Research Inc Research Articles

Evaluation of the Parkinson's Remote Interactive Monitoring System in a Clinical Setting: Usability Study.

The fastest-growing neurological disorder is Parkinson disease (PD), a progressive neurodegenerative disease that affects 10 million people worldwide. PD is typically treated with levodopa, an oral pill taken to increase dopamine levels, and other dopaminergic agonists. As the disease advances, the efficacy of the drug diminishes, necessitating adjustments in treatment dosage according to the patient's symptoms and disease progression. Therefore, remote monitoring systems that can provide more detailed and accurate information on a patient's condition regularly are a valuable tool for clinicians and patients to manage their medication. The Parkinson's Remote Interactive Monitoring System (PRIMS), developed by PragmaClin Research Inc, was designed on the premise that it will be an easy-to-use digital system that can accurately capture motor and nonmotor symptoms of PD remotely. We performed a usability evaluation in a simulated clinical environment to assess the ease of use of the PRIMS and determine whether the product offers suitable functionality for users in a clinical setting. Participants were recruited from a user sign-up web-based database owned by PragmaClin Research Inc. A total of 11 participants were included in the study based on the following criteria: (1) being diagnosed with PD and (2) not being diagnosed with dementia or any other comorbidities that would make it difficult to complete the PRIMS assessment safely and independently. Patient users completed a questionnaire that is based on the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale. Interviews and field notes were analyzed for underlying themes and topics. In total, 11 people with PD participated in the study (female individuals: n=5, 45%; male individuals: n=6, 55%; age: mean 66.7, SD 7.77 years). Thematic analysis of the observer's notes revealed 6 central usability issues associated with the PRIMS. These were the following: (1) the automated voice prompts are confusing, (2) the small camera is problematic, (3) the motor test exhibits excessive sensitivity to the participant's orientation and position in relation to the cameras, (4) the system poses mobility challenges, (5) navigating the system is difficult, and (6) the motor test exhibits inconsistencies and technical issues. Thematic analysis of qualitative interview responses revealed four central themes associated with participants' perspectives and opinions on the PRIMS, which were (1) admiration of purpose, (2) excessive system sensitivity, (3) video instructions preferred, and (4) written instructions disliked. The average system usability score was calculated to be 69.2 (SD 4.92), which failed to meet the acceptable system usability score of 70. Although multiple areas of improvement were identified, most of the participants showed an affinity for the overarching objective of the PRIMS. This feedback is being used to upgrade the current PRIMS so that it aligns more with patients' needs.

Diagnostic speciality enzymes market forecasted to achieve 6.9% CAGR, surpassing $1.8 bn by 2031: report by Transparency Market Research Inc

Diagnostic speciality enzymes market forecasted to achieve 6.9% CAGR, surpassing $1.8 bn by 2031: report by Transparency Market Research Inc

Abstract 128: Multi-Direction Diffusion Weighted Imaging on Portable, Low-Field Magnetic Resonance Imaging

Background and aims: Portable, low-field (LF) MRI has the potential to improve access to expeditious, definitive brain imaging and facilitate diagnosis of acute stroke. Currently available diffusion-weighted imaging (DWI) protocols at LF are limited to a single diffusion direction due to acquisition duration. However, single-direction diffusion has reduced sensitivity for detecting acute ischemic infarcts, particularly small lesions residing in white matter tracts. The purpose of this study was to establish the feasibility of acquiring multi-direction DWI compared with single-direction counterparts on LF-MRI. Methods: Patients presenting with a diagnosis of acute ischemic stroke between July and September 2023 were eligible. Consented patients underwent DWI acquisition on a 0.064T LF-MRI (Mk1.9; Hyperfine Research Inc). Three diffusion directions (x, y, and z) were acquired with a b weighting of 900 s/mm 2 and a single acquisition with a b 0 s/mm 2 . The b 900 images were co-registered to the b 0, trace and apparent diffusion coefficient (ADC) maps calculated, and the final images interpolated at 1 mm 3 . Results: Ten patients presenting to the Massachusetts General Hospital with acute ischemic stroke were consented and imaged within 72 hours of last known well. The total acquisition time was 14 minutes, with all subjects able to tolerate the scan duration. Ischemic lesions as small as 0.1 mL were detectable on the LF-MRI (17.5 +/- 18.2 mL). An example of each diffusion direction individually, the combined trace, and corresponding ADC maps are shown in Figure 1, compared with conventional high-field (HF) diffusion images acquired within 30 minutes of the LF acquisition. Conclusion: Multi-direction DWI imaging is feasible on a 0.064T LF-MRI scanner. Our experience suggests further modifications to the pulse sequence and scanner configuration may facilitate a reduction in acquisition time, improve resolution, or both.

