. Aim: To evaluate the impact of cleaning duration on nosocomial infection rates and estimate the time required to clean care equipment in accordance with national specifications (i.e. a ‘time to clean’). Methods: A systematic review of the published literature on cleaning times and an observational study in which nine healthcare workers cleaned seven items of care equipment while the duration of time taken to clean each item was measured. Results: A limited volume of low-quality evidence indicates that increased cleaning times in hospitals can reduce the incidence of healthcare-associated infections (HCAIs). The mean ‘time to clean’ for care equipment ranged from 166.3 s (95% confidence interval [CI] = 117.8–214.7) for a bed frame to 29.0 s (95% CI = 13.4–44.6) for a blood pressure cuff. Discussion: ‘Time to clean’ estimates for care equipment provide an indication of how much protected time is necessary to ensure acceptable standards of cleanliness. Clinical trials are needed to further evaluate the impact of increased cleaning times on nosocomial infection rates.

This chapter addresses and reconciles often conflicting conclusions published in the professional functional neuroimaging literature regarding the neuronal networks that may mediate consciousness viewed as a function, as well as neuronal circuits that represent specific products of that function, such as concepts, percepts, and experiences that are also referred to as the “contents” or the constituents of the stream of consciousness. The relevant literature is critically reviewed in order to answer the following questions: First, whether and to what degree consciousness-specific networks have been visualized and what are the prospects of their further specification in the future; second, whether imaging of resting neuronal networks can be used for diagnostic and prognostic purposes in cases of compromised consciousness among comatose patients or patients in the vegetative state; and third, whether visualization of the neuronal circuits that represent knowledge in the form of concepts and intentions is feasible.

As a general rule, no further translations are required after the patent specification has been published pursuant to Art 14(6) EPC. Pursuant to Art 14(6) EPC, the specification of an EP is published in the language of proceedings. It also includes a translation of the claims into the other two official languages of the EPO.

Standards are part of our lives. Clinical costing is no exception in this regard. Clinical costing standards are published documents comprising specifications and procedures to build consistent datasets for statutory purposes. The Independent Hospital Pricing Authority publishes and updates Australian Hospital Patient Costing Standards. The standards ensure compatibility and credibility. The standards formulate a consistent and transparent way to process costing. Compliance represents the production of reliable information which could be compared locally, nationally, and internationally. Health professionals could utilize these standards-compliant datasets for testing clinical guidelines for patient safety, developing patient classification systems for counting clinical services, and setting national efficient price for public hospital funding. The ultimate goal is to improve healthcare delivery in an equitable way and reduce human suffering.

Like other information systems in banking and commercial companies, information security is also an important issue in the health care industry. It is a common problem to have security incidences in an information system. Such security incidences include physical attacks, viruses, intrusions, and hacking. For instance, in the USA, more than 10 million security incidences occurred in the year 2003. The total loss was over $2 billion. In the health care industry, damages caused by security incidences could not be measured only by monetary cost. The trouble with inaccurate information in health care systems is that it is possible that someone might believe it and do something that might damage the patient. In a security event in which an unauthorized modification to the drug regime system at Arrowe Park Hospital proved to be a deliberate modification, the perpetrator received a jail sentence under the Computer Misuse Act of 1990. In another security event (The Institute of Physics and Engineering in Medicine, 2003), six patients received severe overdoses of radiation while being treated for cancer on a computerized medical linear accelerator between June 1985 and January 1987. Owing to the misuse of untested software in the control, the patients received radiation doses of about 25,000 rads while the normal therapeutic dose is 200 rads. Some of the patients reported immediate symptoms of burning and electric shock. Two died shortly afterward and others suffered scarring and permanent disability. BS7799 is an information security management standard developed by the British Standards Institution (BSI) for an information security management system (ISMS). The first part of BS7799, which is the code of practice for information security, was later adopted by the International Organization for Standardization (ISO) as ISO17799. The ISO 27002 standard is the rename of the existing ISO 17799 standard. It basically outlines hundreds of potential controls and control mechanisms, which may be implemented. The second part of BS7799 states the specification for ISMS which was replaced by The ISO 27001 standard published in October 2005. The Picture Archiving and Communication System (PACS; Huang, 2004) is a clinical information system tailored for the management of radiological and other medical images for patient care in hospitals and clinics. It was the first time in the world to implement both standards to a clinical information system for the improvement of data security.