The Influence of Tube Thickness on the Shell Side of the Air preheater As a Form of Corrosion Prevention

Air preheater as a heat recovery technology is generally applied in the powerplant industry and used to heat combustion air, which increases the efficiency of the combustion chamber in the boiler. In this case, air preheater has tubular recuperative type typically located at the bottom of the circulating fluidized boiler for utilizing the lowest temperature exhaust gas. A significant presence of SO2 in the exhaust gas can lead to cold-end corrosion and cause leaks. The low tube thickness in the air preheater provides a good heat transfer performance unfortunately the corrosion issue has not been considered. By increasing the tube thickness, its aimed to extend the life time of the tubes with good corrosion resistance. This study is performed with calculations using empirical equations and validated results using Heat Transfer Research Inc (HTRI) software. Increasing the tube thickness impacts decreasing the heat transfer coefficient, increasing the flue gas (shell) pressure drop, and increasing the fouling factor. The tube thickness which determined for the corrosion prevention design of the air preheater give an overdesign of 18.14%, a heat transfer rate coefficient of 1.726 Btu/hr. ft2. °F, a shell pressure drop of 0.000541 psi, and a fouling factor of 0.114 hr. ft2. °F/Btu.

The potential of high temporal resolution automatic measurements of PM2.5 composition as an alternative to the filter-based manual method used in routine monitoring

Under the EU Air Quality Directive (AQD) 2008/50/EC member states are required to undertake routine monitoring of PM2.5 composition at background stations. The AQD states for PM2.5 speciation this should include at least: nitrate (NO3−), sulfate (SO42−), chloride (Cl−), ammonium (NH4+), sodium (Na+), potassium (K+), magnesium (Mg2+), calcium (Ca2+), elemental carbon (EC) and organic carbon (OC). Until 2017, it was the responsibility of each country to determine the methodology used to report the composition for the inorganic components of PM2.5. In August 2017 a European standard method of measurement of PM2.5 inorganic chemical components (NO3−, SO42−, Cl−, NH4+, Na+, K+, Mg2+, Ca2+) as deposited on filters (EN16913:2017) was published. From August 2019 this then became the European standard method. This filter method is labour-intensive and provides limited time resolution and is prone to losses of volatile compounds. There is therefore increasing interest in the use of alternative automated methods. For example, the UK reports hourly PM2.5 chemical composition using the Monitor for AeRosols and Gases in Ambient air (MARGA, Metrohm, NL). This study is a pre-assessment review of available data to demonstrate if or to what extent equivalence is possible using either the MARGA or other available automatic methods, including the Aerosol Chemical Speciation Monitor (ACSM, Aerodyne Research Inc. US) and the Ambient Ion Monitor (AIM, URG, US).To demonstrate equivalence three objectives were to be met. The first two objectives focused on data capture and were met by all three instruments. The third objective was to have less than a 50% expanded uncertainty compared to the reference method for each species. Analysis of this objective was carried out using existing paired datasets available from different regions around the world. It was found that the MARGA (2006–2019 model) had the potential to demonstrate equivalence for all species in the standard, though it was only through a combination of case studies that it passed uncertainty criteria. The ACSM has the potential to demonstrate equivalence for NH4+, SO42−, and in some conditions NO3−, but did not for Cl− due to its inability to quantify refractory aerosol such as sea salt. The AIM has the potential for NH4+, NO3−, SO42−, Cl− and Mg2+. Future investigations are required to determine if the AIM could be optimised to meet the expanded uncertainty criterion for Na+, K+ and Ca2+.The recommendation is that a second stage to demonstrate equivalence is required which would include both laboratory and field studies of the three candidate methods and any other technologies identified with the potential to report the required species.

Sodium antimonate market to surpass $34 M by 2031, rising at a 4.3% CAGR says, Transparency Market Research Inc

Sodium antimonate market to surpass $34 M by 2031, rising at a 4.3% CAGR says, Transparency Market Research Inc

The Association between ideology and resistance to governmental apology depends on political knowledge

AbstractThis study examines the relationship between ideology and resistance to the government's apology to Asian victims of Japan's colonial rule policy, which varies according to political knowledge. Based on existing research, because only a limited percentage of voters consider politics to be ideology based, it is expected that the association between ideology and resistance to intergroup apologies by one's own government differs according to their level of political knowledge. We selected three issues of political apologies: colonial rule in Asian countries, comfort women, and the massacre of Korean people based on false rumors at the time of the 1923 Kanto Earthquake; thereafter, we conducted an online survey of a panel selected by Nikkei Research Inc. The results suggest that the relationship between ideology and resistance among voters to political apologies varies with the level of political knowledge, as expected. On the contrary, social dominance orientations (SDO) were associated with resistance to apology, regardless of their level of political knowledge. We then tested the reproducibility of this finding by conducting a follow-up test on registered users of a crowdsourcing service after conducting a preregistration. In addition, we also measured general attitudes toward personal apologies and neighboring countries victimized by Japan's colonialist policies as factors that might predict resistance to apologies even among the politically uninformed. The association between ideology, SDO, and resistance to governmental apologies was generally replicated in this study.

Acute heart failure is a remitting-relapsing disorder and not a step towards advanced heart failure: Implications for decongestion therapy.

European Journal of Heart FailureAccepted Articles Viewpoint Acute heart failure is a remitting–relapsing disorder and not a step towards advanced heart failure: Implications for decongestion therapy Gad Cotter, Corresponding Author Gad Cotter [email protected] Université Paris Cité, INSERM UMR-S 942(MASCOT), Paris, France Momentum Research Inc, Durham, North Carolina, USA the Heart initiative, Durham, North Carolina, USA Corresponding author. Dr. Gad Cotter, Email: [email protected]Search for more papers by this authorBeth Davison, Beth Davison Université Paris Cité, INSERM UMR-S 942(MASCOT), Paris, France Momentum Research Inc, Durham, North Carolina, USA the Heart initiative, Durham, North Carolina, USASearch for more papers by this author Gad Cotter, Corresponding Author Gad Cotter [email protected] Université Paris Cité, INSERM UMR-S 942(MASCOT), Paris, France Momentum Research Inc, Durham, North Carolina, USA the Heart initiative, Durham, North Carolina, USA Corresponding author. Dr. Gad Cotter, Email: [email protected]Search for more papers by this authorBeth Davison, Beth Davison Université Paris Cité, INSERM UMR-S 942(MASCOT), Paris, France Momentum Research Inc, Durham, North Carolina, USA the Heart initiative, Durham, North Carolina, USASearch for more papers by this author First published: 22 May 2023 https://doi.org/10.1002/ejhf.2916 This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1002/ejhf.2916. AboutPDF ToolsExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Accepted ArticlesAccepted, unedited articles published online and citable. The final edited and typeset version of record will appear in the future. RelatedInformation

Abstract 2525: Analyzing the role of MDMX for regulating cell death in prostate cancer cells

Abstract Prostate cancer (PCa) is the most prominent cancer type and the second leading cause of cancer death among men in the USA. The five-year survival rate for localized PCa is 98% but drops to 31% when PCa spreads to different parts of the body. Various treatment strategies that can induce cell death through different mechanisms are used while treating cancers. In recent years, necroptosis has been established as one of the effective mechanisms of inducing cell death in cancers. Necroptosis can be identified as a regulated form of cell death that can occur independently of executioner caspases. Despite numerous studies on the effects of necroptosis in cancer, it’s role on PCa has not been fully elucidated. In this study, we have evaluated the role of MDMX, a proto-oncogene involved in the negative regulation of p53, in causing cell death through p53-independent mechanisms. We have observed that inhibition of MDMX decreased the cell viability of LNCaP cells in response to 20 µM of NSC (NSC-207895), a MDMX specific inhibitor treatment, in a concentration-dependent manner. MDMX inhibition appears to induce necroptosis in LNCaP prostate cancer cells by elevating the expression of receptor-interacting protein kinase 1 (RIP1), which is a key element of the necroptotic pathway. In general, the necroptosis pathway can trigger two opposing mechanisms in cancer where it can promote tumor migration and metastasis on one hand and can also act as a defensive mechanism on the other hand when apoptosis is disrupted. To further assess the effect of MDMX on cell migration, the LNCaP cells were treated with 20 µM of NSC, which effectively blocked the cancer cell migration for up to 48 h, which was confirmed using the scratch assay. Interestingly, NSC treatment also reduced the expression of Vascular Endothelial Growth Factor A (VEGFA), which is one of the main markers for angiogenesis. Our results show that the p53-independent mechanisms that are activated following MDMX inhibition can regulate both cancer cell migration and angiogenesis. MDMX also seemed to be involved in regulating PCa cell survival through necroptosis. The outcomes of our experiments provide additional knowledge and strategies for making an accurate prognosis and choosing the most suitable therapeutic strategies for offering effective treatments for MDMX-positive PCa. (This research was supported by the Royal Dames of Cancer Research Inc. Ft. Lauderdale, Florida) Citation Format: Ahmed Alsarrani, Umamaheswari Natarajan, Samia Alsubhi, Amal Alzahrani, Appu Rathinavelu. Analyzing the role of MDMX for regulating cell death in prostate cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2525.

Shell and Tube Heat Exchanger Fouling Factor via Heat Transfer Research Inc (HTRI) Software

One of the factories for manufacturing Carboxymethyl Cellulose (CMC) uses a shell and tube-type heat exchanger as a condenser. The shell and tube (HE) heat exchanger consists of small diameter tubes arranged in a cylindrical shell. In the tube and shell sections, hot (ethanol) and cold (water) fluids will flow so that heat transfer occurs directly. The use of heat exchangers regularly will reduce the performance of the tool. Due to the increasing fouling layer inside the HE, the device will work harder, and the heat process could be more optimal. It is necessary to analyze the performance of the heat exchanger using the parameter value of the fouling factor (Rd). The fouling factor can be calculated using the manual calculation method (via the Kern method) and the HTRI program. The involvement of the mathematical equation in the first method will be configured for the calculation results through process simulation in the HTRI software. Both ways are used for calibration between manual calculations and the HTRI software for the Rd values obtained. The fouling factor can be calculated using the manual method and HTRI software. The two methods used for calibration are manual calculations with HTRI software. The results from this analysis give a decrease in tool performance with a fouling factor of 0,01 Btu/(h.ft2.℉). ABSTRAKSalah satu pabrik pembuatan Carboxymethyl Cellulose (CMC) menggunakan heat exchanger tipe shell and tube sebagai kondensor. Heat exchanger (HE) shell and tube terdiri dari sekumpulan tube berdiameter kecil yang disusun di dalam shell berbentuk silindris. Pada bagian tube dan shell akan dialirkan fluida panas (etanol) dan dingin (air) agar terjadi proses perpindahan panas secara tidak langsung. Penggunaan heat exchanger secara berkala akan mengurangi kinerja alat. Hal tersebut disebabkan oleh adanya lapisan fouling yang terus meningkat di bagian dalam HE sehingga alat akan bekerja lebih berat dan proses perpindahan panas tidak maksimal. Untuk mengatasi fenomena tersebut maka perlu dilakukan analisis kinerja heat exchanger menggunakan parameter nilai fouling factor (Rd). Fouling factor dapat dihitung menggunakan metode perhitungan manual (melalui metode Kern) dan penggunaan program HTRI. Keterlibatan persamaan matematis pada metode pertama akan dikonfigurasi hasil perhitungannya melalui simulasi proses pada software HTRI Kedua metode digunakan untuk kalibrasi antara perhitungan manual dengan software HTRI atas nilai Rd yang didapatkan. Hasil analisis perhitungan dengan kedua metode tersebut menghasilkan penurunan kinerja alat dengan nilai fouling factor sebesar 0,011 Btu/(jam.ft2.℉).

Ready for impact? A validity and feasibility study of instrumented mouthguards (iMGs)

ObjectivesAssess the validity and feasibility of current instrumented mouthguards (iMGs) and associated systems.MethodsPhase I; four iMG systems (Biocore-Football Research Inc (FRI), HitIQ, ORB, Prevent) were compared against dummy headform laboratory...

PROMOSI JABATAN DAN ROLLING JABATAN/MUTASI DALAM PEMBERDAYAAN SDM DI MA AL AMIRIYYAH BLOKAGUNG BANYUWANGI

High work performance will have an impact on high work results. Advanced educational institutions will be meaningless without the welfare of their employees. If employees feel more and more welfare from the results of their hard work, then employees do not hesitate to continually increase their sense of ownership and high responsibility for the sake of educational institutions and for their welfare. Therefore promotion and rolling positions/mutations in empowering human resources in educational institutions are significant to support one of the roles in the success of an organization/educational institution. This study uses a descriptive qualitative research method using observation, interviews/interviews, and documentation as data collection techniques. The data sources of this research inc 1) person, namely, (a) the head of the madrasa, (b) waka of the curriculum, and (b) supervisor. 2) place, namely, at MA Al-Amiriyyah Blokagung Banyuwangi. Data analysis techniques, drawing conclusions or verification. This study also checked the validity of the data by triangulation of sources, methods, and investigations. The results of his research: (1) the implementation of promotions and rolling positions at MA AL Amiriyyah includes several basic foundations based on experience, skills, and a combination of experience and skills, as well as using a merit system for the implementation of rolling positions, (2) the contribution of promotions and position rolling includes developing the vision and mission of the madrasa itself as well as producing certain jobs/angels so that the institution can provide recognition of positions and greater service rewards to employees whose performance is increasingly high. (3) evaluation of job promotions and rolling positions, namely with supervision from the institution as well as holding trainings and workshops for teachers and employees as well as seeing RKM for one year.

Global gaskets and seals market forecast to reach US$74.4 billion by 2028

The value of the market worldwide for gaskets and seals is forecast to be worth US$74.4 billion by 2028, according to a report published recently by Grand View Research Inc.

Water desalination equipment market expected to reach U$22.79 billion by 2028

The size of the market worldwide for water desalination equipment is forecast to reach U$22.79 billion by 2028, according to a report produced by Grand View Research Inc.

Assessing nitrous oxide (N2O) isotopic analyzer performance for in-field use

Analysis of N2O isotope ratios is a way to apportion N2O production in soils among source pathways and develop mitigation strategies. Measurement systems employing a field-deployable LAS instrument coupled with automatic and dynamic soil flux chambers, where the soil emitted gas continuously circulates between the analyzer and the chamber can provide direct in situ N2O flux and N2O isotope ratio measurements with high temporal resolution. Reliable use of these measurements, however, requires quantification of measurement accuracy at high analyzer sampling rates - 2 seconds. We evaluated the variability of the measurements of an LAS isotope N2O analyzer – the OA-ICOS (Isotopic N2O Analyzer model 914–0027, Los Gatos Research Inc, Los Gatos, CA), over N2O concentrations observed in field experiments. We calculated the uncertainty of isotope ratios estimated using the Keeling plot method for representative soil N2O fluxes and chamber closure times. The variability of OA-ICOS isotopic ratio measurements is inversely related to N2O concentration leading to high uncertainty in soil emitted N2O isotope ratios estimated using the Keeling plot method in which low concentration measurements have the largest influence. Instrument precision evaluated using reference gasses was propagated through Monte Carlo simulation to predict system performance under a range of conditions. Model predictions of in situ measurement accuracy were evaluated with soil flux simulations using soil emitted gasses. Isotope ratios derived using OA-ICOS measurements during soil flux simulations deviated markedly from IRMS measurements. System performance was limited by the concentration dependence of N2O isotope ratio measurements and the suspected presence of interferents in soil emitted gasses. These characteristics of the OA-ICOS isotopic analyzer make it poorly suited for in situ source partitioning of soil emitted N2O. Until we overcome these limitations in situ N2O isotopic ratio measurements by OA-ICOS and automatic flux chambers are best used qualitatively.

Spontaneous Coronary Artery Dissection (SCAD) and a family history of aortic artery dissection, a case series

Abstract Background/Introduction SCAD typically affects women in their fifth or sixth decade with a paucity of cardiovascular risk factors.(1) It is caused by a coronary artery intramural haematoma with or without intimal tear. Resultant luminal occlusion manifests as myocardial ischaemia/infarction or death. There are two published sporadic cases of SCAD who developed iatrogenic aortic dissection with coronary angiography.(2, 3) We are not aware of any SCAD cases with intercurrent or historical spontaneous aortic dissection. There is a published SCAD case with a familial history of aortic dissection, in her mother.(4) None of these cases reported a connective tissue disorder. Methods We searched our database of 338 SCAD cases, recruited via social media or cardiologist referral, for cases with a family history of aortic dissection. SCAD diagnosis was confirmed by review of coronary angiogram images by an expert interventional cardiologist blinded to the genetic analysis. Genomic DNA was extracted from buccal cells collected using a cheek swab or mouthwash sample. Whole genome sequencing was performed using the Illumina HiSeq X Ten platform with 30x coverage. These data are being analysed for rare variants in genes associated with familial aortopathies or connective tissue disorders (e.g. FBN1, COL3A1, TGFbR-1/2, SMAD3), as well as for novel gene associations with aortic dissection and/or SCAD. Results We identified 12 cases with a first- or second-degree relative with aortic dissection. Of these SCAD cases, 11 were female whereas 10 of 12 relatives with aortic dissection were male. In one instance, a maternal uncle, but not the index SCAD case, had Marfan's syndrome. Whole genome sequencing has been performed on the 12 SCAD cases, 2 living relatives with aortic dissection and 2 relatives linking the SCAD and aortic dissection cases. Conclusions Coronary and aortic dissections have serious consequences and in some families there may be a genetic association between the two conditions. Early identification of variant carriers is critical for disease prevention. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): This work was supported in part by grants from the Cardiac Society of Australia and New Zealand, the National Health and Medical Research Council, Australia (APP1161200), the St Vincent's Clinic Foundation, the Catholic Archdiocese of Sydney, Perpetual Philanthropy, NSW Health and SCAD Research Inc. LMC is funded by a University Postgraduate Scholarship through University of NSW and a grant from the Avant Foundation.

Intravenous Administration of Nicotinamide Adenine Dinucleotide Improves Cognitive Performance in Human Subjects: Implications for Clinical Populations

<h3>Research Objectives</h3> This pilot study was part of a larger study aimed at characterizing the pharmacokinetic profile of intravenous nicotinamide adenine dinucleotide (NAD+) and measured cognitive performance following IV NAD+ in healthy male subjects. We hypothesized that IV NAD+ would improve cognitive performance scores as compared to baseline performance. <h3>Design</h3> Randomized, controlled study. <h3>Setting</h3> Private mental health treatment center located in Springfield, LA. <h3>Participants</h3> Fifteen healthy male participants (4 Saline/11 IV NAD+) between the ages of 30-55 met inclusion criteria. <h3>Interventions</h3> Participants received 5 consecutive days of IV NAD+ (750 mg/day) or saline infusions <h3>Main Outcome Measures</h3> Researchers used the MicroCog™ Assessment of Cognitive Function to measure cognitive abilities on three levels: (Level 1) Attention, reaction time, memory, reasoning and spatial processing; (Level 2) Information processing speed and accuracy; and (Level 3) Global cognitive functioning and global cognitive proficiency. Participants completed baseline assessment (DAY 0) and repeated the task after the end of the IV infusion protocol (DAY 6). <h3>Results</h3> No differences between SAL and NAD+ groups were noted on DAY 0 in any of the 8 subtests evaluated. However, groups showed differences in the magnitude of improvement over days compared to their respective baselines. The NAD+ group reached significance on 6/8 tests, while the SAL group showed significant improvement on 2/8 tests. <h3>Conclusions</h3> The findings when compared to respective baseline performance scores indicated a greater magnitude of change over and above "practice effects". These results combined with case reports in Parkinson's disease patients suggest that implementation of a standardized cognitive assessment is a practical and effective way to establish efficacy of IV NAD+ treatment for clinical conditions involving cognitive impairment <h3>Author(s) Disclosures</h3> Dr. R. Mestayer is a director of NAD+ Research Inc., and medical director of the Springfield Wellness Center that uses IV NAD+ as a clinical therapy. Dr. Broom-Gibson received consulting fees from NAD+ Research Inc.

Elucidating Exposure-Response (Safety and Efficacy) of ADCT-402 (Loncastuximab Tesirine), a Novel Pyrrolobenzodiazepine-Containing Antibody Drug Conjugate, for Recommended Phase 2 Dose Determination in Patients with Relapsed or Refractory Non-Hodgkin Lymphoma

▪Introduction: ADCT-402 (loncastuximab tesirine) is an antibody-drug conjugate (ADC) composed of a humanized CD19-specific IgG1 antibody stochastically conjugated to a pyrrolobenzodiazepine (PBD) dimer cytotoxin via a cleavable maleimide linker. In this Phase 1 dose escalation trial of heavily pre-treated patients with B-cell non-Hodgkin lymphoma (NHL), loncastuximab tesirine (Lonca-T) 15 to 200 µg/kg was administered every 3 weeks (q3w) by intravenous infusion. The dose and pharmacokinetic (PK) exposure of Lonca-T were modeled as drivers of safety (treatment-emergent adverse events [TEAEs]) and efficacy (reduction in tumor size) for the determination of the Recommended Phase 2 Dose (RP2D).Methods:Concentrations of PBD-conjugated antibody (Ab) in serum were determined using a validated electrochemiluminescence immunoassay, then analyzed by population PK methodology using NONMEM (version 7.3, first-order conditional estimation). Associations between exposure (dose and Bayesian-estimated individual-patient exposure metrics) and the maximum severity of early (Cycle 1) and early or later (all cycles) TEAEs were evaluated for overall TEAEs, anemia, platelets, neutrophils, hemoglobin, fatigue, edema and pleural effusion. Associations of dose and PK with maximum change from baseline tumor size were also determined to identify potential relationships between exposure and activity (complete response plus partial response). For the PK population, drug concentrations were described using the log-transformed both sides approach with a 3-compartment open model and zero-order infusion. In the final population model, gender was retained as a covariate on central volume of distribution.Results: Data from 44 patients (28 males and 16 females) were included in the population PK model. Patients had a mean (range) age of 67 years (24-85) and weight of 87 kg (42-143). A positive relationship was apparent for maximum severity TEAEs, anemia, and thrombocytopenia both in Cycle 1 and in later cycles. A positive relationship was evident for neutropenia, edema and pleural effusion in later cycles only. For patients with and without Grade 3/4 TEAEs, median (5th, 95th percentile) PBD-conjugated Ab area under the curve (AUC) was 13.6 mg*Day/L (0.359, 40.8), and 6.33 mg*Day/L (0.308, 35.0), respectively. Increased exposure to Lonca-T in Cycle 1 was associated with decreased tumor size, with the model giving a dosage of 120 µg/kg q3w as a median minimum dose necessary for requisite efficacy. To achieve at least a 50% tumor size reduction from baseline, the median (min, max) PBD-conjugated Ab AUC was ~66 mg*Day/L (4.69, 294), which is close to the median AUC values of 63.9 and 66.9 mg*Day/L from patients in the 120 and 200 µg/kg cohorts, respectively.Conclusions: By quantitating the differences between exposure associated with grade of a given TEAE and the exposure necessary for efficacy, an optimal dose of Lonca-T associated with an acceptable set of toxicity thresholds was preliminarily identified. Since this trial is ongoing, supplemental pending data will be incorporated into the model, particularly for the 150 µg/kg dose, for an alternate dosage frequency (q6w), for individual patient CD19 status at baseline, and for NHL subtype, to provide the rationale for dosage and regimen selection and definition of the RP2D. DisclosuresO'Connor:ADC Therapeutics: Research Funding. Kahl:Seattle Genetics: Consultancy; ADC Therapeutics: Research Funding; Celgene: Consultancy; Gilead: Consultancy; Genentech: Consultancy. Hamadani:Takeda, Otsuka, MedImmune, Merck, ADC Therapeutics: Research Funding; Sanofi Genzyme: Research Funding, Speakers Bureau; Celgene, Cellerant, Jansen, MedImmune: Consultancy. Caimi:Celgene: Speakers Bureau; ADC Therapeutics: Research Funding. Reid:ADC Therapeutics, Millennium: Research Funding. Feingold:ADC Therapeutics: Employment, Other: Potential equity interest. Havenith:ADC Therapeutics: Employment, Other: Stock option interest. He:ADC Therapeutics: Employment, Other: Potential equity interest. Mould:Projections Research Inc, a consulting company for pharmaceutical industry: Consultancy. Freedman:Projections Research Inc, Gerson Lerhrman Group: Consultancy; Freedman patent: Patents & Royalties. Boni:ADC Therapeutics: Employment, Other: Potential equity interest.

Comparison of Immunogenicity between the Proposed Pegfilgrastim Biosimilar MYL-1401H and Reference Pegfilgrastim

Introduction: Pegfilgrastim, a long-acting granulocyte colony-stimulating factor (G-CSF), is indicated for reduction of incidence of febrile neutropenia in patients with non-myeloid malignancies receiving myelosuppressive chemotherapy. Here, the immunogenicity data for MYL-1401H, a proposed biosimilar of pegfilgrastim, from the clinical studies will be presented.Methods: The efficacy, safety, and immunogenicity of MYL-1401H were investigated in 3 clinical studies, 2 in healthy volunteers (HV) and 1 in patients receiving chemotherapy. MYL-1401H-1001 was a 3-way crossover study comparing the pharmacokinetics (PK) and pharmacodynamics (PD) of a single 2-mg dose of MYL-1401H with reference pegfilgrastim (Neulasta®) sourced from both the European Union (EU) and United States (US) in HV. MYL-1401H-1002 was a parallel-group study designed to compare the immunogenicity of MYL-1401H with US-pegfilgrastim at a repeated 6-mg dose in HV. MYL-1401H-3001 was a multicenter, randomized, double-blind, parallel-group equivalence study of MYL-1401H 6 mg vs EU-pegfilgrastim 6 mg in patients with breast cancer receiving chemotherapy for 6 cycles. The primary efficacy endpoint in MYL-1401H-3001 was duration of severe neutropenia in cycle 1, defined as days with absolute neutrophil count <0.5 × 109/L. A thorough assessment of immunogenicity was conducted across the 3 studies. The antidrug antibody (ADA; Covance, Chantilly, VA) analysis was performed using a validated, sensitive, and specific analytical method on the MesoScale Discovery® Platform (Rockville, MD). Serum samples were analyzed for the presence of ADA against MYL-1401H, EU-pegfilgrastim, and US-pegfilgrastim. Samples that resulted positive in the screening assay were further evaluated in a confirmatory assay. The samples confirmed as ADA positive were titrated to elucidate relative levels of the ADA response and further evaluated for domain characterization to determine if the antibodies were specifically directed against the polyethylene glycol (PEG) or the G-CSF domain of the molecule, or both. Samples confirmed as positive for ADA were analyzed for neutralizing antibodies (NAb; CIRION BioPharma Research) using a validated cell-based assay.Results: Overall, these studies demonstrated that the PK, PD, efficacy, and safety of MYL-1401H were equivalent to reference pegfilgrastim. Across all 3 studies, the proportions of subjects who were ADA positive before dosing were similar in the MYL-1401H (30/223; 13.5%) and EU-pegfilgrastim groups (16/139; 11.5%) and were lower in the US-pegfilgrastim group (4/97; 4.1%). Most (86.0%) of the subjects with ADA had antibodies that recognized the PEG domain, which may be attributable to exposure to PEG-related compounds in the environment as well as the highly sensitive nature of the assay, which can detect very low levels of antibodies. Treatment-induced impact on immunogenicity across the 3 studies was evaluated by analyzing the postdose ADA results excluding those subjects who were ADA positive at baseline (Table). Overall, the proportions of subjects with postdose treatment-induced ADA were similar in the MYL-1401H (20/192; 10.4%) and EU-pegfilgrastim groups (17/123; 13.8%), while they were higher in the US-pegfilgrastim group (28/93; 30.1%). Although the proportion of subjects with treatment-induced ADA was higher in the US-pegfilgrastim group, in most cases, the ADA recognized only the PEG moiety, the titers were low, and the antibodies were non-neutralizing. Two subjects (1 each in the MYL-1401H and EU-pegfilgrastim groups) had antibodies against the G-CSF moiety only. Two subjects were NAb positive in the MYL-1401H group, while none were NAb positive in either reference pegfilgrastim group. There was no evidence of loss of efficacy or severe treatment-induced immune-related adverse events in ADA- or NAb-positive subjects.Conclusion: Results in HV indicate that MYL-1401H does not induce either early or late immune response and has a low immunogenic potential, similar to that of EU- and US-pegfilgrastim, after repeated administration in a sensitive population without any confounding illness or immunosuppressive medications. Similarly, the immunogenic potentials of MYL-1401H and EU-pegfilgrastim are low in patients with breast cancer. Overall, MYL-1401H has an immunogenic profile similar to that of EU-pegfilgrastim and US-pegfilgrastim. [Display omitted] DisclosuresWaller:Mylan: Consultancy, Honoraria. Ranganna:Mylan Pharmaceuticals Inc: Employment. Pennella:Mylan: Employment. Mattano:HARP Pharma Consulting, LLC: Employment. Loa:Mylan Pharmaceuticals Inc: Employment. Donnelly:Mylan Pharmaceuticals Inc: Employment. Liu:Mylan Pharmaceuticals Inc: Employment. Watson:Covance: Employment. St-Jean:CIRION BioPharma Research Inc: Employment. Chatterjee:Biocon Research Ltd: Employment. Nayak:Biocon Research Ltd: Employment. Sengupta:Biocon Research Ltd: Employment. Kothekar:Biocon Research Ltd: Employment. Barve:Mylan Pharmaceuticals Inc: Employment.

485-P: Insights from Type 2 Diabetes Patients Reveal Education- and Income-Based Disparities in Awareness Surrounding Kidney Disease Risk and Renoprotective Therapies

Objective: Diabetes is a leading cause of chronic kidney disease (CKD), and new drug classes including SGLT-2 inhibitors and GLP-1 receptor agonists have shown renal benefits for those with type 2 diabetes (T2D). This study evaluated T2D patients’ awareness regarding CKD and renoprotective drugs across household income and educational attainment. Method: In an online survey in September 2020, 2,008 adults with T2D not currently being treated for kidney disease rated their level of agreement with statements about CKD risk and renoprotective drugs. Demographic information was collected. Result: The majority (58%) of patients strongly agreed that diabetes increases risk of CKD. Those with an income of &amp;lt;$50k and a high school diploma were less aware of the link between diabetes and CKD than those with the same income and a bachelor’s degree or higher (51%, vs. 62%) and those with an income of &amp;gt;$100k and a bachelor’s degree or higher (65%). Only 30% of patients indicated strong concern about CKD risk, and 25% were aware that some T2D drugs have renal benefits. Among those earning $50k-$100k, patients with a high school diploma were more concerned about their risk (44%) than those with some college (24%) or a bachelor’s degree or higher (29%). Those earning &amp;gt;$100k with a bachelor’s degree or higher were more likely to indicate strong awareness that some T2D drugs are renoprotective (34%) than those earning &amp;lt;$50k (high school diploma: 23%; some college: 24%), those earning $50k-$100k (some college: 24%; bachelor’s degree or higher: 25%), and those earning &amp;gt;$100k with some college (20%). Conclusion: While few T2D patients are aware that some T2D drugs have renoprotective effects, those with higher education and income are more likely to be aware. These findings emphasize the importance of informing patients about renal health and therapeutic options, in efforts to increase accessibility of SGLT-2 and GLP-1 therapies to all who would benefit. Disclosure J. Stevenson: Other Relationship; Self; Abbott, Ascensia Diabetes Care, Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, LifeScan, Medtronic, Roche Diabetes Care, Senseonics, Tandem Diabetes Care. E. Ye: Other Relationship; Self; dQ&amp;A. S. Suhl: Other Relationship; Self; dQ&amp;A has several clients (&amp;gt;10) in the diabetes field. R. Gowen: Other Relationship; Self; dQ&amp;A. J. Tait: Other Relationship; Self; dQ&amp;A Market Research Inc. C. Florissi: Other Relationship; Self; Abbott Diabetes, Ascensia Diabetes Care, Dexcom, Inc., Insulet Corporation, LifeScan, Lilly Diabetes, Medtronic, Roche Diabetes Care, Senseonics, Tandem Diabetes Care. R. Wood: Research Support; Self; Abbott Diabetes, American Diabetes Association, Ascensia Diabetes Care, Boehringer Ingelheim International GmbH, Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Medtronic, Novo Nordisk Inc., Sanofi.